2019 FMX Gastrointestinal Handouts

Home , Burping

Colorectal Cancer Update: Butt Seriously (CME064‐065)

Diverticulitis Update (CME066‐067)

Gallbladder Disease (CME068‐069)

Gastroesophageal Reflux Disease: Evidence‐Based Approach (CME070‐071)

Colorectal Cancer Update: Butt Seriously

Jason Domagalski, MD, FAAFP

ACTIVITY DISCLAIMER

The material presented here is being made available by the American Academy of Family Physicians for educational purposes only. Please note that medical information is constantly changing; the information contained in this activity was accurate at the time of publication. This material is not intended to represent the only, nor necessarily best, methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar situations.

The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this material and for all claims that might arise out of the use of the techniques demonstrated therein by such individuals, whether these claims shall be asserted by a physician or any other person. Physicians may care to check specific details such as drug doses and contraindications, etc., in standard sources prior to clinical application. This material might contain recommendations/guidelines developed by other organizations. Please note that although these guidelines might be included, this does not necessarily imply the endorsement by the AAFP.

1 DISCLOSURE

It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are resolved prior to confirmation of participation. Only those participants who had no conflict of interest or who agreed to an identified resolution process prior to their participation were involved in this CME activity.

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

Jason Domagalski, MD, FAAFP Program Director, Medical College of Wisconsin Affiliated Hospitals Community Memorial Hospital Family Medicine Residency, Menomonee Falls, WI

Dr. Domagalski practices family medicine in Menomonee Falls, WI. He provides outpatient and inpatient services. Colon cancer screening, gastroesophageal reflux disease (GERD), and inflammatory bowel disease are his specialty topics. Dr. Domagalski believes that access to endoscopy through primary care is an important trend.

2 Learning Objectives

1. Screen for colorectal cancer using evidence-based criteria from current guidelines.

2. Utilize documentation of clinical decision tools to foster patient engagement and facilitate shared decision making about CRC screening options.

3. Establish an automated or staff-driven process, to send CRC screening invitations, containing personalized risk-estimates to patients.

4. Coordinate communication with the oncologist, including formal survivorship care plans, to outline follow-up plans for surveillance after polypectomy and CRC resection.

Audience Engagement System Step 1 Step 2 Step 3

3 https://gis.cdc.gov/Cancer/USCS/DataViz.html. Accessed June 1, 2019

https://gis.cdc.gov/Cancer/USCS/DataViz.html. Accessed June 1, 2019

4 https://fightcolorectalcancer.org/prevent/about‐colorectal‐cancer/facts‐stats/. Accessed June 1, 2019

5 https://gis.cdc.gov/Cancer/USCS/DataViz.html. Accessed June 1, 2019

6 Poll Question 1

Mrs. Pam Lee History is a 54 yo F with a multiple family members diagnosed with colon cancer in their 40s and 50s. She asks what percentage of CRC is attributable to a hereditary cancer syndrome?

A. 1‐2% B. 5‐10% C. 15‐20% D. 25‐30%

Syngal S, Randall E, et al. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes. Am J Gastro. 2015; 110:223‐262.

Risk Factors • 5% lifetime risk of developing CRC • 90% of cases seen after age 50 • Factors that increase risk: • Inherited (HNPCC, FAP) • Personal hx of CRC, adenomas, IBD • Family hx of CRC or polyps in 1st deg relative • Approx 30% of people have these factors

Lynch, HT, Smyrk, TC, Watson, P, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: An updated review. Gastroenterology 1993; 104:1535. Johns LE, Houlston RS. A systematic review and meta‐analysis of familial colorectal cancer risk. Am J Gastroenterol 2001;96:2992‐3003. Winawer SJ, Fletcher RH, Miller RH, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997; 112:594‐642.

7 Associated With CRC

• Heavy alcohol use • Obesity • Cigarettes • Red meat • Diabetes • Acromegaly • HIV

ACG Notable Risk Factors • Cigarette Smoking • Associated with up to 20% of all CRC in US • 20 pk‐yr history has 2‐3x the risk for adenomas • Two‐fold increase in risk for advanced neoplasia • Obesity • 1.5 ‐ 2.8 fold increased risk of CRC • Double the relative risk of adenomas and high risk adenomas • ACG Recommendation: Special effort warranted to ensure screening in these two groups

Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. American college of gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol. 2009 Mar;104(3):739‐50.

8 CRC Clinical Manifestations • Asymptomatic • Abdominal pain • Altered bowel habits • Hematochezia • Melena • Weakness • Weight loss • Iron deficiency anemia

Speights, VO, Johnson, MW, Stoltenberg, PH, et al. Colorectal cancer: Current trends in initial clinical manifestations. South Med J 1991; 84:575.

Adenomatous Polyps

• Dysplastic, have malignant potential • More prevalent with age • Patients require surveillance colonoscopy • 25% men, 15% women after age 50 • Increased right‐sided adenomas in: • Women • African‐American • Elderly

Rex DK, Petrini JL, Baron TH, Chak A, Cohen J, Deal SE, Hoffman B, Jacobson BC, Mergener K, Petersen BT, Safdi MA,Faigel DO, Pike IM. Quality indicators for colonoscopy. Gastrointest Endosc. 2006 Apr;63(4 Suppl):S16‐28.

9 Adenoma Classification

• Glandular histology and level of dysplasia determine malignant potential

Adenoma Type Histology component Percent of adenomas Malignant transformation Tubular Tubular component 75% 80% 4.8% Tubulovillous 26-75% villous component 5-15% 19.0% Villous 75% villous component 5-15% 38.4%

O'Brien, MJ, Winawer, SJ, Zauber, AG, et al. The National Polyp Study: Patient and polyp characteristics associated with high‐grade dysplasia in colorectal adenomas. Gastroenterology 1990; 98:371..

Adenoma‐Dysplasia‐Carcinoma Sequence

TA TVA w/ HGD

TVA

TA CRC DEATH

10 Sessile Serrated Polyps

• Principal precursor of hypermethylated gene cancers • 20‐30% of cancers can arise from this pathway • Can have cytologic dysplasia (more advanced) • Difficult to detect – flat, indiscrete, adherent mucous • Proximal to sigmoid are higher risk • Size > 10 mm are higher risk • Appearance resembles hyperplastic polyps

Lieberman DA, Rex DK, Winawer SJ, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi‐Society Task Force on Colorectal Cancer. Gastroenterology. 2012 Sep;143(3):844‐57.

Adenocarcinoma

• Colonic masses or pedunculated • Colonoscopy test of choice for symptoms • Biopsies and surgical consultation • Endoscopic features suggestive of CRC • Depression • Friability or spontaneous bleeding • Ulcerations

11 Adenocarcinoma

Adenocarcinoma

Ascending colon

12 Poll Question 2

Mrs. Anita Test A 51yo average‐risk female comes to your clinic for a well woman exam. She asks you what test she should do to screen for colorectal cancer. Which of the following is NOT recommended by the USPSTF or ACS?

A. Annual fecal occult blood test

B. Sigmoidoscopy every 5 years

C. Double contrast barium enema every 5 years D. Colonoscopy every 10 years

Society Guideline Date Screening Test and Interval Patient Age (years)

USPSTF 2016 • High Sensitivity‐Fecal Occult Blood Test (HS‐FOBT) annually Start at 50 end at 75* • Fecal Immunochemical Test (FIT) annually • Flexible Sigmoidoscopy (FSIG) every 10 yrs w/ FIT annually • Colonoscopy (Colo) every 10 yrs • Stool DNA (sDNA) every 1‐3 yrs* • CT Colonography every 5 yrs* American College of 2017 First Tier Start at 50 Gastroenterology • Colo every 10 yrs OR (MSTF) • FIT annually 45 in AA Second Tier • FSIG every 5‐10 yrs End at 75 or <10 yr life • CTC every 5 yrs expectancy if prior • Stool DNA every 3 yrs negative Third Tier OR • Capsule Colonoscopy 85 if no prior testing American Cancer 2018 Tests that detect adenomatous polyps and cancer (structural tests) Start at age 45 Society (ACS) • Colo every 10 yrs • FSIG every 5 yrs Through age 75 • CT Colonography every 5 yrs Tests that primarily detect cancer (stool based) 76‐84 Individualized • HS‐FOBT annually • FIT annually Do not screen >85 • sDNA interval uncertain

13 Differences in Screening Guidelines • USPSTF • Formalized process • Generalists and research methodologists • Focuses on clinical outcomes • Excludes high‐risk groups • No preference among the tests recommended

U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. JAMA. 2016 Jun 21; 315(23): 2564‐75). Imperiale TF, Ransohoff DF. Understanding differences in the guidelines for colorectal cancer screening. Gastroenterology. 2010 May;138(5):1642‐1647.

Differences in Screening Guidelines

• American Cancer Society • 11 clinicians and population health professionals + 1 patient advocate • Annual institutional review • Based on scientific evidence and systematic reviews

• American College of Gastroenterologists • Less formalized process • Subspecialists • Focuses on prevention and test sensitivity

Imperiale TF, Ransohoff DF. Understanding differences in the guidelines for colorectal cancer screening. Gastroenterology. 2010 May;138(5):1642‐1647. NCCN Guidelines: Colorectal Cancer Screening. www.nccn.org. Accessed 6/25/2016. .

14 Available Screening Tests • Tests that detect adenomatous polyps and cancer • Flexible sigmoidoscopy • Colonoscopy • Double‐contrast barium enema* • Computed tomography colonography • Capsule colonoscopy • Tests that primarily detect cancer • High sensitivity fecal occult blood testing • Fecal immunochemical test • Stool DNA test

Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi‐Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin 2008; 58:130–160.

