Colorectal Polyps

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DEFINITION
A mass arising from the mucosa and protruding into the lumen of the bowel.
- note a number of other masses such as lipomas, carcinoids etc can protrude into lumen that are not polyps.
See also FAP
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EPIDEMIOLOGY

As for specific polyp type.
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AETIOLOGY

Pathogenesis
Substantial progress in understanding genotype --> histology --> risk.
Also associated with polyposis syndromes.

Classification
1. Non neoplastic
- abnormal architecture, maturation or inflammation
- hyperplastic, hamartomas, inflammatory, lymphoid
2. Neoplastic : Adenomatous
- proliferation and dysplasia.
- tubular, tubulovillous, villous, serrated.
3. Neoplastic : Invasive in Adenomatous polyp
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BIOLOGICAL BEHAVIOUR

Hyperplastic polyps
Increased glandular cells, decreased cytoplasmic mucous.
Lack dysplastic features.
Risk: controversial.
- only slightly increased and only in some circumstances.
- most not considered a risk, especially common smaller polyps in the rectum
- increased if: large size (>1cm, R colon, mixed adenoma / hyperplastic, >20 polyps, or context of familial syndrome or personal history).

Serrated Adenoma
Previously classified as hyperplastic, now considered to carry risk of cancer.
- enlarged crypts at base along muscularis.
Larger, right-sided and associated with BRAF and DNA metrication.
- not common but still accounts for perhaps 20% of sporadic cancer.

Hamartomas
Occur in the context of three familial syndromes:

i) Peutz-Jegher's syndrome (PJ)
STK11 gene mutation in 70%
--> abnormal cell cycle metabolism and cell polarity.
Subcutaneous melanotic macules (e.g. perioral pigment spots), multiple hamartomatous small bowel polyps
- these polyps may bleed, obstruct, intussuscep (commonest polyp problem).
- 10% risk of GI cancer after 30s.
Need a multi-organ surveillance program.
- GI tract; also at risk are: pancreas, lung, breast, cervix, ovaries (sex cord tumor) and testes (Sertoli cells)
--> cumulative risk of any cancer is 85% by 70 years; malignancies are main cause of death.
- 20% CRC; 5% gastric cancer

Indications for operation
1. symptomatic disease
2. asymptomatic polyp >1.5cm not amenable to endoscopic management
3. malignancy.
Note extent and distribution of polyps, enterotomy and polypectomy, or bowel resection.
--> sites of enterotomy and resection strategically planned to minimized cuts
--> remove as many as practically possible ; main burden.
Pseudoinvasion = normal cells at submucosa or muscularis; well described in PJ
- distinguishing from true malignancy can be difficult.  Err on side of wide oncologic resection.

ii) Juvenile polyposis (JP)
Criteria:
1. >5 hamartomatous polyps in colorectum
2. Multiple polyps in upper and lower GI tract.
3. Any number of juvenile polyps with known family history
- SMAD4/DPC4 and PTEN genes.
Distinguished from other PTEN syndromes, e.g. Bannayan-Riley-Ruvalcaba, Cowden

Features
Vary in disease onset, polyp burden and distribution.
May bleed following auto-amputation.
Also may have anaemia, bleeding, prolapse, protein-losing enteropathy and intussusception.
40% risk of colon cancer, commonly around 40y.
20% risk of upper GI cancer

Management
Upper and lower scopes starting at 15y or when symptomatic.
Colectomy reserved for high polyp burden, cancer of severe symptoms above.
Post-op surveillance continuing
Subtotal or total gastrectomy for bleeding, obstruction or malignant disease.

 iii) Cowden syndrome
- PTEN gene mutation.
- microcephaly,  trichilemmomas, gingival papillomatous papules.
- hamartomas but colon cancer not a specific risk and they're not colo screened
- also breast, thyroid, endometrial.

Adenoma
Very common: 10-25% rate in average-risk patients >50y
Histology variants:
- tubular (> two-thirds)
- tubulo-villous (<one quarter)
- villous (remainder; ~5%)
A distal adenoma means there is a fair risk of a proximal neoplasm: 20-40%

Adenoma-Carcinoma Sequence

1. Relationship strongly supported by the following observations:
i) Almost all colon cancer arises in a polyp
ii) 30% synchronous adenomas in resections
iii) risk of cancer increases with more, larger, polyps
iv) high incidence in familial adenomatous polyposis
v) if a polyp is not resected, 4% risk at 5 years, 14% after 10 years.

