Upper GI review 2016

Michael Saunders, MD, Clinical Professor of Medicine, Director, Digestive Disease Center, Division of Gastroenterology, University of

Washington Medical Center

Case presentation:

• 63 year old male with chronic GERD and Barrett’s esophagus presents to establish care.

• The last surveillance endoscopy 2 years ago showed no dysplasia.

• His symptoms are completely resolved on PPI therapy.

• The patient inquires about safety of long term PPI therapy and his risk for esophageal cancer

Safety concern with PPI’s: True or False?

Increased risk of gastric cancer?a) True

b) False

• Contraindicated for use in pregnancy?a) True

b) False

• Increased risk of C difficile infection?a) True

b) False

• Increased risk of community acquired pneumonia?a) True

b) False

• Increased risk of development of pernicious anemia?a) true

b) False

Safety of PPI’s

Concern Reality

Elevated gastrin level Mild; No increased risk of carcinoids

Gastric adenocarcinoma No atrophic gastritis, metaplasia or dysplasia

Infections risk of dysentery during foreign travel

risk of C. diff

No community acquired pneumonia

B12 malabsorption No cases of Pernicious anemia

Pregnancy Category B

Kwok et al. Am J Gastroenterol. 2012;107(7):1011; Khalili et al. BMJ. 2012;344:e372; Zipursky J et al. PLoS Med 2014 Sep 30

Safety concern with PPI’s: True or False?

• Decrease in bone density and calcium malabsorption?a) True

b) False

• Increased cardiovascular events when co-administered with clopidrogel?

a) True

b) False

• Increased risk of dementia?a) True

b) False

• Increased risk of chronic renal failure?a) True

b) false

Calcium and acid secretion

Acid facilitates the release of ionized calcium from insoluble calcium salts

gastrectomy and pernicious anemia are linked to increased risk of osteopenia and fracture

Calcium carbonate absorption decreases at higher pH People with achlorhydria have decreased absorption of calcium carbonate

on an empty stomach

Absorption is normal when calcium carbonate is ingested with a meal

Therapy with a full dose of omeprazole did not reduce the absorption of calcium contained in milk and cheese in normal controls

Yang and Metz. GASTROENTEROLOGY 2010;139:1115–1127

Results of meta-analysis of published studies of risk of hip fracture with chronic use of a proton

pump inhibitor (PPI).

Hamed Khalili et al. BMJ 2012;344:bmj.e372

©2012 by British Medical Journal Publishing Group

Is acid reducing therapy associated with risk of hip fracture?

Several population studies have suggested a weak association between proton pump inhibitor (PPI) use and hip fractures

however, strong evidence of causality and a clear mechanism for this effect are lacking

Increased risk seen primarily in patients with other risk factors (smoking, steroids etc)

long-term PPI use does not affect measures of bone structure and strength that predispose patients to fractures1

Premature to avoid prescribing acid-reducing agents to those who have a clear indication

Weigh risk of fracture to benefit of acid suppression

1 Targownik LE et al. Am J Gastroenterol 2016 Nov 15;

Randomized controlled trials examining outcomes between patients taking PPIs with clopidogrel and those taking only clopidogrel

Cardoso et al. Open Heart 2015;2:e000248

GI bleeding between patients taking PPI with clopidogrel and those taking only clopidogrel

Cardoso RN, et al. Open Heart 2015;2:e000248

Are PPI’s associated an increased risk of chronic kidney disease?

population-based cohort: 10,000 people without CKD at baseline

Over ~14 years, nearly 14% developed CKD. Rates of CKD were higher among patients using PPIs at baseline, compared

with nonusers (14.2 vs. 10.7 events per 1000 person-years)

NSAID use could not be adequately controlled

Association does not prove cause

JAMA Int Medicine 2016

Does PPI use increase risk for dementia?

In a prospective cohort study using insurance claims data (inpatient and outpatient diagnoses and drug prescriptions; 2004 to 2011) from 73,679 German patients aged ≥75

patients receiving regular PPIs were significantly more likely to develop incident dementia compared with those not taking PPIs (hazard ratio, 1.44)

lacks adjustment for well-recognized risk factors for dementia, including family history, heavy alcohol use, hypertension, and atherosclerosis

the proposed mechanism of harm for PPIs is elevation of β-amyloid, which has been independently associated with Alzheimer dementia, yet only 2.5% of patients had this diagnosis

the use of diagnostic codes rather than validated instruments to establish the diagnosis of dementia

Gomm W et al. JAMA Neurol 2016 Feb 15

Which of the following statements pertaining to esophageal cancer and GERD are correct?

a) The incidence of esophageal cancer is rising, surpassing that of colon cancer.