Flexible Sigmoidoscopy

• Complete or partial bowel prep required • Sedation usually not used (discomfort) • Views only lower half of colon (last 60cm) • Concerning findings require colonoscopy

15 Colonoscopy

• Complete bowel prep • Moderate sedation ‐ need driver • Perforation and bleeding risk is higher • View entire colon and remove polyps

Double Contrast Barium Enema

• Complete bowel prep required • Polyps require colonoscopy • Low complication risk • Replaced by CTC (ACG)

Rex DK, Boland R, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the Multi Society Task Force on Colorectal Cancer. AM J of Gastro. 2017 Jun 20. 1‐15

16 Computed Tomography Colonography

• Complete bowel prep required • Colonoscopy for polyps • Low complication risk • AKA “Virtual colonoscopy”

Rex DK, Boland R, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the Multi Society Task Force on Colorectal Cancer. AM J of Gastro. 2017 Jun 20. 1‐15

Capsule Colonoscopy

• Proximal imaging for incomplete colonoscopies • NOT FDA approved for average risk individuals • 88% of adenoma>6mm • Failed to detect serrated adenomas • Requires a 2nd more involved prep

17 High Sensitivity Fecal Occult Blood Testing

• 3 samples collected at home • Stool from a DRE should not be used • False +: Avoid ASA, NSAIDs, red meat, poultry, fish, some raw vegetables • False ‐: Vit C (blocks peroxidase) • Sensitivity improves with each sample

Fecal Immunochemical Test

• Detects human globin, not peroxidase • More specific for human blood • Less false + • Fewer samples and handling of stool • 80 % sensitive

Rex DK, Boland R, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the Multi Society Task Force on Colorectal Cancer. AM J of Gastro. 2017 Jun 20. 1‐15

18 StoolDNA Test

• Tests for known DNA alterations in adenoma‐carcinoma sequence • Adenomas and cancer cells shed altered DNA in the stool • Uses a multi‐target DNA assay to test for many different gene mutations • High False + • $$

Rex DK, Boland R, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the Multi Society Task Force on Colorectal Cancer. AM J of Gastro. 2017 Jun 20. 1‐ 15

Mr. Juan Moore‐Thing

A 42yo male is new to your practice and you find out that he has a father who was diagnosed with colon cancer at age 55. He asks you the following questions:

• When should I start colon cancer screening? • What test should I have? • How often will I need to be tested?

19 Screening Based on Risk

Short MW, Layton MC, Teer BN, Domagalski JE. Colorectal cancer screening and Surveillance. Am Fam Physician. 2015 Jan 15;91(2):93‐100.

Sarfaty, M. How to Increase Colorectal Cancer Screening Rates in Practice: A Primary Care Clinician’s* Evidence‐Based Toolbox and Guide 2008 http://www.cancer.org/acs/groups/content/documents/document/acspc‐024588.pdf

20 Poll Question 3

Mrs. Igottapolyp A 52yo female just underwent her first baseline screening colonoscopy and her pathology returned with 3 “tubular adenomas” all under 1 cm in size. When should she have her next colonoscopy?

A. 1 year B. 3 years C. 5 years D. 10 years

Short MW, Layton MC, Teer BN, Domagalski JE. Colorectal cancer screening and Surveillance. Am Fam Physician. 2015 Jan 15;91(2):93‐100.

21 Short MW, Layton MC, Teer BN, Domagalski JE. Colorectal cancer screening and Surveillance. Am Fam Physician. 2015 Jan 15;91(2):93‐100.

The “State” of Screening

Colorectal screening statistics. Centers of Disease Control. http://www.cdc.gov. Accessed June 1, 2019. https://www.cdc.gov/pcd/issues/2018/17_0535.htm

22 Colorectal screening statistics. Centers of Disease Control. http://www.cdc.gov. Accessed June 1, 2019. https://www.cdc.gov/pcd/issues/2018/17_0535.htm

Healthy People 2020

• Goal to reach 70.5% screening • Lower rates of screening in: • Asians: 46.9% • Hispanics: 46.5%

Fenton JJ, Jerant AF, et al. Physician Counseling for Colorectal Cancer Screening: Impact on Patient Attitudes, Beliefs, and Behavior. The J of Amer Brd of Fam Med. Nov 2011; 24(6):673‐81. Mosen DM, Feldstein AC, et al. More Comprehensive discussion of CRC screening associated with higher screening. The Amer J of Managed Care. 2013; 19 (4): 265‐71.

23 National Colorectal Cancer Roundtable

• Joint Initiative CDC and ACS

• Goal of 80% screening by 2018 • Maine closest 75.9%

• Resources for physicians

Patient Engagement: “Leading A Horse to Water” • Create a Collaborative Care Plan • Address common barriers: • Risks of procedure • Underestimated risk of disease • Option of screening choices • Tailored interventions more successful • Documentation of Decision‐Making

Fenton JJ, Jerant AF, et al. Physician Counseleing for colorectal Cancer Screening: Impact on Patient Attituds, Beliefs, and Behavior. The J of Amer Brd of Fam Med. Nov 2011; 24(6):673‐81. Mosen DM, Feldstein AC, et al. More Comprehensive discussion of CRC screening associated with higher screning. The Amer J of Managed Care. 2013; 19 (4): 265‐71.

24 Comprehensive Discussion

• Explain benefits • Explain how tests are done • Explain accuracy of test • Explain potential test complications • Ask if patient understands/has questions • Ask if patient has all needed info

Mosen DM, Feldstein AC, et al. More Comprehensive discussion of CRC screening associated with higher screening. The Amer J of Managed Care. 2013; 19 (4): 265‐71.

Poll Question 4

Does your practice utilize an Automated or Staff‐Driven process to increase CRC Screening? A. Yes, automated notification B. Yes, staff‐driven outreach C. No D. I don’t know

25 Promoting Improvement in Screening

• Automated notification • EHR linked • More detailed associated with higher compliance • Staff‐driven contact • Medical assistant vs RN • Tailored vs. non‐tailored notification

Christyu SM, Perkins SM, et al. Promoting Colorectal Cancer Screening Discussion: A Randomized Control Trial. Amer J of Prev Med. 2013; 44(4):325‐29. Green BB, Wang CY, et al. An Automated Intervention with Stepped Increases in Support to Increase Uptake of Colorectal Cancer Screening: A Randomized Control Trial. Ann Intern Med. 2013 Mar 5; 158 (501):301‐11.

Resources to Boost Screening

National Colorectal Cancer Roundtable • http://nccrt.org • Manual for Increasing CRC screening Rates • Toolbox for physicians • EHR linked Colon Cancer Risk Calculator • http://www.cancer.gov/colorectalcancerrisk

26 Poll Question 5

Mrs. Priya Venshun is a 56 yo F interested in any medication that may reduce risks for developng colon cancer. Which of the following is true in regards to the USPSTF recommendations on Aspirin and colorectal cancer? It is recommended for only adults > 60 with a life expectancy of 5 + years

A. It is recommended for adults >50 with a life expectancy of 10+ years B. It is Not recommended for any adults for CRC prevention C. It is recommended only for adults with a Family history

Aspirin and CRC

27 55

28 Poll Question 6

Mrs. Ann T Oxidant is a 44 yo F who is relatively healthy and has questions in regard to antioxidants as prevention of colon cancer. Which of the following is true in regards to the current research on antioxidants? A. Diets high in fruits and vegetables reduce CRC rates B. Vegetables not fruit reduced rates in older chinese men C. One study showed high dose Vitamin E was associated with a reduced rate of CRC in women D. Vitamin E reduced CRC in men only

Antioxidants

• Pro‐oxidants theoretically induce DNA damage • Fruits/Vegetables mixed evidence • No protection in US cohorts • High intake of Vitamin E protective • Iowa Women’s Health Study • Vitamin E not protective for CRC in men • SELECT trial • Increased rate of prostate cancer

29 Survivors

https://fightcolorectalcancer.org/prevent/about‐colorectal‐cancer/facts‐stats/. Accessed June 1, 2019

30 https://fightcolorectalcancer.org/prevent/about‐colorectal‐cancer/facts‐stats/. Accessed June 1, 2019

https://fightcolorectalcancer.org/prevent/about‐colorectal‐cancer/facts‐stats/. Accessed June 1, 2019

31 Survivorship Care Plans • Proposed by IOM • Summarized Treatment History • Recommendations for Ongoing Care • Listing of Practical Survivorship Resources • Initiated by primary cancer treatment provider and carried out as a team

Salz T, Oeffinger KC, et al. Primary Care Providers’ Needs and Preferences for Information about Colorectal Cancer Survivorship Care. The J of the Amer Brd of Fam Med. Sep 2012; 25(5): 635‐51.

Survivorship Care Essentials

• Prevention • Recurrence or new cancer • Surveillance • Cancer spread or medical/psychosocial effects • Intervention • For consequences of cancer • Coordination • PCM and specialist

32 Practice Recommendations • Comprehensive discussions addressing benefits/risks, complications of testing and susceptibility to disease should be included in routine health maintenance. (SOR: B)

• Do not repeat CRC screening for 10 years after a high‐quality negative colonoscopy in average risk individuals. (SOR:C)

• Survivorship Care Plans should be developed to assist in the post treatment management of Colorectal Cancer Survivors (SOR:C)

Contact Information • Jason Domagalski • [email protected]

33 Questions

References

1. Seer Database. Available at https://seer.cancer.gov/statfacts/html/colorect.html . Accessed June 1, 2019 2. Christyu SM, Perkins SM, et al. Promoting Colorectal Cancer Screening Discussion: A Randomized Control Trial. Amer J of Prev Med. 2013; 44(4):325‐29. 3. Green BB, Wang CY, et al. An Automated Intervention with Stepped Increases in Support to Increase Uptake of Colorectal Cancer Screening: A Randomized Control Trial. Ann Intern Med. 2013 Mar 5; 158 (501):301‐11 4. Salz T, Oeffinger KC, et al. Primary Care Providers’ Needs and Preferences for Information about Colorectal Cancer Survivorship Care. The J of the Amer Brd of Fam Med. Sep 2012; 25(5): 635‐51. 5. U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. JAMA. 2016 Jun 21; 315(23): 2564‐75). 6. Rex DK, Boland R, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the Multi Society Task Force on Colorectal Cancer. AM J of Gastro. 2017 Jun 20. 1‐15 7. USPSTF. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: Recommendation Statement. 2016 Oct 15; 94(8): 660A‐ 660E. 8. Stone WL, et al. The Role of Antioxidants and Pro‐oxidants in Colon Cancer. World J Gastrointest Oncol. 2014 Mar 15; 6(3):55‐66.

