MEDI7302 Study Guide - Final Guide: Descending Colon, Stenosis, Sexual Dysfunction
Colorectal Cancer
Learning
objectives
List the known risk factors for development of colorectal cancer
Contrast the presenting symptoms and signs for patients with cancer involving the
right colon, left colon, rectum or anus
Understand the differences between right hemicolectomy, left hemicolectomy,
Hartmann’s procedure, high and low anterior resection of the rectum and abdominoperineal
resection of the rectum and anus
Outline the differences in principles of management of colon versus rectal cancers
Contrast the differences between a loop and end ileostomy and understand why a
colostomy may be formed
Colonic polyps Small growths of tissue on the colon wall that are either benign or malignant (<1%
risk)
Types
Adenomatous
polyps/ colonic
adenomas
APC gene mutation (chromosome 5, tumor
suppressor gene)
Benign epithelial cell growth ---> malignant
transition requires other tumour suppressor mutations (k-ras,
p53)
FAP syndrome is inherited APC gene mutation
100s to 1000s polyps develop, hence
colectomy required to prevent malignancy
Histological
Tubular (holes) or villous (tree-like) or
tubulovillous
Pedunculated (stalk attachment to colon
wall) or sessile (firmly attached to colon wall)
Villous and sessile histopathology have
greater risk of malignancy
Serrated polyps CH3 methyl group added to nucleotides of CpG
islands (promoter region of gene), causing inhibition of promoters/
genes
Example - silence DNA repair genes ->
greater mutation rate -> greater malignancy potential
Pathology
'Saw tooth appearance' of cells
Small poylps (hyperplastic polyps) are
rarely malignant VS larger polyps (flat, sessile) have greater
malignancy potential
Inflammatory
polyps
Non-malignant
Usually follow attack of UC or CD
Hamartomatous
polyps
Mixture of tissues
Genetic syndromes - Peutz-Jegher syndrome,
juvenile polyposis
Distorted architecture
Risk factors
Predisposition to genetic mutation via increasing cell division - genetic
condition, bowel wall injury (old age, IBD, smoking)
Clinical presentation
Usually asymptomatic, and incidentally found on colonoscopy
Sometimes ulcerate and cause PR bleed -> slow progressive anemia
Rarely, large polyps causes obstruction (abdominal pain, constipation)
Diagnosis
Stool occult blood test
Flexible sigmoidoscopy
Management
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Healthy diet - vegetables, legumes, fruit
Polypectomy - few solitary or penduculated/ sessile polyps
Colonic resection - multiple intestinal polyps associated with FAP, patients
with long-standing UC with high grade dysplasia, large sessile polyps
Epidemiology Colon cancer is the most common type of GIT cancer
3rd most common cancer incidence (after prostate & melanoma in M, after breast
& melanoma in F)
3rd most common cancer mortality (after lung & prostate in M, after lung & breast
in F)
Sigmoid colon is most common place
M:F ratio 19:25
Risk factors Elderly age (50+yo)
Male
Smoking, alcohol, sedentary lifestyle, overweight/ obese
Family hx (1.5-2x), especially greater # affected and younger age of diagnosis
Past personal hx of colorectal cancer
Long hx of inflammatory bowel disease
Diet - high dietary intake of red meat and animal fat, low fibre diet, low fruit and
vegetable intake
Genetic predispositions - FAP, HNPCC, polyposis syndromes (Peutz-Jegher, juvenile)
Genetic
predisposition
FAP Most common adenomatous polyposis syndrome
Autosomal dominant inheritance
APC gene 'tumour suppressor' germline mutation (also found
in Gardner syndrome, AAPC etc)
Clinical features
100s to 1000s adenomatous polyps throughout colon
Non-specific sx - unexplained PR bleeding, diarrhoea,
abdominal pain
Untreated condition -> colon cancer by age 35-40yo
Usually 100% risk of colon cancer
NOTE: Gardner syndrome is the appearance of polpys in
regions outside colon (eg duodenum, stomach, bone, skin)
Imaging
Flexible sigmoidoscopy
Follow up with esophago-gastro-duodeno-scopy if
sigmoidoscopy is +ve FAP - look for gastric, duodenal or periampullary
adenomas
Endoscopic polypectomy - remove polyps, confirm FAP with
tubular adenoma recognised on histology
Laboratory
CBC
AFP blood test (alpha feto-protein) - <5yo for hepatoblastoma
screening
Genetic testing (3 types)
