Esophageal and Small Bowel

Karthik Ravi
November 14, 2013
Curso Internacional de Actualizacion del
Board de Medicina Interna
No financial disclosures
2010 MFMER | slide-2
Outline
Esophageal
GERD
Diagnosis
Management
Dysphagia
Eosinophilic Esophagitis
Achalasia
Small Bowel
Normal function
Steatorrhea
Celiac Disease
Secretory and Osmotic diarrhea
2010 MFMER | slide-3
Esophagus
2010 MFMER | slide-4
Case
2010 MFMER | slide-5
A 42 year-old female presents with several month history of heartburn
and acid regurgitation. The heartburn is described as substernal
burning, occurring 3 to 4 times a week typically after meals and when
supine. In addition, she complains of nocturnal acid regurgitation
occurring twice weekly. She denies any dysphagia or weight loss.
She has been treated with twice daily PPI therapy without
improvement.
What is the most appropriate next step?
A. Refer for fundoplication
B. Esophageal manometry study
C. Increase PPI to three times daily
D. Ambulatory pH monitoring
Case
2010 MFMER | slide-6
A 42 year-old female presents with several month history of heartburn
and acid regurgitation. The heartburn is described as substernal
burning, occurring 3 to 4 times a week typically after meals and when
supine. In addition, she complains of nocturnal acid regurgitation
occurring twice weekly. She denies any dysphagia or weight loss.
She has been treated with twice daily PPI therapy without
improvement.
What is the most appropriate next step?
A. Refer for fundoplication
B. Esophageal manometry study
C. Increase PPI to three times daily
D. Ambulatory pH monitoring
GERD is common in the community
Up to 20% of the Western population have at least weekly
heartburn and/or acid regurgitation
Clinically troublesome heartburn is seen in 6% of the
population
Patients with GERD have lower quality of life, reflected by
decreased work production and lower scores on sleep
scales
GERD carries a significant health related economic burden:
Responsible for nearly 9 million outpatient visits a year
$5438 cost per patient for evaluation of suspected extra-
esophageal manifestations of GERD


2010 MFMER | slide-7
Dent J . Gut 2005; 54: 710-717
Camilleri M. Clin Gastroenterol Hepatol 2005; 3: 543-552
Becher A. Aliment Pharmacol Ther 2011; 34: 618-627
Peery AF. Gastroenterology 2012; 143: 1179-1187
Francis DO. Am J Gastroenterol 2013; 108: 905-911
Symptoms have limited reliability in diagnosing
GERD
2010 MFMER | slide-8 Moayyedi P. J AMA 2006; 295: 1566-1576
Heartburn and Regurgitation most predictive:
Sensitivity of only 30 -76% for erosive
esophagitis
Specificity of only 62 to 90% for erosive
esophagitis
PPI response has limited utility in diagnosing
GERD
2010 MFMER | slide-9 Numans ME. Ann Intern Med 2004; 140: 518-527
PPI responsiveness in predicting GERD
Sensitivity of 78%
Specificity of 54%
2010 MFMER | slide-10
Erosive esophagitis on EGD is specific but not
sensitive for GERD
~70% of patients have nonerosive reflux disease (NERD)
Symptoms in patients with NERD tend to be more refractory
than in erosive esophagitis.
2010 MFMER | slide-11
Diagnosis of GERD Impedance pH
17 cm
15 cm
9 cm
7 cm
5 cm
3 cm
5 cm esophageal pH
10 cm gastric pH
Impedance
2010 MFMER | slide-12
Diagnosis of GERD pH monitoring
17 cm
15 cm
9 cm
7 cm
5 cm
3 cm
5 cm esophageal pH
10 cm gastric pH
Impedance
>4.2% of the recording time with
Esophageal pH <4 is abnormal
2010 MFMER | slide-13
Diagnosis of GERD Impedance
17 cm
15 cm
9 cm
7 cm
5 cm
3 cm
5 cm esophageal pH
10 cm gastric pH
Impedance
2010 MFMER | slide-14
Diagnosis of GERD Impedance pH
2010 MFMER | slide-15 2012 MFMER | slide-15
Impedance detected nonacid reflux may improve
diagnostic yield
Savarino E. Am J Gastroenterol 2008; 103: 2685-2693
2010 MFMER | slide-16
Diagnosis of GERD - Bravo
TM
Prolonged measurement
48 hours standard, up to 96 hours
Allows assessment of more intermittent symptoms
Better tolerated
More reflux detected (normal pH <4 is 5.4% vs 4.2%)
If patient cannot tolerate catheter
Eliminates problem of catheter drift with swallow
Limitations:
No measurement of gastric pH
Cannot measure nonacid reflux episodes
5% get chest pain
Added cost of EGD

