Poo Do You Know: The Modern Era of Stool Testing. Justin Harberson, MD

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2 Poo Do You Know: The Modern Era of Stool Testing Justin Harberson, MD

3 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.

4 Stoolologists have existed from the earliest era of health and medicine. Background

5 Traditional Testing Blood, electrolytes, microbes, fat, and other exciting stool based substances. Our stool tells a story

6 Bristol Stool Scale!

7 Crazy Diarrhea Workups!

8 Books!

9 Designer Clothing!

10 Fecal Transplant!

11 What does your Poo say about You? Blood? Infection? Cancer? Inflammation? Malabsorption?

12 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

13 Why does blood in the stool matter? CANCER Screening 0% 0% Percent of population 50 to 75 y/o screened for CRC 42% Percent of population 50 to 75 y/o not screened for CRC 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):

14 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?

15 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 Greegor developed gfobt the paper slide gfobt was commercially available.

16 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

17 Hemoglobin (Heme + Globin)

18 Digestion of blood in the intestine Globin is broken down more readily in the upper intestine compared to Heme.

19 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.

20 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.

21 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

22 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.

23 Hemoccult Testing Hemoccult Sensa highly sensitive gfobt test for colon cancer and advanced adenomas.

24 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

25 Fecal Immunochemical Testing Tests specifically for globulin and is much more sensitive for lower GI bleeding. (FIT) Higher sensitivity for colon cancer compared to hemoccult.

26 sdna Combines stool DNA testing with testing for globin. Highest sensitivity for colon cancers and advanced polyps.

27 Stool Testing for Colon Cancer Screening Sensitivity Colorectal Cancer Advanced Adenoma gfobt (sensitive) FIT sdna 50-79% 70% 92% 21-35% 22% 42% Specificity 93-98% 95% 87% Imperiale et al.: Multitarget Stool DNA Testing for Colorectal Cancer, NEJM April 2014.

28 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.

29 QUESTION

30 Stool Studies for Inflammation Why? Look for inflammation and distinguish IBS from IBD.

31 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.

32 Stool Studies for Inflammation

33 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.

34 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.

35 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.

36 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.

37 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

38 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 $ per positive specimen.

39 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

40 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

41 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).

42 QUESTION

43 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.

44 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

45 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.

46 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.

47 Thank you!