Colorectal Cancer Flashcards
Colorectal Cancer Screening - Overview
Overview
most cancers develop from adenomatous polyps. Screening for colorectal cancer has been shown to reduce mortality by 16%
the NHS now has a national screening programme offering screening every 2 years to all men and women aged 60 to 74 years in England, 50 to 74 years in Scotland. IPatients aged over 74 years may request screening
eligible patients are sent faecal occult blood (FOB) tests through the post
patients with abnormal results are offered a colonoscopy
Colonoscopy for Colorectal Cancer - Statistics
At colonoscopy, approximately:
5 out of 10 patients will have a normal exam
4 out of 10 patients will be found to have polyps which may be removed due to their premalignant potential
1 out of 10 patients will be found to have cancer
Duke’s Classification and 5 Year Survival Rates for Colorectal Cancer
Dukes’ classification and 5-year survival rates
Stage > 5-year survival
A - confined to mucosa and submucosa 95% in men and 100% in women
B - extends through the muscularis propria > 80% in men and 90% in women
C - regional lymph nodes involved
65% in men and 65% in women
D - distant spread
> 5% in men and 10% in women
Colorectal Ca: Duke’s Classification - Example Question
A 72-year-old man was diagnosed with colorectal cancer after a positive faecal occult blood test and microcytic anaemia on a routine health check. Following further investigations and resection, he is found to have an adenocarcinoma confined to the mucosa and submucosa. What is his 5-year survival based on his Dukes’ stage?
> 95% 75% 65% 50% 30%
This patient has Dukes’ A bowel cancer which means he has a 95% 5-year survival.
Colorectal Cancer - Genetics
It is currently thought there are three types of colon cancer:
sporadic (95%)
hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
familial adenomatous polyposis (FAP, <1%)
Colorectal Cancer - Sporadic
Studies have shown that sporadic colon cancer may be due to a series of genetic mutations. For example, more than half of colon cancers show allelic loss of the APC gene. It is believed a further series of gene abnormalities e.g. activation of the K-ras oncogene, deletion of p53 and DCC tumour suppressor genes lead to invasive carcinoma
Colorectal Cancer - HNPCC
HNPCC, an autosomal dominant condition, is the most common form of inherited colon cancer. Around 90% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive. Currently seven mutations have been identified, which affect genes involved in DNA mismatch repair leading to microsatellite instability. The most common genes involved are:
MSH2 (60% of cases)
MLH1 (30%)
Patients with HNPCC are also at a higher risk of other cancers, with endometrial cancer being the next most common association, after colon cancer.
The Amsterdam criteria are sometimes used to aid diagnosis:
at least 3 family members with colon cancer
the cases span at least two generations
at least one case diagnosed before the age of 50 years
Colorectal Cancer - FAP
FAP is a rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years. Patients inevitably develop carcinoma. It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5. Genetic testing can be done by analysing DNA from a patients white blood cells. Patients generally have a total colectomy with ileo-anal pouch formation in their twenties.
Patients with FAP are also at risk from duodenal tumours. A variant of FAP called Gardner’s syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
Gardner’s Syndrome - Example Question
A 17 year old male presents with 3 month history of PR bleeding, lower abdominal pain and left jaw pain. He reports an inability to gain weight and appears ‘skinnier than his friends’. He has no other medical history. He knows his father and uncle have ‘some problems with their bowels but they dont talk about it’. On examination, he has BMI 14.7 and abdomen is soft. PR is negative. Cardiovascular and respiratory examinations are normal. Limb neurological examination is unremarkable. However, when testing muscles of mastication, you note a raised boney mass in his left jaw that is tender in a non-cranial nerve distribution to palpation. Colonoscopy reveals hundreds of polyps in his small bowel. What is the diagnosis?
