Colorectal cancer Flashcards by Isla Anderson

What cause of cancer death is colorectal cancer?

2nd leading

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What overall cause of cancer is colorectal cancer?

3rd

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What is the most common histological classification of colorectal cancer?

Adenocarcinoma (95%)

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What percentage of colorectal cancer is colonic and what is rectal?

2/3 is colonic

1/3 is rectal

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What genes are associated with colorectal cancer?

HNPCC (5%)

FAP (<1%)

Other CRP syndromes

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What are risk factors for sporadic cases of colorectal cancer?

Age

Male gender

Previous adenoma

Environmental influences (diet, obesity, lack of exercise, smoking, diabetes)

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What kind of things in your diet are risk factors for colorectal cancer?

Low fibre

Low fruit and veg

Low calcium

High red meat

High alcohol

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What percentage of colorectal cancers have no genetic influence?

85%

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What do majority of colorectal cancers arise from?

Pre-existing polyps

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What are polyps?

Protuberant growths

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What are the different kinds of polyps?

Epithelial or mesenchymal

Benign or malignant

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What is an adenoma?

Benign tumour of glandular tissue

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What is an adenoma in origin?

Epithelial

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What are the different histological types of adenoma?

Tubular (75%)

Indeterminate tubulovillous (15%)

Villous (10%)

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Explain the adenoma-carcinoma sequence?

Activation of oncogene, loss of tumour suppresor gene and defective DNA repair pathway genes (microsatelite instability) cause adenoma to become carcinoma by causing cell growth proliferation apoptosis

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What are examples of oncogenes?

K-ras

C-myc

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What is an oncogene?

A gene that has the potential to cause cancer

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What are examples of tumour suppressor genes?

APC

p53

DCC

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What are tumour suppresor genes?

Ones that control cell growth

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What is the presentation of colorectal cancer?

Rectal bleeding (especially if mixed in with stool)

Altered bowel opening to loose stools (longer than 4 weeks)

Palpable rectal or right lower abdominal mass

Acute chronic obstruction if stenosing tumour

Weight loss

Anorexia

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What investigations are done for colorectal cancer?

Colonoscopy

Radiological imaging

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is a colonoscopy therapeutic or diagnostic?

both

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What can be done with a colonoscopy?

tissue biopsy

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What does a colonoscopy require?

Sedation

Bowel preparation

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What are risks of a colonoscopy?

Perforation Bleeding (particularly in patients with renal disease or bowel failure)

What radiological imaging is done for colorectal cancer?

CT colonography [3d virtual colonoscopy) Barium enema (not gold standard)

what are issues with radiological imaging for colorectal cancer?

Ionising radiation Bowel preparation No histology No therapeutic intervention

What investigations are done to stage colorectal cancer?

CT scan of chest/abdomen/pelvis MRI scan for rectal tumours PET scan/rectal endoscopic ultrasound in selected cases

what type of investigation is done for staging of rectal cancer?

MRI scan for rectal tumours

For Duke’s staging, what is T1 to T4?

T1 - confined to submucosa T2 - confined to muscularis T3 - confined to serosa T4 - breached serosa, invading other structures

For Duke’s staging, what is N0 to N2?

N0 - no lymph node involvement N1 - seen in 3 regional lymph nodes N2 - seen in 4+ regional lymph nodes

For Duke’s staging, what is M0 to M1?

M0 - no metastases to distinct organs M1 - metastasis to distinct organs

What is the treatment for colorectal cancer?

Surgery Chemotherapy Radiotherapy

What are the 2 surgical options for colorectal cancer?

Laparotomy vs laparosopic

how can dukes A and cancer polyps be treated?

endoscopic or local resection

what may have to be formed following surgery?

Stoma formation - colostomy (permanent/temporary) Removal of lymph nodes for histological analysis Partial hepatectomy for metastases

When is radiotherapy used?

rectal cancer only or ‘neoadjuvant’ +/- chemotherapy to control primary tumour prior to surgery

when is chemotherapy used?

‘adjuvant’ Dukes C, ?Dukes B positive lymph node histology Mops up micrometastases Agents - 5-FU (fluorouracil) +/- other agents

What is 5 year survival of Duke’s stage A?

83%

What is 5 year survival of Duke’s stage B?

64%

What is 5 year survival for Duke’s stage C?

38%

What is 5 year survival of Duke’s stage D?

What can prognosis of colorectal cancer be improved by?

Prevention (changing lifestyle factors) Screening (high risk groups and average risk population)

What is the aim of population screening?

Detect pre-malignant adenomas/early cancers in the general population

What are some modalities of screening?

