Colon Cancer

mismatch repair genes

DNA repair genes that fix replication errors (microsatellites)

Microsatellite instability

when mismatch repair genes are defective --->

Lynch syndrome

an autosomal dominant disease caused by abnormal nucleotide mismatch repair. Mutations in MSH2 (codes for MutS) and MLH1 (MutL) are most common.

mutations in MSH2 and MLH1

mismatch repair mutation associated with Lynch syndrome

1. APC mutation (initiation)

2. KRAS mutation (growth)

3. p53 lost (malignant transformation)

stepwise mutation progression associated with colon adenocarcinoma

APC mutation--> early adenoma

initial mutation of colon adenocarcinoma

KRAS mutation

mutation causing adenoma growth

p53 loss

mutation leading to malignant transformation of adenoma

10-15 years

how long does it take Normal mucosa → adenoma → carcinoma

autosomal dominant

inheritance of lynch syndrome

Early onset CRC (<50)

Right-sided colon cancer

Few polyps (NOT polyposis)

key features of lynch syndrome

Endometrial (most common extra-colonic)

Ovarian

Gastric

Pancreatic

Urinary tract

colon

cancers associated with lynch syndrome

endometrial cancer

most common extra-colonic cancer in lynch syndrome

Early and frequent colonoscopy (often starting in 20s)

screening recommendations for pts with lynch syndrome

tubular polyp

most common, lowest risk adenomatous polyp

villous polyp

adenomatous polyp with the highest malignant potential

tubulovillous polyp

intermediate adenomatous polyp

serrated polyps

Premalignant CpG hypermethylation with microsatellite instability

BRAF mutations

Saw-tooth crypts

sessile serrated adenomas

serrated polyps with malignant potential

Peutz-Jeghers syndrome

syndrome associated with harmartomatous polyps

Hamartomatous polyps

Solitary lesions do not have significant risk of transformation.

Growths of normal colonic tissue with distorted architecture.

Associated with Peutz-Jeghers syndrome and juvenile polyposis

high risk features of polyps

rectosigmoid colon

most common site of colon cancer

obstructive symptoms

symptoms associated with left sided colon cancer

anemia, occult bleeding

symptoms associated with right sided colon cancer

~20%

what percentage of colon cancers are familial (not syndromic)

lynch syndrome

right sided young onset colon cancer, think

Start at age 45 (average risk)

Every 10 years if normal

when does average risk pt get colonoscopies

CEA

base line lab to order to monitor for CRC recurrence

Right hemicolectomy

Cecum → ascending colon

surgical managment of right colon cancer

Extended hemicolectomy

surgical management of transverse colon cancer

Low anterior resection (LAR) OR

Abdominoperineal resection (APR)

surgical management of rectal cancer

≥12 nodes

how many nodes are sampled in adequate lymph node sampling

Stage III (node-positive) → ALWAYS

High-risk Stage II (selected)

what what stage of colon cancer is chemotherapy indicated?

FOLFOX (5-FU + leucovorin + oxaliplatin)

common chemo regimen for colon cancer

Mainly for RECTAL cancer

Used preoperatively (neoadjuvant)

is radiotherapy indicated for colorectal cancer?

Fever

Tachycardia

Abdominal pain

Sepsis

signs of anastomotic leak post-operatively

temporary colostomy

colostomy Used to protect distal anastomosis

Low anterior resection

High-risk anastomosis

Severe inflammation/infection

indications for temporary colostomy

abdominoperineal resection

low rectal cancer

surgery indicating need for permanent colostomy

Hartmann's procedure

Resection of diseased colon

End colostomy + rectal stump

Perforation

Obstruction

Diverticulitis

Unstable patient

indications for Hartmann's procedure

monitoring

is a CEA used for monitoring or screening?

anastomotic leak

most feared complication of colectomy