L13 Colonic Cancer

Question 1

At what age does the risk of colon cancer begin?

Answer 1

40-45 (Risk Doubles w/ each succeeding decade)

Question 2

Percent of the Population at risk of colon cancer?

Contribution of genetics/Environment to risk?

Answer 2

5%

20% genetic, 80% environmental (lifestyle, diet => influences microbiome)

Question 3

Risk factors of Colon Cancer?

Answer 3

• Processed meat (WHO group 1 carcinogen)
• Red meat (group 2A –probable)
• Cigarettes
• Alcohol
• High BMI
  *Sulfur-Metabolizing Microbiome

Question 4

Protective factors for colon cancer?

Answer 4

*Healthy diet
*Physical activity
*Medication: HRT, NSAIDs

GOAL=Diverse microbiome with short-chain fatty acid-producing anaerobes & fiber-fermenting bacteria

Question 5

Clinical Presentation of Colorectal Cancer?

Answer 5

• Change of bowel habit
• Mucus or blood PR
• Anemia (Iron deficiency)
• Pain if an obstruction

Question 6

Investigations for Colorectal Cancer?

Answer 6

Physical Rectal Exam
Fecal Occult Blood (FIT Positive 50% adenoma, 50% Carcinoma)
Endoscopy (Screening Programs)
Biopsy
CT Collagraphy

Question 7

Answer 7

Question 8

5 year survival of Various stages of Colorectal Cancer?

Answer 8

Question 9

Answer 9

Question 10

_________________________________:
Left-Sided, Benign Neoplastic Polyps of the Rectosigmoid
Two Types (based on cytoplasmic Differentiation):
________________________
________________________
Usually _________ diameter.
Usually affects ________________

Answer 10

Hyperplastic Polyp:
Left-Sided, Benign Neoplastic Polyps of the Rectosigmoid
Two Types (based on cytoplasmic Differentiation):
Micro-vesicular (most common)
Goblet cell rich
Usually < 5mm in diameter.
Usually middle to old age ( mean 62 years)

Question 11

__________________________
Right-sided Benign Lesion of the colon responsible for ______of CRCs
Risk of developing ____________________________ within the polyp.
→ should be removed where possible.
Usually _______________ in diamter
Associated with ________________________________

Answer 11

*Sessile Serrated Lesion (SSL): *
Right-sided Benign Lesion of the colon responsible for 30% of CRCs
Risk of developing high grade dysplasia and carcinoma within the polyp.
→ should be removed where possible.
Usually *large (typically > 10mm) *
SSLs associated with synchronous advanced colorectal neoplasia

Question 12

Sessile Serrated Lesion (SSL) with _________ carry an increased & accelerated risk of progression

Answer 12

Sessile Serrated Lesion (SSL) with dysplasia carry an increased & accelerated risk of progression

Question 13

Evidence fot Adenoma-Carcinoma Sequence?

Answer 13

Question 14

Risk of development of Malignanacy in Adenomas?

Answer 14

• Size > 1cm (large size is the most important risk factor)
• Multiple adenomas
• High-grade dysplasia
• Prominent villous component

Question 15

Most common type of colorectal cancer and its location?

Answer 15

Adenocarcinoma (98%)

Rectosigmoid most common location

Question 16

Colon Cancer with 1 metastatic lesion, can be resected, survival rate high

Answer 16

Oligometastatic

Question 17

Risks/Manifestations of Cancer in Ulcerative Colitis

Answer 17

<1% of all Colon Cancer
Risks
a) > 8-10yrs
b) pan-colitis
Flat pre-malignant dysplasia
May be multifocal
Aggressive
Advanced stage at diagnosis

Question 18

Examples of Colorectal Cancer Syndromes and their inheritance?

Answer 18

Question 19

Inheritance/Pathogenesis of Lynch Syndrome?

Answer 19

Autosomal Dominant Inheritance
Usually inherited, can be new mutation

Most common form of familial Colorectal Cancer (3% CRC)
Caused by mutation in mismatch repair gene (MMR) leading to microsatellite instability

Question 20

Most common form of familial Colorectal Cancer?

Answer 20

Lynch Syndrome - 3% CRC

Question 21

Inheritance/Pathogenesis/Epidemiology/Manifestations of Lynch Syndrome?

Answer 21

Familial Adenomatous Polyposis:
Autosomal Dominant Inheritance
Loss of APC Gene!!- APC targets Beta-catenin for degradation (Wnt pathway)
=> Colorectal adenocarcinomas < 40 years old

> 100 polyps predominantly in the large intestine (typically 1000s of polyps!!)
Extra-intestinal manifestations

Duodenal carcinoma desmoid tumour (fibromatosis) commonest cause of death

Question 22

Commonest cause of death for Pts. with Familial Adenomatous Polyposis?

Answer 22

Duodenal carcinoma desmoid tumour (fibromatosis)

Question 23

Inheritance/ Epidemiology/Manifestations of MYH-Associated Polyposis

Answer 23

Autosomal recessive inheritance
Mean age of cancer diagnosis = 50 years old
Penetrance near 100%.
Clinically similar to attenuated FAP (30% of NON-APC Familial Adenomatous Polyposis)

Question 24

Inheritance/Epidemiology/Manifestations of Serrated Polyposis?

Answer 24

Unknown Genetics

Develop multiple serrated polyps:
20 serrated polyps (Hyperplastic or SSLs) of any size distributed throughout the colon

Up to 50% may develop colorectal cancer

Question 25

Inheritance/ Epidemiology/Pathogenesis of Juvenile Polyposis

Answer 25

Autosomal dominant inheritance (Incomplete Penetrance)
Half of cases are de novo (No family history)

Average age of onset is 18 years old!!

Germline mutations involve the TGF-β signal transduction pathway
–SMAD- 4
–BMPR1A

Significant Risk of Colorectal Cancer

Question 26

Diagnostic Criteria for Juvenile Polyposis??

Answer 26

> 3-5 Juvenile polyps in the colorectum.
or
Juvenile polyps throughout the GI tract.
or
Juvenile polyp + family history.

Question 27

Why is Microsatellite Instable (MSI) Status Important for colorectal cancer?

Answer 27

Prognostic Indicator:MSI+ CRC patients have a better prognosis compared with Microsatellite Stable (MSS)
Therapeutic biomarker
–Benefit from FOLFOX
–Stage IV benefit from Immune checkpoint inhibitors
Diagnosis of Lynch syndrome

Question 28

Answer 28

Question 29

Mechanism of Erbitux in Colorectal Cancer treatment?

Answer 29

Erbitux blocks EGFR signal transduction and inhibits intracellular signaling

The anti-tumor effects mediated by EGFR blockade require normal/wild-type KRAS & are bypassed by mutated KRAS, which signals WITHOUT prior EGFR-mediated signaling rendering Eribitux innefective