Colorectal Cancer Flashcards
What are the histological layers of the GI tract from the inside out?
- Mucosa
- Submucosa
- Muscularis propria
- Subserosa
- Serosa - adventitia, peritoneum
What type of cancer are the vast majority of colorectal cancers and how common is it in the UK?
- Adenocarcinoma
2. 3rd most common cancer in the UK
In which age group is colorectal cancer usually found?
Uncommon <40, 86% in those >60.
What is significant in the history of someone presenting with colorectal cancer?
- FHx of colorectal cancer
- PMHx of colorectal cancer, previous polyps >1cm with high grade dysplasia
- Long standing - Crohn’s and ulcerative colitis, DM, immunosuppression, radiation exposure to the abdomen.
- Smoking, obesity, processed red meat, low fibre, alcohol.
What is the defect in Lynch syndrome and what is the inheritance pattern?
- Microsatellite instability - germline mutation in DNA mismatch repair genes (80% lifetime risk of colorectal cancer)
- Autosomal dominant (3% of colorectal cancers)
Which cancers does Lynch syndrome predispose to?
Endometrial (most common in women), ovarian, and GIT cancers (colorectal most common in men).
What is the surveillance for people with Lynch syndrome?
Colonoscopic surveillance at least every other year from 25 years old.
Where does Lynch syndrome colorectal cancer arise in the colon and how well differentiated are the cells?
- Right side of colon
2. Moor poorly differentiated
What is familial adenomatous polyposis?
Hundreds of adenomatous polyps develop in the colon during the 2nd to 3rd decade of life.
At what age is adenocarcinoma development inevitable in familial adenomatous polyposis?
35 years
What is the defect in familial adenomatous polyposis and what is the inheritance pattern?
- Germline mutation in APC gene (tumour suppressor)
2. Autosomal dominant
What is the surveillance and management for familial adenomatous polyposis?
- Surveillance sigmoidoscopy from 12 years
2. Prophylactic total bowel removal (panproctocolectomy) <25 years
Which cancers is familial adenomatous polyposis most associated with?
Small bowel, gastric, and thyroid cancers
What are the two main inherited disorders which increase your risk of developing colorectal cancer?
- Lynch syndrome
2. Familial adenomatous polyposis
What is the main protective factor for colorectal cancer?
- Vegetarian and high fibre diet
2. Daily aspirin use
What are colorectal adenomas?
Polyps derived from the epithelial cells lining the mucosa.
What is the epidemiology for colorectal adenomas?
- Very common
2. Incidence increases with age such that at 60, they are found in 20% of the population.
What are the two main types of polyp?
- Pedunculated (attached to mucosa by stalk)
2. Sessile (attached to mucosa by a broad base)
What are the factors associated with a greater risk of progression from a polyp to a malignancy?
Increasing size, high grade dysplasia, histological type (villous > tubular).
What are the features of colorectal dysplasia and how is it graded?
- Disordered growth
- Increase in nuclear:cytoplasmic ratio
- Premalignant - left untreated may become malignant
- Graded as low or high
What is an adenoma?
A benign tumour of glandular epithelium which does not have malignant potential (except in the GI tract).
What is the pathway for the majority of colorectal cancers?
Chromosomal instability pathway
What is the progression of the chromosomal instability pathway?
Normal mucosa - adenoma - invasive adenocarcinoma
What causes the progression of cancer in the chromosomal instability pathway?
Accumulation of mutation in these growth-regulating genes:
- Inappropriate activation of proto-oncogenes (K-ras)
- Inactivation of tumour suppressor genes (APC, both copes must be activated, two-hit hypothesis)
How are mutations acquired by patients in the adenoma-carcinoma pathway of colorectal cancer?
- Sporadic throughout life (majority)
2. Germline mutation in APC with 2nd hit (FAP)
What is the microsatellite instability pathway for colorectal cancer?
Cancers arise from serrated polyps, polyps acquired sporadic mutations which accumulate to cause carcinoma.
What is the national screening programme for colorectal cancer?
- Faecal occult blood test every 2 years between 60-74 years old - colonoscopy if +ve, detects at early stage.
- One-off flexisig performed at age 55 - detect adenomatous polyps for removal, preventing progression.
What is this a presentation of?
Bleeding/mucus PR, altered bowel habit (looser), constipation in obstruction, tenesmus, PR mass. Weight loss, night sweats, fever.
Left sided colorectal cancer
What is this a presentation of?
Right-sided abdominal mass, vague symptoms, weight loss, iron deficiency anaemia, occult bleeding, abdominal pain, obstruction unlikely.
Right-sided colorectal cancer
What is this a presentation of?
Jaundice from hepatic metastases, anorexia, weight loss, ascites, pneumaturia/recurrent UTIs due to colovesical fistula.
Metastatic colorectal cancer
How is a suspected colorectal cancer investigated?
- FBC (microcytic iron deficiency anaemia), U&Es, LFTs, calcium, CEA (monitor for relapse, not diagnostic).
- Colonoscopy - full bowel prep and laxatives (histology/biopsy/resection)
- CT colonography if cannot tolerate colonoscopy.
- CT/MRI CAP if cancer confirmed to assess invasion.
Why is staging a colorectal cancer important?
Single most important pathological prognostic indicator.
What are the stages of T in TNM for colorectal cancer?
T1 - into submucosa but not muscularis propria
T2 - submucosa and muscularis propria but not subserosa
T3 - subserosa but not serosa
T4 - through serosal surface
What is the Duke’s staging criteria?
Colorectal cancer: A. Invades submucosa and/or muscularis propria but not beyond. B. Into subserosa/beyond C. Involves lymph nodes D. Distant metastasis deposits
What is the management of dysplastic polyps/carcinoma in situ in colorectal cancer?
Colonoscopic excision is curative if the margins are clear.
What is the surgical management of stage I-III colorectal adenocarcinomas?
Laparoscopic:
- Right hemicolectomy - caecal, ascending and proximal transverse colon.
- Left hemicolectomy - distal transverse and descending colon.
- High anterior resection - sigmoid tumours.
- Anterior resection - low sigmoid or high rectal tumours.
- Abdominal-perineal (AP) resection and colostomy for very low rectal tumours.
- Total mesorectal excision for rectal cancers in combination with anterior/AP resection.
What is the FOLFOX regime and what is it used for?
- Fluorouracil, folinic acid, oxaplatin.
2. Medical management of colorectal cancer.
What is the management for metastatic colorectal cancer?
- Surgery with liver resection may be curative if confined to single lobe.
- Chemotherapy and endoscopic stenting in palliation.
- Radiotherapy mostly used in palliation.
What is the prognosis of colorectal cancer based on Duke’s staging?
5-year survival: A. 95% B. 80% C. 65% D. 5% (20% if resectable)
