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
Describe stool-based tests
- Detect bleeding (i.e., more advanced disease)
- Used annually, reduces mortality from CRC by 33% over 10-15 years follow-up
- Detects 50-80% of cancers
- Cancers or advanced polyps present in <10% of those with positive test results (cancer in 3.2%)
- Of no use in those with symptoms or abnormal test results (e.g., iron deficiency anaemia)- investigate
Describe national screening program
Overall Population Screening Strategy
- The recommended strategy for population screening in Australia, directed at those at average risk of colorectal cancer and without relevant symptoms, is immunochemical faecal occult blood testing every 2 years, starting at age 50 years and continuing to age 74 years.
- Cancer Council Australia – clinical guidelines
- Target age group: Although modeling indicated that it may be cost-effective, starting screening at age 45 is not recommended for population screening because there is a much less favorable ratio of benefits to harms than for 50–74 years.
- Resources should be invested in increasing participation in the existing NBCSP target age group of 50–74, rather than by lowering the starting age of screening, to optimize the balance of effectiveness, cost-effectiveness, and ratio of benefits to harms.
Population-Based Cancer Screening
My Comments / Salient Points on NBCSP:
- Participation rate is relatively low 39% vs 54 mammos or 57 cerv screen
- Approximately 3% of patients who had a positive FOBT had cancer
D
DEscribe imaging techniques
- Barium enemas detect half adenomas >1 cm and 80-85% CRC
- Virtual colonoscopy
- Currently requires bowel preparation
- Identifies 90% of cancers or adenomas >1cm - useful for those who can’t tolerate oscopy
Descrieb the role of sigmoidoscopy/colonoscopy
- Decrease CRC mortality
- Colonoscopy – gold standard [98-99%]
- Expensive
- Operator-dependent
- Risks: perforation in <1/1,000; bleeding 1/100
- Reduces mortality from CRC
nb we are doing too many colonoscopies
Describe colonoscopy interval guidelines
- Recommendations of 10-year intervals for colonoscopy screening may be adequate, and repeated screening within the first 10 years after a negative colonoscopy has little additional benefit.
- not a protective factor
- you are likely in the group not to develop adenomas
- removal of polyps associated with colonoscopy improves outcomes because of removal and NOT oscopy
- For many patients, a colonoscopy screening interval of ten years is appropriate:
- No polyps on first colonoscopy
- 1 or 2 small adenomas (<10 mm, no high-grade dysplasia or villosity)
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Coeliac19
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Intra-abdominal sepsis28
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GERD27
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Liver disease32
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Alcohol22
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Haemochromatosis14
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IBS IBD18
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Gallstones23
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Acute pancreatitis and chronic*15
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Viral hepatitis19
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Hepatitis C16
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CRC20
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Cirrhosis, CLD complication, fatty liver disease29
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CONSEQUENCES OF OBESITY18
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Control of body weight6
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Surgery to cure obesity and diabetes5
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Nutrition in adults20
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Nutrition in infants21
