Cancer 13:colorectal cancer as a disease

Question 1

What is the role of the colon

Answer 1

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

Question 2

What are the layers of the colon?

Answer 2

epithelium
lamina propria 
muscularis mucosa 
submucosa 
muscularis propria 
fat and blood vessels

Question 3

What type of cancer is usually found in colon?

Answer 3

adenocarcinomas - in the glandular epithelium

Question 4

What is the role of the crypts of lieberkuhn?

Answer 4

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

Question 5

What is the turnover of the colon?

Answer 5

• 2-5 million cells die perminute

- proliferation renders cells vulnerable

Question 6

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

Answer 6

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

Question 7

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

Answer 7

• natural loss
• DNA monitors
• repair enzymes

Question 8

What is a polyp?

Answer 8

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

Question 9

What is an adenoma?

Answer 9

a benign neoplasm of the mucosal epithelial cells

Question 10

What are the main types of colonic polyp types?

Answer 10

• metaplastic/hyperplastic

- adenomas

Question 11

What are the features of hyperplastic polyps?

Answer 11

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

Question 12

What are the colonic adenoma types?

Answer 12

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

Question 13

What are the two different shapes of adenomas?

Answer 13

• pedunculated adenomas are on a stalk

- sessile adenomas are flat and raised

Question 14

What is the microscopic structure of tubular adenomas?

Answer 14

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

Question 15

What is the microscopic structure of tubular adenomas?

Answer 15

• 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

Question 16

Define dysplasia

Answer 16

-abnormal growth of cells with some features of cancer

indefinite has low grade and high grade

Question 17

Which condition increases the number of polyps?

Answer 17

-familial adenomatous polyposis (FAP)

Question 18

What causes adenomatous polyposis coli?

Answer 18

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

Question 19

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

Answer 19

• 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

Question 20

How does an adenoma progress to carcinoma?

Answer 20

• 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

Question 21

What are the THREE genetic pathways in colorectal cancer?

Answer 21

-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

Question 22

What dietary deficiencies can impact on colorectal cancer and why?

Answer 22

-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

Question 23

Which foods are associated with anti-cancer properties?

Answer 23

• vitamin C
• vitamin E
• isothiocyanates
• polyphenols

Question 24

What are the clinical presentations of colorectal cancer?

Answer 24

• 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

Question 25

What are the macroscopic features of colorectal cancer?

Answer 25

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

Question 26

What is the distribution of colorectal cancer?

Answer 26

- caecum/ascending colon 22% - transverse colon 11% - descending colon 6% - rectosigmoid 55%

Question 27

What are the possible structure of microscopic carcinomas?

Answer 27

- mucinous carcinoma - signet ring cell - neuroendocrine almost all of the carcinomas are adenocarcinomas

Question 28

How is the adenocarcinoma graded?

Answer 28

- 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

Question 29

How does Dukes Classification work?

Answer 29

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

Question 30

What clinical features affect prognosis?

Answer 30

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

Question 31

What pathological features affect prognosis?

Answer 31

- 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

Question 32

In what circumstances are people screened for cancer?

Answer 32

- 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

Question 33

What is the definition of screening?

Answer 33

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

Question 34

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

Answer 34

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