Clin Med II (GI II) - Polyps & Colorectal Cancer

discrete, precancerous mass/lesion that protrudes into the intestinal lumen

colon polyps

colon polyps are most commonly ______________ but may be inherited as part of __________

sporadic, FPS (familial polyposis syndrome)

there are _____ pathologic groups of colon polyps but the most common is _____________

4, adenomatous

tubular, tubulovillous and villous are all types of mucosal ________________ polyps

adenomatous

hyperplastic, sessile serrated polyps and traditional serrated adenoma are all types of mucosal __________ polyps

serrated

______________________ pathway is more well-known vs _____________ is less frequently recognized pathway

Adenomatous, serrated

95% of adenocarcinoma of the colon arise from _______________ or ______________________ polyps

Adenomatous, sessile serrated

out of all polyps, 70% are ____________ and 20-30% are _________________

Adenomatous, sessile serrated

it takes about _________ for an adenoma to develop into a cancer

10yrs

mutational events occur within a polyp including the activation of _____________ and loss of _______________ genes

oncogenes, tumor suppression

tumor suppression gene seen in adenomatous polyp pathway

APC gene

oncotic genes seen in serrated polyp pathway

Kras, BRAF

Normal mucosa → inactivation of the APC gene → chromosomal instability and inactivation or loss of other tumor suppressor genes → carcinoma

adenomatous pathway

Hyperplastic polyps → develop Kras mutation → traditional serrated adenomas

serrated pathway

Hyperplastic polyps → BRAF oncogene activation → sessile serrated lesions → widespread methylation of CpG-rich promoter regions → inactivation of tumor suppressor genes or mismatch repair genes (MLH1) with microsatellite instability.

serrated pathway

extremely common polyps that are under 5mm and are believed to be without significant risk

Diminutive hyperplastic polyps

colorectal adenomas are seen in ___% of men and ___% of women over the age of 50

30, 20

small adenomas under _______ have a low risk of malignant transformation

5mm

______________ adenomas have a high risk of malignancy

advanced

advanced adenomas are ________ or larger OR have ___________ features or high grade ____________

1cm, villous, dysplasia

tubular adenomas tend to be _______________ and villous tend to be ____________

pedunculated, sessile

tubular lesion --> ________________ --> ___________ (increased risk of malignancy)

tubulovillous, villous

diminutive colon polyps are ___________ or less and have a low risk of cancer

5mm

large colon polyps are __________ or more and have the highest risk of cancer

1cm

small colon polyps are between ______________

6-9mm

there is a higher risk of colorectal cancer when there are ____________________ within _______ of eachother

multiple polyps, 6mm

S/Sx:

-asymptomatic

-unexplained IDA

-hematochezia

-melena

colon polyps

any pt with unexplained IDA (esp over 45yo) needs a _________, ____________, or both

colonoscopy, EGD

the MC bleeding seen in ruptured polyps is _______________ and is most commonly from a _____________ source

hematochezia, rectosigmoid

bleeding likely coming form the ascending colon (less common)

melena

stool based colon cancer screening options

FOBT, FIT, cologaurd

Guaiac-based fecal occult blood test

FOBT

MCC of a false positive of FOBT

red meat

stool based CRC screening with 80% sensitivity (more sensitive than FOBT)

FIT

highly specific and sensitive stool based CRC screening approved for average risk pts (combo of FOBT and FIT)

Cologaurd

gold standard CRC screening

colonoscopy

colonoscopy indications:

-unexplained _________

-positive _______ screening

-those who meet __________________

-positive __________________ or flexible sigmoidoscopy

IDA, stool based, guidelines, CT colonography

CRC screening that has over 85% sensitivity and specificity for adenomas over 6mm

video capsule

video capture requires extensive _________________ and is reserved for unsuitable/unwilling colonoscopy pts

bowel prep

colon polyps tx

colonoscopy w polypectomy, surgical excision

colon polyp tx indicated if large (particularly sessile) and cannot be removed via colonoscopy

surgical excision

after a surgical excision of a colon polyp, pts must receive a repeat __________ in ___________

colonoscopy, 6mo

an adenoma that appears grossly benign, but on histologic assessment is found to contain cancer that has penetrated the mucosa to submucosa

malignant polyp

malignant polyps can be treated with ________________ if alone if completely excised, well-differentiated, clear margins, and no vascular invasion

polypectomy

adenomas and serrated polyps need repeat colonoscopies within ___________

3-5yrs

normal healthy pts with no PMH or family Hx receive their first colonoscopy at _____

45

colonoscopy surveillance recommended if normal colonoscopy or less than 20 hyperplastic polyps less than 10 mm in the distal colon

10yrs

colonoscopy surveillance recommended if only 1–2 adenomas less than 10mm

7-10yrs

colonoscopy surveillance recommended if 1–2 sessile serrated polyps less than 10mm

5-10yrs

colonoscopy surveillance recommended if 3–4 adenomas or sessile serrated polyps less than 10mm

3-5yrs

colonoscopy surveillance recommended if 5–10 adenomas or sessile serrated polyps less than 10mm

3yrs

colonoscopy surveillance recommended if 1 or more adenomas or sessile serrated polyp 10mm or larger

3yrs

colonoscopy surveillance recommended if there is an adenoma containing villous features or high-grade dysplasia

3yrs

colonoscopy surveillance recommended if there is a sessile serrated polyp with dysplasia

3yrs

Patients with more than 10 adenomas should have a repeat colonoscopy at ____ and may be considered for evaluation for a _________

1yr, FPS (familial polyposis syndrome)

______% of all colorectal cancers are caused by germline genetic mutation syndromes

3-4

consider hereditary polyposis in pts w:

