GERD in Pediatric Patients2009

Philip M.
Sherman
Chairperson, Global Definition of GERD Consensus Hospital for Sick Children, University of Toronto, Toronto, Ontario, CANADA
Consensus Panel
Eric Hassall Ulysses Fagundes-Neto Benjamin j D. Gold Seiichi Kato Sibylle Koletzko S Susan R. R Orenstein O t i Colin Rudolph Nimish Vakil Yvan Vandenplas
University of British Columbia, Vancouver, British Columbia, CANADA Universidade Federal de So Paulo, BRAZIL Emory y University y School of Medicine, Atlanta, GA, USA Tohoku University School of Medicine, Sendai, JAPAN Ludwig Maximillians University, Munich, GERMANY University of Pittsburgh School of Medicine, Medicine Pittsburgh Pittsburgh, PA PA, USA Medical College of Wisconsin, Milwaukee, WI, USA University of Wisconsin School of Medicine and Public Health, Mil k WI, Milwaukee, WI USA Free University of Brussels, Brussels, BELGIUM
Consensus Panel
Disclosure
No significant financial interest to report
UF-N, SK, CR
Yes, a significant financial interest as follows

Advisory Board Consultant
Abbott (EH, PS, SKol), AstraZeneca (SKol), Mead Johnson (PS), Movetis (SKol, YV), Santarus (BG) Abbott Abb tt (EH) (EH), Altana Alt (EH) (EH), A AstraZeneca t Z (BG, (BG NV), NV) Axcan A (BG) (BG), Bi Biocodex d (YV) (YV), B Braintree i t Labs (SO), Bristol Myers Squibb (SO), INSINConsulting (PS), Malesci (NV), McNeil (SO), Mead, Meridian (NV), Johnson (SO), Novartis (NV), Orexo (NV), Proctor & Gamble (NV), Reliant (SO), Salix (SO), Santarus (BG), Shire (NV), SHS (SKol, YV), TAP (BG, EH, SO, NV) Wyeth NV), W th (BG, (BG SO) Altana (NV), AGI (NV), AstraZeneca (EH, SKol, NV, YV), Boston Scientific (NV), Fresenius (SKol), Institute Rosell (PS), Medtronics (NV), Nestle (YV), Novartis (NV), Numico (YV), Shire (NV), SHS (SKol, YV), TAP (BG), Wyeth (YV) AstraZeneca (BG, SKol, NV), Novartis (NV), Takeda (NV), TAP (BG, NV) Antibe Therapeutics (PS), Orexo (NV) Nestle Nutrition (PS educational program, YV)
Research Support Speakers Bureau Stockholder Other
Background

Research and clinical practice in gastroesophageal reflux disease (GERD) have traditionally been hampered by inconsistent definitions of the disease. The Montreal Definition of GERD in adults was recently developed using a rigorous process and aimed to simplify disease management by providing a universally accepted understanding d t di of f the th disease. di There is a need for clarity about GERD in infants, children, and adolescents. adolescents
Vakil N et al. Am J Gastroenterol 2006;101:190020
Montreal Definition of GERD
Vakil N et al. Am J Gastroenterol 2006;101:190020
Delphi Technique
A modified Delphi technique was used to develop a set of statements regarding the definition of GERD in pediatric patients.
Lindstone et al, 2002. www.is.njit.edu/pubs/delphibook/
Consensus Group Selection

The group was led by a non-voting Chair The chair selected eight expert consensus group members based on their
relevant p peer-reviewed p publications research activities in the field, and participation in national or regional activities related to GERD in pediatric patients.
Sherman et al. Am J Gastroenterol 2009;104:1278-95
Consensus Group Selection

An adult gastroenterologist who chaired the Montreal Definition working group, joined the pediatric consensus group as a non-voting ti member. b A general pediatrician, a family physician, four neonatologists a pediatric pulmonologist neonatologists, pulmonologist, a pediatric otolaryngologist and a pediatric general surgeon also commented on statements, but did not vote.
Systematic Literature Searches & Grades of Evidence

S Systematic i Literature Li Searches S h
Relevant English-language studies in humans published b t between 1 January J 1980 and d 31 J July l 2007 were id identified tifi d via i systematic searches of Medline, EMBASE and CINAHL.
Grades of Evidence
The strength of evidence for each statement was evaluated using the GRADE system.
Grade Working Group. BMJ 2004;328:14904
Voting