b) Approximately 10% of patients with chronic GERD develop esophageal cancer

c) Acid suppression and antireflux surgery do not eliminate BE or its cancer risk

d) Most patients with Barrett’s esophagus will present with chronic GERD symptoms and be detected at upper endoscopy

Esophageal Adenocarcinoma Is One of the Fastest Growing Cancers of the Past Four Decades

Esophagus

Melanoma

Colorectal

Lung/Breast

Prostate

Pohl H, Welch HG. Natl Cancer Inst 200514

In 2009, ~10,000 new cases 5-year survival rate, 15 to 20%

Barrett’s esophagus

premalignant lesion detected in the majority of patients with esophageal adenocarcinoma

Occurs in ~10% of patients having endoscopies for chronic GERD

The reported incidence of Barrett’s esophagus is rising

Risk factors include advanced age, male sex, white race, symptoms of reflux, and obesity

30 fold risk of esophageal cancer

Acid suppression/antireflux surgery do not eliminate BE or its cancer risk

Sharma. N Engl J Med 2009;361:2548-56

What is the best estimate of annual risk for

developing adenocarcinoma with Barrett’s

esophagus?

a) 100%

b) 50%

c) 25%

d) 5%

e) 0.5%

Incidence of Cancer in Barrett’s dysplasia

Paulson, Reid. Cancer Cell. 2004 Jul;6(1):11-6.

Mean annual incidence <0.5%

Management of Barrett’s esophagus

Sharma. N Engl J Med 2009;361:2548-56

Management of Barrett’s dysplasia

Sharma. N Engl J Med 2009; Spechler et al. Gastroenterol 2011

*HGD should be treated;LGD consider treatment

Case Presentation

58 year old Japanese female presents with 2 months of daily epigastric burning discomfort that is aggravated by eating, particularly spicy or fatty foods, partially relieved with topical antacids, and associated with anorexia and a 10 lb. weight loss. No prior history of peptic ulcer disease. Denies NSAIDS use.

The most appropriate course of action would be?

a) Give an empiric trial of PPI therapy

b) Test and treat for H pylori

c) UGI barium study

d) Upper endoscopy

e) CT scan of the abdomen

Answer D: upper endoscopy

Clinical pearls: management strategy for uninvestigated dyspepsia

Trial of PPI’s and/or H pylori test and treat if under the age of 55 years and have no "alarm features“

Upper endoscopy for those over 55 years, have alarm symptoms or fail PPI’s or H pylori eradication

Which of the following statements regarding H pylori is correct?

1 2 3 4 5

20% 20% 20%20%20%a) The prevalence in the United States

is increasing

b) H pylori has a low prevalence in Asia with only 20% of the population infected by age 30

c) First line therapy with a proton pump inhibitor + clarithromycin (500 mg) + amoxicillin (1 gm) all bid for 7 days results in eradication rates of >90%

d) H pylori has been implicated with the development of gastric adenocarcinoma and lymphoma

e) H pylori is rarely asymptomatic

Answer D: H pylori has been implicated with the development of gastric adenocarcinoma and lymphoma

Clinical pearls:

Prevalence in U.S is decreasing

Prevalence in Asia is 80% by age 30

Majority of chronic H pylori infection is asymptomatic

antibiotic resistance of Helicobacter pylori increases, eradication rates with standard therapy decrease (70 % with 7 day therapy)

treatment should be based on local antibiotic resistance patterns

triple therapy (PPI, amoxicillin, and clarithromycin) be administered only in the setting of low clarithromycin resistance(<15%)

Li B-Z et al. BMJ 2015; Liou et al. Lancet 2016Fallone et al. Gastroenterology 2016

Guideline for Treating Patients with Helicobacter Pylori Infection

First-line treatments may include:

Quadruple bismuth-based therapy for 10 to 14 days (bismuth, PPI, tetracycline, and metronidazole)

Concomitant (PPI plus amoxicillin, clarithromycin, and metronidazole) therapy for 10 to 14 days

Salvage therapy should avoid antibiotics previously taken, should be based on resistance information, and may include:

Bismuth quadruple therapy or levofloxacin therapy for 14 days after failure of clarithromycin therapy

Clarithromycin or levofloxacin-containing therapy for 14 days after failure of bismuth-based therapy

Chey WD et al. Am J Gastroenterol 2017 Jan 10

Documented peptic ulcer or h/o

peptic ulcer disease

Untreated patients with positive

serology

Treated or untreated patients

with positive

biopsy or rapid urease test

urea breath test

stool antigen

H pylori associated MALT

lymphoma

Family hx/o gastric cancer

When to Treat H. pylori

H pylori Testing Caveats

Serology remains positive after treatment

Proton pump inhibitors, H2-receptor antagonists, antibiotics, and bismuth can cause false negative results Urea breath test Stool antigen test

Histology

Culture

Case Presentation

A 52-year-old woman with sudden onset of RUQ painPmHx: s/p cholecystectomy 8 years ago

PE: temp 37.0 C; HR 90, BP 110/70 mm Hg; no scleral icterus; Abdominal exam reveals mild RUQ tenderness without guarding or rebound

Labs: WBC 12,000; aminotransferases: AST 935 ALT 1346; alk phos 98 , amylase 143, bilirubin (total) 1.8

abd u/s reveals a CBD 9 mm, slight intrahepatic bile duct dilatation; No biliary stones are noted

What is the most likely diagnosis?