-family hx of _______ in multiple ppl

-PMH or family hx of CRC in someone ___________

-PMH or family hx of __________ polyps

-PMH or family hx of multiple ____________________

CRC, under 50, over 10, extracolonic malignancies

Rare, inherited cancer predisposition syndrome characterized by hundreds to thousands of precancerous colorectal polyps (adenomatous polyps)

FAP (Familial Adenomatous Polyposis)

Develop hundreds to thousands of colonic adenomas and associated with extracolonic manifestations

FAP (Familial Adenomatous Polyposis)

MC familial polyposis

FAP (Familial Adenomatous Polyposis)

extracolonic manifestations of FAP (Familial Adenomatous Polyposis)

duodenal adenomas, desmoid tumors, osteomas

extracolonic cancers of FAP (Familial Adenomatous Polyposis)

stomach, duodenum, thyroid

MC form of FAP (Familial Adenomatous Polyposis) is an autosomal _______________ inheritance of the ______ gene mutation (80%)

dominant, APC

less common form of FAP (Familial Adenomatous Polyposis) is an autosomal __________________ inheritance of the _________ gene mutation (5-10%)

recessive, MUTYH

MUTYH gene is a cell ____________ gene that is associated with _________

repair, FAP

FAP (Familial Adenomatous Polyposis) can arise ___________ in ~10% (no gene mutations in parents)

de novo

FAP (Familial Adenomatous Polyposis) population

young healthy men

in FAP, colorectal polyps develop by a mean age of ____ and cancer by _____

15, 40

colorectal cancer is inevitable by ___ in FAP (Familial Adenomatous Polyposis) pts unless prophylactic ______________

50, colectomy

90% of the polyps of FAP (Familial Adenomatous Polyposis) are found in the ____________ and _____________ area but can also be seen in the gastric antrum and small bowel

duodenum, periampullary

S/Sx:

-colon polyps

-soft tissue tumors of the skin

-desmoid tumors

-osteomas

-congenital hypertrophy of retinal pigment

FAP (Familial Adenomatous Polyposis)

locally invasive fibromas commonly seen in FAP (Familial Adenomatous Polyposis)

desmoid tumors

MC location of desmoid tumors (may cause bowel obstruction, ischemia or hemorrhage)

intra abdominal

FAP (Familial Adenomatous Polyposis) Dx

genetic testing/counseling

FAP (Familial Adenomatous Polyposis) genetic testing is indicated in those with ________________________ on endoscopy, or a ____________________

over 10 adenomas, FDR w FAP

testing for FAP (Familial Adenomatous Polyposis) is usually a multigene panel of hereditary cancer genes including ______ and ___________

APC, MUTYH

FAP (Familial Adenomatous Polyposis) Tx

complete proctocolectomy w ileoanal anastomosis or colectomy w ileorectal anastomosis

FAP (Familial Adenomatous Polyposis) typically needs to be treated before age ____

20

FAP (Familial Adenomatous Polyposis) monitoring after tx includes a colonoscopy every _________ and an EGD every ________

1-2yrs, 1-3yrs

___________________ combination of normal tissue and initially benign hyperplastic tissue mixed together can be seen in multiple different syndromes

Hamartomatous

Hamartomatous Polyposis Syndromes

Peutz Jeghers, Familial Juvenile, Cowden Disease

autosomal dominant syndrome with hamartomatous polyps throughout the GI tract (MC SB) WITH the development of cancers in the breast and gonad

Peutz Jeghers Syndrome

GI polyps plus breast cancer

Peutz Jeghers Syndrome

autosomal dominant syndrome with hamartomatous polyps throughout the GI tract presenting at around 10yo

Familial Juvenile Polyposis

Hamartomas and lipomas in GIT with trichilemmomas, and cerebellar lesions and an increased risk of cancer: thyroid, breast and urogenital tract

Cowden Disease (PTEN multiple hamartoma syndrome)

MC cancer seen in Cowden Disease (PTEN multiple hamartoma syndrome)

thyroid

GI polyps plus thyroid cancer

Cowden Disease (PTEN multiple hamartoma syndrome)

Hereditary Nonpolyposis Colon Cancer [HNPCC]

Lynch Syndrome

autosomal dominant inherited mutations in gene that detects and repairs DNA base-pair mismatches; results in DNA microsatellite instability (MSI) and inactivation of tumor suppressor genes

Lynch syndrome

Lynch syndrome increases the lifetime risk of _________, ___________ cancer, and other cancers at a young age

CRC, endometrial

suspect _____________ with a personal or family hx of early onset CRC, endometrial cancer or multiple cancers

Lynch Syndrome

Lynch Syndrome Screening

PREMM5

if a pt with suspected lynch syndrome scores over a ____% on the PREMM5 screening, ___________ is indicated

5, genetic testing

Those with Lynch syndrome gene mutation should be screened with colonoscopy every ______ years beginning at age _____ (or __ years younger than the age at diagnosis of youngest affected family member)

1-2, 25, 5

women with lynch syndrome should undergo endometrial/ovarian screening at age _______ and a prophylactic hysterectomy/oophorectomy at age _____

30-35, 40

consider an EGD to screen for ________________ at age 30-35 in pts with lynch syndrome and then EGD every _______

gastric cancer, 2-3yrs

Lynch Syndrome tx

complete proctocolectomy w ileoanal anastomosis or colectomy w ileorectal anastomosis

_______ is the 2nd leading cause of cancer death in the us (following lung) and has a 5yr survival rate of ____%

CRC, 60

OVERALL incidence of CRC is about equal in men and women- but reached about ________ later in ___________

4-6yrs, women

has been shown to reduce the risk of CRC, but given the risks associated with GI bleeding, it is not recommended for prevention

Aspirin