Colorectal and Anal Cancer Flashcards
What is a polyp?
-Excrescence of mucosal lining
-Does not formally indicate nature of the lesion
Classification of large bowel polyps
-Neoplastic
-Hamartomata’s
-Inflammatory
-Unclassified
Neoplastic polyps
-Solitary= adenoma (tubular, tubulovillous, villous architecture)
-Multiple= familial adenomatous polyposis
Hamartomata’s polyps
-Solitary= juvenile polyp/ Peutz-Jeghers
-Multiple= juvenile polyposis/ Peutz-Jeghers syndrome/ Cronkhite-Canada syndrome/ Cowden’s disease
Inflammatory polyps
-Solitary= Benign lymphoid polyp/ pseudo-polyp
-Multiple= Benign lymphoid polyposis/ pseudo-polyposis (UC)
Unclassified polyps
-Solitary= metaplastic/ hyperplastic lipoma/ neurofibroma
-Multiple= Multiple metaplastic polyps/ MAP (MYTH associated polyposis)
Chance of malignant potential conversion with colorectal adenomas
-Size
=<1cm: 1%
=1-2cm: 9.5%
=>2cm: 50%
-Type
=Tubular: 5%
=Tubulo-villous: 22%
=Villous: 40%
-Dysplasia
=<1cm no dysplasia: 1%
=>1cm with dysplasia 27%
Molecular events in colorectal carcinogenesis
-Normal epithelium suffers Wnt signalling aberrations (APC/ b catenin mutations)
-Aberrant crypt foci
-Early adenoma then has K-ras mutation/ TGFb-R2 inactivation
-Intermediate adenoma then has loss of 18q genes
-Late adenoma
=SEQUENTIAL ACCUMULATION OF GENETIC MUTATION- HYPOMETHYLATION
-p53 mutation/ stabilisation= carcinoma= metastasis
Colorectal cancer aetiology
-Age
-Western diet
=High fat, red meat, total energy, low fibre, hight stool pH
-Lifestyle: smoking, lack of exercise, beer in rectal
-IBD: pan UC and Crohn’s
-Sporadic 95%
-Genetic predisposition
=35% overall contribution
=Dominant gene disorders: HNPCC (hereditary nonpolyposis colorectal cancer 5%), FAP (familial adenomatous polyposis) <1%
Overview of Lynch syndrome
-HNPCC
-Autosomal dominant
-Most common form of inherited colon cancer
-Around 70-80% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive
-Most common genes involved: MSH2 (60%), 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
-HNPCC family may be better served with a panproctocolectomy rather than segmental resection
Pragmatic Amsterdam criteria for HNPCC
->3 family member with histologically proven CC
-1 relative a 1st first degree
->2 generations affected
-Age at onset <50 years in at least one member
-Uterine cancer in 1> relatives acceptable as part of 3 members
Overview of FAP
-Rare autosomal dominant condition
-Formation of hundreds of polyps be age 30-40
=Carcinoma inevitably
-Mutation in tumour suppressor gene (APC) chromosome 5
-Genetic testing from DNA white blood cells
-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
-Total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their twenties.
Emergency clinical presentations of CC
-Obstruction: abdo pain, nausea, vomiting
-Perforation
-Bleeding
-Localised pain
Elective clinical presentations of CC
-Altered bowel habit: diarrhoea/ constipation/ urgency/ frequency
-Rectal bleeding: bright red or melena
-Colicky pain: obstruction/inflammation
-Unexplained anaemia
-Anorexia/ weight loss/ malaise: chronic bleeding
-Flatulence
Topographical distribution of CC
- 35% = Rectum
- 26%= Sigmoid
- 22% = Caecum
- 12%= Splenic flexure
- 5%= Transverse
rectal: 40%
sigmoid: 30%
descending colon: 5%
transverse colon: 10%
ascending colon and caecum: 15%