Part two - colorectal Flashcards
Risk of colorectal cancer
Cumulative risk 6% by 75 years
Slight increase x2 -> no specific surveillance
- one 1st degree relative with CRC > 55 years
Moderate increased risk x2-6 -> 5 yearly scopes from 50 years or 10 years before relative’s dx
- one 1st degree relative with CRC < 55 years
- two 1st degree relatives any age on same side
High risk up to 50x -> refer to genetic service
- family hx of FAP, HNPCC or other familial cancer service
- one 1st degree & 2+ 1st or 2nd degree relatives on same side any age
- one 1st degree < 50 especially if loss of MLH1, MSH2, MSH6, PMS2
- one 1st/2nd degree with CRC and multiple polyps
- two 1st or 2nd degree relatives on same side whom:
- diagnosed < 55, or
- developed multiple bowel cancers, or
- developed extra-colonic tumour(s) suggestive of HNPCC
- endometrial
- ovarian
- stomach
- small bowel
- renal pelvis
- pancreas
- brain
Distribution of colorectal cancer
Right colon - 30% Transverse colon - 10% Left colon - 15% Sigmoid colon - 25% Rectum - 20%
TNM staging colorectal cancer
T1 = invades submucosa T2 = invades muscularis propria T3 = invades through musc prop into subserosa, nonperitoneal peri-colic or -rectal tissues T4 = perforates visceral peritoneum or directly invades other organs or structures
N1 = 1-3 peri-colic or peri-rectal lymph node metastases N2 = 4+ peri-colic or peri-rectal lymph node metastases
M1 = distant metastases
Stage I = T1 and T2 with no nodal disease
Stage II = T3 and T4 with no nodal disease
Stage III = any T with nodal disease
Stage IV = any T, any N with distant metastases
Duke’s classification
Dukes’ A = invasion into but not through bowel wall - 90% five year survival
Dukes’ B = invasion through the bowel wall but not involving nodes - 70%
Dukes’ C = involvement of lymph nodes - 30%
Dukes’ D = distant metastases - <15%
FAP
FAP = familial adenomatous polyposis = cluster of genetic syndromes characterised by development of numerous GIT polyps
Actual FAP is an inherited disorder causing hundreds to thousands of polyps in the colon and rectum of varying size and configuration with associated increased risk of CRC due to mutated APC gene.
CRC approaches 100% by aged 35.
Duodenal & periampullary polyps -> cululative cancer risk 10% by 60 and second most common cause of disease related morbidity.
FAP
FAP = familial adenomatous polyposis = cluster of genetic syndromes characterised by development of numerous GIT polyps
Actual FAP is an inherited disorder causing hundreds to thousands of polyps in the colon and rectum of varying size and configuration with associated increased risk of CRC due to mutated APC gene.
CRC approaches 100% by aged 35.
Duodenal & periampullary polyps -> cumulative cancer risk 10% by 60 and second most common cause of disease related morbidity.
AD inheritance, chromosome 5, >100 mutations
Gardner syndrome
An example of FAP with variations in expression of the extra colonic manifestation:
- polyposis
- desmoid tumours
- osteomas of mandible or skull
- sebaceous cysts
Turcot syndrome
An example of FAP with variations in expression of the extra colonic manifestations:
- polyposis
- childhood cerebellar medulloblastoma
- May also be associated with HNPCC and defects in MMR genes - CRC with gliomas
Amsterdam II criteria
Defines HNPCC by history alone
At least 3 relatives must have a cancer associated with HNPCC - CRC, endometrial, stomach, ovary, ureter, renal pelvis, brain, small bowel, hepatobiliary tract, skin sebaceous tumours:
- One must be a first degree relative of the other two
- At least two successive generations must be affected
- At least one of the relatives must haves received the diagnosis by age 50
Revised Bethesda Criteria for HNPCC
In a new diagnosis of CRC, the presence of any one of the Revised Bethesda Criteria warrants testing for MSI:
- < 50 years
- Synchronous or metachronous HNPCC-related tumour regardless of age
- MSI-H-like histology < 60 years
- 1+ 1st degree relative with HNPCC-related tumour with one in <50 years
- 2+ first- or second-degree relatives with HNPCC-related tumours regardless of age
What is the pathogenesis of colorectal cancer?
