Colorectal Cancer Flashcards

1
Q

What are the characteristics of malignancy pathology?

A
  1. Abnormal signal transduction
  2. Loss of apoptosis
  3. Tissue invasion & Metastasis
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2
Q
  1. Abnormal signal transduction, what happens?
A

Ligand-independent signalling
Structural changes to receptors
EGFR- epidermal growth factor receptors are over expressed ligands & TGF-a (transforming growth factor)
Things attach to ligands–> signal transduction–> activate transcription of genes.

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3
Q

What can neutralise ligands?

A

Monoclonal Antibodies (Abs)

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4
Q

What mitogen is involved in colorectal cancers abnormal signal transduction? + what does it do?

A

RAS mitogen

Deregulation

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5
Q

What happens?

A

Mutations–> ⬆️⬆️ transcription –> overexpression of receptors
⬆️⬆️ potential to be triggered by ligands
↪️ ⬆️⬆️ Growth tp express receptors.

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6
Q

What happens during Loss of Apoptosis?

A

Too little apoptosis + ⬆️ cell proliferation (can be genetic)
There are 2 pathways acitivating apoptosis:
Extrinsic & intrinsic

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7
Q

Whats the extrinsic pathway?

A

Death Receptors-

Activation of tumour necrosis Factor family (caspases enzymes)

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8
Q

Whats the intrinsic pathway?

A

Mitochondrial activation, by damaged DNA.

Apoptosis inhibitor proteins) (IAP

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9
Q

What happens in tussue invasion & metastasis?

A

Malignant cells enter blood stream/lymph.
EGFR pathway aCtivates & promotes metastasis
MMP released; breaks basement membrane
↪️ enter blood by tight junctions
↪️tissue invasion
⭐️marks territory once in.

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10
Q

What are some common metastatic sites?

A

Liver, lung, brain & bone marrow.

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11
Q

What do you check in moles?

A

Appearance
Colour
Diameter
Border

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12
Q

What 2 genes are asscw/ breast cancer? What types of genes are they?

A

BRAC1 & BRAC2
They are both tumour supressors.
If invaded, no more effect of protection.

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13
Q

What are some common genes implicated w/ colorectal cancer? Ascc mutations

A
APC-->T suppressor
RAS--> oncogene
Kras- oncogene. 
TP53--> T supressor
SMAD4--> T supressor

How? Impaired cellular stress & DNA damage response.

APC( adenomatous polyposis coli)

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14
Q

Whats the Jukes classification of colorectal cancer?

A

A- mucosa of bowel
B. Through mucosa muscularis
C. Local nodes invaded.
D. Metastasis.

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15
Q

What drugs can be pritective of colorectal cancer?

A

Aspirin & NSAIDs

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16
Q

What 2 types of colon diases do we have?

A

FAP- familial adenomatous polyps —> 100% cancer
Autosomal dominant condition

HNPCC

17
Q

What happens when we have mutations?

A

Mutator genes–> results in hypermutation

Oncogenes–> activated– overexpression! selective growth advantage to cell.

18
Q

Whats the volegram for colorectal cancer?

A

Normal–> hyperplastic–>early adenoma–>

Late adenoma–> T2M0N0 –> T4N0M0—> T1M1..

19
Q

Colorectal C

A

Most are sporadic! 5-10% Hereditary polyposis colorectal cancer (HNPCC)
Or FAP.
May also occur on backround of 10Y pancolitis, UC, or colonic Crohns disease.

20
Q

Sporadiac colorectal cancer

A

2nd most commom cauce of cancer death.
Incidence imcreases w/age, >50Y.
Rare in Africa and Asia due to diff env fx.
Aerological fx- high in animal meat and animal fat and low in fibre.

⭐️Activation of tumor- promoting genes/ oncogenes - Kras, c-myc
⭐️ inactivation of tumour supressor genes (MCC, DCC, p53) .
Risk of tumor increases w/ increased genetic abnormalities.

