Transcript The gold standard for colon cancer PREVENTION is a colonoscopy.

Poo Do You Know:
The Modern Era of Stool
Testing
Justin Harberson, MD
Goals and Objectives
• Briefly review the history of stool testing.
• Discuss the traditional stool testing.
• Discuss the role of newer stool studies
and the novel insights they provide.
Background
• Stoolologists have
existed from the
earliest era of
health and
medicine.
Traditional Testing
• Blood, electrolytes, microbes, fat, and
other exciting stool based substances.
• Our stool tells a story…
Bristol Stool Scale!
Crazy Diarrhea Workups!
Books!
Designer Clothing!
Fecal Transplant!
What does your Poo say about
You?
Blood
?
Cancer
?
Infection?
Malabsorption?
Inflammation
?
Why do we look for blood in the
stool?
Blood in the stool
Non-malignant causes:
• Ulcers
• AVMs
• IBD
• Ischemia
• Infection
Malignant Causes
• Colon Cancer
• Everything else
Why does blood in the stool
matter?
Percent of population 50
CANCER Screening
to 75 y/o screened for
CRC
Percent of population 50
to 75 y/o not screened
for CRC
42%
58%
Appropriately screened for
colon cancer with
colonoscopy, flexible
sigmoidoscopy, CT
colonography or stool testing
Cancer Screening Test Use – United States 2013, MMWR weekly
2015;64(17):464-468.
Colon Cancer Screening is a BIG
DEAL
• Colon cancer is the # 2 cause of cancer
death in the US, it is the #3 cause of
cancer.
• The gold standard for colon cancer
PREVENTION is a colonoscopy.
• What about the other 42% of people not
getting screened?
A brief history of blood in the stool
• In 1862, Dutch scientist
J. Van Deen developed
a test for blood using
guaiac, a resin derived
from Guaicam wood.
• 1967 Greegor
developed gFOBT.
• 1970 the paper slide
gFOBT was
commercially available.
A brief history of blood in the
stool
• 2001 Fecal Immunochemical
Testing (FIT) became
available and FDA approved
• 2014 Stool DNA Testing
(sDNA) is approved as colon
cancer screening modality by
FDA
Hemoglobin (Heme + Globin)
Digestion of blood in the
intestine
Globin is broken down
more readily in the upper
intestine compared to
Heme.
Stool Studies for Blood in Stool
• Guaiac Fecal Occult Blood Tests (gFOBT)–
test for heme.
• Fecal Immunochemical Test (FIT)– tests for
globins.
• sDNA– tests for globins and DNA associated
with colon cancer and advanced adenomas.
Hemoccult Testing
• A test for the “Heme”
component of hemoglobin.
– A “Guaiac” based test where a
guaiac resin is embedded in
the paper and Heme in the
stool catalyzes the reaction.
Hemoccult Testing
• PROs– more sensitive for
upper GI bleeding, cheap,
widely available
• CONs–
– False positives from animal
proteins, raw vegetables,
iron supplements, NSAIDs
– False negatives from
vitamin C
– NOT adequate for colon
cancer screening
Hemoccult Testing
• False sense of security:
– A single digital rectal exam
and hemoccult test in the
PCP office has a 5-10%
sensitivity for colon cancer.
– NOT adequate for colon
cancer screening
Collins JF et al. Ann Intern Med.
2005;142(2):81-85.
Hemoccult Testing
• Hemoccult Sensa–
highly sensitive
gFOBT test for colon
cancer and advanced
adenomas.
Hemoccult Testing
Hemoccult II and similar early versions of gFOBT testing should not
be used for Colon Cancer Screening
2015 Clinicians Reference: FOBT for Colon Cancer
Screening
Fecal Immunochemical Testing
(FIT)
• Tests specifically for
globulin and is much
more sensitive for
lower GI bleeding.
• Higher sensitivity for
colon cancer
compared to
hemoccult.
sDNA
• Combines stool DNA
testing with testing for
globin.
• Highest sensitivity for
colon cancers and
advanced polyps.
Stool Testing for
Colon Cancer Screening
Sensitivity
Specificity
gFOBT
(sensitive)
FIT
sDNA
Colorectal
Cancer
50-79%
70%
92%
Advanced
Adenoma
21-35%
22%
42%
93-98%
95%
87%
Imperiale et al.: “Multitarget Stool DNA Testing for
Colorectal Cancer,” NEJM April 2014.
Stool Testing for CRC Prevention
(USPSTF and ACG
Recommendations)
• Old Guaiac based stool testing no longer
recommended as screening tool for colon cancer.
• Annual FIT testing is the preferred method of stool
testing for colon cancer detection.
• Highly sensitive gFOBT (Hemoccult Sensa) testing
endorsed as an alternative stool test for colon cancer
detection.
• sDNA (Cologuard) testing is an alternative test
recommended every 3 years for colon cancer
detection.
QUESTION
Stool Studies for Inflammation
• Why?
• Look for inflammation and distinguish
IBS from IBD.
