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Flashcards in Tumors of the bowel Deck (68):
1

What is the lifetime risk of colorectal cancer?

5-6%

However, the incidence is declining

2

How much time does it take for a benign adenoma to become a colon cancer?

5-12 yrs

3

How common is CRC?

3rd most common form of cancer in men and women. 3rd leading cause of cancer death in US

4

What are the intrinsic risk factors of colorectal cancer?

Race
Ethnic background
Occupational hazards

5

What are the controllable risk factors in colorectal cancer?

1. Caloric intake/obesity
2. Red meat consumption
3. Alcohol consumption
4. Smoking

6

Where are most colorectal cancers found?

Distal to the splenic flexure of the colon

7

What genetic factors increase your risk of CRC?

1. History of colorectal neoplasia
2. IBD
3. HNPCC mutation
4. FAP

8

Most cases of CRC occur after the age of:

50

9

If you meet someone who has CRC under the age of 50...what are you worried about?

FAP/HNPCC/PJS/IBD/MUTYH

10

How is FAP inherited? What gene is mutated?

Autosomal dominant disorder
-Mutated APC gene

11

What is peutz-jeghers syndrome?

Autosomal dominant disorder
-Multiple hamartomatous polyps of the entire GI tract
-melanosis of lips and buccal mucosa

12

Are PJ polyps malignant?

No, but these patients have a higher incidence of carcinoma elsewhere in the colon (breast, pancreas, ovary, uterus, lung)

13

How and when should you treat FAP?

Cancer develops early (late 30's). Treat early on with a total colectomy, before the age of 25

14

What are the carcinogens identified in colorectal cancer?

1. Fecal bile acids
2. Heterocyclic amines
3. Fecapentenes (anaerobic breakdown of fatty acids)
4. 3-ketosteroids (oxidation product of cholesterol)

15

What are some protective measures for colorectal cancer?

NSAIDS
vitamin D
calcium
folic acid
Fiber consumption

16

Does the two-hit hypothesis apply to CRC?

Yes. Molecular pathways to sporadic and inherited cancers are the same

17

How is familial colorectal cancer inherited?

We don't understand this. Family hx plays a role but this isn't a typical inherited syndrome

18

Do you have to have a family history of FAP to get FAP?

No. 25% have a spontaneous germline mutation

19

How do you diagnose FAp?

>100 polyps in the colon and rectum

20

What is the most common cause of death in FAP?

Desmoid tumors

21

How is MYH polyposis inherited?

autosomal recessive

22

Which gene is mutated in MYH polyposis?

mutY homolog gene, which does base excision repair for oxidative DNA damage

23

What does MYH polyposis look like when you do endoscopy?

usually 15-100 adenomas. Early (age 45) CRC

24

Where do MYH polyposis cancers occur?

In the ascending colon. Important to consider if early polyps and many polyps but no APC gene abnormality

25

What is the most common inherited colon cancer syndrome?

Hereditary Non-Polyposis Colon Cancer (HNPCC)

26

How is HNPCC inherited?

autosomal dominant

27

Where is the mutation in HNPCC?

Mismatch repair genes (MMR)

28

How do you diagnose HNPCC?

Clinically indistinguishable from sporadic CRC (only one poly developing into CRC) Can only diagnose through personal and family history

29

What are the two types of HNPCC (lynch syndrome)

Lynch syndrome 1: CRC only
Lynch syndrome 2: CRC + endometrial and other cancers)

30

What is the main difference btw HNPCC and Sporadic CRC?

HNPCC has an accelerated development of cancer (3.5 years btw polyp-carcinoma)
The polyps themselves are flatter and smaller.

31

Where are HNPCC cancers localized?

In proximal colon usually
--High rate of synchronous/metachronous cancers

32

What would lead to test for HNPCC genetically?

CRC < 50
Synchronous/metachronous CRC
Microsatellite instability
CRC diagnosed in 1+ relatives, with one of them diagnosed under age of 50
CRC diagnosed in 2 or more 1st/2nd degree relatives

33

What is the amsterdam criteria for HNPCC?

3-2-1 rule:
3+ relatives with HNPCC cancer/associated cancer
2+ generations
1+ diagnosed before age 50

34

What are microsatellite repeats? Why do they increase the risk of mutation?

repetitive sequences. Replication machinery slips and makes more errors on these sequences

35

How is MSI related to HNPCC?