34 Diverticulitis Update

Justin Bailey, MD, FAAFP

ACTIVITY DISCLAIMER

1 DISCLOSURE

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

Justin Bailey, MD, FAAFP

Director, Procedures Institute, Family Medicine Residency of Idaho, Boise

Dr. Bailey loves any and all procedures. In his current position, his focus is teaching full- spectrum medicine and helping family physicians gain all the tools they need to provide exceptional care for their patients. He loves exploring and understanding evidence-based mainstream and alternative treatments that benefit patients, and he has refined a hands-on system for treating musculoskeletal disorders to dramatically diminish opioid dependence in his practice. In addition, he trains family physicians in endoscopy, skin surgeries, hospitalist procedures, and point-of-care ultrasound. In national and local settings, he lectures on primary care endoscopy, musculoskeletal medicine, procedural medicine, and the health benefits of relationships. The author of multiple textbook chapters, journal articles, and Family Physicians Inquiries Network (FPIN) Clinical Inquiries, he currently acts as a local editor for FPIN. Dr. Bailey earned his medical degree from the Medical College of Wisconsin. He completed residency at Eglin Air Force Base Family Medicine Residency, Fort Walton Beach, Florida, and a faculty development fellowship at the University of North Carolina at Chapel Hill. While active-duty Air Force, he taught full-spectrum family medicine and was deployed to Iraq during the Gulf War and to Haiti after the 2010 earthquake.

2 Learning Objectives

1. Provide patients with the appropriate tools and resources to create a healthful high-fiber diet to prevent diverticular disease.

2. Determine the appropriate imaging study based on current recommendations, the patient’s symptoms, and suspected diagnosis.

3. Formulate a treatment plan based on the severity of the diverticulitis.

Audience Engagement System Step 1 Step 2 Step 3

3 Question Based Diverticulitis? • Does fiber work, help, cure or prevent new diverticulitis? • Is history and physical exam enough for diagnosis? • Does everyone need a CT to confirm? • Who has to be admitted and who can be outpatient? • Do I have to use antibiotics to treat, and if so, which are the best choice? • Should patients get a colectomy after a severe case of diverticulitis? • Does colonoscopy have any role in diverticulitis? • Is there such a thing as chronic diverticulitis?

Definitions

• Diverticula - out pouching of colonic lumen

• True Herniation - all layers (Mekels)

• False herniation or pseudodiverticula - mucosa and submucosa through muscular layer at vascular perforation

• Diverticulosis - Presence of diverticula without inflammation

• Diverticulitis - localized inflammation of colonic diverticula

4 Prevalence • US, Europe, Australia > Africa, Asia • 180/100,000 Diverticulitis (130,000 hospitalized cases a yr in US)

• Diverticula- 10% <40 yr old, 50-70% >85 (Clin Colon Rectal Sure 2018 Jul 31(4):209)

• 1-4% of patients with diverticula will develop diverticulitis. 20% will have a reoccurrence in 10 years. (Ann Int Med 2018 May 1;168) By melvil - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=62875735 • Incidence is going up from 115/100,000 (1980-1989) up to 188/100,000 (2000- 2007) (Am J GastroEnt 2015 Nov;110 (11):1589)

Risk Factors • Increasing age • Constipation ? (arguable) • Low dietary fiber ? (arguable) • Smoking (RR 1.89 95% CI1.14-3.1 for diverticula developing diverticular abscess) • Red meat consumption (RR 1.55 95% CI 1.36-2) • Obesity (BMI <22.5 vs >35 HR 1.42 95% CI 1.08-1.85) • Weight Gain (maintain vs gain >20kg over 20 yrs HR 1.73 95% CI 1.27-2.36) • Lack of exercise • NSAID (Diverticulitis HR 1.72 95% CI 1.4-2.11, Diverticular Bleed 1.7 95% CI 1.21-2.6) • ASA use (Diverticulitis HR 1.25 95% CI 1.05-1.47, Diverticular Bleed 1.7 95% CI 1.21-2.4)

5 Skip the Popcorn and Nuts? • N= 47,288, prospective cohort - men w/o GI diverticula, cancer, or IBD. F/u every 2-4 years x 18 year. No pre-study colonoscopy

• 801 (1.7%) developed Diverticulitis, 383 (0.8%) had diverticular bleeding. • Popcorn helped! (HR 0.72 95%CI 0.56-0.92) • Nuts might help (HR 0.8 95% CI 0.63-1.01) • No association between diverticular bleed and intake of nuts, corn, popcorn (Except to help, maybe) No significant association of seeded berries, (strawberries, blueberries) and diverticulitis and diverticular bleeding

Nut, corn, and popcorn consumption and the incidence of diverticular disease. Strate LL1, Liu YL, Syngal S, Aldoori WH, Giovannucci EL.JAMA. 2008 Aug 27;300(8):907-14. doi: 10.1001/jama.300.8.907.

Diverticulosis: Cause

• Abnormal colonic motility • Things that might affect development of diverticulitis • Alterations in colonic wall resistance • Obstruction of • Increased intraluminal diverticula pressure • Stasis • Dietary deficiencies (fiber) • Alterations of local • Colonic defect bacteria flora

• Ischemia

6 Case #1

• 67 y/o female with known diverticulosis on colonoscopy 5 years ago. Presents with left lower quadrant ab pain 7/10, mildly distended abdomen but still passing gas, able to take po • PE T-100.0 F, HR 95, RR 12 BP 145/63, Pox 99% RA • LLQ tenderness, no rebound, no palpable mass, otherwise exam normal https://commons.wikimedia.org/wiki/File:Oprah_Winfrey_at_2011_TCA_2.jpg

7 Poll Question 1 Most likely diagnosis? 1. Acute diverticulitis 2. Complicated acute diverticulitis 3. Symptomatic Uncomplicated Diverticular Disease 4. Rectal abscess 5. Stercoral ulcer

Most Likely Diagnosis • No fever, able to take po, vitals stable, known diverticulosis, isolated LLQ pain, so not complex • nothing to suggest complicated • SUDD more chronic in nature • Sterocoral ulcers caused by long term constipation in elderly, may be asymptomatic

8 History • Do you have diverticulosis? (colonoscopy or CT Exam) • Left sided tenderness (76-98% specific, 22%-65 sensitive (Asian descent with much higher right sided diverticulitis so symptoms may present on right side))

• Fever +/-, N/V, diarrhea, constipation, poor po intake, illness, dysuria, anorexia, abdominal distention, decreased bowel sounds, dysuria

Complicated Diverticulitis

• Tender or palpable rectal mass, rebound tenderness, rigidity, absence of bowel sounds

• Tachycardia and hypotension, (orthostatic), fever Surgery as gold standard) (only asking diverticulitis)Br Med J 1972; 3: pp. 393-398 ., Ann Surg 2011; 253: pp. 940-946 Evidence Base Physical Exam Steve McGee 445-456),Ann Coloproctol 2017 Oct;33(5):178

Physical Exam

• Vitals- Tachycardia? Hypotension?

• Mucous membranes dry? Moist?

• Tachycardia, tachypnea?

• Ab exam: Isolated LLQ tenderness, rebound tenderness, bowel sounds

• Rectal exam- tenderness, mass?, blood?

9 • (Am Fam Phys 2013 may 1:87(9):612-20.)

Differential Diagnosis

• GI: appendicitis, inflammatory bowel, colorectal cancer, colonic spasm, gastroenteritis, hernia, ischemic colitis, acute or chronic pancreatitis, peritonitis from other cause, small bowel obstruction, IBS • Gynecologic: ectopic pregnancy, ovarian abscess, cyst, cancer, torsion, pelvic inflammatory disease • Urologic: cystitis, nephrolithiasis, UTI

10 Poll Question 2 Next step workup?

1. It’s a clinical diagnosis, no further workup needed 2. CBC, UA, Plain Ab Xray 3. CT Abdomen Pelvis 4. Colonoscopy

So Are Your Symptoms Mild? • Able to tolerate PO, no signs or Peritonitis, or other complications. You may be ok to clinically diagnose. Test that may be useful: CBC, UA, Ab X-rays Grade 1C • If you have more severe symptoms, a CT is warranted. • Colonoscopy- immediately increases risk of perforation. Potentially helpful 6 weeks later

• (Am Fam Phys 2013 may 1:87(9):612-20.) , American society of Colorectal surgeons. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014 Mar;57(3):284-94

11 Severe Symptoms

• Peritonitis • Rebound tenderness, rigidity, lack of bowel sounds • Tachycardia & Hypotension (sepsis), lactic acidosis • Fever • Illeus • Worsening abdominal pain • Rectal bleeding, rectal mass

What Labs are Helpful?

• CBC-infections, blood loss • UA- rule out UTI as a cause • CRP (>50 +LR 2.2, - LR 0.4)/ESR higher correlates with more severe diseases- inflammation • Lactate • CMP- electrolyte abnormalities, renal Marta D, behind the lab work, Wiki commons • Fecal calprotectin?

12 Poll Question 3

Have you heard of Fecal Calprotectin?

•Yes •No

Fecal Calprotectin

• Measures of calprotectin in stool • Indicates a migration of neutrophils to intestinal mucosa as seen with intestinal inflammation • So inflammatory bowel disease, colon cancer, infectious colitis, celiac, necrotizing enterocolitis and diverticulitis! • Not IBS, not diverticulosis • Chronic NSAID use can give false positives

13 The Imaging Exam

• X ray reasonable 1st step - free air, ileus, pneumoperitoneum, bowel obstruction, soft tissue density (abscess) • 1st choice advanced imaging = computerized tomography (Low-dose unenhanced = IV contrast, Level 1 evidence). Eur Radiol. 2008;18(11):2498-2511. • CT - 94% Sensitivity (95%CI: 87%-97%) • Ultrasound - 92% Sensitivity (95% CI: 80%-97%) • What does ultrasound miss? = misses free air, abscess; obesity & bowel gas can obscure images • Good for use in pregnant women

• MRI? 94 Sensitivity 88 Specificity -LR 0.07(delay of care, cost). Dis Colon Rectum. 2008;51(12):1810-1815.

