Cancer 13 - Colorectal Cancer

Question 1

Describe colon physiology and function

Answer 1

1. Extraction of water from faeces - electrolyte balance
2. Faecal reservoir (evolutionary advantage)
3. Bacterial digestion for vitamins (e.g. B and K)

Question 2

In cell turnover, proliferation renders cells vulnerable. What are the protective mechanisms we have to eliminate genetically defective cells?

Answer 2

1. Natural loss
2. DNA monitors
3. Repair enzymes

Question 3

Distinguish polyps and adenomas

Answer 3

Polyp = any projection from mucosal surface into a hollow viscous, may be any phenotype (e.g. hyper plastic, neoplastic, inflammatory, hamartomatous, etc)

Adenoma = benign neoplasm of mucosal epithelial cells

Question 4

Describe hyper plastic polyps

Answer 4

Very common

Often multiple - not much malignant potential

Dont cause cancer

Question 5

Describe colonic adenoma types

Answer 5

1. Tubular (more common) - looks like a row of test tubes
2. Villous (looks more villous-like) - less common, more worrying
3. Tubulovillous = mixture of both

Another way to categorise colonic adenoma types is Pedunculated vs Sessile

Pedunculated: like a tree in a field

Sessile: posh carpet

Can mix and match tubular, pedunculated, etc

Question 6

What are the microscopic structural features of tubular adenomas

Answer 6

1. Columnar cells - there is nuclear enlargement, elongation, multilayering and loss of polarity
2. Increased proliferative activity
3. Reduced differentiation
4. Higher complexity / disorganisation of archtecture

Darker as increased nuclear:cytoplasmic ratio

Question 7

Describe microscopic structure of villous adenomas

Answer 7

1. Mucinous cells - nuclear enlargement, elongation, multilayering and loss of polarity
2. Exophytic, frond like extensions
3. Rarely may have hypersecretory function and result in excess mucus discharge and hypokalaemia - may cause electrolyte problems

More purple, less pink. Pink good, purple bad

Question 8

What is dysplasia

Answer 8

Abnormal growth of cells with some features of cancer

Can be indefinite, low grade or high grade

Question 9

Name a condition which increases the risk of dysplasia occuring

Answer 9

Ulcerative colitis

Question 10

Describe Adenomatous Polyposis Coli (APC / FAP)

Answer 10

5q21 gene mutation

Site of mutation determines clinical variants (e.g. classic, attenuated, Gardner, Turcot, etc)

Many patients have prophylactic colectomy

Question 11

Colonic adenomas stay curable for 2 years (if you remove it). Large polyps have …. risk than small polyps

Answer 11

Large polyps = higher risk

Question 12

Describe the progression from adenoma to carcinoma

Answer 12

Gradual accumulation of genetic abnormalities leads to cancer

Adenomas precede cancers by about 15 years

Question 13

Describe the genetic pathways to get colorectal cancer

Answer 13

1. Adenoma carcinoma sequence. APC, K ras, Smads, p53, telomerase activation. Accumulation of genetic damage until you get a carcinoma
2. Microsatellite instability - mismatch repair genes causing incorrect repair and proliferation. Recessive genes requiring 2 hits

Microsatellite = repeat sequences prone to misalignment

Question 14

What are the 2 genetic predispositions to colorectal cancer

Answer 14

1. FAP - inactivation of APC tumour suppressor genes

2. HNPCC - micro satellite instability

Question 15

Which dietary factors contribute to colonic carcinoma

Answer 15

1. High fat
2. Low fibre
3. High red meat
4. Refined carbohydrates

Question 16

Dietary deficiencies that may contribute to cancer?

Answer 16

1. Folate

Question 17

What are some anticancer food elements

Answer 17

1. Vit C (ROS scavenger)
2. Vit E (ROS scavenger)
3. Isothiocyanates
4. Polyphenols - activate MAPK which regulates phase2 detoxifying enzymes.- reduce DNA oxidation

Question 18

What is the clinical presentation of colon cancer?

Answer 18

1. Change in bowel habit
2. Bleeding PR (often Lt sided)
3. Unexplained iron deficiency anaemia (more common Rt side)

Other things e.g. mucus PR, bloating, cramps, constitutional

Question 19

Where is the most common area of colorectal cancer?

Answer 19

Rectosigmoid (55%)

Caecum ascending colon = 22%

TV colon = 11%

Descending colon = 6%

Question 20

Adenocarcinomas are malignant tumours of the …….?

Answer 20

Glandular epithelium

Graded on differentiation from 1-3 (well / moderate (70%) / poor)

Subtypes of adenocarcinomas include: mucinous carcinomas, signet ring cell, neuroendocrine

Question 21

What is the basis behind Dukes classification

Answer 21

How far the cancer has spread

Dukes A - limited to wall (i.e. muscularis propria), nodes negative

Dukes B - growth beyond musc propria, nodes negative

Dukes C1 - nodes positive, apical LN negative

Dukes C2 - apical LN positive

Question 22

What are the 2 types of screening for colon cancer?

Answer 22

1. High risk colon cancer - e.g. UC / Crohns / 1st degree relative affected by Crohns before 45, etc
2. Population screening