COLORECTAL CANCER Flashcards
Whats the incidence of colorectal cancer?
Common
13% of all cancer cases and 10% of cancer deaths in the UK
4th most common cancer
Second most common cause of cancer death
95% of pt are aged over 50 at time of diagnosis
Equally common in men and women
Incidence increasing due to ageing population but mortality is decreasing
What is the adenoma-carcinoma sequence?
Most colorectal cancers develop via a progression of normal mucosa to colonic adenoma (‘polyps’) to invasive adenocarcinoma
Adenomas may be present for >10 years before becoming malignant and 10% of adenomas progress to adenocarcinoma
Hyperproliferation of mucosa -> APC gene mutation -> early adenoma -> K-RAS mutation -> intermediate adenoma -> DCC mutation -> late adenoma -> p53 mutation -> adenocarcinoma
What genetic mutations are associated with colorectal cancer?
Adenomatous polyposis coli (APC) - note: more than half colon cancer show allelic loss of this gene
MSH-2, MSH6, MLH1, PMS2 (DNA mismatch repair genes) - HNPCC/lynch syndrome
Activation of the K-ras oncogene
Delection of DCC tumour suppressor gene
Deletion of P53 tumour suppressor gene
MYH - MYH-associated polyposis
Is colorectal cancer inherited?
Only 5% of cases are truly inherited
The vast majority occur spontaneously
What are adenomas?
a benign, dysplastic tumour of columnar cells or glandular tissue.
What are the hereditary syndromes that increase the risk of colorectal cancer?
Hereditary non polyposis colorectal cancer (lynch syndrome)
Familial adenomatous polyposis
MYH-associated polyposis
Serrated polyposis syndrome
Peutz-jeghers syndrome
Juvenile polyposis syndrome
What is HNPCC? What proportion of cases of colorectal cancer is it responsible for?
Autosomal dominant condition where there are mutations to DNA mismatch repair genes (usually MSH2 60% of cases or MLH1 in 30% of cases) 0 cases microsatellite instability
It increases the incidence of many malignancies (stomach, small intestine, bladder, skin, brain, hepatobilliary system, endometrial and ovarian cancer). Lifetime risk of colorectal cancer in mutation carriers is 70-80%
3%
What is FAP? What proportion will develop colorectal cancer?
an autosomal dominant condition arising from germiline mutations of The (APC) gene - a tumour suppressor gene.
Penetrance is virtually 100%
Accounts for <1% of all colorectal cancers
characterized by the presence of hundreds to thousands of colorectal and duodenal adenomas, some of which undergo malignant change.
90% will develop CRC before the age of 45 if not treated.
What screening is done for FAP?
Annual colonoscopies from age 12-14
Prophylactic surgical resection can be offered if anything is found
What is Gardner’s syndrome?
A form of FAP
It can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
What is MYH-associated polyposis?
An autosomal recessive condition characterised by colorectal adenomas and cancers caused by a mutation to MYH (MUT Y homologue) gene.
MUTYH is a base excision repair gene and failure of its normal action increases the risk of colorectal cancer.
What are serrated polyps?
a heterogeneous group of colorectal lesions that includes the benign hyperplastic polyps, and the pre-malignant sessile serrated adenoma and traditional serrated adenoma. They are characterized by the saw-tooth appearance of the crypt epithelium.
Supposedly BRAF gene mutations and gene promoter hypermethylation
What is peutz-jeghers syndrome? Whats the risk of colorectal cancer?
An autosomal dominant condition characterised by hamartomatous polyps in the gastrointestinal tract, pigmented mucocutaneous lesions and an increased risk of gastrointestinal and extragastrointestinal malignancies.
The polyps, which are hamartomas, can occur anywhere in the gastrointestinal tract but are most frequent in the small bowel.
There is an estimated 40% lifetime risk of colorectal cancer.
What is juvenile polyposis syndrome?
Autosomal dominant condition with incomplete penetrant
It is characterised by hamartomatous polyps throughout the GI tract but mainly found in the colon. It causes an increased risk of CRC and gastric cancer.
Occurs mainly in children and teenagers
Characterised by >3-5 juvenile colonic polyps, juvenile polyps throughout the GIT or any number of polyps with a family history
Polyps are a cause of bleeding and intussesception in the first decade of life
Whats the onset of cancer in lynch syndrome?
40-50 or younger (earlier than in sporadic cases!)
Whats the mean age of adenoma development in FAP? Whats the average age at which colorectal cancer develops?
