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Flashcards in Colon cancer Deck (41)
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1
Q

Discuss the epidemiology of colorectal cancer.

A

Major cancer in ‘developed’ countries
4th most common cancer overall
2nd leading cause of cancer death overall, behind lung cancer
Environmental (diet) and genetic factors in aetiology

2
Q

What are the functions of the colon?

A

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

3
Q

How many cells die per minute in the colon?

A

2-5 million

4
Q

What is the problem with the high turnover in the colon?

A

High proliferation rate renders cells vulnerable to mutation.

5
Q

What are the protective mechanisms usually in place to eliminate genetically defective cells?

A

Natural loss
DNA monitors
Repair enzymes

6
Q

What is a polyp?

A

Any projection from a mucosal surface into a hollow viscus, and may be hyper plastic, neoplastic, inflammatory, hamartomatous, etc.

7
Q

What is an adenoma?

A

A benign neoplasm of the mucosal epithelial cells.

8
Q

What are the types of colonic polyps?

A
Metaplastic/hyperplastic
Adenomas
Juvenile
Peutz Jeghers
Lipomas
Others (essentially any circumscribed intramucosal lesions)
9
Q

What percentage of hyperplastic polyps have a k-Ras mutation?

A

15%

10
Q

What percentage of lower intestinal polyps are hyperplastic?

A

90%

11
Q

How big are hyperplastic polyps?

A

<0.5cm

12
Q

Do hyperplastic polyps have malignant potential?

A

No

13
Q

What are the different types of colonic adenoma?

A

Tubular
Tubulovillous
Villous
May be pedunculate (tree) or sessile (carpet).

14
Q

Describe 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.

15
Q

Describe the microscopic structure of villous 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 hypokalaemia.

16
Q

What causes adenomatous polyposis coli (APC/FAP)?

A

5q21 gene mutation

17
Q

What does the site of the mutation in FAP determine?

A

Clinical variants: classic, attenuated, Gardner, Turcot, etc.

18
Q

What percentage of adults have adenomas by the age of 50?

A

25%

5% of these become cancerous if left untreated.

19
Q

How do we know that adenoma can progress to carcinoma?

A

Most colorectal cancers arise from adenomas.
Residual adenoma in 10-30% of colorectal cancers.
Adenomas and carcinomas have similar distribution.
Adenomas usually precede cancer by 15 years.
Endoscopic removal of polyps decreases the incidence of subsequent colorectal cancer.

20
Q

What are microsatellites?

A

Repeat sequences prone to misalignment.

Some are in coding sequences of genes which inhibit growth or apoptosis, e.g. TGFbR11.

21
Q

What are mismatch repair genes?

A

Repair DNA damage, e.g. MSH2, MLH1 + 4 others.
If mismatch repair genes are damaged in microsatellite instability, cannot repair DNA.
Recessive genes requiring 2 hits.

22
Q

What are the 2 main pathways of genetic predisposition to colorectal cancer?

A

FAP- inactivation of APC tumour suppressor genes

HNPCC- microsatellite instability

23
Q

Discuss the epidemiology of colon cancer.

A

35,000 cases per year in UK
10% of cancer related deaths (16,000 per year UK)
Most common in 50-80 year olds. Sporadic rare <30y/o
High in US, Eastern Europe, Australia
Low in Japan, Mexico, Africa
Dietary factors contribute to risk: high fat, low fibre, high red meat, refined carbohydrates

24
Q

What can MTHFR (methylene tetrahydrofolate reductase) deficiency lead to?

A

Disruption in DNA synthesis causing DNA instability (strand breaks and uracil incorporation), leading to mutations.

25
Q

What are folates important in colorectal cancer?

A

Coenzyme for nucleotide synthesis and DNA methylation.

26
Q

What can decreased methionine synthesis lead to?

A

Genomic hypomethylation and focal hypermethylation, leading to gene activation and silencing.

27
Q

Why is food important in colorectal cancer?

A
Contains 5000-10,000 bioactive chemicals
Contains carcinogens
Also contains anti-cancer agents
Heat modifies chemicals further
Bacteria modify food residues
28
Q

Name some anti-cancer food elements.

A

Vitamin C and E (ROS scavengers)
Isothiocyanates (cruciferous veg)
Polyphenols (green tea, fruit juice)- activate MAPK; regulate phase 2 detoxifying enzymes as well as other genes (e.g. glut-S transferase) and reduce DNA oxidation

29
Q

What is the clinical presentation of colorectal cancer?

A
Change in bowel habit
Bleeding PR
Unexplained iron deficiency anaemia
Mucus PR
Bloating
Cramps ('colic')
Constitutional (weight loss, fatigue)
Patients rationalise these symptoms as 'getting old, piles or irritable bowel', and so do doctors.
30
Q

What is the distribution of cancers around the bowel?

A

Caecum/ascending colon = 22%
Transverse colon = 11%
Descending colon = 6%
Rectosigmoid = 55%

31
Q

What are the types of carcinoma that exist in the large bowel, and which is most common?

A

Adenocarcinomas grade 1-3 (most common, from glands)
Mucinous carcinomas
Signet ring cell
Neuroendocrine

32
Q

How are colonic carcinomas graded?

A

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.

33
Q

How are colonic carcinomas staged?

A

Dukes classification.
Dukes A: growth limited to wall; nodes negative
Dukes B: growth beyond muscular propria; nodes negative
Dukes C1: nodes positive; apical lymph node negative
Dukes C2: apical lymph node positive

34
Q

What clinical features affect prognosis in colon cancer?

A

Diagnosis in asymptomatic patients → ?improved prognosis
Rectal bleeding as presenting symptom → improved prognosis
Bowel obstruction/proliferation → diminished prognosis
Tumor location:
?colon better than rectum
?left colon better than right colon
Age <30 → diminished prognosis
Preoperative serum CEA → diminished prognosis with high CEA level
Distant metastases → markedly diminished prognosis

35
Q

What are the pathological features affecting prognosis in colon cancer?

A

Depth of bowel wall penetration → increased penetration diminishes prognosis
Number of regional lymph nodes involved → 1-4 nodes better than >4 nodes
Degree of differentiation → well > poorly differentiated
Mucinous (colloid) or signet ring cell → diminished prognosis
Venous invasion → diminished prognosis
Lymphatic invasion → diminished prognosis
Perineural invasion → diminished prognosis
Local inflammation and immunologic reaction → improved prognosis

36
Q

What are the criteria for screening for high risk colon cancer?

A

Previous adenoma
1st degree relative affected by colorectal cancer before the age of 45
2 affected first degree relatives
Evidence of dominant familial cancer trait including colorectal, uterine, and other cancers
UC and Crohn’s disease
Heritable cancer families (include other sites)

37
Q

What is screening?

A

The practice of investigating apparently 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 the occurrence of disease or improve the prognosis when it develops.

38
Q

Why is colon cancer screened for?

A

Important condition in respect to the seriousness and/or frequency
Natural history of disease known
Test is simple and accessible to patient
Test is sensitive and selective
Screening population has equal access to screening procedure
Cost effective

39
Q

Why must the natural history of the disease be known for it to be screened for?

A

To identify where screening can take place

To enable the effects of any intervention to be assessed

40
Q

How is colon cancer screened for?

A

Faecal occult blood (FOB)

Colonoscopy/sigmoidoscopy if positive.

41
Q

If a 76-year-old man presents with new onset rectal bleeding to the GP, what must be excluded in the first instance?

A

Colorectal malignancy.