Colon Flashcards
What are risk factors for colorectal cancer?
Smoking Age (70% of patients with CRC are over 65y) Physical inactivity High red meat consumption Obesity Heavy alcohol intake Family history and inherited syndromes
Clinical presentation of CRC?
Change in bowel habit, abdo pain, weight loss, anaemia iron deficiency, PR bleeding
What are options for screening for CRC?
Flexible sigmoidoscopy
Colonoscopy
CT colongraphy
Faecal occult blood (shown to reduce CRC mortality by 32%)
When to screen average population?
Start at age 50y
Continue until life expectancy
When to screen for CRC in IBD?
if crohns colitis or ulcerative colitis - start colonscopic screening after 8 years of disease, then annually
When to screen in patients with family history?
If family history of CRC
When to screen Lynch syndrome?
Colonscopy every 1-2 years starting at age 20-25, or 5y before youngest case in family
When to screen FAP?
Sigmoidoscopy every 2 years starting age 12-14, once adenomas detected then annual colonoscopy until colectomy
How to diagnose CRC?
Colonoscopy - biopsy, removal of polyps
LFTs, CT abdo/pelvis, CXR
What is value of CEA test?
Low diagnostic ability (sensitivity 46%, specificity 89%)
Prognostic value - if CEA >5 pre op = worse prognosis
Useful monitoring test post operatively
What is the staging of CRC?
Need adequate sampling of at least 12 nodes
Stage 1: confined to muscularis
Stage 2: invasion through muscularis into pericolorectal tissues
Stage 3: spread to lymph nodes
Stage 4: distant metastases
What are high risk features of Stage 2 CRC?
Presentation with perforation or obstruction
Inadequate lymph node sampling (
What is the management strategy for Stage 1-2 CRC?
Wide surgical resection
No role for adjuvant chemotherapy
- if high risk stage 2 - can consider adjuvant chemotherapy
What is the management strategy for Stage 3 CRC?
Wide surgical resection
Standard of care is adjuvant doublet chemotherapy with oxaliplatin and 5-FU derivative (capecitabine or 5-FU)
How is advanced CRC stratified?
Resectable disease - resect with perioperative or post operative chemotherapy
Potentially resectable disease - neoadjuvant chemotherapy to down stage disease in attempt to become resectable
Unresectable disease - palliative chemotherapy
What are the options for unresectable advanced CRC?
Backbone of treatment is 5-FU chemotherapy
Cycle combinations of 5-FU, oxaliplatin and irinotecan
Targeted therapies (bevacizumab and cetuximab) improve OS in first line
When can cetuximab be used?
Only proven in KRAS wildtype (no RAS mutation)
Only in advanced disease
What is recommended follow up after adjuvant treatment?
Colonosopy in first years, then every 3-5 years
History, physical examination and CEA monitoring everyr 3-6 months for 3 years, then every 6-12 months for next 2 years
CT CAP every 6-12 months for 3 years in high risk pt
What is mutation in Lynch syndrome?
Mutations in mismatch repair genes (MMR)
Most common is MLH1 or MSH2 (account for 80%)
Also MSH6, PMS2
Mutations result in tumour DNA microsatellite instability
What are patients with Lynch syndrome at risk of?
Colorectal cancer (30-70%) Endometrial ca (30-60%)) Urinary tract ca Small intestine ca Ovary ca Gastric ca Pancreatic ca Biliary tree ca Skin ca Brain ca
What are Bethesda guidelines?
When to test patient with CRC for MSI (Lynch syndrome)
- age
What is FAP, what are the manifestations and mutations involved?
Familial adenomatous polyposis
Autosomal dominance inheritance
APC mutations - correlate with number of polyps
Presence of multiple polyps in colon and rectum
Extraintestinal manifestations: gastric and duodenal polyps, desmoid tumours, thyroid and brain cancer, supernumerary teeth
What are the two types of FAP?
Classical - more thatn 100 polyps, complete penetrance, will develop CRC by 40-50y
Attenuated - fewer polyps, later onset of disease, incomplete penetrance, develop CRC at 50-60y
What is most important aspect of management of rectal cancer?
Excision of mesorectum (technically difficult)
Requires staging with MRI to adequately asses tumour penetration
If full thickness – standard of care is pre-operative chemoradiation with 5-FU, followed by surgery, followed by adjuvant chemotherapy
What is the main association and risk factors for anal cancer?
Associated with Human Papilloma Virus (HPV) in 80-85%)
Increased risk in HIV positive, MSM, immunosuppresion
What is treatment strategy for anal cancer?
Tends to relapse loco-regionally
First line treatment is radical chemoradiation with Mitomycin/5-FU and external beam radiation
If relapse - proceed to salvage surgery
What is MSI and how does it occur?
Microsatellite instability
Occurs when abnormalities of the mismatch repair proteins mean that they are unable to correct errors occurring during DNA replication
This causes repeated sequences of DNA (called micro satellites)
Presence of MSI indicates that there is an abnormality of MMR (mismatch repair)
What are the types of mutations causing MSI?
Sporadic - caused by hyper methylation of MLH 1 gene promotor
Germline - mutations of MLH1 or MSH2 (80%), MSH6 or PMS2 (20%)
What are the clinical features of MSI- H colorectal cancer?
Proximal tumours Poorly differentiated Often mucinous or signet ring Less likely to metastasize Younger patients Better prognosis than micro satellite stable CRC Often chemo resistant Respond better to surgery alone (esp stage 2)