16 years
39 years
How should FAP be managed?
Affected individuals should be offered a prophylactic colectomy
What is attenuated FAP?
A type of FAP which presents slater in life at about 44 years and has fewer polyps (<100) which tend to occur on the right side of the colon
What proportion of colorectal cancers originate from serrated polyps?
30%
What are the risk factors of colorectal cancer?
FHx of colorectal cancer/polyps - most common risk factor
Longstanding/chronic IBD
PMHx of colorectal cancer/polyps
Genetic syndrome e.g. FAP or lynch syndrome
Obesity
Red and processed meat
Eating too little fibre
Alcohol and smoking
Increasing age
Medical conditions - gallstones, diabetes, acromegaly
Radiation exposure
H.pylori infections
What are the protective factors for colorectal cancer?
Regular physical exercise
Dietary fibre
Non-starchy vegetables
Pulses
High calcium intake
Garlic
What proportion of cases of colorectal cancer have a positive family history?
10-20%
What are the most common sites for colorectal cancer to develop?
Rectum 40%
Sigmoid colon 30%
Caecum 15%
Transverse colon 10%
Descending colon 5%
(2/3rds occur distal to splenic flexure)
What proportion of colorectal cancers have metastatic spread at diagnosis?
25%
What are the 4 modes of spread of colorectal cancer?
Direct invasion of adjacent organs e.g. bladder
Lymphatic to adjacent lymph nodes
Haematogenous to distant organs (most commonly liver but also likely lungs)
Trans-coelomic e.g. peritoneum or ovaries
Whats the process for referral of colorectal cancer
Referred as a fast track - have to be seen in secondary care within 14 days and begin treatment within 62 days 1
How does colorectal cancer typically first present
20% acutely - due to obstruction, bleeding or perforation
Often diagnosed through screening or incidentally due to investigations for other reasons, also commonly found due to unexplained FDA
How does colorectal cancer present?
Change in bowel habit
Rectal bleeding
Unexplained weight loss (when associated with metastasis)
Abdominal pain
Symptoms of anaemia
What are the features of right-sided colon cancers?
Abdominal pain - relative late symptom!
IDA (due to chronic occult bleeding)
Palpable mass in RIF
Often presents later than left sided colon cancers
What are the clinical features of left-sided colon cancers
Rectal bleeding
Change in bowel habit
Tenesmus
Abdominal pain
Palpable mass in LIF or on PR exam
What does it suggest if someone with colorectal cancer has had unexplained weight loss?
Metastatic disease
What does NICE recommend for who should be referred for urgent investigation of suspected bowel cancer?
Urgent referral within 2 weeks:
≥40yrs with unexplained weight loss and abdominal pain
≥50yrs with unexplained rectal bleeding
≥60yrs with iron‑deficiency anaemia or change in bowel habit
Positive occult blood screening test
Consider it for pt with a rectal or abdominal mass
Consider for unexplained anal mass or ulceration
Consider for adults under 50 with rectal bleeding and any of the following: abdo pain, change in bowel habit, weight loss or IDA
What investigations should be done for colorectal cancer?
Colonoscopy - gold standard (advantage is it can take biopsies)
CT colonography - visualises colon and other organs (CXR AXR and PXR to look for metastases also)
FBC - microcytic anaemia, LFTs, clotting
MRI to evaluate mesorectal in pt with tumours lying below the peritoneal reflection
Double contrast barium enema - used less often
Conventional CT - less sensitive for small lesions but doesnt require full bowel prep
Flexible sigmoidoscopy (will identify any lesions distal to the splenic flexure so should be sufficient for pt with fresh bleeding PR)
Who is not suitable for a colonoscopy?
Frailty >75 years old
Intolerance
Recent MI
Haemodynamic instability
Peritonitis
Recent surgery with colonic anastomosis or bowel injury and repair
Known/suspected colon perforation
Fulminant colitis and severe toxic megacolon
Whats the aim of screening in colorectal cancer?
To diagnose the disease at an earlier stage so more pt undergo curative treatment, thus reducing overall mortality
When did the national bowel cancer screening programme start?
2006
Outline the screening for colorectal cancer?
Pt aged 60-74 are sent a FIT testing kit every 2 years (in Scotland its 50-74)
If test is positive, pt is offered a colonoscopy
After the age of 75, pt can request further tests every 2 years
What proportion of those with a positive FIT test done in the colorectal cancer screening will polyps or cancer be found?
5/10 normal exam
4/10 polyps
1/10 cancer