CRC, FAP, HNPCC Flashcards
Age of CRC
Peak in 60s
Role of adenomatous polyposis coli (APC) in colorectal cancer?
- APC is a protein that promotes degradation of β-catenin.
- Mutations in APC lead to increased β-catenin
= Increased cell proliferation
Sequence of events from formation of adenomas to colorectal carcinomas caused by APC mutation?
- First hit: mutation of one APC copy
- Second hit: mutation of second copy of APC (leads to adenoma formation)
- Further mutations (eg in KRAS and p53) in the adenoma –> malignant transformation
Risk factors for colorectal cancer?
- Diet: ↓ fibre + ↑ refined carbohydrate
- Inflammatory bowel disease
- Familial: FAP, HNPCC, Peut-Jeghers
- Smoking
- Genetic
Meds protective against CRC
Aspirin
NSAIDs
What type of carcinoma are the majority of colorectal cancers?
- 95% adenocarcinoma
- others: lymphoma, GIST, carcinoid
The 3 common sites for colorectal cancers?
Rectum: 35%
Sigmoid: 25%
Caecum and ascending colon: 20%
Symptoms of left sided colorectal cancer?
Left sided cancer:
- Altered bowel habit
- PR mass- Obstruction
- bleeding/ mucus
Sx of right sided CRC
anaemia
Anal fistula
a narrow tunnel with its internal opening in the anal canal and its external opening in the skin near the anus
MRI use for colorectal carcinoma?
MRI best for rectal Ca and liver mets
Tumour marker for CRC
CEA (carcinoembryonic Ag)
Staging of rectal tumour
Endoanal ultrasound
Findings of Ba enema in CRC
apple-core lesion
DUKES staging of colorectal cancer?
A. confined to bowel wall
B. through bowel wall but not lymph nodes
C. regional lymph nodes
D. distant mets
T in TNM staging of colorectal cancer?
TIS: carcinoma in situ
T1: submucosa
T2: muscularis propria
T3: subserosa
T4: through the serosa to adjacent organs
N in TNM staging of CRC
N1: 1-3 nodes
N2: >4 nodes
Grading of colorectal cancer?
Grading from low to high
- Based on cell morphology
- Dysplasia, mitotic index, hyperchromatism
Pre-operative preparation for colorectal cancer resection surgery?
Kleen Prep (Macrogol: osmotic laxative) the day before
Phosphate enema in the morning of surgery.
Discuss stomas (Stoma nurse consult for siting)
Surgical options for rectal cancer management?
- Anterior resection:
- Abdominoperineal resection
- Total mesorectal excision (TME)
Anterior resection
used for proximal 2/3 of the rectum (tumour 4-5cm from anal verge)
- takes out rectum
- spares sphincter
- needs loop ileostomy
Abdominoperineal resection
- used for distal 1/3 of the rectum ( tumour <4cm from anal verge)
- takes out rectum, anus
- permenant colostomy
Total mesorectal excision (TME)
- removal of mesorectum
- for tumours of the middle and lower third of rectum
- it reduces the cancer recurrence
- Side effect: ↑ risk of faecal incontinence
Mesorectum?
is the perirectal fat separated by the rectal fascia
Surgical options for sigmoid tumours
high anterior resection
or sigmoid colectomy
Surgical option for left sided tumour
left hemicolectomy
Surgical option for tansverse tunmours
extended right hemicolectomy
Surgical option for caecal tumours
right hemicolectomy
Screening programs for colorectal cancer?
- FOB (faecal occult blood) Testing
- every 2 yrs: from 2 bowel motions
- 60-75yrs
- if +, colonoscopy - Flexi Sigmoidoscopy
- 55-60yrs
Genetics of Familial adenomatous polyposis (FAP) ?
- Autosomal dominant
- Mutated APC gene
Presentation features of Familial adenomatous polyposis (FAP) ?
- 100-1000s of adenomas by ~16yrs,
- mainly in large bowel (But also stomach and duodenum, near ampula)
- 100% CRC by ~40s
Variants of Familial adenomatous polyposis (FAP) ?
- attenuated FAP
- Gardener’s syndrome
- Turcot’s syndrome
Attenuated FAP?
- <100 adenomas,
- Later CRC; >50yrs
Gardener’s syndrome 4 features?
TODE
- Thyroid tumours
- Osteomas of the mandible, skull and long bones
- Dental abnormalities: supernumerary teeth
- Epidermal cysts
Turcot’s syndrome?
Polyps + CNS tumours: medullo- and glio-blastomas
Management of FAP?
Prophylactic colectomy before 20yrs
Total colectomy + ileorectal anastomosis (IRA)
Proctocolectomy + ileal pouch anal anastomosis (IPAA)
Regular endoscopic screening as risk of stomach and duodenum Ca
Proctocolectomy + ileal pouch anal anastomosis (IPAA)?
- removal of rectum and large colon
- surgical construction of internal reservoir by folding loops of small intestine (the ileum) back on themselves and stitching them together
- The internal walls are removed
- retains or restores functionality of the anus with stools passed under voluntary control of the patient
Hereditary Non-Polyposis Colorectal Cancer (HNPCC) genetics?
- Autosomal dominant
- Mutation of mismatch repair enzymes (eg MSH2)
Presentation of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) ?
Lynch 1 syndrome
Lynch 2 syndrome
Lynch 1 fx
right sided CRC
Lynch 2 fx
CRC
gastric
endometrial
prostate
breast
Diagnosis of Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
“3, 2, 1, rule”
≥3 family members
over 2 generations
with one <50yrs
Peutz-Jeghers Syndrome genetics?
- Autosomal dominant
- STK11 mutation
Age of presentation of Peutz-Jeghers Syndrome?
at the age of ~ 10-15yrs
Symptoms of Peutz-Jeghers Syndrome?
Mucocutaneous hyperpigmentation
Multiple GI hamartomatous polyps (Intussusception/haemorrhage)
Risk associated with Peutz-Jeghers Syndrome?
↑ Cancer risk:
- Colorectal
- pancreas
- lung
- breast
- ovaries
- uterus
Different types of GI polyps?
I. Inflammatory pseudopolyps
II. Hyperplastic polyps
III. Hamartomatous
IV. neoplastic
What are inflammatory pseudopolyps?
regenerating islands of mucosa in ulcerative colitis
What are hyperplastic polyps?
- Piling up of goblet cells and absorptive cells
- No malignant potential
What are Hamartomatous polyps
Tumour-like growths composed of tissues present at site where they develop
Sporadic or part of familial syndromes
Tenesmus?
- refers to cramping rectal pain
Tenesmus makes patient feel like they need to have a bowel movement, even if they had one recently