Colorectal carcinoma > Gardners syndrome Peutz-Jeghers syndrome Hereditary non-polyposis colorectal cancer Ulcerative colitis
This is a difficult question requiring knowledge of combination of colorectal polyps with extracolonic manifestations. Presence of classically osteomas with a familial polyposis syndrome, sometimes also with cutaenous, adrenal or nasal lesions, is diagnostic of Gardners syndrome, a variant of familial adenomatous polyposis. Peutz-Jeghers is a reasonable differential but its polyps are more frequently associated with pigmented lesions instead of boney outgrowths. HNPCC increases the risk of colonic cancer without polyps, a diagnosis of carcinoma, despite at high risk, cannot be made at this stage without positive malignant histology.
Colorectal Ca - Genetics: Example Question
A 24 year-old man presents to his GP because he is worried that he may have bowel cancer. He does not currently have any clinical features that would suggest bowel cancer and is taking no medication. His father died of colon cancer at the age of 49 and his paternal uncle also had bowel cancer diagnosed at the age of 44. He was previously referred for a colonoscopy four months ago which was normal.
His abdominal examination is normal. You rearrange for the patient to have a colonoscopy in 2 years time.
What is the most appropriate next management step?
Check for a mutation in chromosome 5q21 > Check for a DNA mismatch repair gene mutation Perform a computed tomography (CT) with contrast scan of his abdomen Check carcinoembryonic antigen (CEA) level Check for a P53 mutation
The most likely diagnosis in this instance is hereditary non-polyposis colorectal cancer, given his strong family history. This accounts for roughly 2% of all colorectal cancers and is due to a mutation in the DNA mismatch repair gene. Once a diagnosis has been established, the preferred treatment is a colonoscopy every 1-3 years.
Gardner’s Syndrome - Example Question
A 29 year-old adopted woman is referred by her GP with a two week history of blood in her stools. Furthermore, over the last three months her stools have become more loose and she has 2-3 bowels motions a day. Her past medical history includes an osteoma of her left tibia as well as one of her skull. The only relevant family history she is aware of is a brother who has ulcerative colitis. She currently smokes five cigarettes per day and drinks 10 units of alcohol per week. Her occupation is a lawyer.
What is her most likely diagnosis?
Crohn's disease Ulcerative colitis > Gardener's syndrome Peutz-Jeghers syndrome Familial adenomatous polyposis
Gardener’s syndrome is a condition that is inherited in an autosomal dominant fashion. It’s main clinical features include adenomatous intestinal polyposis, which can present with changes in bowel habit and rectal bleeding, osteomas and fibromas. 50% of patients with Gardener’s syndrome have colon cancer by the age of 39.
Colorectal Cancer - Overview
Overview
Most cancers develop from adenomatous polyps. Screening for colorectal cancer has been shown to reduce mortality by 16%
The NHS now has a national screening programme offering screening every 2 years to all men and women aged 60 to 69 years. Patients aged over 70 years may request screening
Eligible patients are sent faecal occult blood (FOB) tests through the post
Patients with abnormal results are offered a colonoscopy
At colonoscopy, approximately:
5 out of 10 patients will have a normal exam
4 out of 10 patients will be found to have polyps which may be removed due to their premalignant potential
1 out of 10 patients will be found to have cancer
Colorectal Cancer - Diagnosis
Diagnosis
Essentially the following patients need referral:
- Altered bowel habit for more than six weeks
- New onset of rectal bleeding
- Symptoms of tenesmus
Colonoscopy is the gold standard, provided it is complete and good mucosal visualisation is achieved. Other options include double contrast barium enema and CT colonography.
Colorectal Cancer - Staging
Staging
Once a malignant diagnosis is made patients with colonic cancer will be staged using chest / abdomen and pelvic CT. Patients with rectal cancer will also undergo evaluation of the mesorectum with pelvic MRI scanning.
For examination purposes the Dukes and TNM systems are preferred.
Colorectal Cancer - Tumour Markers
Tumour markers Carcinoembryonic antigen (CEA) is the main tumour marker in colorectal cancer. Not all tumours secrete this, and it may be raised in conditions such as IBD. However, absolute levels do correlate (roughly) with disease burden and it is once again being used routinely in follow up.