oIn vitro protein synthesis assay - genetic test of choice;
analyse DNA peripheral blood for truncated APC gene
oGene sequencing - APC gene sequencing
oLinkage testing - DNA markers near or at APC locus
used to identify mutant gene carriers (need at least 2 affected family
members)
Management
Medical - endoscopic surveillance (flexible sigmoidoscopy,
colonoscopy, esophago-gastro-duodeno-scopy)
Surgical - proctocolectomy + ileoanal pouch/ J pouch/ IPAA is
the procedure of choice (retain renal function)
oCreation of pouch from 2+ loops of intestine sutured/
stapled together to form a “makeshift rectum”
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oAttach “makeshift rectum” to anus, and have
temporary diverting ileostomy while the anastomoses is healing
Complications
Colorectal cancer
Duodenal or periampullary adenocarcinoma
HNPCC Most common hereditary colorectal cancer
2-5% all colorectal carcinomas
Autosomal dominant inheritance
Defective DNA mismatch repair proteins (MMR) -> usually high
microsatellite instability (MSI-H), meaning at least 2+ genes are mutated
Usually 60% risk of colon cancer
Two different types
Lynch syndrome I (familial colon cancer)
Lynch syndrome II (HNPCC-associated with other cancers of GI/
repro tract)
Clinical features
+ve family hx, tumour testing, genetic testing
Change in bowel habit (constipation or diarrhoea), +ve FOBT,
black tarry stool, iron deficiency, abdominal pain or distension, fatigue and
weakness, anorexia, unexplained weight loss
Usually sessile, serrated polyps
MSI-+ tumour characteristics
Arise in proximal colon
Lymphocytic infiltration
Poorly differentiated mucinous or signet ring appearance
Amsterdam criteria
Diagnostic criteria to aid identification of families with Lynch
syndrome
o3-2-1: at least 3 relatives with histologically confirmed
colorectal cancer (one is 1st degree relative of other two relatives) + 2
successive generations involved + at least 1 cancer diagnosed before
age 50
Increased risk of other cancers (endometrial, ovarian, stomach, SI, HB
tract, pancreas etc)
Prognosis - 5-year survival rate is 60% (HNPCC patient) vs 40-50%
(sporadic colon cancer)
Pathogenesis Adenoma -> carcinoma sequence via series of genetic mutations
Polyp derived disease (8-15yrs duration for colon cancer to develop)
APC mutation (overexpression of oncogene c-myc and cyclin D1) = FAP
Epigenetic events - DNA methylation to silence tumour suppressors OR active
oncogenes
Other important genes
KRAS oncogene
Chromosome 18 LOH -> inactivation of SMAD4
DCC tumour suppressor
Chromosome 17p deletion + p53 mutations (both confer resistance to
apoptosis -> late carcinogenesis events)
Gene mutation of MSH2, MLH1, PMS2 -> high frequency microsatellite instability
(H-MSI) & defective DNA mismatch repair proteins = HNPCC, Lunch syndrome
Staging TMN staging can only be histologically determined, not radiologically determined
TMN classification
T stage N stage M stage
T0 - no primary cancer
Tis - in situ carcinoma (only
muscularis mucosa)
T1 - through muscularis mucosa,
N0 - no LN
N1 - 1-3 LN
N2 - 3+ LN
M0 - no distant mets
M1 - distant mets (liver,
lungs)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
List the known risk factors for development of colorectal cancer. Contrast the presenting symptoms and signs for patients with cancer involving the right colon, left colon, rectum or anus. Understand the differences between right hemicolectomy, left hemicolectomy, Hartmann"s procedure, high and low anterior resection of the rectum and abdominoperineal resection of the rectum and anus. Outline the differences in principles of management of colon versus rectal cancers. Contrast the differences between a loop and end ileostomy and understand why a colostomy may be formed. Small growths of tissue on the colon wall that are either benign or malignant (<1% Apc gene mutation (chromosome 5, tumor suppressor gene) Benign epithelial cell growth ---> malignant transition requires other tumour suppressor mutations (k-ras, p53) 100s to 1000s polyps develop, hence colectomy required to prevent malignancy tubulovillous. Pedunculated (stalk attachment to colon wall) or sessile (firmly attached to colon wall) Villous and sessile histopathology have greater risk of malignancy.