Diagnosis of GERD Bravo vs MII-pH
2010 MFMER | slide-18
Dietary changes have limited efficacy in GERD
Katz PO. Am J Gastroenterol 2013; 108: 308-328
2010 MFMER | slide-19
Treatment of GERD PPI therapy
Typical
Heartburn
Acid regurgitation
Erosive esophagitis
Stricture
Barretts esophagus
Atypical
Chest pain
Laryngitis
Laryngoedema
Chronic cough
Asthma
Enamel erosion
Sinusitis
Otitis
2010 MFMER | slide-20
Typical
Generally responsive
Moderate dose PPI
Objective findings of
reflux common
Atypical
ENT signs non-specific
and poorly predictive
Objective testing poorly
predicts response
Cause commonly
multifactorial
Treatment to response
is the best indicator
High dose PPI and
nighttime H2-antagonist
Treatment for 3-6
months

Atypical GERD symptoms are unusual and rarely
respond to PPI therapy
2010 MFMER | slide-21 2012 MFMER | slide-21
Fass R. Gastroenterology 1998; 115: 42-49
PPI therapy trial is cost effective
Fass R. Aliment Pharmacol Ther 2000; 14: 389-396
2010 MFMER | slide-22 2012 MFMER | slide-22
PPIs superior to H2 blockers
PPI therapy to H2 blockers in treating NERD:
Thirty-four trials (1314 participants) were
included in Cochrane review
Relative risk of 0.66 with PPI compared with H2
blockers, 95% CI 0.60 to 0.73
Sigterman KE. Cochrane Database Syst Rev; 2013: 5: CD002095
PPI therapy superior to H2 blockers in treating
erosive esophagitis:
Symptom relief with omeprazole versus
ranitidine at 4 weeks: 85% versus 24%
Healing of esophagitis with omeprazole versus
ranitidine at 8 weeks: 96% versus 52%
Robinson M. Aliment Pharmacol Ther 1995; 9: 25-31
2010 MFMER | slide-23 2012 MFMER | slide-23
Mean follow up of 41 months
64% on medication at follow
up
Only 13 of 41 off
medications without
symptoms


Schindlbeck NE. Gut 1992; 33: 1016-1019
Pace F. Aliment Pharmacol Ther 2007; 26: 195-204
NERD can be treated with on demand PPI
2010 MFMER | slide-24 2012 MFMER | slide-24
Long term PPI is needed in erosive esophagitis
Vigneri S. N Engl J Med 1995; 333: 1106-1110
2010 MFMER | slide-25 2012 MFMER | slide-25
Treatment failure is often due to non compliance
El Serag HB. Am J Gastroenterol 2009; 104: 2161-2167
2010 MFMER | slide-26 2012 MFMER | slide-26
Optimizing timing of PPI therapy is important
Gunaratnam NT. Aliment Pharmacol Ther 2006; 23: 1473-1477
Timing of PPI therapy:
Optimal if 30 min to 1 hour prior to meals
PPI accumulate in acid environment of actively secreting parietal
cells and be converted to a reactive species via an acid-catalyzed
reaction.
They then covalently inhibit ATPase molecules recruited to the
luminal parietal cell surface
2010 MFMER | slide-27 2012 MFMER | slide-27
Escalation of PPI therapy has limited efficacy
Fass R. Aliment Pharmacol Ther 2000; 14: 595-603
Increasing PPI to BID or
switching PPI
Symptom scores suggest
possible better benefit
with switching PPI
Effective ~20% of cases
with either strategy
2010 MFMER | slide-28
Side effects of PPI
2010 MFMER | slide-29 2012 MFMER | slide-29
Side effects of PPI - osteoporosis
Targownik LE. Gastroenterology 2010; 138: 896-904
2010 MFMER | slide-30
PPI Safety
No clear guidelines for monitoring bone density
changed for PPI users or changing dose in
known patients with osteoporosis
No definitive evidence that PPIs should be
stopped in patients on clopidogrel for CAD
Some evidence suggesting increased risk of C.
dificile infection but no large studies. In
addition, current evidence seems related to
factors such as age and systemic illness rather
than PPI use itself.

2010 MFMER | slide-31
Persistence of disease on therapy
Erosive esophagitis
Persistent symptoms with + pH study
Symptoms from non-acid reflux
Large hiatal hernia
Aspiration
Data unclear or not proven
Atypical manifestations
Equal alternative to medical therapy
Prevention of progression of Barretts to cancer
When do you consider fundoplication?
2010 MFMER | slide-32
Fundoplication works best in typical GERD
Morgenthal CB. Surg Endosc 2007; 21: 1978-1984
Fundoplication is
most effective in:
Young patients
Typical
symptoms
Complete PPI
response
2010 MFMER | slide-33 2012 MFMER | slide-33
Limitations of fundoplication
Spechler SJ . J AMA 2001; 285: 2331-2338
Richter J E. Clin Gastroenterol Hepatol 2013; 11: 465-471
Fundoplication is associated with significant limitations:
~ 50% of patients require medical therapy within 5 years
5-10% experience significant dysphagia
5-10% develop gas-bloat syndrome
~ 50% fail at 10 years follow up
Case
2010 MFMER | slide-34
A 78 yo man presents with dysphagia to solids and liquids for 3
months. He reports a sense of fullness towards the end of the meal
and reports frequent nocturnal regurgitation, awakening with food on
the pillow. He reports an associated 20 pound weight loss since
onset of symptoms. An esophageal manometry is performed and
reveals aperistalsis with incomplete lower esophageal sphincter
relaxation.

