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Year 2 - Cancer > Colorectal cancer > Flashcards

Colorectal cancer Flashcards

1
Q

…

A
  • Colorectal cancer is a major cause of cancer in ‘developed’ countries
  • It is the 4th most common cancer overall
  • 2nd leading cause of cancer death overall, behind lung cancer
  • Environmental (diet) and genetic factors in aetiology
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2
Q

What does colon cancer include?

A

Anything from the caecum, all the way round to where the mucosa becomes squamous mucosa at the anus

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3
Q

What is function of the colon?

A
  • The colon extracts water from faeces, and is therefore slightly involved in electrolyte balance
  • The colon is a faecal reservoir (evolutionary advantage)
  • The colon is involves in bacterial digestion of vitamins (e.g. vitamin B and K)
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4
Q

Describe the turnover of bowel cells and what does this mean?

A
  • The bowel cells have an enormous turnover: 2-5 million cells die per minute in the colon
  • Proliferation renders cells very vulnerable – a problem with the genetics may result in cancer
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5
Q

What are polyps?

A

A polyp is any projection from a mucosal surface into a hollow viscus

It may be hyperplastic, neoplastic, inflammatory, hamartomatous (a mostly benign, focal malformation that resembles a neoplasm in the tissue of its origin) etc.

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6
Q

What is an adenoma?

A

An adenoma is a benign neoplasm of the mucosal epithelial cells – associated with increased cancer risk

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7
Q

What are the types of colonic polyps?

A
  • Metaplastic/Hyperplastic: completely benign and very common (associated with mucosal damage)
  • Adenomas: increase risk of cancer
  • Juvenile
  • Peutz Jeghers
  • Lipomas
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8
Q

Hyperplastic polyps: how common are they, benign or maligant?
What mutation do they commonly have?

A
  • Very common and benign (not dysplastic), <0.5 cm
  • 90% of all LI polyps
  • Often multiple
  • No malignant potential (they don’t cause cancer)
  • 15% have k-ras mutation
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9
Q

What are the types of colonic adenomas?

A
  • Tubular - 90%
  • Tubulovillous villous) - 10%
  • Villous
  • Flat and serrated
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10
Q

What are pendunculated and sessile adenomas?

A

A pedunculated polyp is like a tree. The mucosa is like the grass. A sessile polyp is like a rug on top of a carpet – it is slightly raised but much less so than the pedunculated one

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11
Q

What are tubuluar adenomas?

A
  • Columnar cells will have some nuclear enlargement, elongation, multi-layering and loss of polarity
  • Increased proliferative activityl
  • Reduced differentiation
  • Complexity/disorganisation of architecture
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12
Q

What are villous adenomas?

A
  • Mucinous cells with nuclear enlargement, elongation, multi-layering and loss of polarity
  • Exophytic, frond-like extensions
  • Rarely may have hyper-secretory function and result in excess mucus discharge and hypokalemia
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13
Q

What is dysplasia?

A
  • Abnormal growth of cells with some features of cancer
  • Haven’t become cancer yet
  • Indefinite, low grade and high grade
  • Cells are not all lining up properly
  • We see pseudostratification and granular hyper-chromatic dark nuclei
  • There is an increased nucleo-cytoplasmic ratio
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14
Q

Difference between high and low grade dysplasia

A

In high grade dysplasia,we see these things but worse:

  • Cells are not all lining up properly
  • We see pseudostratification and granular hyper-chromatic dark nuclei
  • There is an increased nucleo-cytoplasmic ratio
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15
Q

Polyps and cancer

A
  • Polyps increase risk of cancer and adenomas can lead into cancer
  • Adenomatous polyposis coli is a disease in which people have thousands of polyps in the bowel
  • They inevitably get cancer, unless the bowel is removed
  • APC is a familial condition (genetic mutation in 5q21 gene)
  • Site of mutation determines clinical variants (classic, attenuated, Gardner, Turcot etc.)
  • Many patients have prophylactic colectomy
  • Large polyps have higher risk of cancer development than small ones
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16
Q