14 By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15376348

By Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12358638

Management: Medical Treatment

• Determine complicated vs uncomplicated

• Inpatient vs Outpatient treatment • Mesalamine • Antibiotics • Probiotics • Alternative tx

15 Case #2 • 65 y/o male with worsening, LLQ ab pain, rebound tenderness on exam, minimal bowel sounds, vomiting, unable to maintain po intake • vitals T 102, HR 110, BP 150/90, RR 16, POx 98% • WBC=18, CRP 25, lactate 3.4 improved to 1.2 with fluids • CT- descending colon with thickened fascia and fat stranding, no free air

https://commons.wikimedia.org/wiki/File:Arnold_Schwarzenegger_-_2019_(33730956438)

Poll Question 4 What’s your plan? 1. Outpatient- clear liquids, ciprofloxacin, metronidazole, f/u in 2 days 2. Inpatient- medical floor, NPO, fluids, observation 3. Inpatient- medical floor, NPO, fluids, piperacillin-tazobactam 4. Inpatient- medical floor, NPO, fluids, piperacillin-tazobactam, surgery consults for possible colectomy 5. Inpatient- ICU, NPO, fluids, pressure support, meropenem

16 General Principles of Treatment • Diet- outpatient, clear liquids x 2-3 days, inpatient NPO • Antibiotics • Pain Management

Outpatient Antibiotics • trimethoprim-sulfamethoxazole 160/800mg po bid + metronidazole 500mg po q6-8hr • ciprofloxacin 750 mg po bid + metronidazole 500mg orally every 6-8 hrs • levofloxacin 750 mg po qday + metronidazole 500 mg po q6-8 hr • amoxicillin-clavulanate 875-125mg po q12hr • moxifloxacin 400 mg po q12

17 Inpatient Abx

• piperacillin-tazobactam 3.375g IV q6hr or 4.5 q8hr

• ticarcillin-clavulanate 3.1g IV q6hr

• ertapenem 1g IV q24hr

• moxifloxacin 400mg IV q24hr

ICU/Severe Symptoms Abx

• imipenem-cilastatin 500 mg IV q 6hr • meropenem 1 gr iv q24hrs • doripenem 500 mg IV q8hr

18 How Good is Inpatient vs Outpatient Tx? • RCT, N=131 acute uncomplicated diverticulitis confirmed by CT scan

• OP amoxicillin-clavulanate 875/125q8 or ciprofloxacin 500q12+ metronidazole 500mg q8hr if penicillin allergy

• Inpatient IV abx + fluids, x >36-48hrs and oral feeds tolerated

• OP readmitted OP 4.5% vs IP 6.2%

• No death or surgery in either group Ann Surg 2014 Jan 259(1):38 (Level 1)

• Failure of OP treatment in 6% pt (retrospective cohort n=693, tx failure return to ER or admission)

Does All Diverticulitis Need Abx? • N=623 RCT, uncomplicated diverticulitis (no fever, no free air on CT) admitted. IV Abx vs IV saline x 5 days

• At 5 days no difference in abdominal pain, temperature, or abdominal tenderness

• At 1 year, no difference in mean hospital stay, perforation, abscess(3 abscess in no abx group vs 0 in abx p=0.8), recurrent diverticulitis, or hospital readmission

• AGA-selective and not routine abx use in uncomplicated diverticulitis (low quality evidence) ASCRC- usually recommends oral or IV abx

• Is diverticulitis just inflammatory vs infectious? Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis Colorectal Dis 2011; 12(Suppl S3): 1

19 How Good Are Abx? • SR of 2 RCT’s, 5 cohorts, 1 case control. (n=2469) acute uncomplicated diverticulitis • 32% abx, 68% no abx • Major complications 20.2% vs 17.7 essentially the same in each group • treatment failure 4.5% vs 2.1% • reoccurrence 13.3vs 11.5 • abscess 1% in both groups • perforation 1% • surgery 2% • emergent surgery 1% (Am J Surg 2108 Sep;216(3):604)

How Good are Abx?

• Antibiotics-Don’t reduce complications or reoccurrence in patients with uncomplicated left-sided diverticulitis. (Br J Surg 2012 Apr: 99(4);532)

• Antibiotics – may not decrease time to recovery in patients with acute uncomplicated left sided diverticulitis. BR J Sure 2017 Jan;104(1);52

20 Initial Abscess Management

• Percutaneous drainage of abscess recommended 1st line for stable patients with large diverticular abscess • Not associated with increased risk of reoccurrence

• Avoids all the surgical risk (Am Fam Physician, 2013 Mya 1:87(9):612)

By https://wellcomeimages.org/indexplus/obf_images/1d/68/995a100f086bc56ab0509abba5c4.jpgGallery: https://wellcomeimages.org/indexplus/image/V0011083.htmlWellcome Collection gallery (2018-03-21): https://wellcomecollection.org/works/s9k57emj C CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36460364

Who Needs Urgent Surgical Management?

• Acutely ill, septic, multi quadrant peritonitis- CT abd & consult surgery • Consider in failed medical management, evidence of fistula, phlegmon, or fistula • How good is your interventional radiology? • High risk patients -organ transplant, chronic steroid use, immunosuppression, chronic renal failure, collagen, vascular disease

• Younger Patients (overall relative risk is low) Hospitalization for acute diverticulitis does not mandate routine elective colectomy. Arch Surg. 2005 Jun;140(6):576-81; discussion 581-3.)

21 Everyone is All Better, Now What? •Fiber to prevent? •Surgery to prevent? •Persistent

By The U.S. Food and Drug Administration - Kids ‘n Fiber, Public Domain, symptoms (SUDD) https://commons.wikimedia.org/w/index.php?curid=33628084

Does High Fiber Help With Symptom Reduction? • AGA recommends fiber for prevention but recommends consideration of patient preference since there is no good studies to show benefit and can have side effects of bloating

• Review of 3 RCT’s 9 (n=124) and 1 case control (n=56). • May reduce pain • 2 prospective cohorts show reduced risk of diverticular disease • n=47,888, 387 incident cases, increase in total dietary showed decrease diverticular disease

• n=47,033, 812 incident cases, decreased risk of disease in vegetarian diet (RR 0.69 95% CI 0.55-0.86 vegetarian diet, higher dietary fiber (RR 0.59, 95% CI 0.46-0.78)

22 Does High Fiber Prevent Diverticulosis? • N=539 match to 1569 controls. Constipation and dietary habits collected before colonoscopy. • Constipation was NOT associated with an increased risk of diverticulosis. • Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40–0.80).

• Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55–1.02). • There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59–1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61–1.20).

• We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71–1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). Clin Gastroenterol Hepatol. 2013 Dec; 11(12): 10.1016/j.cgh.2013.04.048.

Case #3: Who Needs Surgical Management?

62 y/o male admitted with diverticulitis confirmed on CT. Initial fevers, WBC 25, never septic, abscess in pelvis drained by IR. Abx piperacillin-tazobactam 3.375g IV q6hr x 5 days, symptoms resolved

By Gaspare Traversi - August Bernhard Rave (Hrsg.): "Gaspare Traversi. Heiterkeit im Schatten". Ausstellungskatalog, StaatsgalerieStuttgart 2003. Hatje Cantz Verlag. ISBN 3-7757- 1354-9., Public Domain, https://commons.wikimedia.org/w/index.php?curid=5993694

23 Poll Question 5

Should this patient get surgery for prevention of possible reoccurrence?

• Yes • No

Should We Cut to Prevent? • After 1 uncomplicated episode, risk of 2nd episode being complicated = 5% over 8 years • Baseline risk 13-19%, risk of recurrence over 9-16 years • Of those 13-19%, only 4.7% had >1 episode • Urgent surgery estimated in 1 in 2000 pt/yrs

24 Surgical Management

• Elective sigmoid colectomy should be considered on a case by case basis (ASCRS grade 1B)

• Elective sigmoid colectomy after recovery from uncomplicated acute diverticulitis is discouraged but decisions should be individualized (AGA)

• Pt’s with >2 episodes don’t have increased mortality • Factors to consider- severity of attacks, smoldering disease, potential for poor outcomes, medical needs of patient

• Elective resection may reduce risk of recurrence (level 2) n=107 RCT 26 elective resection, 81 non operative, 36 month followup

• Recurrent diverticulitis at 24 months 8% in operative group vs 32% in non operative (p=0.019, NNT 5) Br J Surg 2018 Jul; 105(8):971

I Still Hurt! Is It SUDD? • Symptomatic Uncomplicated Diverticular Disease (SUDD)- known diverticulosis, >24 hour pain, bloating, usually in iliac fossa, not relieved with bowel movement • IBS -generalized pain vs SUDD -left iliac fossa • IBS -diarrhea/constipation vs SUDD -diarrhea • IBS -pain relieved defecation or flatulence vs SUDD - pain not relieved • Fecal calprotectin- ?

25 Fecal Calprotectin (FC)

• Case control study, N=48, Endoscopically diagnosed diverticular disease;16 asymptomatic, 16 with SUDD, 16 acute uncomplicated diverticulitis, vs 16 IBS patient without diverticulosis and 16 healthy controls

• <15=neg; 16-60=inflammation; >60 high grade inflammation

• no significant difference in FC concentrations among IBS group (100% < 15), asymptomatic diverticulosis group (95% <15), and healthy controls (100% <15)

• in SUDD group, FC concentrations were 15-60 mcg/g in 90%, (< 15 mcg/g in 5%, and > 60 in 5%)

• elevated fecal calprotectin concentration appears to distinguish symptomatic diverticular disease (DD) from both asymptomatic diverticulosis and irritable bowel syndrome.

• after 8 weeks of treatment (mesalazine/rifaximin for 10 days followed by mesalazine alone for 8 weeks), FC concentrations decreased to normal values in both SUDD (p < 0.005 compared to baseline) and acute uncomplicated diverticulitis (p < 0.0005 compared to baseline) Int J Colorectal Dis 2009 Jan;24(1):49

Fecal Calprotectin (FC)

• Cohort study, n=42 with Symptomatic Diverticular disease (SUDD) vs N=30 diverticula + abdominal pain (D+AB) suggestive of IBS based on ROME III

• Diverticula endoscopically conformed in all patients • Postive Fecal Calprotectin 64.3% SUDD vs 0% D+AB • Higher Fecal Calprotectin correlated with increased pain in Diverticulitis, and larger segment involvement.- J Clin Gastroenterol 2015 Mar;49(3):218

• Can Mesalamine treat Diverticulitis

26 SUDD:Tx • Fiber supplementation is inconsistent in benefit • Probiotic- some studies show benefit, however systematic review unable to be done due to poor heterogeneity of strain choices. (J gastrointestinal Liver Dis. 2016 Mar, 25 (1):79- 86)

• Rifaximin- Beneficial 64% vs 34% placebo showed improvement at a 1 year

(29% pooled rate difference 95% CI 24.5-33.6) NNT=3 (aliment Pharmacol There 2013 Apr;37(7):680)

• Dosing 400 mg po bid x 7-10days a month x 3 months • Mesalamine- not helpful in diverticular flairs but was more helpful than Rifaximin in SUDD

• RCT n=268, Mesalamine greater reduction in Global symptom score vs

rifaximin (Dig Dis Sci 2007 Nov;52(11):2934)

Should an Acute Attack Be Followed by a Colonoscopy? • Probably if > 1 year after last scope • Wait 6 weeks (increased risk of perforation immediately)

• Increased risk of colon cancer (OR 25 95% CI 17-38) diagnosed within 6 months of a bout of diverticulitis. Diverticular Disease and the risk By Joachim Guntau (=J.Guntau) - Endoskopiebilder.de, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=66176561 of colon cancer- a population-based case control study. Aliment Pharmacol There 2011:;34:675-681.