1. Acute viral hepatitis

2. Ischemic hepatitis

3. Acute common bile duct obstruction

4. Acute pancreatitis

1 2 3 4

0% 0%0%0%

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10

Differential diagnosis of acute transaminase elevation > 1000

Viral hepatitis

Toxin/drug

Ischemia

Acute CBD obstruction (stone)

Biliary tract stone disease

•Cholelithiasis :

•symptomatic cholelithiasis

•acute cholecystitis

•Choledocholithiasis

•symptomatic CBD stone

• cholangitis

•pancreatitis

An 82-year-old woman presents with sudden onset of right upper quadrant abdominal pain, fever, and shaking chills.

EXAM: temperature 39.0 C (102.2 F). Pulse 110/ min, blood pressure 90/70 mm Hg. Slight jaundice is noted. Abd - mild right upper quadrant tenderness without guarding or reboundMental status is normal.

Leukocyte count 12,000 ; AST 235 ALT 343, alkaline phosphatase 298 , amylase 78, bilirubin (total) 4.5

Abd u/s : common bile duct measuring 15 mm in diameter distended gallbladder with sludge no peri-cholecystic fluid or stones are noted.

The most likely diagnosis is?

1. Acute cholangitis

2. Acute cholecystitis

3. Perforated peptic ulcer disease

4. Acute mesenteric ischemia

1 2 3 4

0% 0%0%0%

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10

Cholangitis - infection in biliary tree

Cholangitis requires:• Bacteria (Bile is normally sterile)

❖Source of bacteria in bile:

• intestinal translocation and portal bacteremia

• reflux from duodenum

• gallbladder/stones

• Obstruction of biliary tract

Death may result within hours of presentation

Associated with significant morbidity/mortality

Early recognition and treatment are essential

Urgent biliary decompression

Acute cholangitis:

Clinical Presentation and diagnosis

Charcot’s Triad (~70%):• Abdominal pain• Fever• Jaundice

Labs: Leukocytosis

Abnormal LFT’s

Blood cultures

Imaging: Ultrasound/CT scan

- choledocholithiasis (<50%)

- biliary dilation (~75%)

Case (continued)

Broad spectrum ABx are begun, but the patient develops rigors after receiving the initial dose.

Temperature is now 39.6 C (103.3 F). Pulse rate is 120 per minute, and blood pressure is 82/60 mm Hg. She appears slightly confused.

Which of the following is most appropriate now?

1. Continuation of antibiotic regimen with the addition of imipenem

2. Immediate ERCP with biliary drainage

3. Immediate percutaneous transhepatic cholangiography and external biliary drainage

4. Immediate surgery1 2 3 4

0% 0%0%0%

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10

Management of Cholangitis

• Volume resuscitation

• Antibiotics (Pip/Tazo,

Amp/Sul, Ticar/Clav,

3o Ceph, Imipenem,

Levofloxacin, Cipro)

• Biliary decompression

Timing

Route (ERCP > PTC

> Surgery)

ERCP

Case Presentation

45 yo man developed acute onset of epigastric pain requiring transport via ambulance to the ER

PMHX: unremarkable. No chronic meds. No EtOH.Exam: T 38.0, BP 150/100, HR 110

Moderate distress, in obvious discomfort mod-severe tenderness with guarding, distention,

hypoactive BS, no peritoneal signs

LABS: WBC 20,000, Hct 50, BUN 60, Cr 2.2, AST 350, ALT 460, Total

Bilirubin 5.0, Alk phos 270, Lipase 5200

The most likely diagnosis is?

1. Acute mesenteric ischemia

2. Acute cholecysitis

3. Acute pancreatitis

4. Small bowel obstruction

5. Rupture abdominal aortic aneurysm

1 2 3 4 5

0% 0% 0%0%0%

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10

Diagnosis of acute pancreatitis

Clinical (requires 2 of the following):

Characteristic epigastricpain

Elevated pancreatic enzyme levels (>3x upper limits of normal)

Abnormal imaging (inflammatory changes in pancreas)

The most likely cause of the pancreatitis is?

a) Alcohol abuse

b) Gallstones

c) Hypertriglyceridemia

d) Trauma

e) idiopathic

Etiology of acute pancreatitis

Obstructive

Toxins/drugs

Metabolic

Infection

Vascular

Trauma

Idiopathic

*ALT 3x normal has a 95% PPV for biliary pancreatitis

Am J Gastro 1994; 89:1863

Case presentation

52 year old male referred for evaluation of anemia detected on routine blood work. No significant complaints or past history. Occasional loose stools but no abdominal pain or weight loss

Exam - Pale with slight temporal wasting; skin w/out lesions; abdomen non-distended/nontender

Labs - Hct 23, MCV 120

B12 < 60 (>224), folate nl; ferritin 3 albumin 3.2, calcium 8.2

fecal fat > 60 droplets per hpf

The most appropriate diagnostic test is?