Colonic adenoma

A
  • 25% of adults have adenomas before the age 50

- 5% of these become cancers if they are left alone

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17
Q

Lead time on polyp to cancer

A

There’s about 10-15 years between getting a polyp and getting cancer

18
Q

Adenoma and carcinoma

A
  • Most CRCs arise from adenomas
  • There is a residual adenoma in around 10-30% of CRCs
  • Adenomas and CRC have a similar distribution
  • Adenomas usually precede cancer by 15 years
  • Endoscopic removal of polyps decreases the incidence of subsequent CRC
  • If you have a polyp and it is left, the incidence of cancer is around 5%
  • Adenomas are associated with some genetic abnormalities
19
Q

,,,,,

A

Genetic damage is ‘collected’. There is an accumulation of different bits of damage caused by different things. This causes cumulative damage to the DNA. Control of cell growth is lost -> adenoma -> carcinoma

20
Q

What are the two main genetic pathways leading to CR cancer?

A

FAP: inactivation of APC tumour suppressor genes

HNPCC: microsatellite instability

21
Q

How does an adenoma progress to carcinoma?

A

Cells are atypical and dysplastic. We see disorganised adenomatous polyps. As the adenoma progresses, you completely lose control, and the cancer invades the adjacent tissue. This is when you have a carcinoma.

22
Q

Incidence, number of deaths from colonic cancer?

Who is affected?

Epidemiology - where is it common?

Male and female ratios?

A
  • 35,000 cases a year in the UK
  • 10% of cancer related deaths (16,000 per year) in the UK
  • Incidence between men and women is the same
  • A disease of middle-aged to older people: ages range from 50 to 80 (sporadic rare < 30)
  • High in US, Eastern Europe, Australia, low in Japan, Mexico, Africa
23
Q

What are dietary factors affecting the risk of colonic cancer?

A
  • High Fat, Low Fibre, High Red meat, Refined carbohydrates
  • Food contains carcinogen, but may also contains anti-cancer agents
  • Bacteria modify food residues
  • When food is cooked, it can be damaged and destroyed. This also releases materials in the food that may be carcinogenic. This includes heterocyclic amines (released from meat cooked at high temperatures)
24
Q

Dietary deficiencies and colon cancer

A
  • Folate and colorectal cancer: folate is a protector of cells (destroyed by over-cooking)
  • Folate: co-enzyme for nucleotide synthesis and DNA methylation
  • MTHFR deficiency leads to disruption in DNA synthesis causing DNA instability (strand breaks and uracil incorporation) -> mutations
  • Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation -> gene activation and silencing
25
Q

What are some anti-cancer vitamins or food elements?

A

Vitamin C: ROS scavenger (scavenge free radicals that cause damage to the DNA)

Vitamin E: ROS scavenger (scavenge free radicals that cause damage to the DNA)

Isothiocyanates (cruciferous vegetables)

Polyphenols (green tea, fruit juice) – Activate MAPK

These foods regulate phase 2 detoxifying enzymes as well as other genes (e.g. glut-S transferase) and reduce DNA oxidation.

26
Q

What are some foods good for cancer?

A
  • Garlic is associated with apoptosis (Ajoene, allicin)
  • Green tea (EGCG-induced telomerase activity)
  • These are good because they scavenge free radicals and carcinogenic chemicals/products they produce
27
Q

What is the clinical presentation of colorectal cancer?

A
  • Classically, there is a change in bowel habit (people going to the toilet a lot more or less)
  • Rectal bleeding
  • Unexplained iron deficiency anaemia
  • Mucus, bloating, cramps (‘colic’) and constitutional (weight loss, fatigue)

Problem with colon cancer: people ignore the symptomatic presentation. Its bad prognosis may be attributable to this. Patients rationalise these symptoms as ‘getting old, piles or irritable bowel’

28
Q

What are the macroscopic features of CRC?