What is the most appropriate next step?
A. Heller myotomy with partial fundoplication
B. Endoscopic pneumatic dilation
C. Esophagogastroduodenoscopy (EGD)
D. Video fluoroscopy swallow study
E. Ambulatory pH monitoring
Case
2010 MFMER | slide-35
A 78 yo man presents with dysphagia to solids and liquids for 3
months. He reports a sense of fullness towards the end of the meal
and reports frequent nocturnal regurgitation, awakening with food on
the pillow. He reports an associated 20 pound weight loss since
onset of symptoms. An esophageal manometry is performed and
reveals aperistalsis with incomplete lower esophageal sphincter
relaxation.

What is the most appropriate next step?
A. Heller myotomy with partial fundoplication
B. Endoscopic pneumatic dilation
C. Esophagogastroduodenoscopy (EGD)
D. Video fluoroscopy swallow study
E. Ambulatory pH monitoring
Differentiating the etiology of dysphagia
2010 MFMER | slide-36
Structural abnormality
progressive solid food
dysphagia
Episodic
Often can continue meal
after resolution
Ring
Stricture
Eosinophilic esophagitis
Infectious esophagitis
Pill or caustic esophagitis
Dermatologic disorders
Cricopharyngeal bar
Extrinsic compression
Primary or secondary
tumor
Motility disorder
Dysphagia for solids and
liquids
Often occurs towards end
of the meal
Regurgitation is frequent
Peristaltic weakness
Aperistalsis
Hypertensive peristalsis
DES
Achalasia
Functional Obstruction
2010 MFMER | slide-37
Definition of Achalasia
Manometric definition of achalasia:
Aperistalsis
Incomplete LES relaxation
Resting LES pressure is normal in up to 50% of cases
Clinical presentation of Achalasia
Birgisson S. Dig Dis Sci 2007; 52: 1855-1860
2010 MFMER | slide-39
Diagnosis of Achalasia - Esophagram
Diagnosis of Achalasia - EGD
Howard PJ . Gut 1992; 33: 1011-1015
EGD is normal in 40% of
patients with achalasia
Rule out pseudoachalasia
up to 5% of cases
Older patient, rapid
progression of
symptoms and weight
loss
Most often
gastroesophageal
junction malignancy
Can represent a
paraneoplastic
phenomenon (lung
cancer)
Kharilas PJ . Am J Med 1987; 82: 439-446
Campos GM. Ann Surg 2009; 249: 45-57
Botox injection is transiently effective in achalasia
Achalasia treatment
Achalasia treatment Pneumatic dilation
Katzka DA. Aliment Pharmacol Ther 2011; 34: 832839
Achalasia Heller myotomy
Zaninotto G. Ann Surg 2008; 248: 986-993
Symptom
Remission
Achalasia: Pneumatic dilation versus myotomy
0
20
40
60
80
100
Myotomy Pneumatic dilation
P=0.46
%

T
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e
a
t
m
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t

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c
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s
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Boeckxstaens GE. N Engl J Med 2011; 364: 1807-16
201 patients randomized
2 year follow up
Treatment success based on symptoms (Eckhardt score)
No difference between myotomy and dilation
Aggressive pneumatic dilation, overall 7.5% perforation rate
2010 MFMER | slide-46
Risk of perforation in pneumatic dilation
Katzka DA. Aliment Pharmacol Ther 2011; 34: 832839
Meta-analysis assessing
risk of perforation with
pneumatic dilation in
achalasia:
2.3% with perforation
0.9% of all cases with
perforation requiring
surgery
Subtypes of Achalasia
Pandolfino J E et al, Gastroenterology 2008Nov;135(5):1526-33
Type 1 Achalasia (classic)
Type 2 Achalasia,
Panesophageal pressure
20% with >20mmHg


Type 3 Achalasia,
20% spastic
DL <4.5sec, CFV >10cm/s)
Early
Type II
Late
Type I
Chronic
Type II--I
Netter Atlas
Subtypes of Achalasia
Botulinum toxin 0% (0/2) 86% (6/7) 22% (2/9) 39% (7/18)
Pneumatic dilation 38% (3/8) 73% (19/26) 0% (0/11) 53% (24/45)
Heller Myotomy 67% (4/6) 100% (13/13) 0% (0/1) 85% (17/20)
All (any) interventions 44% (7/16) 83% (38/46) 9% (2/21) 56% (47/83)
Number of interventions 1.6 1.5 1.2 0.4* 2.4 1.0 1.8 0.7
Successful last intervention 56% 96%* 29%* 71%
Last intervention type B-0,P-10,M-6 B-6,P-25,M-15 B-8,P-8,M-5 B-14,P-43,M-
26
Subsequent Interventions
*P<0.05 vs Type I, p<0.05 vs Type III
Achalasia
Intervention
Type I
Classic
Type II
compression
Type III
Spasm
All
Types
Treatment outcomes differ in achalasia subtypes
Pandolfino J E et al, Gastroenterology 2008Nov;135(5):1526-33
Type 2 achalasia (early): Best response regardless of therapy
Type 3 (spastic) achalasia: Worst response