Four rounds of anonymous voting: two during two face-toface workshops and two via e-mail. e mail Between each round of voting, statements were revised by the Chair, Chair based on feedback from the group and outside experts. The consensus group voted using a 6 6-point point scale:
Agree strongly (A+), Agree with minor reservations (A), Agree with major reservations (A) Disagree g with major j reservations ( (D), ), Disagree g with minor reservations (D), ( ), Disagree strongly (D+)
Agreement with a statement (A+, A or A) by 75% of the voting group members was defined a priori as consensus. consensus
Voting
For the first (electronic) vote 62 statements were presented:
43 statements t t t f from th the M Montreal t l Definition D fi iti 7 Montreal Definition statements revised by the Chair, plus 12 additional pediatric-specific statements proposed by the Chair.
Before the second vote, which took place at the first workshop, many of the statements were separated for each of three age groups
newborns and infants [012 months] toddlers and children [110 years] adolescents [1117 years])
At this point in the process the number of statements increased to 117. 117
Voting
43 Montreal Definition statements; 7 revised Montreal Definition statements; 12 new statements
Number of statements Proportion of statements with consensus
Vote 1 (e-mail), July 2007 Vote 2 (1st workshop), Sept 2007 Vote ote 3 (e (e-mail), a ), Nov o 2007 00 Vote 4 (2nd workshop), Dec 2007
62 117 86 59
76% 67% 66% 98%
2 Montreal Definition statements; 29 revised Montreal Definition statements; 28 new statements

Voting
Level of Agreement A+ A ADD D+ Agree strongly Agree moderately Just agree Just disagree Di Disagree moderately d t l Disagree Strongly Agreement (% of Statements) 40 40 16 2 1 1
The Global Definition
GERD in p pediatric p patients is p present when reflux of g gastric contents is the cause of troublesome symptoms and/or complications
Esophageal
Symptoms purported to be due to GERD GERD* Infant or younger child (08 years), or older without cognitive ability to reliably report symptoms Symptomatic syndromes Older child or adolescent with cognitive ability to reliably report symptoms Syndromes with esophageal injury
Extraesophageal
Definite associations i ti
Possible associations i ti
Sandifers syndrome Dental erosion Bronchopulmonary Asthma Pulmonary fibrosis Bronchopulmonary y dysplasia Laryngotracheal and pharyngeal Chronic cough Chronic laryngitis Hoarseness Pharyngitis Rhinological and otological Sinusitis Serous otitis media Infants Pathological apnea Bradycardia Apparent lifethreatening events
Excessive regurgitation Feeding refusal/anorexia Unexplained crying Ch ki / Choking/gagging/ i / coughing Sleep disturbance Abdominal pain
Typical reflux syndrome
Reflux esophagitis Reflux stricture Barretts esophagus Ad Adenocarcinoma i
*Where other causes have been ruled out (e.g. food allergy, especially in infants)
Statement #1
GERD in pediatric patients is present when the reflux of gastric content is the cause of troublesome symptoms and / or complications. Agreement 100%
A+, 87.5%; A, 12.5% GRADE: not applicable
However, this definition is complicated by unreliable symptom reporting by:
children younger than 8 years and pediatric patients of any age who have cognitive impairment
Statement #2
Symptoms of GERD vary by age age. Agreement 100%
A+, 87.5%; A-, 12.5% GRADE: high
Statement #3
Symptoms due to gastroesophageal reflux (GER) are troublesome when they have an adverse effect on the wellwell-being of the pediatric patient. Agreement 100%
A+, 12.5%; A, 75%; A-, 12.5% Grade: not applicable
Statement #4
Otherwise healthy newborns (age 1 130 days) and infants (age > 30 days < 1 year) with reflux fl symptoms t th t are not that t troublesome t bl and d are without complications should not be diagnosed with GERD. Agreement 87.5%
A+, 62.5%; A, 12.5%; A-, 12.5%; D-, 12.5% Grade: not applicable
Statement #5
Reflux symptoms that are not troublesome in toddlers and children (age 1 110) should not be diagnosed as GERD. Agreement 75%
A+, 37.5%; A, 37.5%; D-, 12.5%; D, 12.5% GRADE: not applicable
Statement #6
Reflux symptoms that are not troublesome in adolescents (age 11 11 17) should not be diagnosed as GERD. Agreement 87.5%
A+, 50%; A, 37.5%; D-, 12.5% GRADE: not applicable
Statement #7
Regurgitation in pediatrics is defined as the passage of refluxed contents into the pharynx, pharynx mouth or from the mouth. Agreement 100%
Statement #8
Bilious vomiting g should not be diagnosed g as GERD. Agreement 100%
A+, 75%; A, 12.5%; A-, 12.5% GRADE: high
Statement #9
Regurgitation is a characteristic symptom of reflux in infants, , but is neither necessary y nor sufficient for a diagnosis of GERD, because it is not sensitive or specific. Agreement 100%
A+, 62.5%; A, 37.5% GRADE: high
Statement #10
Symptoms of GERD, particularly in infants, may be indistinguishable from those of food allergy. Agreement 100%
A+, 62.5%; A, 25%; A-, 12.5% GRADE: high
Statement #11
In clinical practice, adolescents are generally able to describe specific p GERD symptoms y p and to determine if those symptoms are troublesome. Agreement 100%
A+, 62.5%; A, 37.5% GRADE: low
Statement #12
Pediatric populationpopulation-based studies of reflux symptoms are insufficient and are a priority for further research. Agreement 100%
A+, 75%; A, 25% GRADE: not applicable
Statement #13
The pediatric patient with central nervous system impairment has an increased risk of GERD. Agreement 100%
A+, 62.5%; A, 12.5%; A-, 25% GRADE: high
Statement #14
Esophageal atresia is associated with an increased risk of GERD. Agreement A t 100%
A+, 75%; A, 12.5%; A-, 12.5% GRADE: high
Statement #15
Cystic fibrosis is associated with an increased risk of GERD. Agreement A t 100%
A+, 75%; A, 12.5%; A-, 12.5% GRADE: high
Symptomatic Syndromes & y p Purported p to be due to GERD Symptoms
Esophageal
Extraesophageal
Statement #16
Heartburn in older children is defined as a burning sensation in the retrosternal area. Agreement 100%
A+, 50%; A, 37.5%; A-, 12.5% GRADE: not applicable
Statement #17
Heartburn in adolescents is defined as a burning sensation in the retrosternal area. Agreement 100%
Typical Reflux Syndrome
Definition of GERD in Pediatric Patients