A

Small carcinomas may be present within larger polypoid adenomas, pedunculated or sessile

29
Q

Distribution of colon cancer/adenoma in the bowel

A
  • Carcinoma has a different distribution around the bowel
  • But the distribution is very similar to adenomas
  • Caecum/ascending colon (22%), transverse colon (11%), descending colon (6%) recto-sigmoid (55%)
  • Almost all carcinomas in the large bowel are adenocarcinomas
  • Adenocarcinoma means that they derive from glands
30
Q

What are the subtypes of adenocarcinomas?

A

Mucinous carcinoma, signet ring cell, neuroendocrine

31
Q

How is colonic cancer graded?

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

~ 10% well differentiated – looks like the glands it originally come from

~ 70% moderately differentiated – most cancers in GI tract

~ 20% poorly differentiated

32
Q

Dukes classification - staging

A

Dukes A: growth limited to wall (nodes negative)

Dukes B: growth beyond muscularis propria (nodes still negative)

Dukes C1: nodes positive (But apical lymph node negative)

Dukes C2: apical lymph node is positive

33
Q

..

A

SURVIVAL PROBABILITIES ACCORDING TO STAGE OF DISEASE The prognosis is largely based on the histology. We can look at how far the cancer has invaded, lymph node involvement and whether the cancer has spread into the blood. This allows us to figure out the prognosis. The prognosis will determine the treatment of the patient.

TABLE

34
Q

What are the pathological features affecting prognosis/

A

…

35
Q

What are the clinical features affecting prognosis/

A

..

36
Q

What are the treatment options?

A

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37
Q

..

A

SCREENING FOR HIGH RISK COLON CANCER – catching it early improves prognosis

  • 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
  • Ulcerative colitis and Crohn’s disease (inflammation increases the risk of cancer)
  • Hereditable cancer families (include other sites)

POPULATION SCREENING FOR COLON CANCER – individuals who are not necessarily high risk

Screening is 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

..

A

,,

39
Q

What is the criteria needed for a screening programme to be created?

A
  • Importance of the disease: The condition should be important in respect to the seriousness and/or frequency
  • The natural history of the disease must be known in order to:
    1. To identify where screening can take place
    2. To enable the effects of any intervention to be assessed
  • The screening test characteristics must be simple and acceptable to the patient
  • Screening tests must also be sensitive and selective
  • The screening population should have equal access to the screening procedure
  • There must be cost effectiveness
40
Q

NHS screening for colon cancer

A
  • At age 55, the NHS send out a faecal test to see if there is any blood in the faeces

Positives are referred for colonoscopy (60-75 years) or sigmoidoscopy (55-60 years)

41
Q

..

A

GENETIC PATHWAYS

  • Adenoma carcinoma sequence: APC, K-ras, Smads, p53, telomerase activation
  • Mutations in these genes can increase the risk of getting polyps
  • Microsatellite instability
  • Microsatellites are repeat sequences prone to misalignment
  • Some microsatellites are in coding sequences of genes which inhibit growth or apoptosis e.g.TGFbR11
  • Mismatch repair genes (MSH2, MLH1 + 4 others) – these repair mistakes in the genetic code
  • If the mismatch repair genes are damaged (microsatellite instability), DNA cannot be repaired
  • Recessive genes requiring 2 hits
  • HNPCC- germline mutation in these genes
42
Q

…

A

COLONIC CARCINOMA
Whereas the adenomas and polyps had NOT invaded, these carcinomas HAVE invaded. Carcinoma is invading into the wall of the bowel, and starting to form glands. All the features of cancer can be seen.

  • Big, dark and hyper-chromatic cells, and increased nucleo-cytoplasmic ratio
  • Many mitoses occurring (increased mitotic activity)
  • Disordered architecture and invasion
  • The glands themselves make mucin, so the cancer can also make mucin

Year 2 - Cancer (9 decks)

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