27 Practice Recommendation: Prevention • Nuts, seeds and popcorn do not cause diverticulitis and may help prevent it • Fiber is of unsure benefit at preventing diverticular formation

Practice Recommendation: Diagnosis • Don’t assume diverticulitis unless you know they have diverticula • Isolated LLQ pain with a history of diverticula a good start to a diagnosis • Suggested workup includes WBC, UA, CXR • CT best study to assess severity but MRI and ultrasound can be used in the right settings

28 Practice Recommendation: Treatment • Outpatient antibiotics in mild diverticulitis • Moderate to severe cases admitted to the hospital • IR drainage of abscess 1st choice before surgery • Surgery reserved for severe life-threatening cases, failed antibiotics and/or IR drainage

Practice Recommendation: Follow-up • Colectomy eval on a person to person basis, surgery for prevention no longer standard recommendation • 5% chance of a second flare • 6 weeks after attack consider a colonoscopy in those who haven’t been screened in the last year. Much higher risk of finding colon cancer.

29 Practice Recommendation: The Times Are a-Changing!

• Antibiotics may not improve outcomes in mild to moderate cases • Fiber may not help prevent new cases • SUDD- Symptomatic Uncomplicated Diverticular Disease • Fecal calprotectin- newer test that can help differentiate between inflammatory and non inflammatory conditions

Question Based Diverticulitis? • Does fiber work, help, cure or prevent new diverticulitis? Unproven • Is history and physical exam enough for diagnosis? Maybe • Does everyone need a CT to confirm? No • Who has to be admitted and who can be outpatient? Mild vs Severe • Do I have to use antibiotics to treat, and if so, which are the best choice? For right now lean yes, but this may change. • Should patients get a colectomy after a severe case of diverticulitis? No • Does colonoscopy have any role in diverticulitis? Yes • Is there such a thing as chronic diverticulitis? Yes, SUDD

30 Other References • Diverticulitits Dynamed Plus

• Diverticulitis American Family Physician May 2013

• Clin Colon Rectal Sure 2018 Jul 31(4):209

• Clinc Gastro and Hepatology December 2013 Volume 11, Issue 12, Pages 1622–1627

• Am J Gastroenterol. 2017;112(12):1868

• Gastroenterology 2011 May 140(5): 1427

• Gastroent 2018 Jul 155(1);58-66

• Gastroent 2018 Jul 155(1);58-66)

• Gastroenterology 2011 May;140(5): 1427

• Clinc Jnl of Gastro and Hep December 2013Volume 11, Issue 12, Pages 1532–1537

Contact Information

• Justin Bailey

• [email protected]

31 Questions

32 Gallbladder Disease

Joel Heidelbaugh, MD, FAAFP, FACG

ACTIVITY DISCLAIMER

1 DISCLOSURE

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

Joel Heidelbaugh, MD, FAAFP, FACG

Clinical Professor, Departments of Family Medicine and Urology/Director of Medical Student Education and Clerkship Director, Department of Family Medicine/Director, Patients and Populations Branch, University of Michigan Medical School, Ann Arbor

Dr. Heidelbaugh is a family physician who has 20 years of academic teaching experience. His specialty topics include gastrointestinal disorders, men's health, and primary care urology. He is a member of the American Gastroenterological Association guideline panels for irritable bowel syndrome, inflammatory bowel disease, and Lynch syndrome. He is the co editor and co author of the textbook ROME IV: Functional Gastrointestinal Disorders for Primary Care and Non GI Clinicians, published through the Rome Foundation. In addition, he is the consulting editor of Primary Care: Clinics in Office Practice and the president elect of the American Society for Men's Health. Dr. Heidelbaugh believes that increasing awareness and education about gastrointestinal and men's health issues is an important trend in medical education, clinical practice, and research.

2 Learning Objectives

1. Recognize the signs and symptoms of common gallbladder diseases (Cholecystitis, Choledocholithiasis, and Cholangitis).

2. Apply the treatment algorithm for patients with suspected biliary cause of GI symptoms.

3. Discuss the diagnostic criteria for common gallbladder diseases.

4. Compare the diagnostic characteristics of imaging modalities for common gallbladder diseases.

5. Discuss the severity grading of acute cholangitis and treatment options based on grade of severity.

Audience Engagement System Step 1 Step 2 Step 3

3 Professional Practice Gaps

• Motility disorders of the biliary tree (e.g. biliary dyskinesia - gallbladder dysfunction, sphincter of Oddi dysfunction) are difficult to diagnose and treat • Early laparoscopy cholecystectomy (CCY) (within 1 week of symptom onset) for uncomplicated acute GBD is safe • Survey data demonstrates early laparoscopic CCY is performed only by a minority of surgeons • Controversy exists in the literature regarding criteria that should be used to select patients for CCY

Professional Practice Gaps

• Approximately 85% of patients with suspected GBD have relief following (laparoscopic) CCY • This is a much lower rate than a reported success rate of ~100% following lap CCY for known GBD • The current literature is lacking regarding universally accepted criteria for selecting which patients with GBD for potential surgical intervention • Family medicine residents may not be receiving adequate point-of-care ultrasound training to adequate diagnose GBD

4 Source: WebMD / https://www.webmd.com/digestive-disorders/ss/slideshow-gallbladder-overview

Source: WebMD / https://www.webmd.com/digestive-disorders/ss/slideshow-gallbladder-overview

5 Epidemiology • 10-15% of adult population • 20-25 million Americans annually • $6.2 billion annually • Healthcare burden increased > 20% in last 3 decades • 1.8 million ambulatory care visits yearly • Leading cause of hospital admissions due to GI disease • Data likely underestimated as lap CCY is often a same-day procedure and not captured in hospital admission data • Mortality rate in patients with GBD is < 0.6% • Data is over a decade old…

Stinton LM, et al. Gut Liver 2012;6(2):172-187.

Epidemiology • 80% of patients with gallstones will never experience biliary pain or complications • Acute cholecystitis, cholangitis, pancreatitis • Often discovered incidentally on US or CT • Only 10-20% of asymptomatic patients will become symptomatic with 5-20 of diagnosis • 2% per year will develop symptomatic gallstones • Fatality rates have decreased at greatest rate of any GI disease, from > 5,000 deaths in 1950 to 1,092 in 2004

Stinton LM, et al. Gut Liver 2012;6(2):172-187.

6 Poll Question 1

Which of the following represents the most common type of gallstone? 1. Pigment stones 2. Protein stones 3. Calcium carbonate stones 4. Cholesterol stones 5. Mixed stones

Systematic Classification of Gallstones

• 8 types, over 10 subtypes - (807) • Cholesterol stones (297 / 37%) • Pigment stones (217 / 27%) • Calcium carbonate stones (139 / 17%) • Mixed stones - 2 or more subtypes (129 / 16%) • Phosphate stones (12) • Calcium stearate stones (9) • Protein stones (3) • Cystine stones (1)

Qiao T, et al. PLoS One 2013;8(10):e74887.

7 Systematic Classification of Gallstones

• Cholesterol stones • Cholesterol content > 70% • Pigment stones • Cholesterol content < 30% • Mixed stones • Cholesterol content 30-70%

Qiao T, et al. PLoS One 2013;8(10):e74887.

Source: WebMD / https://www.webmd.com/digestive-disorders/ss/slideshow-gallbladder-overview

8 9 Risk Factors

• Family history • Alcoholic cirrhosis • Female gender • Bariatric surgery • Increasing age • Diabetes mellitus • Limited physical activity •Diet • Dyslipidemia • High in calories • Estrogens / OCPs • High in carbohydrates • Hyperinsulinemia • High in saturated fats • Metabolic syndrome • Low in fiber • Total parental nutrition • Multiparity •Race • Obesity (BMI > 30) • Mexican Americans • Pregnancy • Chilean • Rapid weight loss / cycling • Pima Indians

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Diagnosis - Clinical Presentation

• Biliary colic / acute RUQ pain / epigastric pain +/- fever & chills • Usually steady pain, moderate to severe • May start abruptly, without fluctuation • Pain usually peaks within an hour • Not relieved by meal, bowel movement • Pain may resolve as stone dislodges • If pain escalates or doesn’t quickly resolve - - -> suspect complications • Over 90% of patients with first episode of biliary colic have an episode of recurrent pain within 10 years; 2/3 within 2 years

Wittenburg H. Best Pract Res Clin Gastroenterol 2010;24(5):747-756.

10 Epidemiology Review

Assessing the value of performing a diagnostic test • Positive likelihood ratio • Sensitivity / 1 - specificity • Negative likelihood ratio • 1 - sensitivity / specificity • Sensitivity (true positive) • True positives / true positives + false negatives • Specificity (true negative) • True negatives / true negatives + false positives

Altman DG, et al. Statistics with confidence, 2nd edition. London: BMJ Books, 2000.

Poll Question 2

Which of the following clinical findings has the highest positive likelihood ratio to suggest gallstones? 1. Fat intolerance 2. Tenderness of upper abdomen 3. Use of analgesics 4. Pain radiating to the back 5. Biliary colic

11 Diagnosis - Clinical Findings

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Poll Question 3 Which of the following clinical findings has the highest sensitivity to suggest acute cholecystitis?

