Wk 6: GI

Question 1

1) What is the most prevalent chronic bacterial infection?
2) Who is infected?
3) What is it a common cause of?

Answer 1

1) H. pylori
2) Many people (~50% globally) infected, usually asymptomatic
3) Dyspepsia, gastritis, peptic ulcers, and increased gastric cancer risk

Question 2

H. pylori diagnostic tests: What are the 2 categories? What are some tests included in each?

Answer 2

1) Non-invasive:
Stool antigen test
Urea Breath test
Serology (blood) test: not preferred
2) Invasive (endoscopic):
Biopsy urease test
Histology
Culture

Question 3

1) Choice of test to diagnose H. pylori depends on what?
2) What should you do if it doesn’t need the more invasive form of testing?

Answer 3

1) Whether patient requires upper endoscopy to evaluate symptoms or for surveillance (such as to exclude malignancy); Endoscopy is not indicated solely to diagnose H. pylori
If gastric cancer needs to be excluded = endoscopy
2) Generally, if gastric cancer does not need to be excluded (i.e., endoscopy not indicated), then start with non-invasive testing to identify active H. pylori infection (stool antigen or urea breath test)

Question 4

H. pylori tests:
1) How does Recent Proton Pump Inhibitor (PPI)/bismuth/antibiotic use (reduces bacterial load) affect them?
2) How long should a pt stop using PPIs?
3) What else can affect H. pylori tests?

Answer 4

1) Reduces test sensitivity for all endoscopic-based and non-invasive tests for active H. pylori infection
2) 1-2 weeks after stopping PPIs and at least 4 weeks after last bismuth/antibiotic use
3) Active peptic ulcer bleeding
Can limit sensitivity of endoscopic-based tests

Question 5

Urea breath test (UBT) (non-invasive H. pylori test):
1) What is it commonly considered?
2) How does it work?
3) Describe the process/ interpretation

Answer 5

1) “Gold standard”: high sensitivity and specificity
2) H. pylori produces urease, which breaks down urea to produce CO2 and ammonia
3) Patient is given a drink of urea labeled with carbon 13 isotope (nonradioactive)
-If H. pylori is present,urease will break down urea which leads to C13-labeled CO2
Labeled CO2 is absorbed by capillaries and detectable in breath samples

Question 6

Stool antigen test/assay (for H. pylori):
1) How does it work?
2) What are 2 pros to this method?
3) What version is not often used?

Answer 6

1) Uses monoclonal antibodies specific for H. pylori antigens
H. pyloriorganism does notsurvive in stool, but H. pylori antigen can be detected in fresh stool
2) More convenient and less expensive than urea breath test (but some pts don’t like using stool sample)
-Lab based monoclonal enzyme immunoassay has high sensitivity and specificity (comparable to UBT)
3) Rapid in-office monoclonal immunochromatographic test not highly utilized (low sensitivity)

Question 7

Both the ____________ and __________ have good sensitivity/specificity either are recommended as the initial diagnostic tool for active H. pylori infection in patients who do not require endoscopy

Answer 7

urea breath test and stool antigen test

Question 8

1) How does a Serology (Blood) test work for H. pylori?
2) Can it distinguish between all forms of infection?

Answer 8

1) Detects anti-H. pylori antibodies (IgG) using ELISA test
2) Cannot distinguish between active and past infection

Question 9

Serology (Blood) test for H. Pylori
1) Is it expensive? Are the sensitivity and specificity good?
2) When should this type of testing not be used? Why?

Answer 9

1) Inexpensive and noninvasive but many of the commercial versions (especially rapid office tests) do not perform well (low sensitivity and specificity)
2) Guidelines do not recommend serologic testing for populations with low prevalence of H. pylori (much of the U.S.) due to high number of false positives

Question 10

Describe biopsy urease tests for H. pylori (endoscopic)

Answer 10

-Biopsy specimen(s) placed into gel with urea > if H. pylori (with urease) is present, urea is broken down releasing ammonia, raising pH and leading to color change (+ test)
-Test results can occur within minutes but may require up to 24 h. More convenient than histologic test.

Question 11

Describe histologic exam of biopsy specimen for H. pylori

Answer 11

-Antral or duodenal biopsy specimen obtained, special stain for H. pylori added, and tissue viewed under microscopy to look for H. pylori organisms
-Can also give information about associated tissue lesions on the biopsy (inflammation, etc.)