Is by a combination of molecular events that are heterogeneous and include genetic and epigenetic abnormalities.
There are two well described genetic pathways which involve the stepwise accumulation of multiple mutations with differing genes and mechanisms by which the mutations accumulate.
Epigenetic events, most commonly methylation-induced gene silencing, may enhance progression along both pathways.
The adenoma-carcinoma-sequence
Also known as chromosomal instability.
80% of sporadic cancers.
Requires “two” hits to the APC tumour suppressor gene to mutate both alleles - the first may be acquired or sporadic.
Subsequent accumulation of mutations in KRAS, SMAD2, SMAD4 and p53 causes adenomas and then carcinomas.
DNA mismatch repair deficiency
Also known as micro satellite instability.
15% sporadic cancers.
Loss of mismatch repair genes causes mutations to accumulate in microsatellite repeats which may be located in promoting or coding region of genes regulating growth such as type II TGF-beta, BRAF and BAX protein. Dysregulated growth, differentiation and apoptosis predispose to carcinogenesis.
Morphologically this involves sessile serrated adenoma.
Pathologic features associated with microsatellite instability
- L = lymphocytes / lymphoid aggregates
- A = associated extra-colonic cancers - endometrial, small bowel, uroepithelial, ovarian, stomach
- M = mucinous / metachronous tumours / medullary growth pattern
- P = proximal colon tumours
- S = signet ring / synchronous tumours
What is FOLFOX?
FOLinic acid-Fluorouracil-OXaliplatin regimen
Chemotherapy regimen that includes:
- leucovorin calcium (calcium folinate)
- 5-fluorouracil
- oxaliplatin
Used in advanced-stage and metastatic colorectal cancer.
FOLFOX regimens differ in agent dosing and administration schedule and include FOLFOX 4, FOLFOX 6 and FOLFOX 7.
What is a polyp?
Masses of tissue that project into a lumen.
Morphological term only as does not imply histological diagnosis.
Polyposis = multiple polyps
Incidence of colorectal polyps
30% at 50 years
40% at 60 years
50% at 70 years
55% at 80 years
50% have more than one polyp
15% have more than two polyps
HNPCC-related tumours
Colorectal cancer Stomach cancer Ovarian cancer Uterine cancer Small bowel cancer Uroepithelial cancer Pancreas cancer
MSI-H histological features
- Tumour infiltrating lymphocytes
- Crohn-like lymphocytic reaction
- Mucinous/signet ring differentiation
- Medullary growth pattern
Levels of rectum in cm
From anal verge:
- lower 0-6 cm
- middle 7-11 cm
- upper 12-15cm
Peritoneal reflection - 7-9cm and may be as low as 5cm from the anal verge in women
Levels of rectum in cm
From anal verge:
- lower 0-6 cm
- middle 7-11 cm
- upper 12-15cm
When is oncological segmental resection indicated for a malignant colorectal polyp
1) Haggitt level 4 lesions with distal third submucosa invasion
2) Malignant polyp with margin of resection < 2 mm
3) Evidence of vascular or lymphatic invasion
4) Incomplete resection or inability to assess margin (piecemeal technique)
5) Sessile lesion with Sm3 invasion
What is serrated polyposis syndrome
hyperplastic polyposis syndrome
Clinical diagnosis based on 1+ of WHO criteria:
1) More than 20 polyps of any size distributed throughout the colon
2) At least five serrated polyps proximal to the sigmoid colon with 2+ larger than 10mm
3) Any number of serrated polyps proximal to the sigmoid colon in an individual who has a first degree relative with SPS
Define pseudopolyp
Inflammatory pseudopolyps are irregularly shaped islands of residual intact mucosa resultant from ulceration and regeneration in IBD.
What is juvenile polyposis coli (JPC)?
10+ juvenile polyps where a juvenile polyp is a hamartomatous lesion consisting of dilated cystic glands rather than increased epithelial cells.
- Any age though more common in children
- Removed due to high likelihood of bleeding