1. Right upper quadrant pain 2. Palpable gallbladder 3. Murphy’s sign 4. Fevers 5. Chills

12 Diagnosis - Clinical Findings

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Complications of Gallstones Acute calculous cholecystitis • 1/3 of all surgical emergency hospital admissions • Accounts for 14-30% of CCY in many countries • Second most common source of intra-abdominal infection • Increase LFTs, WBC, +/- fevers, chills Obstructive cholangitis due to choledocholithiasis • Gallstones become stuck in common bile duct • Bile backs up into the liver • RUQ pain, jaundice • Increase LFTs, WBC • Can lead to gallstone pancreatitis Gallstone pancreatitis • Increase LFTs, amylase, lipase • Best identified on CT; small stones best seen on US Gomes CA, et al. World J Gastrointest Surg 2017;9(5):118-126. Baiu I, at al. JAMA 2018;320(14):1506.

13 Poll Question 4

Which of the following is the recommend initial modality to detect gallstones and acute calculous cholecystitis? 1. Plain film abdominal radiograph 2. Ultrasound 3. Abdominal CT 4. Abdominal MRI 5. Hepatobiliary iminodiacetic acid scan

Diagnostic Evaluation

Abdominal (plain film) radiography • Will not demonstrate gallbladder or offending pathology • Useful to exclude other causes of abdominal pain • Perforation (free air under diaphragm) • Constipation (significant fecal loading) • Obstruction (dilated bowel) • Stones (e.g. renal) • Pancreatitis (e.g. chronic calcifications)

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

14 Diagnostic Evaluation

Ultrasonography • Sensitivity > 98% / Specificity > 95% for gallstones • False negative rate 1-4% • Inexpensive, noninvasive • Excellent determination of anatomy and pathology • Gallstones • Acute cholecystitis • Polyps • CBD diameter • Parenchymal hepatic abnormalities

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

radiopaedia.org

15 Diagnostic Evaluation

Hepatobiliary iminodiacetic acid (HIDA) scan • Sensitivity 97% / Specificity 77% for acute cholecystitis • Normal findings rule out acute cholecystitis • Visualize biliary tree to assess GB function • Can diagnose or rule out biliary dyskinesia • HIDA taken up by liver, excreted into bile • Positive test = failure of HIDA to fill GB 2 hours after injection indicated obstruction of cystic duct

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

www.stritch.luc.edu

16 Diagnostic Evaluation

Magnetic resonance cholangiopancreatography (MRCP) • Sensitivity 97% / Specificity 98% for gallstones • Noninvasive yet expensive • Can identify gallstones anywhere in biliary tract • Reserved when choledocholithiasis is suspected

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Researchgate.net

17 Researchgate.net

Diagnostic Evaluation

Endoscopic retrograde cholangiopancreatography (ERCP) • Sensitivity 85-87% / Specificity 100% for determining normal biliary system, bile duct obstruction, and choledocholithiasis • 94% effective for stone removal • Success depends upon endoscopist • Diagnostic and therapeutic • Usually performed with endoscopic retrograde sphincterotomy and gallstone extraction

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

18 Researchgate.net

Algorithm for Management of Gallstones

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

19 Algorithm for Management of Gallstones

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Treatment Options

• Expectant management • Surgery - laparoscopy CCY • Oral dissolution therapy • Extracorporeal shock wave lithotripsy • CCY with natural orifice trans luminal endoscopy • Percutaneous CCY • Peroral endoscopic GB drainage

Abraham S, et al. Am Fam Physician 2014;89(10);795-802; Baron TH, et al. NEJM 2015;373:357-365.

20 Expectant Management

• For incidental findings of gallstones in an asymptomatic patient, no medical therapy is required • For asymptomatic pigmented or calcified gallstones, no medical therapy is required • Dietary and lifestyle strategies to prevent further stone formation should be discussed • Advise against rapid or substantial weight loss if possible

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Expectant Management - Exceptions • GB calcification (porcelain gallbladder) • High risk of GB cancer • Hemolytic anemia • High risk of forming calcium bilirubinate stones • Large gallstones (> 3 cm) • High risk of GB cancer • Morbidly obese patient undergoing bariatric surgery • High risk of becoming symptomatic during rapid weight loss • Awaiting transplant • High risk of developing sepsis due to immunosuppression • Small gallstones and dysmotility • High risk of pancreatitis

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

21 Indications for Surgery

• Acute cholecystitis • Severe RUQ pain, elevated WBCs • Broad-spectrum antibiotic therapy • Biliary dyskinesia • CBD complications • Gallstones - symptomatic, asymptomatic

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

Contraindications to Surgery

Absolute • GB cancer • Inability to tolerate general anesthesia • Uncontrolled coagulopathy Relative • Advanced cirrhosis / liver failure • Coagulopathy • Peritonitis • Previous upper abdominal surgery • Septic shock • Severe acute peritonitis

Abraham S, et al. Am Fam Physician 2014;89(10);795-802.

22 Oral Dissolution Therapy • For patients with cholesterol-containing gallstones, oral dissolution therapy may be an option • Symptomatic patients who are not candidates for surgery or with small gallstones (< 5mm) in a functioning gallbladder with a patent cystic duct • Ursodeoxycholic acid, chenodeoxycholic acid • Decrease hepatic secretion of biliary cholesterol • Cause formation of unsaturated bile • Promote dissolution of cholesterol crystals and gallstones • Success rates 65-90% (+/- EWSL) • Recurrence rate > 50% after 6-12 months • Fewer than 10% of patients with gallstones are candidates

Pereria SP, et al. Dig Dis Sci 1997;42(8):1775-1782.

Extracorporeal Shock Wave Lithotripsy • Can be considered when surgery is not possible • Noninvasive yet not always available • Risk of adverse effects • Biliary pancreatitis • Liver hematoma • Difficult to achieve complete ductal clearance due to size and position of gallstone(s) • Some data suggests ESWL for large pancreatic and common bile duct stones followed by ERCP have results comparable to lap CCY for pain and duct clearance

Tandan M, et al. World J Gastroenterol 2011;17(39):4365-4371.

23 Severity Grading of Acute Cholangitis - Tokyo Guidelines 2018

https://www.mdcalc.com/tokyo-guidelines-acute-cholangitis-2018

Poll Question 5

Which of the following is a mechanism that contributes to gallstone formation during rapid weight loss? 1. Diet of 1600 kcal/day 2. Decreased bile salt production 3. Decreased bile stasis 4. Decreased cholesterol saturation 5. Enhanced gallbladder motility

24 Rapid Weight Loss and Formation of Gallstones

• Very low calorie (500 kcal/day) vs. low calorie diets (1200-1500 kcal/day) • Incidence correlated with calorie restriction and duration of diet • Faster weight loss = higher associated risk • Supersaturation in GB • Decreased bile salt production • Increased bile stasis • Increased cholesterol saturation • Impaired GB motility - reduced GB stimulation due to low-fat diet • Bile composition normalized following reduction in body weight • Increased risk of gallstones 15-25x higher than general population

Johansson K, et al. Int J Obesity 2014;38:279-284. Weinsier RL, et al. Obes Res 1993;1(1):51-56.

Prevention of Gallstones

• Eat regularly - don’t skip meals • Whole grains and fiber • Vegetarian ? Fruits, vegetables, nuts • Maintain ideal weight • Limit fried and fatty foods - use unsaturated oils • Berries, kiwi, melons, • Avoid crash diets, rapid weight cycling, “cleanses” • Alcohol (in moderation…) • HYDRATE WITH PLENTY OF WATER

25 Etiologies of Long-term Post-Cholecystecomy Symptoms

• CCY did not relieve symptoms in ~ 40% of patients • Psychological distress - 16-58% • Visceral hyperalgesia, functional GI symptoms, somatization • Coexistent diseases - 1-65% • GERD, PUD, hiatal hernia, constipation • Newly formed gallstones, retained CBD stones/sludge - 0.2-23% • Usually self-limiting, may require additional therapy • Sphincter of Oddi dysfunction - 3-40% • Usually due to interrupted neural pathways between duodenum, gallbladder and Sphincter of Oddi leading to sphincter spasm • Surgical complications - 1-3%

Latenstein CSS, et al. Gastroenterol Res Pract 2019 Apr 14;2019:4278373.

Practice Recommendations

• Ultrasonography is an appropriate initial imaging study in persons with suspected gallstones or complications of gallstones [SOR C] • Expectant management is the best approach for patients with incidentally detected, asymptomatic gallstones [SOR B] • Laparoscopic cholecystectomy remains the standard treatment for gallstones when possible [SOR A] • Antibiotic prophylaxis is not required in low-risk patients undergoing elective laparoscopic cholecystectomy [SOR A] • When indicated, laparoscopic cholecystectomy can be safely performed during any trimester of pregnancy [SOR C]

26 Contact Information

• Joel Heidelbaugh • [email protected]

Questions

27 Key References • Abraham S, et al. Surgical and nonsurgical management of gallstones. Am Fam Physician 2-04;89(10):795-802. • Baiu I, et al. Choledocholithiasis. JAMA 2018;320(14):1506. • Gomes CA, et al. Acute calculous cholecystitis: review of current best practices. World J Gastrointest Surg 2017;9(5):118-126. • Wittenburg H. Best Pract Res Clin Gastroenterol 2010;24(5):747-756. • Sankarankutty A, et al. Uncomplicated acute cholecystitis: early or delayed laparoscopic cholecystectomy? Revista do Colegio Brasilerio de Cirurgioes 2012;39(5):436-440. • Latenstein CSS, et al. Etiologies of long-term postcholecystectomy symptoms: a systematic review. Gastroenterol Res Pract 2019 Apr 14;2019:4278373.

28 Gastroesophageal Reflux Disease: Evidence-Based Approach

Joel Heidelbaugh, MD, FAAFP, FACG

ACTIVITY DISCLAIMER

1 DISCLOSURE

All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose.

The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices.

Joel Heidelbaugh, MD, FAAFP, FACG

2 Learning Objectives

1. Distinguish between gastroesophageal reflux, dyspepsia, or GERD in patients who present with typical and atypical symptoms.

2. Screen patients with asthma for symptoms of GERD.

3. Educate parents of infants and children with GERD or dyspepsia on effective feeding strategies and safe medication use.

4. Select appropriate imaging studies to confirm the diagnosis of GERD from dyspepsia and appropriately interpret test results for patients.

5. Develop collaborative treatment plans for patients with GERD or dyspepsia to include lifestyle modifications and effective medication use, and ensure patient compliance with treatment.

