CRC Flashcards
Describe the epidemiology of CRC
## Epidemiology
The 2nd most common cancer in Australia for both males and females.
Most Common Cancer Deaths in 2017
2nd most common across sexes.
Age-specific rates, generally low until 50.
Steadily rises after 50 with slight male predominance, then drops over time.
Incidence and mortality are falling over time.
5YS: Improved to 70%.
Colon Cancer: Lifetime Risk
- male 1/10 if lives to 85
- female 1/15
Colon Cancer Risk from Age 50-84
- 1/10 in males, 1/15 in females
- hence >50 y cut off for screening
Describe risk factors for CRC
Risk Factors for Colon Cancer
- Age
- Family history
- Personal history of CRC or “at-risk” polyps
- Inflammatory bowel disease
Epidemiological Risk Factors for CRC
- Diabetes mellitus
- Alcohol
- Obesity
- Acromegaly
Controversial Associations
- Smoking
- Coronary artery disease
- Ingestion of red meat
- Role of the microbiome
| Proportion | Type |
———- | ————————————————- |
| 74% | No family history |
| 20% | Family history (but no obvious heritable pattern) |
| 5% | Lynch Syndrome |
| 1% | Polyposis |
| | |
Describe the genetics of CRC
- ~1-5% of CRC is associated with germline mutations:
- Familial adenomatous polyposis (FAP: APC genes)
- MUTYH-associated polyposis (MAP)
- Hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome: mismatch repair (MMR) genes)
- Hamartomatous polyposis syndromes - v. rare
- Juvenile polyposis
- Peutz-Jegher’s syndrome
- ~20% of CRC is familial - there is a family history, but the pattern of inheritance does not conform to the above syndromes
- ~75% of CRC is sporadic - no family history is apparent
Describe the proportion of CRC as a function of age
10-13% of Cancers are Diagnosed in Those <50 Years
- rare
- but increased incidence
CRC in Those Under 50 Years - 2021 from AIHW Tables
- though proportion is 10-13% rate per 1000 and deaths still low
- may lower screen threshold to 45
What are risk factors and protective factors for early onset
Risk Factors for Early-Onset CRC
- males
- caucasian
- family history
- obesity and hyperlipidemia– may explain high rates
- NOT smoking
- but alcohol does
O’Sullivan DE et al CGH 2021
Protective Factors: Drugs
- Aspirin
- Other NSAIDs (e.g., sulindac)
- Statins (controversial)
- Hormone replacement therapy (HRT)
- Antioxidants (controversial)
- Green tea
Protective Factors: Uncertain
- Physical activity
- Diet – fruit and vegetables
- Fibre intake
- Resistant starch
- Folic acid
- Vitamin B6 (pyridoxine)
- Calcium
- Vitamin D
- Magnesium
- Garlic
- Fish consumption
Chemoprevention
- if cardiovascular rsk facter >10% over 10 years–> aspirin, which you probably would have used anyway
- consider metformin in preferene to other antidiabetes in typ3 2 diabetes
- either or is acceptabele for family history
Best practice advice to prevent colorectal neoplasia:
What Not to Do
- In individuals at average risk for CRC:
- Clinicians should not use:
- Non-aspirin NSAIDs due to a substantial risk of cardiovascular and gastrointestinal adverse events
- Calcium or vitamin D (alone or together)
- Folic acid
- In individuals with a history of CRC:
- Clinicians should not use statins to reduce mortality
Describe clinical features of CRC
- Abdominal pain (site of neoplasm dictates location of pain and pattern e.g. periumbilical and colicky if near ileo-caecal valve, bilateral lower abdomen if in left side of colon)
- Obstruction
- Perforation
- Localized spread (especially rectal cancers)
- Peritoneal spread
- Change in bowel habit esp if sigmoid/rectum, unlikely if right-sided
- Bleeding (= ulceration)
- Visible/identifiable blood per rectum (overt)
- Occult (covert) bleeding leading to iron deficiency anaemia
- Anaemia (Fe deficient, fairly common presentation)
- Weakness
- Weight loss
Compare features of R and L sided cancers
Right-Sided
- Liquid stool
- Iron deficiency anaemia without other symptoms (falling Hb and MCV even if still in normal range)
Left-Sided
- Formed stool
- Abdominal pain
- Change in bowel habit
- Rectal bleeding
Describe features of metastatic disease
- Anorexia, vomiting, early satiety
- Fatigue
- Weight loss
- Abnormal liver tests
- Abdominal distension (ascites or hepatomegaly)
- Spread most commonly to draining lymph nodes and liver but also to lungs, bone, brain, skin (nodules)
Describe relationship between symptoms and prognosis
- Asymptomatic cancers (picked up by screening) generally have a better prognosis
- Acute surgical presentations (bowel obstruction or perforation), likely to have peritoneal seeding, and have a poor prognosis
- Presence of metastatic disease (20% of cases) indicates a poor prognosis
Describe diagnosis
Diagnosis
- Symptoms (see above)
- Asymptomatic (population screening)
- Examination
- Abdominal mass - liver, RIF mass
- Lymphadenopathy
- Hepatomegaly or ascites
- Rectal mass eg on DRE - rare
- Supportive blood tests
- Iron deficiency anaemia (in appropriate age group)
- Abnormal liver tests (possible metastatic disease)
- Diagnostic tests
- Colonoscopy - definitive test
- Barium enema
- CT colonography
Describe the significance of iron deficiency anaemia
- In acute phase response, serum iron falls: low serum iron does not indicate iron deficiency. Even fluctuates through day
- Serum ferritin is definitive; check other AP proteins
- Reference: Diagnosis and management of iron deficiency anaemia: a clinical update
MJA * 193 Number 9 * 1 November 2010 525-532
An Aside: The Importance of MCV
Indicates chronic blood loss
Describe staging and treatment
- Colon and rectal cancer treatment
- See guidelines at NCCN.org
- Treatment depends on staging, and location (above reflection may be resected first, rectal may need NAC)
- For rectal cancer (below the peritoneal reflection) ^[difficult to excise and more likely to spread locally], consider surgery, radiotherapy, and chemotherapy.
- For colonic cancer, treatment is generally surgery with or without chemotherapy
Describe the polyp cancer sequence
- Main types of colonic polyps:
- Adenomatous polyps
- Sessile serrated polyps
- Hyperplastic polyps
- Inflammatory polyps
- Hamartomatous polyps - most are not pre-malignant
- Early cancers are sometimes seen in adenomas; larger polyps more likely to have invasive cancer
- Adenomas found in the same distribution as cancers and are observed 10-20 years before the development of cancers in both familial and sporadic forms
- Animal models show progression from adenoma to cancer
- Removing polyps reduces the incidence of CRC in trials
- Removal of polyps prevents the development of cancer
Describe screening tools
- Stool tests:
- Guaiac-based tests - not used as much today
- Immunochemical tests - detected Hb Positive indicates cancer ^[note: intermittent bleeding]
- DNA-based tests
- Imaging techniques: - not great, misses 10%
- (Double-contrast) barium enema
- CT colonography (virtual colonoscopy)
- Videocapsule
- Endoscopic examinations:
- Flexible sigmoidoscopy
- Colonoscopy
Describe CRC prevention: who should be screened vs surveilled?
Prevention of CRC: Population Screening
- Screening in “average risk” patients who do not have symptoms of CRC
- Those with symptoms should undergo formal investigation
- Those at increased risk (history of adenomatous polyps, previous cancer, or IBD) should undergo surveillance
