Cancer 13: Colon cancer

Question 1

Describe epidimiology of colon cancer?

Answer 1

4th most common cancer overall
2nd highest in mortality rate

genetic and diet aetiology

Question 2

Describe anatomy of the colon? Role? Cellular organisation?

Answer 2

starts in right illiac fossa where illium joins caecum
Ascending colon-hepatic flexture, transverse, splenic flexture, descending, sigmoid
In front-perineum, at back-mesentery

Extraction of water from feaces-electrolyte balance
Faecal reservoir
bacterial digestion for vitamins- (Vit B, Vit K)

Colon folds-haustra-epithelial and lamina propria, then muscluaris mucosa, then submucosa, muscularis propria-
Folds form crypts of leukbrahan-stem cells deep in crypt proliferating and pushing cells up
Mainly columnar, goblet, Endorine cells

Question 3

How often do colon cells turnover?

Answer 3

2-5million cell die per second -> vulnerable for cancer
APC mutations preventing cell less->accumulation of mutation

3ways to eliminate: Natural loss (as pushed out of crypt)
DNA monitors (p53, etc)
Repair enzymes

Question 4

Define polyp and adenoma? Which from is more common

Answer 4

Polyp is general term-any projection into the lumen -from the mucosal membrane-can be hyperplastic. neoplastic, inflammatory, lipomas, Peutz Jegher (mucosal hyperpigmentation)
Much more commonly hyperplastic-often multiple
-> Histologically-look like very long crypes

adenoma-type of polyp-benign neoplasm of mucosal epithelial cells

Question 5

What are the different types of colon adenomas?

Answer 5

Majority-tubular adenomas-90%
10%-tubivillous (between tubular and villous-some cells are tubualr, some villous)
Villous
VERY RARE-flat/serrated

Question 6

What is a pedunculated adenoma and sessile adenoma?

Answer 6

pedunculated-polyp on a stalk of normal tissue-cancer usually develops in head of stalk-easier to remove in surgery even if starts spreading in stalk
Serrated-flat

Question 7

Describe the microscopic sturcture of tubular adenoma?

Answer 7

Columnar cells with nuclear enlargement (darker histological), elongation, multilayering and loss of polarity
-Increase proliferative activity and reduced differentiation
Disorganised architecture

look like tubules

Question 8

Describe the microscopic sturcture of villous adenoma?

Answer 8

same dysplasia features-nuclear enlargement (darker histological), elongation, multilayering and loss of polarity
Exophytic, frond like extensions-finger like projection, elongation

Rarely results i hypersecretory function, resulting in lot of mucus discharge and hypokalemia

Question 9

What does dysplasia means?

Answer 9

Abnormal growth of cells with some features of cancer —-(nuclear enlargement (darker histological), elongation, multilayering and loss of polarity)

indefinite, low grade, high grade
step before neoplasm

Question 10

What is familial adenomatous polyposis coli?

Answer 10

FAP/APC
5q21 gene mutation-APC gene
site determines which clinical varient
but overall-develop thousands of poly adenomas-covered-100% of cancer over life
prophylatic colectomy<30

can also lead to other tumours-brain etc

Question 11

How common are colonic adenomas?

Answer 11

25% of adults will have it by 50
5% become cancer if left
large polyps have higher risks

stay curable for 2 years +/-

Question 12

How does colon adenomas progress to carcinoma?

Answer 12

MOST CRC arrise from adenoma
residual after CrC
adenomas usually precede cancer by 10 years

Question 13

What is the genetics pathways of colon cancer?

Answer 13

carcinoma sequence=-APC, Kras, p53, telomerase activation

but not all adenoma/carci fit in there
microsatellite instability- they are repeats in DNA prone to missalignemet-some microsaterllits code for inhbit growths or apoptosis
need 2 hits to lose it-
(HPNCC (its a disease)-classically has germline mutation in these genes)

Question 14

What are the histological sequences leading to colon cancer?

Answer 14

Normal colon -> risky mucosa (APC, B caterninn, MSH2 mutations?-cause increased risks of mutations leading to accumulations)
-> Rise of polyp (Kras, p53)-adenoma
=>carcinoma–many genes

Question 15

Why is APC specifically important in colon cancer? how does p53 levels change in cancer?

Answer 15

APC holds/inhbits a TF (Bcatenin) off the nucleus-if mutated-acts as TF -> increase proliferation and stuff

in colon-stem cells want to proliferate-APC on purpose stopped but turned back on as the the cells diffferentiate and reach the top of the cryppt-if mutated can turn APC bak on-b catenin stays working

p53 levels atually increase cause it has mutation causing it ti not function-cell contunues producing it

Question 16

What causes colonic carcinoma? Specific exemple of food molecules?

Answer 16

More common in west
Less fibre, more fats-

food in general contains carcinogens, but also protectors (depending on cooking)
HCA-heterocylic acids-heat on meat causes them-fors junctures with DNA-complex that lead to mutation
Folate-from veg-needed for DNA methylatiob
MTHFR-deficiency leads to DNA instability

Anticancer-VitC and E-Ros scavenger, garlic, green tee

Question 17

What are the clinical symptoms of colon cancer?

Answer 17

change in bowel habits, bleeding PR, unexplained aneamia

Mucus PR, bloating, cramps, weight loss, fatigue

Question 18

Where is colon cancer more common?

Answer 18

Caecum and ascending-22%
transverse0-11%
rectosigmoid-55%-but block the passage fast so signs
descending-rest

Question 19

How is colon cancer graded? What is dukes?

Answer 19

Proportion of gland differentitation to solid area or nest and cord of cell without lumina (continous cancer
70%-moderatly differentiation

Drukes-A-limited to wall
B-musc propria
C1-nodes poititive but LN negative
C2-LN positive

Question 20

What are the worse characteristics for prognosis?

Answer 20

asymtomatic-better prog
Tumour location-colon better than rectum, left better than right
age <30-bad
distant metastases- very bad
depth of penetration-lower better
Lymph nodes-less is better
Differentiation-well is better
type of carcinoma-muscinous/signet ring cell-worse
invasion-bad
local inflammation and immunological reaction-good

Question 21

what are the treatment options of colon cnacer?

Answer 21

Stage I- surgery
II-surgery + 5FU
III-Sruegry + 5FU-leucovorin
IV-surgery, surgery on metastasis, chemo, palliative Radio

Question 22

what are good indicatiors of high risk of colon cnacer?

Answer 22

Previous adenoma
1st degree relative with youth colon cancer
2affected first degree relative
evidence of familial trait
UC and chrons
herediablt cancer

want to pick up as early as possible
=> colonoscopy