1 2 3 4

25% 25%25%25%1. Colonoscopy

2. H pylori stool antigen

3. Upper endoscopy with small bowel biopsy

4. CT scan of the abdomen

5. Stool for enteric pathogens, ova/parasites

Answer: 3 upper endoscopy with small bowel biopsy

Pearls

The patient has evidence of malabsorption Colonic pathology would not account for all the findings

Endoscopy with biopsy more sensitive than CT scan

H pylori infection would not explain the clinical findings

•An upper endoscopy is performed which reveals

abnormal appearing duodenal folds.

•Histology reveals intra-epithelial lymphocytosis with

blunted villi.

The most likely diagnosis is?

1 2 3 4

25% 25%25%25%

1. NSAID-induced injury

2. Crohn’s disease

3. H pylori infection

4. Celiac disease

Answer: 4 celiac disease

Pearls:

Although the histology is non-specific, celiac disease is the most common small bowel malabsorptive disorder in the U.S

H pylori infection would not account for the histology or clinical findings

True statements regarding celiac disease include all of the following except?

1. The prevalence in the U.S. is 1:300

2. Diagnosis requires a compatible small bowel biopsy with clinical response to gluten withdrawal

3. Tissue transglutaminase IgA is the most sensitive serologic test

4. Is strongly associated with HLA DQ locus

5. Serologic tests are not affected by dietary gluten restriction 1 2 3 4 5

20% 20% 20%20%20%

Answer 5

Pearls: Celiac disease

20% of patients > 60 years at diagnosis HLA-DQ2 and/or DQ8 > 95%*

IgA tissue transglutaminase and endomysial antibodies have sensitivities and specificities > 85%

Anti-gliadin non specific (PPV ~30%) Levels fall with adherence to gluten-free diet

*Kaukinen et al. Am J Gastroenterol 2002

Celiac disease: fact or fiction?

A clinical response to a gluten free diet proves celiac disease is present: True False

Patients who are asymptomatic with normal duodenal biopsy but positive serologies should be on a gluten free diet: True False

The most common presentation of celiac disease is adults is iron deficiency anemia: True False

Celiac disease is more common in patients with IBS symptoms than in the general population: True false

Prevalence of Organic Disease in IBS vs. the General Population

Prevalence (%)

Organic GI disease IBS General Population

Colon cancer 0-0.5 0-6

IBD 0.5-1.0 0.3-1.2

Celiac disease 5 0.25-0.5

Infection 0-1.5 n/a

Thyroid disease 6 5-9

Lactose intolerance 22-26 25

Brandt et al. Am J Gastroenterol 2002

Diseases associated with Celiac Sprue

Ciclitiria. Gastroenterol 2001; 120:1526

Prevalence

Turner’s syndrome 10-20%

Dermatitis herpetiformis >90%

Down’s syndrome 10-15%

IgA deficiency 2-5%

IDDM 8-10%

Thyroid disease 6-8%

Who should be tested for celiac disease?

Those with gastrointestinal symptoms chronic diarrhea, malabsorption, weight loss, and abdominal

distension/bloating

Individuals without other explanations for signs and symptoms persistent elevation in serum aminotransferases, short stature,

delayed puberty, iron-deficiency anemia, recurrent fetal loss, and infertility.

Individuals at high risk for celiac disease type 1 diabetes mellitus or other autoimmune endocrinopathies,

first- and second-degree relatives of individuals with celiac disease, patients with Turner or Down’s syndromes

National Institutes of Health Consensus Development Conference Statement. Celiac Disease 2004

Detection of Celiac Disease inPrimary Care Practices

Catassi et al. Am J Gastroenterol 2007; 102:1454

Prevalence of Celiac Disease (and 95% CI) in 976 at-risk patients

Approach to the Diagnosis of Celiac Disease

Farrell and Kelly. N Engl J Med 2002; 346:180

Is strict gluten avoidance necessary?

Micronutrient deficiencies that may have clinical sequelae

overall mortality c/w general population Risk is in pts. adhering to gluten free diet

Mothers with untreated CD are at risk for having low birth weight newborns

Level and duration of gluten exposure may be related to development of other autoimmune disorders