Colorectal cancer

Question 1

RISK FACTORS
i) which type of IBD increases the risk?
ii) name three genetic predispositions
iii) name three other RFs

Answer 1

i) UC (not crohns)
ii) familial adenomatous polyposis coli (FAP)
hereditary non polyposis colon cancer (HNPCC - Lynch syndrome)
Li fraumeni (p53 mutation)
iii) increased age, diet (high red meat), obesity, sedentary, smoking, ETOH

Question 2

GENETIC PREDISPOSITION SYNDROMES
i) which gene is mutated in FAP? what is the inheritance pattern? what is done for the majority of patients with this mutation?
ii) what is HNPCC aka? what is the inheritance pattern? where is the mutation? how does it differ from FAP? which mutation worsens prognosis
iii) which syndrome implicates loss of MSH6/MSH2/MLH1/PMS2
iv) name three other cancers there is increased risk of in HPNCC
v) which syndrome is more likely to be right sided? have large tumoours with late mets? dont respond to 5FU?
vi) which syndrome is more likely to be left sided/rectal? M>F? KRAS mut frequent?

Answer 2

i) APC (tumour supressor) > auto dominant
most patients have entire large intestine removed prophylactically to prevent the development of bowel Ca
ii) HNPCC = lynch syndrome
auto dom condition that resultsfrom mutations in DNA mismatch repair genes
does not have excessive polyps
BRAF mutation worsens prognosis
iii) HPNCC - DNA mismatch repair genes
iv) 80% lifetime risk of colorectal, inc risk of endometrial, small bowel, ovary
v) HPNCC
vi) FAP - these do better

Question 3

BOWEL CANCER SCREENING
i) what is the classic screening criteria for any screening test?
ii) what does the FIT test look at? why did it replace FOB?
iii) between what age are people routinely offered a FIT test? how often do they do it?
iv) what is done for pts with RFs eg FAP, HNPCC, IBD?

Answer 3

i) wilson and junger classic screening criteria
ii) FIT looks at human Hb in stool
replaced FOB as it detected blood in stool but gave lots of false pos eg blood from food
iii) FIT test 60-74yrs every 2 years
iv) regular colonoscopy

Question 4

LOCALISED COLON CANCER
i) what is first line tx? what is given if there are positive LNs?
ii) what constitutes Dukes A/B/C/D?
iii) which two resections may be done for rectal cancers? which results in a permanent colostomy?

Answer 4

i) laparoscopic surgery
give adjuvant chemo if node positive - 3 or 6 months
ii) dukes A - no musc invasion
dukes B - involves bowel wall but no nodes
Dukes C - LN involvement
Dukes D - metastatic
iii) anterior resection or AP resection (colostomy)

Question 5

RECTAL CANCER
i) what type of surgery is usually done? what may be given pre surgery?
ii) what imaging is done pre op for staging?
iii) what two therapies have a response rate of >80% if locally advanced? what does this allow for

Answer 5

i) total mesorectal excision - reduces recurrence rate to 4%
give short course of pre op RT if high risk
ii) do MRI to assess tumour extent
iii) neoadj chemo and radical RT > may convert to operable and improve survival

Question 6

METASTATIC DISEASE
i) what imaging is done for met disease? what procedure may be done if oligomet?
ii) which chemo regimen is given for met disease? (2) is it usually curative?
iii) name two targeted agents that may be given and what they target? which one isnt really used anymore?
iv) which drug should be stopped if patient is admitted and not written on drug chart? why?

Answer 6

i) MRI or FDG PET
met resection or radiofreq ablation
ii) 5FU tablets (capecitabine) + oxiplatin/irinotecan - usually palliative
iii) cetuximab against EGFR
bevacizumab against VEGF
iv) stop capecitabine (oral 5FU) - SEs are neutropenic sepsis and angina

Question 7

TARGETED THERAPIES
i) how does cetuximab work? why is it not always effective?
ii) why is bevacizumab not really used anymore?

Answer 7

i) targets EGFR > attacks tumour cells
not so effective as there is usually downstream mutated genes eg ras, raf, mek, pi3k that will be constituatively active regardless of whether it is getting signals from EGFR
ii) weak effect and very expensive
stops action of VEGF

Question 8

INVESTIGATIONS
i) what is the gold standard investigation?
ii) what may be used when the only feature is rectal bleeding?
iii) what may be used if patient is less fit? what is a downside?
iv) what scan is used to stage?
v) which blood marker is a tumour marker? when is it useful?

Answer 8

i) colonoscopy
ii) sigmoidoscopy (risk of missing cancers elsewhere)
iii) CT colography - less detailed and cant biopsy
iv) CT thorax, abdo, pelvis
v) CEA - useful in predicting progression but not in screening