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cancer - year 2 > colorectal cancer > Flashcards

colorectal cancer Flashcards

1
Q

epidemiology of colorectal cancer

A

major cancer in developed countries

4th most common cancer overall

2nd leading cause of cancer death overall

environmental (diet) factors and genetic factors are the aetiology

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2
Q

anatomy of the colon

A

caecum is hollow, large part of colon in R ileum

then have ascending colon

then hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, rectum

in front of colon is the peritoneum

behind the colon is the mesentry where bv come in and out, it is fatty tissue

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3
Q

what is the function of the colon

A

extract water from faeces and therefore maintain electrolyte balance - therefore people with colorectomy become dehydrated - so gastroenterologists need to give them more water than normal and monitor electrolyte destrubances

is a faecal resevoir - this is an evolutionary advantage

bacterial digestion for vitamens especiall`y B and K

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4
Q

describe the structure of the colon

A

has mucosal surface folds

layers:

  • area where the stool is
  • epithelium (part of mucosa)
  • lamina propria (part of mucosa)
  • muscularis mucosa - thin layer of muscle
  • muscularis externa
  • submucosal
  • muscularis propria - thick muscle
  • fat and bv - this is the mesentry
  • abdominal cavity
    *
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5
Q

describe the colorectal crypt of lieberkuhn

A

have goblet cells that produce mucin - for immune function and lubrication

stem cells - constantly proliferating - move the cells up the crypt

mesenchymal cells are support cells - hold other cells in place

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6
Q

describe the colonic microanatomy

A

can see the lamina propria full of inflammatory cells

nucleus at the base of the cells and cytoplasm comes all the way up

below the nucleus have neuroendocrine cells

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7
Q

describe the turnover of colon cells *

A

a lot of turnover

proliferation renders cells vulnerable because that is the area where they are more likely to mutate

APC mutation prevents cell loss = mutation

normally there are protective mechanisms to eliminate genetically defective cells by natural loss of cells that are then replaced by normal cells, DNA monitors, repair enzymes that remove the damaged pieces of DNA and replace it

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8
Q

what is a polyp*

A

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

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9
Q

what is an adenoma *

A

a benign neoplasm of the mucosal epithelial cells - type of polyp

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10
Q

what are the colonic polyp types *

A

metaplastic/hyperplastic

adenomas

juvenille

peutz jeghers - familial disorder where get mucosal hyperpigmentation and polyps in GIT - can lead to higher risk of cancer

lipomas - benign growths of fatty tissue

others - any circumscribed intramucosal lesions

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11
Q

describe hyperplastic polyps *

A

very common

<0.5cm

90% of all lower intestinal polyps

often multiple

no malignant potential

15% have K-ras mutation

on histopath - still pink similar to normal, have serrated appearance

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12
Q

what are the different colonic adenoma types *

A

tubular when >75% adenoma is tubular - 90%

tubulovillous - 25-50% is villous - 10%

villous >50% is villous

flat - not polyp

serrated - similar to hyperplastic polyp but displastic

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13
Q

describe pedunculated and sessile adenomas *

A

pedunculated - means on stalk - A is intramucosal carcinoma that has not reached the musclaris propria; B has reached the muscularis propria it is invasive- but cutting stalk you can easily remove the adenoma

sessile adenoma - flat - more likely to spread into the muscle

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14
Q

what are the microscopic features of tubular adenomas *

A

columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity (nucleus has moved to the lumen side of the epi)

increased proliferative activity - look at the mitotic count

reduced differentiation - how much look like normal colon

complexty/disorganisation of the architecture

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15
Q

histopath of colonic adenoma *

A

more purple - increased nuclear material

nuclei look larger than hyperplastic

there is a loss of polarity

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16
Q

microscopic structure of villus adenomas *

A

mucinous cells with nucleus enlargement, elongation, multilayering and loss of polarity - these are signs of dysplasia

are exophytic frond-like extensions

may have hypersecretory function and result in excess mucus discharge and hypokalaemia - lose K into Gi tract because of mucin

small nucleoli

increased nucleocytoplasmic ratio

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17
Q

describe dysplasia *

A

means bad growth

abnormal growth of cells with some features of cancer

not invasive

there is subjective analysis - low, high or intermediate grade

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18
Q

describe the dysplasia

A

normal on R - relatively small nuclei on bottom and cells have plenty of mucin

low grade dysplasia on L - architecture still the same as normal

but nuclei are bigger, increased nucleocytoplasmic ratio, small nucleoli

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19
Q

describe this high grade dysplasia *

A

cells dont have normal architecture

high nucleocytoplasmic ratio

there is higher risk of it being carcinoma because of the high grade dysplasia

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20
Q

describe this high grade dysplasia *

A

nuclei becoming big

back to back glands

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21
Q

describe the polyp *

A

Large villous adenoma with an ulcerated adenocarcinoma in its center.