Audience Engagement System Step 1 Step 2 Step 3

3 “Thought depends absolutely on the stomach, but in spite of that, those who have the best stomachs are not the best thinkers…”

‐ Voltaire, 1770

Pathophysiology of GERD

• Disorder of excessive acid secretion in the stomach (or is it too little???) – Conventional anti-secretory therapy is aimed at raising gastric pH via decreasing gastric acid production • Transient lower esophageal sphincter relaxations (TLESRs) allow for reflux of gastric contents into esophagus causing a burning sensation – Smoking, alcohol, caffeine, carbonated beverages, large meals, fatty meals, spicy meals, stress, anxiety, depression, etc., etc., etc.

4 Pathophysiology of GERD

• Lower esophageal dysmotility / prolonged relaxation vs. contraction of the esophagus • Visceral hypersensitivity • GERD is differentiated from dyspepsia and peptic ulcer disease: – Intermittent gnawing/aching epigastric pain that may improve with meals – Lack of heartburn and regurgitation – GERD shouldn’t be bloody… – Most common referral to gastroenterology: “refractory GERD”

Dyspepsia • Classically confused with “refractory GERD” – Most common cause of GI referral from primary care • Up to 1/3 of GERD cases don’t have classical symptoms of heartburn and regurgitation - So, how do we know ? • 60% of cases are due to peptic ulcer disease – NSAIDs, ASA (yes, even enteric coated…) – H. pylori, although incidence is decreasing – History of conflicting guidelines with respect to GERD • 40% of cases are due to functional dyspepsia – VERY challenging to treat, may overlap with other diagnoses – No proven effective pharmacotherapy

Talley NJ. Gastroenterology 2005;129(5): 1753-1755.

5 Poll Question 1 Which of the following is a proposed mechanism to explain functional dyspepsia?

1. Delayed gastric emptying 2. Chronic upper gastrointestinal infections 3. Insensitivity to gastric acid 4. Hyperdistensible stomach 5. Decreased acid secretion

Functional Dyspepsia Current Theories for Causality: • Hyperactive acid secretion • Delayed stomach emptying • Stiff stomach that doesn't expand easily to accommodate food • Hypersensitivity to stomach acid or expansion Potential Theories: • Accelerated stomach emptying • Abnormal responses to food by the duodenum • Poor coordination between the upper and lower parts of the stomach • Abnormal processing of internal organ activity by the brain and nerves • Abnormal stomach contractions • Acute or chronic infections • Altered neurohormonal responses to meals

6 Infantile GERD

•“The happy spitter” • Increased amounts of vomiting or persistent projectile (forceful) vomiting - - -> R/O pyloric stenosis • Vomiting fluid that is green, yellow or coffee grounds/blood • Difficulty breathing after vomiting or spitting up • Food refusal that causes weight loss or poor weight gain • Pain related to eating • Difficult or painful swallowing

Acid reflux (GER and GERD) in infants. NIDDK. Available at: https://www.niddk.nih.gov/health- information/digestive-diseases/acid-reflux-ger-gerd-infants, Accessed June 5, 2019.

Infantile GERD - Diagnosis

• “Test and treat” – Histamine-2 receptor antagonists – Proton pump inhibitors – Prokinetics (erythromycin) – Antacids (maalox, gaviscon) – Cytoprotective agents (carafate, cytotec) • Barium swallow or upper GI series • pH probe • Upper endoscopy • Gastric emptying study

Acid reflux (GER and GERD) in infants. NIDDK. Available at: https://www.niddk.nih.gov/health- information/digestive-diseases/acid-reflux-ger-gerd-infants, Accessed June 5, 2019.

7 Infantile GERD - Treatment • Parental education and reassurance! • Smaller, more frequent feedings throughout the day • Change feeding schedules (“discuss with the child's doctor first”) • Elevate the head of the baby's crib or bassinet – DO NOT RECOMMEND BABY SLEEPING PRONE - - -> INCREASES RISK OF SIDS • Hold the baby upright for 30 minutes after a feeding – Burping, special bottles may help • Thicken bottle feedings with cereal (“not without doctor’s supervision”) • Try solid food (“discuss with the child's doctor first”) • Medications (previous slide) • Surgery (fundoplication) Acid reflux (GER and GERD) in infants. NIDDK. Available at: https://www.niddk.nih.gov/health- information/digestive-diseases/acid-reflux-ger-gerd-infants, Accessed June 5, 2019.

Classification and Risk

• NERD (non-erosive reflux disease) – 90+% of cases • Erosive esophagitis – Los Angeles (LA) Classification A - D • Barrett’s esophagus (BE) • Esophageal adenocarcinoma (EAC)

8 Poll Question 2 Which of the following is considered the “gold standard” test for diagnosing GERD? 1. Upper endoscopy 2. Esophageal manometry 3. 24-hr pH probe 4. Barium swallow 5. There isn’t one

Gastroesophageal Reflux Disease. University of Michigan Health System. http://www.cme.med.umich.edu/pdf/guideline/GERD12.pdf

9 Diagnosis • No gold standard test exists for the diagnosis of GERD • EGD is to assess complications; > 50% will be normal! • Presumptive diagnosis of GERD can be established with typical symptoms of heartburn and regurgitation • Consider empiric trial of PPI [SOR A] • Patients with non-cardiac chest pain suspected due to GERD should be investigated and cardiac causes excluded [SOR B] • Barium radiographs should not be performed to diagnose GERD (but may discover complications…) [SOR A] • Upper endoscopy is not required for typical GERD symptoms, but recommended in presence of alarm symptoms and for screening high risk patients [SOR A]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Diagnosis • Routine endoscopic biopsy of distal esophagus is not required to diagnose GERD [SOR B] • Esophageal manometry has no role in the diagnosis of GERD and should only be used for pre-operative evaluation [SOR C] • Ambulatory esophageal reflux monitoring (pH probe) is the only test that can assess reflux symptom association [SOR B] • Ambulatory esophageal reflux monitoring is indicated prior to consideration of surgical therapy, and in evaluation of patients refractory to AST [SOR C] • Screening for H. pylori is not recommended in patients with GERD; treatment is not required as anti-reflux therapy [SOR C]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

10 Diagnosis • An empiric trial of acid suppression therapy for 4 to 8 weeks can identify patients with GERD who do not have alarm symptoms “test and treat” [SORT A] • Acid suppression may be helpful in the evaluation of patients with atypical or extraesophageal manifestations of GERD [SORT B] • Lifestyle modifications should be recommended throughout the treatment of GERD, but there is no evidence-based data to support efficacy (it’s never been randomized…) [SORT C] – Avoid smoking, alcohol, caffeine, fatty meals, spicy or citrus foods – Elevate head of bed 6-8 inches (not just pillows…) – Avoid eating 3-4 hours prior to recumbency Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Alarm Symptoms

• Black or bloody stools • Choking • Chronic cough • Dysphagia • Early satiety • Hematemesis • Hoarseness • Iron deficiency anemia • Odynophagia • Weight loss

Gastroesophageal Reflux Disease. University of Michigan Health System. http://www.cme.med.umich.edu/pdf/guideline/GERD12.pdf

11 Poll Question 3 Which of the following is the most common extraesophageal manifestation of GERD?

1. Asthma 2. Diarrhea 3. Hoarseness 4. Globus sensation 5. Non-cardiac chest pain

Extra-Esophageal Manifestations • Nasopharyngeal • Respiratory – Globus sensation – Asthma (microaspiration) - 82% – Granulomas – Bronchitis – Hoarseness - 78% – Chronic cough – Laryngitis (recurrent) – Interstitial fibrosis –Polyps – Pneumonia – Sinusitis • Cardiac – Sore or burning throat – Chest pain (non-cardiac) - 50% – Throat clearing • Other – Ulcerations – Dental erosions – Halitosis

Gastroesophageal Reflux Disease. University of Michigan Health System. http://www.cme.med.umich.edu/pdf/guideline/GERD12.pdf

12 Pharmacologic Treatment

• H2-receptor antagonists (H2RAs), PPIs, and prokinetics have proven efficacy in the treatment of GERD [SORT A] • PPI’s should be taken 30 – 60 minutes prior to a meal (the first meal of the day) to optimize effectiveness [SORT B] • Non-erosive reflux disease (NERD): – Step-up (H2RAs followed by a PPI if no improvement) and step-down (PPI followed by the lowest dose of acid suppression) therapy are equally effective for both acute treatment and maintenance [SORT A] – Step-down therapy (transitioning from a twice daily or once daily PPI to the least potent and lowest effective dose of anti-secretory therapy) has not been shown to change the natural history of GERD-related disease but may decrease pharmacy costs [SORT B]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Pharmacologic Treatment • Documented Erosive Esophagitis: – Initial PPI therapy is the treatment of choice for acute and maintenance therapy for patients with documented erosive esophagitis [SORT A] • Pharmacy costs for step-down treatment are mainly medications, while step-up treatment requires more frequent endoscopy [SORT A] • On demand (patient-directed) therapy is the most cost- effective strategy [SORT A]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

13 Lifestyle Modifications [SORT C]

• Avoid spicy, fatty, citrus foods • Avoid acidic and carbonated beverages • Avoid smoking, alcohol, caffeine, chocolate • Avoid large meals • Elevate head of bed 3-4 inches • Avoid recumbency 3-4 hours after eating • Avoid tight clothing around waist

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Treatment for Atypical GERD

• Aggressive acid reduction using PPIs twice daily before meals for three to four months is the standard treatment for atypical GERD and may be the best way to demonstrate a causal relationship between GERD and extraesophageal symptoms [SORT B] • Randomized trials have not shown significant benefit for twice daily treatment with a PPI for laryngeal symptoms [SORT B]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

14 Treatment for Atypical GERD

• In patients with moderate to severe persistent asthma and symptoms of GERD, BID PPI therapy for 24 weeks reduces: – Asthma exacerbations and improves quality of life – Does not reduce symptoms, albuterol use, or pulmonary function [SORT B] • Patients with chronic cough have a high likelihood of GERD and should be prescribed a trial of antisecretory therapy, even when they have no reportable GI symptoms [SORT B] • PPI therapy reduces symptoms of noncardiac chest pain and may be useful as a diagnostic test in identifying abnormal esophageal reflux [SORT B]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Richter JE. Aliment Pharmacol Ther 2005;22(suppl 1):78.