Question 12

Microbiologic culture for H. pylori:
1) How can this be obtained?
2) How long does it take?
3) Sens. and specificity?
4) Pro to using it?

Answer 12

1) Can be cultured from a mucosal specimen obtained through a gastroscope
2) Takes several weeks (don’t wait for results before beginning treatment)
3) Most specific, but low sensitivity because H. pylori is difficult to isolate with culture
4) Added benefit of being able to determine antibiotic susceptibility to guide treatment

Question 13

1) What do urea breath test/stool antigen tests and endoscopy-based testing do for H. pylori?
2) What does choice of test depend on?
3) What does not distinguish active and past infection?

Answer 13

1) Identify active infection and can be used to confirm eradication after treatment
2) Need for upper endoscopy
3) Serology

Question 14

1) What is celiac?
2) What happens with this condition?
3) What develop?

Answer 14

1) Immune disorder triggered by environmental allergen (dietary gluten, which is made of gliadins and glutenins)
2) Presence of gluten-derived peptides (e.g., gliadin) triggers mucosal inflammation of the small intestine
-Damages the lining, affecting the small intestine’s ability to absorb nutrients
3) Antibodies develop

Question 15

Celiac:
1) When is a diagnostic test ideally performed?
2) In most pts how is Dx established?
3) Generally what Dx tool do you start with?

Answer 15

1) Ideally performed while patient is on gluten-containing diet
2) In most patients, the diagnosis is established by positive celiac serology + positive small bowel biopsy
Sometimes results are discordant, in which case additional testing can help establish diagnosis
3) Generally, will start with serologic testing and then if indicated follow-up with biopsy

Question 16

What are the classic CD duodenal biopsy findings?

Answer 16

Increased intraepithelial lymphocytes with crypt hyperplasia +/- villous atrophy

Question 17

1) What is the preferred test for celiac disease in adults?
2) What else can be used?

Answer 17

1) tTg-IgA (an anti-tissue transglutaminase antibody)
2) tTg-IgG (or DGP-IgG)

Question 18

What are the two groups of autoantibodies regarding celiac?

Answer 18

1) Anti-tissue transglutaminase antibodies (tTg-IgA, tTg-IgG)
2) Anti-endomysial antibody (EMA-IgA)

Question 19

20

Question 20

20

Question 21

20

Question 22

1) Second leading cause of cancer death in men and women in U.S. is what?
2) Is it easy to screen? Should it be screened?

Answer 22

1) Colorectal cancer (CRC)
2) Easy to screen (Embarrassment/bowel prep are the biggest hurdles)
Much higher survival rate with early treatment
USPSTF recommends screening ages 45*-75 (asymptomatic, average risk)

Question 23

CRC Screening Tests: List 2 and describe what they detect

Answer 23

1) Stool-based tests, to detect:
-Hemoglobin in stool (bleeding from CRC lesion): e.g., gFOBT, FIT
-DNA alterations suggestive of malignancy
-Examinations that visualize structure of colon
-Radiologic imaging to visualize lesions (e.g., CT colonography)
2) Direct visualization with endoscopy:
a) Flexible Sigmoidoscopy: only visualizes rectosigmoid and descending colon
b) Colonoscopy: exams entire colon; scope allows biopsy and lesion removal at time of test

Question 24

Describe the recommendations for colorectal cancer screening for average-risk individuals aged ≥ 45 years

Answer 24

1) Stool-based tests:
-Annual fecal occult blood testing (FOBT) using higher sensitivity tests (Hemoccult SENSA) [gFOBT]
-Annual fecal immunochemical test (FIT)
-Fecal DNA test (with FIT every 1–3 years)
2) Endoscopic tests: Colonoscopy every 10 years
Flexible sigmoidoscopy every 5 years
3) Radiologic tests: CT colonography every 5 years

Question 25

True or false: any abnormal screening test for CRC (other than colonoscopy itself) requires follow-up with a timely colonoscopy

Answer 25

True

Question 26

slide 25

Answer 26

Selecting the “best” test for CRC screening: Compliance is important (if the pt won’t complete the test, it doesn’t matter how sensitive/specific the test is)

Question 27

CRC Screening: Fecal Occult Blood Testing (FOBT) & Stool Testing 1) Why is this testing appropriate for CRC? 2) What are some pros compared to colonoscopy? 2) What are two limiting factors to this type of test?