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22
Q

describe adenomatous polyposis coli *

A

it is a mutation on 5q21

the site of mutation determines clinical variants

  • classic - 100% sure will get colon carcinoma
  • attenuated - less adenomas
  • gardner - tumour in bone and skin
  • turcot - tumour in brain - glioblastoma and blastoma

develop 1000s of polyps

many pts have a profylactic colectomy <30yrs

23
Q

describe the natural history of colonic adenoma *

A

25% of adults have adenomas at age 50

5% of these become cancers if left

large polyps have higher risk than small - because there are more cells

lead time 10yrs - time from development of adenoma to development of carcinoma

cancers stay at a curable stage for 2yrs

24
Q

describe the progression from adenoma to carcinoma *

A

most colon carcinomas (CRC) arise from adenomas

there is residual adenoma in 10-30% of CRCs

adenomas and CRC have similar distribution within the kidney

adenomas usually precede carcinomas by 10-20yrs

endoscopic removal of polyps reduces chances of CRC

25
Q

describe the genetic pathways that lead to CRC *

A

adenoma sequence - APC then K-ras then Smads then p53 then telomerase activation

microsatellite instability - microsatillites are repeat sequences prone to misalignment - some are in coding sequences of genes which inhibit growth or apoptosis or involved in surveillance eg TGFbR11

happens because you have mismatch repair genes repair mutations in the microsatellite regions - MSH2, MLH1 and 4 others - they are recessive genes - survive with 1, but if mutation in both = cancer

HNPCC is a germline mutation in these DNA repair genes

26
Q

describe the adenoma-carcinoma sequence *

A

not when you have a problem with the microsatellite

  1. germline (inherited) mutations or somatic (acquired) mutation of cancer suppressor genes - 1st hit - APC, mismatch repair genes
  2. creates mucosa at risk - leads to methylation abnormalities = inactivation of normal alleles - 2nd hit - APC, B-catenin, MSH2
  3. protoonchogene mutation - K-ras - adenoma
  4. homozygoud loss of additional caner suppressor gene - p53 and LOH (p53 drives cell into apoptosis, stop mitosis and tell cell to repair DNA)
  5. additional mutations and gross chromosomal alterations - carcinoma

in same adenoma - see differnet stages ie some areas relatively normal - some are high grade

27
Q

what are the 2 main pathways for genetic predisposition for CRC *

A

FAP - inactivation of APC tumour suppressor genes

HNPCC - microsatellite instability

28
Q

why is APC particularly important in colon cancer *

A

APC holds B-catenin in the cytoplasm

if APC becomes mutated - b-catenin moves into nucleus = increase in cell proliferation by interferring with TFs

at bottom of crypt APC normally allows B-catenin into nucleus because want proliferation here

29
Q

describe p53 in adenoma progression *

A

dark areas stain showing p53 - here p53 is overexpressed because there is a mutation in it so cells are making it more - this is block/diffuse positivity p53

normally p53 is presented at low and varying levels

30
Q

describe the epidemiology of CRC *

A

35k per anum in UK

10% cancer related deaths

age range 50-80, sporadic rare <30

high in west, low in japan, mexico and africa - relate to the dietry factors - high fat, low fibre, high redmeat, refined carbohydrates

31
Q

describe contribution of food to CRC *

A

contains carcinogens

also contains anti-cancer agents

heat modifies the chemicals further

bacteria modifies food residues

heterolytic amines are carcinogens found in red meat PhIP is formed when it is cooked

PhIP oxidation to N-OH-PhIP combined with deoxyguanosine leads to mutageneis

folate from green leafy veg is a co-enzyme for nucleotide synthesis and DNA methylation

MTHFR deficiency leads to disruption in DNA synthesis causing DNA instability - strands break and uracil incorporation = mutations, and decreased methionine synthesis leading to genomic hypomethylation and focal hypermethylation = gene activation and silencing

32
Q

describe anti-cancer food elements *

A

Vit C and E - ROS scavenger - anti-oxidents - remove ROS that oxidise DNA which lead to mutations and cancer

isothiocyanites - cruciferous veg

polyphenols - green tea and fruit juice - activate MAPK - regulates phase 2 detoxifying enzymes as well as other genes (eg glut-s transferase) and reduce DNA oxidation

garlic associated apoptosis - ajoene, allicin

green tea - EGCG induced telomerase activity

usefulness of this unknown because difficult to isolate individual chemicals in food