15 Surgical Treatment

• Anti-reflux surgery is an alternative modality in the treatment of GERD in patients who have documented chronic reflux with recalcitrant symptoms [SORT A] • Surgery has a significant complication rate (10-20%) • Resumption of pre-operative medication treatment is common (> 50%) and will likely increase over time • Alternative endoscopic modalities (e.g. Stretta procedure) are less invasive and have fewer complications, but have lower response rates than anti-reflux surgery, and have not been shown to reduce acid exposure [SORT C]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

CAM Options

• Demulcents – Licorice (Glycyrrhiza glabra) – Marshmallow (Althea officinalis) – Slippery elm (Ulmus fulva, Ulmus rubra) • Ginger (Zingiber officinal) • Apple Cider Vinegar • Probiotics • Digestive enzymes • Relaxation, transcendental meditation, biofeedback • Acupuncture

16 Follow-Up and Surveillance • If symptoms remain unchanged in a patient with a prior normal endoscopy, repeating endoscopy is not recommended FOR 10 YEARS [SORT C] – what about patient-directed direct access endoscopy ? • Patients with warning signs and symptoms suggesting complications from GERD should be referred to a gastroenterologist [SORT C] • Further diagnostic testing (e.g. EGD, pH monitoring) should be considered in patients who do not respond to acid suppression therapy and in patients with a chronic history of GERD who are at risk for complications [SORT C] – Esophageal strictures, webs, rings – Barrett’s esophagus – Esophageal adenocarcinoma

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

Follow-Up and Surveillance

• Chronic reflux has been suspected to play a major role in the development of Barrett’s esophagus, yet it is unknown if outcomes can be improved through surveillance and medical treatment [SORT C] • Antisecretory therapy has been shown to reduce the need for recurrent dilation from esophageal stricture formation [SORT A]

Katz PO, et al. Guidelines for the Diagnosis and Management of GERD. Am J Gastroenterol 2013;108:308-328.

17 Poll Question 4 Which population represents the highest risk for development of Barrett’s esophagus? 1. Asian men 2. African American men 3. Hispanic men 4. Caucasian men 5. Middle Eastern men

Barrett’s Esophagus

•“Change in the distal esophageal epithelium of any length that can be recognized as columnar type mucosa at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus” • Screening for BE is controversial – Lack of documented impact on mortality from EAC [SOR B] • The large number of patients that lack reflux symptoms but have Barrett’s esophagus provides a diagnostic challenge • The highest yield for BE is in older (age 50 or more) Caucasian males with longstanding heartburn

AGA Medical Position Statement on Management of Barrett’s Esophagus https://doi.org/10.1053/j.gastro.2011.01.030

18 Barrett’s Esophagus

• The grade of dysplasia determines the appropriate surveillance interval; any grade of dysplasia by histology should be confirmed by an expert pathologist • Any mucosal irregularity, such as nodularity or ulcer, is best assessed with endoscopic resection for a more extensive histologic evaluation and exclusion of cancer • For patients with BE, the goal of pharmacologic acid suppression with agents such as the PPIs is to control reflux symptoms • Proton pump inhibitors do not cure Barrett’s esophagus!

AGA Medical Position Statement on Management of Barrett’s Esophagus https://doi.org/10.1053/j.gastro.2011.01.030

Barrett’s Esophagus

AGE Symptoms <=20 years Symptoms > 20 years Onset < 30 years OR 4.09 (95% CI 2.75- OR 31.4 (95% CI 13.0- 6.54) 75.8) Onset 30-49 years OR 6.93 (95% CI 1.43- OR 6.29 (95% CI 3.48- 11.7) 11.4) Onset 50-79 years OR 4.51 (95% CI 2.43- OR 5.03 (95% CI 2.72- 8.37) 9.29)

• Based upon weekly reported symptoms • Risk of BE increases linearly with earlier age of onset of GERD symptoms • Age at symptom onset may direct primary care clinicians in deciding which patients with GERD symptoms to refer for endoscopic screening for BE

Thrift AP et al. Am J Gastroenterol 2013

19 Esophageal Adenocarcinoma • GERD symptoms are “relative risks” for EAC • Absolute incidence of EAC in patients with GERD is unknown • Screening for EAC should not be performed in men younger than 50 years or in women at any age because of very low incidences of cancer, regardless of the frequency of GERD symptoms • Incidence of EAC in men < 50 yrs with GERD symptoms is 1.0/100,000; incidence of colorectal cancer is 6.7X greater • Incidence of EAC in men > 70 yrs with weekly GERD symptoms is 60.8/100,000; incidence of colorectal cancer is 3X greater • Incidence of EAC in women with GERD is similar to that of breast cancer in men (3.9/100,000 at 60 yrs)

Rubenstein JH, et al. Am J Gastroenterol 2010

H. Pylori Diagnosis

• ELISA IgG - “once positive, always positive” • Sensitivity - 85% / Specificity - 79% • Stool Antigen • Sensitive / Specificity - 90% • False negatives - antibiotics, bismuth, PPIs • Test for eradication 8-14 weeks after treatment 13 14 • C / C Urea Breath Test • Accurate for pre- or post-Rx testing • Sensitive / Specificity - 90% • False negatives • Antibiotics or bismuth within 2 to 4 weeks • PPIs within 1 to 2 weeks – High dose H2RAs

Chey WD, et al. Am J Gastroenterology 2017

20 H. Pylori Treatment

Chey WD, et al. Am J Gastroenterology 2017

H. Pylori Treatment

Chey WD, et al. Am J Gastroenterology 2017

21 H. Pylori Treatment

Chey WD, et al. Am J Gastroenterology 2017

H. Pylori Treatment

22 H. Pylori Treatment

Chey WD, et al. Am J Gastroenterology 2017

Scope of the PPI Problem

• Many patients begin with a self-directed trial of OTC anti-secretory therapy (AST) • Most will consult their PCP due to persistence of symptoms or to obtain reimbursement for prescribed anti-secretory therapy • “Refractory GERD” remains most common referring diagnosis from primary care to gastroenterology (non-procedural)

American Academy of Family Physicians 2009 National Ambulatory Care Medical Survey 2008

23 Scope of the PPI Problem

• Since they are superior, patients are often started on PPIs and left on them until… • What are our endpoints in treatment? • PPIs are commonly used in non-ICU settings for stress ulcer prophylaxis – little evidence to support this • These practices cost millions (preventable) • “Knee jerk” phenomenon of prescribing – “Nobody uses H2RAs any more, PPIs are much better” – “My attending told me to use PPIs…” – The concept of “automatic refills”

The REAL Problem

• Clinicians often leave patients on PPI therapy indefinitely without readdressing: – If patient takes PPI daily – If patient needs to take PPI daily – If patient has breakthrough or alarm symptoms suggestive of advanced upper gastrointestinal disease – If patient can avoid symptoms without it • THESE ARE SAFE MEDICATIONS

24 PPI Overutilization in Ambulatory Care • What is the prevalence and economic impact of inappropriate PPI utilization in the ambulatory care (primary care) setting? • Retrospective cohort study of 946 patients in a VA setting who were receiving PPI therapy • Patients categorized according to appropriateness of PPI therapy • Costs and adverse events were charted

Heidelbaugh JJ et al. Am J Managed Care 2010

PPI Overutilization in Ambulatory Care

Heidelbaugh JJ et al. Am J Managed Care 2010

25 PPI Overutilization in Ambulatory Care • 48.6% of patients across all 4 categories received PPIs without re-evaluation – 1034 patient/years of PPI use • Total cost of inappropriate PPI use – $233,994 based on OTC PPI costs – $1,566,252 based on AWP costs • Adverse events – 6 cases of community-acquired pneumonia – 1 case of Clostridium difficile-associated colitis – No reported cases of vitamin or mineral deficiency – No reported cases of hip fracture

Heidelbaugh JJ et al. Am J Managed Care 2010

Poll Question 5 Which of the following is the most likely sequela from chronic use of PPIs? 1. Renal insufficiency 2. Dementia 3. Clostridium difficile-associated diarrhea 4. Osteoporosis 5. Community-acquired pneumonia

26 Potential Risks of PPI Therapy • Excessive pharmacy costs when left unmonitored! (now OTC) • Community-acquired pneumonia • Clostridium difficile-associated diarrhea • Bone fractures, mostly hip (? Osteoporotic) • Vitamin B12, calcium, zinc deficiencies • Interactions with clopidogrel (omeprazole / + or -) • Renal insufficiency / failure / chronic kidney disease • Heart disease • Dementia • Decreases magnesium (FDA warning), contraindicated in pregnancy… – Data from ALL studies was extracted retrospectively – Cannot prove direct cause-and-effect relationship

Heidelbaugh JJ, et al. Gastroenterology and Hepatology 2009

Risks Associated with Long-term PPI Use

Nehra AK, et al. Mayo Clin Proc 2018

27 “The benefits of your efforts are not always oblivious”

‐ Fortune Cookie # 2235

Practice Recommendations

• Diagnose and manage non-erosive reflux disease (NERD) via a test and treat strategy with anti-secretory therapy, and implementation of lifestyle and dietary modifications • Minimize the likelihood of development of advanced disease (e.g. esophageal strictures, Barrett’s esophagus, and esophageal adenocarcinoma) with appropriate diagnosis and management of GERD via atypical or extraesophageal symptoms • Consider testing for H. pylori in patients with dyspepsia (not GERD) and use current diagnostic and treatment algorithms to foster eradication • Use anti-secretory therapy with H2RAs or PPIs according to evidence-based guidelines, including frequent reassessment of GERD and related symptoms, to minimize over-utilization and potential adverse risks of pharmacotherapy

28 Contact Info

• Joel Heidelbaugh • [email protected]

Questions

29 Key References • Katz PO, Gerson LB, Vela MF. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2013;108:308-328. • Kahrilas PJ, Shaheen NJ, Vaezi, MF. American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease. Gastroenterology 2008;135:1383-91. • Richter JE. Review article: extraoesophageal manifestations of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005;22(suppl 1):78. • Gastroesophageal Reflux Disease. University of Michigan Health System. http://www.cme.med.umich.edu/pdf/guideline/GERD12.pdf • Nehra AK, Alexander JA, Loftus CG, et al. Proton pump inhibitors: review of emerging concerns. Mayo Clin Proc 2018;93(2):240-246. • Heidelbaugh JJ, Metz DC, Yang YX. Proton pump inhibitors: are they over utilized in clinical practice and do they pose significant risk? Int J Clin Pract 2012;66(6):582-591.