21
Q

Pathology of colorectal C

A

Other than backround of IBD
Start as benign adenomas (aka adeno-carcinoma) sequence.
Spread- direct invasion through bowel wall, later- invasion of blood vessels + lymphatics + Liver !!! Lymp after GI goes to liver.

22
Q

Stages for classification?

A

TNM- tumour, node, metastasis and modified Dukes criteria
Dukes A. Tumour confined to bowel wall
Dukes B. T extendinh through bowel wall
Dukes C. Regional lymph nodes involved
Dukes D. Distant metastasis

23
Q

Cfs

A

Mostbare in Left side of colon
Rectal bleeding +’stenosis
W/ sx of imcreasing intestn obstruction like bowel habbit alterations + colicky abdo pain.

Carcinoma of caecum and ascwnding colon- Fe anaemia and RIF mass.
O/E unhelpful altho mass
Hepatomegaly when liver metastisised.

24
Q

Invx

A

Double contrast barium enema or colonoscopy
FBC- anaemia, abn LfTs- 2o liver
Faecal occult blood tests- population screen, not dx.

25
Q

Mx

A

Tx- surgical w/ tumor resection and end-to-end anastomosis of bowel.
Adjuvant chemo w/ 5-Fluoroutacil + leucovorin ⬆️ survival in Dukes C (TNM III) and some Dukes B.

Pre-op radio might help in rectal cancer
Radio also in pallative in pts w/ locally advanced disease.

Pts w/ 2-3 liver metastasis in 1 lobe may be offered liver resection.

Pts unresecrable: chemo in form of 5-Fluorouracil + leucovorin in combo w/ irinotecan or oxplatinin- increase median survival + improve QOfLife.

26
Q

Prognosis

A

5Y survival 40%

>95% in dukes A- confined to bowel wall.

27
Q

Screening

A

High risk individuals
Fmembers w/ HNPCC first degree or 1st degree with colon cancer offered colonoscopy.
Mass screening
FOB test w/ colonoscopy if +ve.
(Sigmoidoscopy shown to reduce mortality?! ) but not adopted yet.

28
Q

HNPCC

A

Autosomal dominat transmission w/ incomplete penetrance.
Mutation in 1/6 repair genes –> leading to widespread genome instability.
Mutations in 2 of these: hMLH1 and hMSH2 account for >95% of HNPCC families.

Risk of camcer at any age, usually right sided.
Many also have increased incidence of gynae, urinary, biliary and other malignancies.

29
Q

What are the dx criteria for HNPCC?

A

Amsterdam criteria - fhx

3> relatives w/ HNPCC- assc cancer- colorectal, endometrial, small bowel, ureter, or renal pelvis) one of whome is a 1st degree relative and FAP excluded.

Families w/ colorectal cancer involving at least 2 generations

One or more cancers diagnosed before the age of 50.

30
Q

RED FLAGS FOR COLORECTAL CANCER

A

2 week referral immediately if:
Palpable rectal mass (any age)
Iron deficiency anaemia in men at any age
Iron def anaemia in non menstruating women any age
Rectal bleed + changed bowel habits >6w for >40Y
Rectal bleed for >6w >50Y

Wt loss
Anaemia
Abdo pain
Mucus passed PR
Anorexia
Altered blood PR
Change in bowel habbit
31
Q

O/E

Of bleed

A

Rectal cancers-80% at fingertip of rectum so PR exam.
Blood on toilet paper or on top of motion-> cause likely to be seen on proctoscopy. (Rigit sigm)

Blood mixed w/ stool:
Young middle aged men: gastroenteritis- campylobacter or colitis

Inv- abdo exam + PR exam
FBC, CRP, stool studies- FOB, microscopy, cultures and sensitivity
Coeliac studies and clotting screen.

Palpable- fast track surgical,assesment if necs.

32
Q

DDx for PR bleed?

A
Haemorrhois
Anal fistula
Diverticulitis,
IBD
Colitis
DIC, clotting problems, / Anticoagulation/NSAIDs therapy
Trauma
Gastroenteritis
Colorectal malignancy⭐️