33
Q

describe the clinical presentation of CRC *

A

change in bowel habit

bleeding PR

unexplained iron def anaemia

mucus PR

bloating

cramps - colic

constitutional - weight loss, fatigue

people rationalise these symptoms with getting old, piles or irritable bowel - need to think about CRC

34
Q

describe this barium enema *

A

apple core illusion

growth that is suppressing the lumen into the size of an apple core

35
Q

describe macroscopic features of CRC *

A

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

on top is polyp, then muscularis propria and then mesentry

36
Q

describe the districution and presentation of CRC *

A

caecum/ascending colon- 22% - caecum is big so tumour not blocking the colon so present with IDA

transverse colon - 11%

descending colon - 6%

rectosigmoid - 55% - blood in rectum - close to anus - bleed PR

37
Q

what are the microscopic structures of CRCs *

A

adenocarcinomas grade 1-3

mucinous carcinomas

singlet ring cell - worse prognosis

neuroendocrine - rarer

38
Q

describe this micrograph of colonic carcinoma *

A

form glands embedded in desmoplastic/inflammatory reaction

39
Q

describe this - colonic cancer *

A

nuclei wilder

various size nucleoli

large nucleus

increased nucleocytoplasmic ratio

40
Q

describe this mucinous carcinoma *

A

worse prognosis

carcinoma in pool of mucin

41
Q

describe this adenocarcinoma *

A

invaded through the muscularis propria = worse prognosis

42
Q

describe this colon cancer *

A

breached the serosa - into the peritoneal cavity = worse prognosis

43
Q

describe grading *

A

proportion of gland differentiation relative to solid areas or nests and cords of cells without lumina

can be well, moderately or poorly differentiated

44
Q

describe Duke’s classification *

A

dukes A - growth limited to mucosa/submucosa - nodes negatibe

dukes B - growth into or beyond the muscularis propria - nodes -ve

dukes c1 - nodes +ve, apical LN -ve

dukes c2 - apical LN +VE

prognosis decreases down the levels

45
Q

what are the clinical features that affect prognosis and how *

A

diagnosis in asymtomatic pts - improved

PR bleeding - improved

bowel obstruction/perforation - diminished prognosis

tumour location - colon better than rectum, L better than R (present earlier if close to the rectum),

age <30 diminished prognosis - more aggressive/not expecting to find CRC in this age gp

distant met - markedly worsened prog

46
Q

pathological features that determine prognosis *

A

depth of bowel penetration - more = diminished prog

number of regional lymph nodes involved - more = worse

differentiation - well=better prog

mucinous (colloid) or signet ring - diminished prog

venous, lymphatic, peineural invasion - diminished prog

local inflamm and immunogenic reaction - if body is fighting the infection there is a better prognosis

47
Q

why is it important to have an idea of prognosis *

A

because it determines treatment and how aggressive it should be - dont want to be too aggressive because treatment have SE

48
Q

describe this tumour *

A

extramural vascular invasion

out of the bowel wall

adenocarcinoma in vessel

=bad prognosis

49
Q

what are the treatment options for different stages of CRC*

A

1 - surgery

2 - sugery and 5FU

3 - surgery and 5FU/leucovorin (chemo)

4 - surgery and metastectomy, chemo, palliative RT

50
Q

what makes people at high risk of colon cancer and so should be screened *

A

previous adenoma

1st degree relative affected by colorectal cancer before age 45 or >1 1st degree relative

evidence of dominant familial cancer trait including colorectal, uterine and other cancers

UC and CDs

heritable cancer families - including other sites

51
Q

what is screening *

A

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.

52
Q

what are the criteria for screening program *

A

importance of the disease - in respect to seriousness and frequency - in this case it is frequent and kills people

the natural history must be known to identify where screening can take place and to enable the effects of any intervention to be assessed

test characteristics - simple and acceptible to ptm sensitive and selective

the screening pop should have equal access to teh screening procedure

cost effectiveness

53
Q

what is the NHS screening kit for colon cancer &

A

FOB - fecal occult blood test /FIT- fecal immunochemical blood test kit - find blood pt might have missed

FIT has replaced FOB

if positive send 60-75yrs for colonoscopy, 55-60 years to a sigmoidoscopy

cancer - year 2 (18 decks)

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