Answer 27

1) Most CRCs and some large adenomas result in increased chronic blood loss > hemoglobin in stool 2) Do not require bowel prep, sedation, or time off work 3) Sensitivity is reduced if stool sample is delayed in being tested after collection or if exposed to high ambient temperatures. -Generally, less sensitive for lesions in right side of colon vs. left side of colon.

Question 28

There are a variety of FOBTs with varying sensitivity/specificity for CRC; list 3

Answer 28

1) Guaiac-based fecal occult blood tests (gFOBT): e.g., Hemoccult SENSA 2) Fecal immunochemical test (FIT) 3) Multitarget stool DNA test with FIT (MT-sDNA, FIT-DNA, sDNA-FIT)

Question 29

CRC Screening: FOBTsGuaiac-based fecal occult blood (gFOBT) 1) How does it work? What version is preferred for CRC? 2) What is the frequency? 3) What does it require?

Answer 29

Hemoglobin identified when reagent-impregnated paper turns blue (peroxidase reaction) Highly sensitive versions preferred for CRC screening (e.g., Hemoccult SENSA) Frequency: performed annually Requires 3 consecutive stool samples

Question 30

Guaiac-based fecal occult blood (gFOBT): 1) What can cause false positives? 2) What can cause false negatives?

Answer 30

Can be affected by diet and some medications 1) False positives: Peroxidase-rich foods (certain fruits/vegetables and red meats). Manufacturer recommends not eating red meat for 3 days prior. -Upper GI bleeding 2) False negatives: High doses of Vitamin C

Question 31

Fecal immunochemical test (FIT) for blood: 1) What does it measure? 2) Frequency? 3) What does the pt provide? Are there restrictions to meds/ diet?

Answer 31

1) Directly measures hemoglobin in the stool (human globin) 2) Annually 3) Patient provides 1 small stool sample in a special container (more convenient than gFOBT) -No restrictions to medications or diet prior to testing

Question 32

Fecal immunochemical test (FIT) for blood: Compare its sensitivity and specificity to gFOBT

Answer 32

1) FIT has superior sensitivity for CRC/advanced adenomas and similar specificity (preferred over gFOBT) 2) FIT has high specificity for lower GI bleeding if positive (but large upper GI bleeds can sometimes cause positives)

Question 33

CRC Screening: Stool Tests: Multitarget stool DNA test with fecal immunochemical testing (MT-sDNA, FIT-DNA, sDNA-FIT) 1) What is this called in the US? 2) What is it? 3) What is required of the pt?

Answer 33

1) sDNA-FIT: “Cologuard” test in U.S. 2) Composite of tests that include DNA mutation detection, cancer biomarkers, and hemoglobin detection (FIT) 3) Patient collects a full stool sample in provided kit No diet/medication changes needed

Question 34

CRC Screening: Stool Tests: Multitarget stool DNA test with fecal immunochemical testing (MT-sDNA, FIT-DNA, sDNA-FIT) 1) How often is it done? 2) What are the cons? (3)

Answer 34

1) Reduced frequency (every 1-3 years) 2) a) Patients sometimes don't want to collect a full stool sample b) More expensive than FIT c) More sensitive but less specific than FIT (higher false + rate)

Question 35

Colonoscopy: 1) What is it? What can be done during it? 2) How often is it done?

Answer 35

1) Endoscopic visualization of the rectum, colon, and terminal ileum -Lesions can be removed and biopsied 2) Every 10 years starting at age 45; frequency may be increased

Question 36

What are some pros and cons of colonoscopy?

Answer 36

Pros: 1) Gold standard for detecting CRC early 2) Detection, removal, and subsequent biopsy Cons: 1) Requires sedation, extensive bowel prep, time off work 2) Risk of perforation and bleeding 3) People don't want to do it

Question 37

1) What do emerging CRC screening tests include? 2) Describe the sensitivity and specificity of the one approved blood based test

Answer 37

1) Next generation mt-sDΝΑ test, multitarget stool RNA test, blood-based cell-free DNA (cfDNA) tests, and multicancer detection tests that include СRC in the panel1 2) 1 currently approved by FDA (“Shield”) that uses cfDNA: Compared to colonoscopy, has 83% sensitivity and 90% specificity for colorectal cancer However, only 13% sensitivity for advanced precancerous polyps (less potential benefit compared to FIT, mt-sDNA, colonoscopy… unless pt won’t do other tests)

