Colorectal Cancer

Question 1

What are the histological layers of the GI tract from the inside out?

Answer 1

1. Mucosa
2. Submucosa
3. Muscularis propria
4. Subserosa
5. Serosa - adventitia, peritoneum

Question 2

What type of cancer are the vast majority of colorectal cancers and how common is it in the UK?

Answer 2

1. Adenocarcinoma

2. 3rd most common cancer in the UK

Question 3

In which age group is colorectal cancer usually found?

Answer 3

Uncommon <40, 86% in those >60.

Question 4

What is significant in the history of someone presenting with colorectal cancer?

Answer 4

1. FHx of colorectal cancer
2. PMHx of colorectal cancer, previous polyps >1cm with high grade dysplasia
3. Long standing - Crohn’s and ulcerative colitis, DM, immunosuppression, radiation exposure to the abdomen.
4. Smoking, obesity, processed red meat, low fibre, alcohol.

Question 5

What is the defect in Lynch syndrome and what is the inheritance pattern?

Answer 5

1. Microsatellite instability - germline mutation in DNA mismatch repair genes (80% lifetime risk of colorectal cancer)
2. Autosomal dominant (3% of colorectal cancers)

Question 6

Which cancers does Lynch syndrome predispose to?

Answer 6

Endometrial (most common in women), ovarian, and GIT cancers (colorectal most common in men).

Question 7

What is the surveillance for people with Lynch syndrome?

Answer 7

Colonoscopic surveillance at least every other year from 25 years old.

Question 8

Where does Lynch syndrome colorectal cancer arise in the colon and how well differentiated are the cells?

Answer 8

1. Right side of colon

2. Moor poorly differentiated

Question 9

What is familial adenomatous polyposis?

Answer 9

Hundreds of adenomatous polyps develop in the colon during the 2nd to 3rd decade of life.

Question 10

At what age is adenocarcinoma development inevitable in familial adenomatous polyposis?

Answer 10

35 years

Question 11

What is the defect in familial adenomatous polyposis and what is the inheritance pattern?

Answer 11

1. Germline mutation in APC gene (tumour suppressor)

2. Autosomal dominant

Question 12

What is the surveillance and management for familial adenomatous polyposis?

Answer 12

1. Surveillance sigmoidoscopy from 12 years

2. Prophylactic total bowel removal (panproctocolectomy) <25 years

Question 13

Which cancers is familial adenomatous polyposis most associated with?

Answer 13

Small bowel, gastric, and thyroid cancers

Question 14

What are the two main inherited disorders which increase your risk of developing colorectal cancer?

Answer 14

1. Lynch syndrome

2. Familial adenomatous polyposis

Question 15

What is the main protective factor for colorectal cancer?

Answer 15

1. Vegetarian and high fibre diet

2. Daily aspirin use

Question 16

What are colorectal adenomas?

Answer 16

Polyps derived from the epithelial cells lining the mucosa.

Question 17

What is the epidemiology for colorectal adenomas?

Answer 17

1. Very common

2. Incidence increases with age such that at 60, they are found in 20% of the population.

Question 18

What are the two main types of polyp?

Answer 18

1. Pedunculated (attached to mucosa by stalk)

2. Sessile (attached to mucosa by a broad base)

Question 19

What are the factors associated with a greater risk of progression from a polyp to a malignancy?

Answer 19

Increasing size, high grade dysplasia, histological type (villous > tubular).

Question 20

What are the features of colorectal dysplasia and how is it graded?

Answer 20

1. Disordered growth
2. Increase in nuclear:cytoplasmic ratio
3. Premalignant - left untreated may become malignant
4. Graded as low or high

Question 21

What is an adenoma?

Answer 21

A benign tumour of glandular epithelium which does not have malignant potential (except in the GI tract).

Question 22

What is the pathway for the majority of colorectal cancers?

Answer 22

Chromosomal instability pathway

Question 23

What is the progression of the chromosomal instability pathway?