Stool Studies for Inflammation
• Fecal Lactoferrin and Fecal Calprotectin
– Inflammatory proteins in the stool used to
determine inflammation from inflammatory
bowel disease, irritable bowel syndrome,
infection and cancer.
Stool Studies for Inflammation
Stool Studies for Inflammation–
Fecal Biomarkers for IBD
Viennois et al. “Biomarkers of Inflammatory
Bowel Disease: From Classical Laboratory Tools
to Personalized Medicine,” Inflamm Bowel Dis,
Vol 21, No 10, Oct 2015.
Stool Studies for Inflammation
• In a meta-analysis of 6 studies with 670 patients:
– Elevated Fecal Calprotectin was 93%
sensitive and 96% specific for identifying
IBD.
– Fecal Lactoferrin has a somewhat lower sensitivity
(80%) and specificity (78%).
Van Rheenan et al., “Faecal calprotectin for screening patients with suspected inflammatory
bowel disease: diagnostic meta-analyses,” BMJ 2010.
Stool Studies for Inflammation
• In a large meta-analysis, found that a
normal Fecal Calprotectin level could be
used to exclude IBD in patients with IBS
symptoms
• Lactoferrin could not distinguish IBD from
IBS.
Menees et al., “A Meta-Analysis of the Utility of C-Reactive Protein, Erythrocyte
Sedimentation Rate, Fecal Calprotectin, and Fecal Lactoferrin to Exclude Inflammatory
Bowel Disease in Adults With IBS,” AJG, March 2015.
Stool Studies for Inflammation
• Conclusion:
–Fecal Calprotectin is a useful
screening tool for ruling out
IBD in a patient with IBS
symptoms.
– Fecal Calprotectin has a clear role for
helping to distinguish IBD from IBS.
Stool Studies for Infection
• Who should be checked?
– Diarrhea with fever >38.5 C
– Diarrhea persistent (14 days or
more)
– Profuse watery
diarrhea/dehydration/dysentery
– Diarrhea in a hospitalized patient
– Diarrhea in the elderly, pregnant
or immunocompromised
Stool Studies for Infection-Bacterial
• Top bacterial causes of infectious
diarrhea (NOT C. Diff):
1. Salmonella (16.4 per 100,000)
2. Campylobacter (14.3 per 100,000)
3. E. Coli 0157H7 (1.1 per 100,000)
• Bacterial stool studies have a 1.5 to
5.6% diagnostic yield (very low).
• In one study, the cost was $900-1200
per positive specimen.
Stool Studies for Infection-- Viral
• Generally, a clinical
diagnosis
– Norovirus
• (50% of adult gastroenteritis)
– Rotavirus
– Adenovirus
– Astrovirus
• Stool testing by PCR has
utility in large outbreaks
Stool Studies for Infection– O + P
• When to check an O+P
– Not generally cost-effective in
most cases of acute diarrhea.
– Persistent diarrhea in a “high risk”
patient
• Travel to Nepal, Russia, or other
high risk area
• AIDS and other severe
immunocompromised state
• Well water, campers
• Daycare outbreaks
• Check O+P 2-3 times, 24 hours
apart to improve diagnostic
yield
Giardia
Stool Studies for Infection– C. Diff
ACG 2013 Guidelines:
1. Only stools from patients with diarrhea should be tested for Clostridium
difficile . (Strong recommendation, high-quality evidence).
2. Nucleic acid amplification tests (NAAT) for C. difficile toxin genes such as
PCR are superior to toxins A + B EIA testing as a standard diagnostic test for
CDI. (Strong recommendation, moderate-quality evidence).
3. Glutamate dehydrogenase (GDH) screening tests for C difficile can be
used in two- or three-step screening algorithms with subsequent toxin A and B
EIA testing, but the sensitivity of such strategies is lower than NAATs. (Strong
recommendation, moderate-quality evidence).
4. Repeat testing should be discouraged. (Strong recommendation,
moderate-quality evidence).
5. Testing for cure should not be done. (Strong recommendation, moderatequality evidence).
QUESTION
What about Stool WBCs and
Lactoferrin?
• Some utility in appropriate setting
– Fever, bloody stools, persistent, dysentery, etc
• Help to distinguish inflammatory diarrhea
(bacteria) vs. non-inflammatory diarrhea
(viral and parasitic).
• WBC testing is 20 to 90% sensitive for
inflammatory diarrhea.
• Lactoferrin is likely more sensitive (90%), but
less widely used.
Stool for H. Pylori Antigen
• Why test the stool?
• High sensitivity 94%, High specificity
92%
• Great utility for initial diagnosis of H.
Pylori infection and to make sure H.
Pylori has been eradicated.
– Need to be off PPI therapy for 2 weeks
Conclusions
• Your Poo can say a lot about you!
• Stool testing for blood and DNA can provide
valuable non-invasive modality for helping to
detect colon cancer and some large polyps.
• Fecal calprotectin is a valuable tool for
evaluating IBD.
Conclusions
• Stool studies for infectious organisms
should be ordered in appropriate patients.
• PCR testing for C. diff toxin has become
the recommended standard of care.
• H. Pylori stool antigen is both sensitive
and specific for active H. Pylori infection.
Thank you!