2. Cascade of sequentially accumulated genetic mutations.
- combination of loss of function and gain of function defects.
- mismatch repair genes are tightly involved in familial cancers and in 15% of sporadic cancers.
- e.g. APC -->
- APC gene is causal mutation in FAP, but also in 80% of sporadic cancers = early mutation leading to sporadic polyps; gene is involved in cell migration and adhesion.
- transition to cancer requires additional mutations.
- loss of gene 'deleted in colon cancer' (DCC) plays a key role in transition to more advanced adenoma because of dysfunction of adhesion molecule receptor and alterations in apoptosis.
- p53 (normally arrests cell cycle to allow DNA repair) is a key component from advanced adenoma to carcinoma.
- K-ras gene (signal transduction) = gain of function mutation that leads to increased replication and exophytic growth; 50% of cancers.

Adenomatous Polyposis Syndromes

i) FAP
See FAP notes

ii) MYH-Associated Polyposis
Clinical identification difficult; no distinct phenotype.
Most overlap with attenuated FAP.
<10 adenomas, us. 4th decade, few extracolonic manifestations.
AR inheritance, biallelic germline MYH mutations.
Test if >15 adenomas, AR inheritance, no APC.
Screen 1-2 yearly endoscopically starting at 25 y.
Then surgical management similar to FAP

Risk factors for Malignant Potential
- Size >1cm
- Sessile > Polypoid
- Villous > Tubulovillous > Tubular
- Firm
- Pit pattern.


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MANIFESTATIONS

May obstruct, intussuscept or haemorrhage (us. if large)
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MANAGEMENT

Polypectomy
Remove anything >5mm with biopsy polypectomy; remove anything larger with a snare.
Piecemeal excision techniques can allow larger sessile lesions to be treated
- often with injection of saline into the submucosal plane to lift it off the muscularis.
Important to tattoo area with Indian ink.

Contraindications
Coagulopathy, colitis
Invasive malignancy
- ie central ulceration, hard, fixed, necrosis, can't be raised by submucosal injection

Complications
Bleeding: 0.5% (immediate or delayed)
Perforation: 0.1%
- operation aided by putting patient in lithotomy to enable on-table colonoscopy in case perf hard to find.
Post-polypectomy syndrome
- abdo pain, fever, leukocytosis, probably microperf / bacterial translocation, treat expectantly in most cases.
Death very rare 1:15,000

Missed lesions?
Polyps >1cm can be missed in 5-10%
Withdrawal time >6 minutes is average.
So warn patients that there is still a risk and to present if symptoms.

EMR
Suction cautery and saline injection with a conventional colonoscope.
Useful for flat lesions difficult to snare.
NBI (narrow band imaging) can help to show complete removal.

Guidelines for Screening After Polypectomy
2008 US Task force

Risk	Recommended	Interval
1-2 small low risk polyps (tubular adenomas)	Colonoscopy; low risk	5-10 y
1. 3-10 small adenomas OR 2. One adenoma > 1cm OR 3. Polyp with villous / high grade dysplasia	Colonoscopy; at risk	3y
>10 adenomas	Colonoscopy; at risk	<3y
1 large polyp	Colonoscopy: at risk	1 yr
Sessile adenomas removed piecemeal	Colonoscopy; high risk	3-6mo

And should surveillance serrated adenomas at yearly intervals as more rapid progression by alternative pathway.

Approach to a Malignant Polyp
Adenocarcinoma that invades into the submucosal layer (T1)
- distinguish from carcinoma in-situ or high-grade dysplasia, where changes confined to mucosa / submucosa.

5% of benign-appearing polyps will harbor malignancy.
- correlates with size; >2cm = 30% risk

Even if not suspected, area should be tattooed.

Treatment depends on morphology and histology
The main reason to proceed with resection is to harvest lymph nodes
- gross risk of lymph mets is 8-15%

Risk Factors for Lymph Node Mets
- any one = 20%
- any 2 = 36%
- in order of increasing risk:

1. Haggitt Level
1) invades head (5% risk)
2) invades neck
3) invades stalk
4) invades base (or submucosal invasion in a sessile polyp) (25% risk)



2. Submucosal Invasion
Upper third = s1; middle third = s2; deep third = s3
Lymphovascular

3. Tumour Grade
Well / moderate / poorly
And Lymphovascular Invasion

4. Tumour budding
Malignant cells in submucosa remote from main invasion

OK to leave it alone (no resection) if:
- complete excision
- accurate assessment of depth of invasion, completeness of excision, grade
- Haggits 1-2 (no invasion at margin of stalk)
- well or moderately differentiated
- lymph / vascular involvement
--> endoscopic surveillance



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REFERENCES
Cameron 10th

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