Answer 23

Normal mucosa - adenoma - invasive adenocarcinoma

Question 24

What causes the progression of cancer in the chromosomal instability pathway?

Answer 24

Accumulation of mutation in these growth-regulating genes:

1. Inappropriate activation of proto-oncogenes (K-ras)
2. Inactivation of tumour suppressor genes (APC, both copes must be activated, two-hit hypothesis)

Question 25

How are mutations acquired by patients in the adenoma-carcinoma pathway of colorectal cancer?

Answer 25

1. Sporadic throughout life (majority) | 2. Germline mutation in APC with 2nd hit (FAP)

Question 26

What is the microsatellite instability pathway for colorectal cancer?

Answer 26

Cancers arise from serrated polyps, polyps acquired sporadic mutations which accumulate to cause carcinoma.

Question 27

What is the national screening programme for colorectal cancer?

Answer 27

1. Faecal occult blood test every 2 years between 60-74 years old - colonoscopy if +ve, detects at early stage. 2. One-off flexisig performed at age 55 - detect adenomatous polyps for removal, preventing progression.

Question 28

What is this a presentation of? Bleeding/mucus PR, altered bowel habit (looser), constipation in obstruction, tenesmus, PR mass. Weight loss, night sweats, fever.

Answer 28

Left sided colorectal cancer

Question 29

What is this a presentation of? Right-sided abdominal mass, vague symptoms, weight loss, iron deficiency anaemia, occult bleeding, abdominal pain, obstruction unlikely.

Answer 29

Right-sided colorectal cancer

Question 30

What is this a presentation of? | Jaundice from hepatic metastases, anorexia, weight loss, ascites, pneumaturia/recurrent UTIs due to colovesical fistula.

Answer 30

Metastatic colorectal cancer

Question 31

How is a suspected colorectal cancer investigated?

Answer 31

1. FBC (microcytic iron deficiency anaemia), U&Es, LFTs, calcium, CEA (monitor for relapse, not diagnostic). 2. Colonoscopy - full bowel prep and laxatives (histology/biopsy/resection) 3. CT colonography if cannot tolerate colonoscopy. 4. CT/MRI CAP if cancer confirmed to assess invasion.

Question 32

Why is staging a colorectal cancer important?

Answer 32

Single most important pathological prognostic indicator.

Question 33

What are the stages of T in TNM for colorectal cancer?

Answer 33

T1 - into submucosa but not muscularis propria T2 - submucosa and muscularis propria but not subserosa T3 - subserosa but not serosa T4 - through serosal surface

Question 34

What is the Duke's staging criteria?

Answer 34

``` Colorectal cancer: A. Invades submucosa and/or muscularis propria but not beyond. B. Into subserosa/beyond C. Involves lymph nodes D. Distant metastasis deposits ```

Question 35

What is the management of dysplastic polyps/carcinoma in situ in colorectal cancer?

Answer 35

Colonoscopic excision is curative if the margins are clear.

Question 36

What is the surgical management of stage I-III colorectal adenocarcinomas?

Answer 36

Laparoscopic: 1. Right hemicolectomy - caecal, ascending and proximal transverse colon. 2. Left hemicolectomy - distal transverse and descending colon. 3. High anterior resection - sigmoid tumours. 4. Anterior resection - low sigmoid or high rectal tumours. 5. Abdominal-perineal (AP) resection and colostomy for very low rectal tumours. 6. Total mesorectal excision for rectal cancers in combination with anterior/AP resection.

Question 37

What is the FOLFOX regime and what is it used for?

Answer 37

1. Fluorouracil, folinic acid, oxaplatin. | 2. Medical management of colorectal cancer.

Question 38

What is the management for metastatic colorectal cancer?

Answer 38

1. Surgery with liver resection may be curative if confined to single lobe. 2. Chemotherapy and endoscopic stenting in palliation. 3. Radiotherapy mostly used in palliation.

Question 39

What is the prognosis of colorectal cancer based on Duke's staging?

Answer 39

``` 5-year survival: A. 95% B. 80% C. 65% D. 5% (20% if resectable) ```