Colorectal Cancer

Question 1

6 Modifiable Risk Factors

Answer 1

obesity
physical inactivity 
high red meat/processed meat diet 
alcohol
smoking
very low fruit/veggie intake

Question 2

6 Non-Modifiable Risk Factors

Answer 2

age
family or personal hx polyps
UC/Chron's
inherited genetic disorders (FAP, Lynch, type 2 DM)
family hx colorectal cancer
H pylori or other infections

Question 3

Chromosomal Instability

Answer 3

• Changes in # chromosomes or major structural chromosomal changes in tumor cells
• Adenocarcinoma sequence
• Mutations: APC (beta-catenin degradation), KRAS (oncogene), TP53 (tumor supp gene), chromosome 18q loss, SMAD4
• APC inc risk of polyps –> KRAS mutation leads to polyp formation –> p53 causes transformation to cancer
• Worse prognosis
• Familial adenomatous polyposis (APC mutation from birth)

Question 4

Microsatellite Instability

Answer 4

• Deficiency of mismatch repair system - inability to properly copy microsatellites (repeated DNA sequences)
• Usually not in adenomas
• Mutations: Wnt signaling, BRAF (oncogene), CpG island methylator phenotype
• Better prognosis
• Lynch Syndrome (HNPCC - hereditary non-polyposis colorectal cancer); also inc risk of ovarian and endometrial cancer

Question 5

Staging

Answer 5

• T = invasion
  
  • T0 - carcinoma in situ
  • T1 -invades submucosa
  • T2- invades muscularis propria
  • T3- invades subserosa and beyond
  • T4- perforation and invasion into adjacent organs
• N = nodes
  
  • N0 - none
  • N1 - 1 to 3 nodes
  • N2 - 4+ nodes
• M = mets
  
  • M1 is any (automatically stage IV if mets)

Question 6

Most Common Mets in Colon v. Rectal Cancer

Answer 6

Colon = liver

Rectal = lungs

Question 7

Presentation

Answer 7

• Often asymptomatic and found via screening or incidental imaging
• Primary Symptoms - obstructs lumen –> blood in stool and anemia; pain if extend into parietal peritoneum; fistula manifestations (ex - if bladder fistula then frequent UTIs or feces in urine)
• Systemic Symptoms - wt loss, fever, anorexia, ab pain
  
  • Signs of mets - ex) jaundice if liver mets

Question 8

CEA

Answer 8

• (carcinoembryonic antigen)

- high levels mean poor prognosis and can be used to monitor recurrence and treatment response (NOT USED FOR SCREENING)

Question 9

When is preventative surgery indicated?

Answer 9

FAP

or UC w/ dysplasia

Question 10

Treatment (by stage and in rectal cancer specifically)

Answer 10

• If lower stages … endoscopic removal OR surgically removed (resect blood supply and regional nodes too)
  
  • If rectal cancer then resect entire rectal mesentery
• If stage III - use adjuvant chemo after surgery (Fluorouracil 5-FU based)
• If stage II - less clear whether to use adjuvant chemo
• If Stage IV (mets) - may or may not resect
  
  • If lots of mets but colon cancer itself is not causing symptoms then may not resect (no known benefit)
  • If colon cancer itself is obstructing and causing symptoms then may resect b/f starting chemo
  • If unsuitable for surgery there is poor prognosis but use FOLFOX4 + bevacizumab
• Rectal cancer - often give radiation and chemo b/f surgery (neoadjuvant) to reduce chances of recurrence later

Question 11

FOLFOX4 (3 components + how ea works)

Answer 11

5-FU + oxaliplatin + folinic acid

• Oxaliplatin is a platinum complex that forms crosslinks in DNA –> disruption of DNA replication and transcription
• Folinic acid stabilizes 5-FU’s binding to thymidylate synthase
• 5-FU (5-fluorouracil) - pyrimidine analogue
  
  • Converted to FdUMP which inhibits thymidylate synthase –> less dTMP needed for DNA synthesis
  • Converted to FUTP which is incorporated into RNA to interfere w/ function
  • Converted to F-dCTP which is incorporated into DNA to interfere w/ function

Question 12

Bevacizumab

Answer 12

• monoclonal ab against VEGF (improves survival when added to FOLFOX4)