90% of HNPCC cancers have microsatellite instability. This is b/c MMR defects cannot repair microsatellite repeats

36

How can you diagnose a mutation in MMR?

Immunohistochemistry for MMR proteins

37

What are some examples of non-neoplastic polyps?

1. Hyperplastic
2. Hamartomatous (juvenile or peutz-jeghers)
3. Inflammatory pseudopolyps

38

What polyp characteristics imply an increased risk of malignant behavior?

size > 2cm
Villous adenoma>tubulovillous>tubular

39

What is the most common type of adenoma?

tubular adenoma

40

What is the morphology of a tubular adenoma?

Pedunculated with packed glands. The stalk is made out of submucosa material

41

How common is a villous adenoma?

Uncommon (1%)

42

Where do villous adenomas show up?

Rectum and rectosigmoid

43

What kind of polyps do you see in villous adenomas?

sessile masses with frond-like villi. Mucus is rich of K+

44

Tubulovillous adenoma: What are you at risk for?

in situ or invasive carcinoma. Risk correlates with amount of villous material.

45

How do you treat invasive CRC?

Controversial resectqability. But try to remove!

46

Hyperplastic polyp

A small sessile polyp that is NOT neoplastic.

47

Juvenile/retention polyp

Hamartomatous malformation in the rectum. Seen in children. Not malignant

48

What do juvenile polyps look like?

Cystically dilated glands and inflamed lamina propria

49

What are Peutz-Jeghers polyposis pts at risk for?

Cancer of the pancreas, breast, lung, ovary, and uterus.

-LKB1 mutation

50

Left sided colorectal adenocarcinomas

Left sided tumors grow as annular, circumferential masses. Obstruction is common

51

Right sided colorectal adenocarcinomas

Right sided tumors grow as polypoid exophytic masses. Occult bleeding/melena seen INSTEAD of obstruction

52

How do you stage in CRC?

In situ (intraepithelial and intramucosal) has low risk of metastasis
-pT1: invasion into submucosa
-pT2: muscularis propria
-pT3: muscularis propria
-pT4: penetration of serosa/adjacent viscera

53

What staging indicates a poor prognosis?

Nodal involvement, penetration into the serosa, and distant mets

54

Why are there more complications with cancers of the rectum?

Anatomic constraints of the pelvis. Local recurrence following surgery ends up happening more often. Lower risk of recurrence by using postop chemo/XRT

55

What do you do if you see a hepatic metastasis?

En bloc resection and follow up chemo

56

When should you begin CRC screening in someone with a family history?

age 40 or 10 years younger than when family member got it.
LYNCH: screen every 1-2 years
FAP: yearly from age 12-13 years
IBD: Screen every 2 years after 10 years of dz

57

How does small bowel carcinoma present?

Vague symptoms usually from bowel obstruction(pain, nausea, wt loss, bleeding)
Diagnostic delay at advanced stages
Poor outcomes

58

How do you diagnose small bowel neoplasms?

If pain, use CT or MRI enterography
If bleeding, use Colonoscopy or UGI endoscopy

59

How do you treat small bowel neoplasms?

Segmental resection OR whipple if the duodenum is involved

60

Carcinoid tumors represent a proliferation of what kind of cells?

Neuroendocrine

61

When is the prognosis of carcinoid tumors good?

Benign if in appendix or rectum
Benign if not penetrating the muscularis
Benign if tumor < 2 cm

62

What is the most common symptom of carcinoid tumors?

pain/obstruction. 90% of symptomatic pts will have metastatic dz

63

What is carcinoid syndrome?

Release of serotonin into the systemic circulation with skin flushing/cyanosis
diarrhea/cramps
bronchospasm
subendocardial fibrosis

64

Where do adenocarcinomas of the small intestine occur?

Duodenum and proximal jejunum. Often advanced at time of diagnosis.

65

What are the risk factors for adenocarcinoma?

Crohn's and FAP/HNPCC

66

What are gastrointestinal stromal tumors?

Mesenchymal tumor resembling modified smooth muscle and neural tissue

67

What kinds of cells make up GIST?

Interstitial cells of cajal, the pacemaker cells of the gut. They can range from benign to malignant

68

What are Cajal cells positive for?

CD117.