Question 38

The pancreas secretes ____-______ L of fluid/day containing bicarbonate and ~____enzymes, to help with digestion

Answer 38

1.5-3 L; ~20 enzymes

Question 39

List and describe the 3 categories of pancreatic enzymes

Answer 39

1) **Proteolytic enzymes:**: Break down proteins to AAs 2) **Lipolytic enzymes:**: Break down fat (with the help of bile) -Lipase 3) **Amylolytic enzymes:** Breaks carbohydrates into glucose -Amylase -Also in the mouth (salivary gland production)

Question 40

1) What is pancreatitis? 2) What happens during acute pancreatitis? 3) What can acute pancreatitis lead to?

Answer 40

1) Inflammation of the pancreas (can be acute or chronic) 2) Digestive enzyme production continues but secretion is impaired > enzymes become activated within pancreas (abnormal), leading to autodigestive injury to pancreas 3) Damage to vascular endothelium/interstitium from enzymes > increased vascular permeability > fluid leaks out of pancreatic cells and collects in interstitial space (extravascular, “third-spacing”)

Question 41

What are the diagnostic criteria for pancreatitis?

Answer 41

At least 2 of the following 1) Acute onset of persistent, severe, epigastric pain often radiating to the back 2) Elevation in serum lipase or amylase to ≥3 times the upper limit of normal 3) Or characteristic findings of acute pancreatitis on imaging (contrast-enhanced CT, MRI, or transabdominal ultrasonography) -Diagnosis can be made without imaging if pt has characteristic pain + sufficient lipase/amylase elevation

Question 42

Amylase (pancreatitis testing): 1) What does it do? 2) When does it rise? Is it cleared rapidly? Describe 3) What can be detected in urine after onset of acute pancreatitis?

Answer 42

1) Hydrolyzes carbohydrates 2) Rises within 6-12 hours of onset of acute pancreatitis Cleared rapidly by kidneys (short half-life) 3) Returns to normal within 3-5 days Amylase can also be detected in urine after serum amylase normalizes

Question 43

Amylase: Describe the sensitivity and specificity

Answer 43

Sensitivity: limited (false negatives) Can be falsely negative in 20% of alcoholic- and 50% of hypertriglyceridemia-associated pancreatitis cases. Dx of pancreatitis can be missed in patients presenting >24 hours after onset. Specificity: good but some limitations (false positives) Not specific to acute pancreatitis (seen in other conditions) Bowel perforation, penetrating peptic ulcer, duodenal obstruction, parotitis (salivary amylase), etc.

Question 44

Lipase (acute pancreatitis testing): 1) What does lipase do? 2) Describe its rise, peak, and return to normal after acute pancreatitis 3) Describe its window of detection

Answer 44

1) Hydrolyzes triglycerides 2) Rises within 4-8 hours, peaks at 24 hours, returns to normal within 8-14 days (elevations occur earlier and last longer than amylase) 3) Greater window for detection (esp. helpful in evaluating pts presenting >24 hrs after onset of pain)

Question 45

Lipase (acute pancreatitis testing): 1) Sensitivity? 2) Specificity?

Answer 45

1) Good/superior: slightly **higher sensitivity** than amylase for acute pancreatitis -Good marker for **alcoholic pancreatitis**: lipase is usually higher than amylase in alcoholic pancreatitis, and is more sensitive for the condition 2) **Good but some limitations** (false positives) -Like amylase, can be elevated in conditions other than acute pancreatitis (renal failure, acute cholecystitis, etc.)

Question 46

Other pancreatitis laboratory findings that may occur (in addition to elevated pancreatic enzymes), include what 9 things?

Answer 46

1) Altered glucose regulation (hyper- or hypoglycemia), usually hyper- 2) Leukocytosis from inflammation and hemoconcentration (due to third-spacing of fluids) 3) Elevated hematocrit (hemoconcentration) 4) Hyperbilirubinemia 5) Pancreatic edema obstructs the bile duct 6) Hypocalcemia 7) Exact mechanism unknown, associated with increased mortality 8) Elevated BUN 9) Elevated CRP/ESR (inflammation)

Question 47

Review slide 40 chart (note to self, rate as 5 to ignore)