Faecal occult blood test (FOBT) Faecal immunochemical (FIT) Flexible sigmoidoscopy Colonoscopy CT colonography

When does the Scottish population start getting an FOBT every 2 years?

Between age 50 to 74

What happens if a FOBT is positive?

Colonoscopy

What does FOBT stand for?

Faecal occult blood test

Does FOBT have a greater positivity in men or woman?

men

What does faecal immunochemical testing check?

Specific for human haemoglobin

What are examples of high risk groups for colorectal cancer that require screening?

Heritable conditions (FAP and HNPCC) Inflammatory bowel disease Familial risk Previous adenomas/colorectal cancer

What does FAP stand for?

Familial adenomatous polyposis

what are disadvantages of screening?

high interval cancer rate FOBT has lower positivity in women

what is a more recent method of screening?

Faecal Immunochemical Testing (FIT) introduced in Scotland in Nov 2017 Specific for human haemoglobin Automated Quantitative User friendly format that increases uptake Provides flexibility to alter the cut-off to accommodate risk factors including age and gender which could reduce the interval cancer rate

What does HNPCC stand for?

Hereditary non-polyposis colorectal cancer

What kind of genetic condition if FAP?

Autosomal dominant

What gene is FAP a mutation of?

ACP gene on chromosome 5

What do people with FAP have a high risk of?

Malignant change in early adulthood, in almost all cases by age 40 years if left untreated

What screening is done for people with FAP?

Annual colonoscopy from age 10-12

Other than screening, what else is often done for people with FAP to reduce the risk of colorectal cancer?

Prophylactic proctocolectomy usually age 16 to 25

What is proctocolectomy?

Surgical removal of all of the rectum and part of the colon Prophylactic proctocolectomy usually age 16 - 25 yrs

What are extracolonic manifestations of FAP?

Benign gastric fundic cystic hyperplastic Duodenal adenomas with periampullary cancer

What kind of chemoprevention is often given to people with FAP?

NSAIDs chemoprevention

What does NSAIDs chemoprevention do?

Reduces the number of polyps and prevent recurrence of higher grade adenomas in the retained rectal segment

what type of genetic mutation is MAP?

Autosomal recessive

what gene is responsible for the genetic mutation in MAP?

pathogenic variants in the MUTYH base-excision repair gene

what is CRC in MAP more likely to be?

right sided and synchronous

Cumulative CRC risk of 63% at 60 years Polyposis predisposition syndrome with significant phenotypic overlap with FAP; polyps develop in early adult life. Annual colorectal surveillance commencing age 18–20 years Duodenal adenomas have been reported in 17–34%; upper GI surveillance starting at the age of 35 years

What kind of genetic condition is HNPCC?

Autosomal dominant condition

What gene causes HNPCC?

Mutation in DNA mismatch repair (MMR) genes

What are examples of DNA mismatch repair genes (MMR) that cause HNPCC?

MLH1 MSH2

What characteristics do tumours caused by HNPCC usually have?

Microsatellite instability (MSI) which are frequent mutations in short repeated DNA sequences (microsatellites)

Where in the colon does HNPCC usually cause cancer?

Right sided

Other than the colon, what other sites can HNPCC cause cancer?

Endometrial Genitourinary Stomach Pancreas

How is HNPCC diagnosed?

Clinical criteria (Amsterdam/Bethesda) Genetic testing

What is done for people with HNPCC to reduce the change of them developing colorectal cancer?

Screening is given every 2 years as a colonoscopy

In terms of a family history of colorectal cancer, who is considered a high moderate risk?

Colorectal cancer in 3 first degree relatives where none <50 or Colorectal cancer in 2 first degree relatives mean age <60

What is done for people who are considered a high moderate risk with a family history of colorectal cancer?

5 yearly colonoscopy from age 50 years

In terms of a family history of colorectal cancer, who is considered to be low moderate risk?

Colorectal cancer in 2 first degree relatives >60 or Colorectal cancer in 1 first degree relative <50 years

What is done for people with a family history of colorectal cancer who are considered low moderate risk?

Once only colonoscopy at 55 years

What are people with IBD given to reduce change of getting colorectal cancer?

Index surveillance colonoscopy 10 years post diagnosis, then dependent on duration, extent and activity of inflammation and presence of dysplasia

What are people with previous colorectal cancer given to reduce the chance of getting it again?

5 yearly colonoscopy

What are people with previous adenomas given to reduce the chances of developing colorectal cancer?

Colonoscopy dependent on number of polyps, size and degree of dysplasia

FIT occult blood for Symptomatic Patients?

FIT (at 100 µg Hb/g cut-off) more accurate than standard alarm symptoms NICE or SIGN referral criteria for detection of CRC