GERD in pediatric patients is present when the reflux of gastric content is the cause of troublesome symptoms and/or complications
Esophageal
Extraesophageal
Symptoms purported to be due to GERD Infant* or younger child (08 years), or older without cognitive ability to reliably report symptoms
Symptomatic syndromes Older child or adolescent with cognitive ability to reliably report symptoms
Syndromes with esophageal injury
Possible associations
Bronchopulmonary Asthma Pulmonary fibrosis Bronchopulmonary dysplasia Reflux esophagitis Reflux stricture Barretts oesophagus Adenocarcinoma Laryngotracheal Chronic cough Chronic laryngitis Hoarseness Pharyngeal and oral Pharyngitis Dental erosion
Rhinological and otological Sinusitis Serious otitis media Infants Pathological apnea Bradycardia Apparent life lifethreatening events Sandifers syndrome
Excessive regurgitation g refusal/anorexia Feeding Unexplained crying Choking/gagging/ coughing Sleep disturbance Abdominal pain
*Where other causes have been ruled out (e.g. food allergy)
Statement #18
The Typical yp Reflux Syndrome y is characterized by heartburn with or without regurgitation. Agreement 100%
A+, 37.5%; A, 37.5%; A-, 25% GRADE: not applicable
Statement #19
Heartburn and regurgitation in adolescents and older children, with cognitive development sufficient ffi i t to t reliably li bl report t symptoms, t are characteristic symptoms of the Typical Reflux y Syndrome. Agreement 100%
Statement #20
Typical Reflux Syndrome cannot be diagnosed in infants and children who lack the cognitive ability to reliably report symptoms. Agreement 75%
A+, 37.5%; A, 37.5%; D-, 12.5%, D+, 12.5% GRADE: not applicable
Statement #21
Gastroesophageal reflux in older children and adolescents is the most common cause of heartburn Agreement 87.5%
A+, 37.5%; A, 50%; D-, 12.5% GRADE: low
Statement #22
Heartburn in older children and adolescents can have a number of non non-reflux related causes. The prevalence of these is unknown. Agreement 100%
A+, 50%; A, 37.5%; A-, 12.5% GRADE: high
Statement #23
In neurologically intact adolescents, the Typical yp Reflux Syndrome y can be diagnosed g on the basis of the characteristic symptoms, without additional diagnostic testing. Agreement 87.5%
A+, 12.5%; A, 62.5%; A-, 12.5%; D-, 12.5% GRADE: low
Statement #24
Non-erosive reflux disease in the pediatric Nonpatient is defined by the presence of troublesome symptoms caused by the reflux of gastric contents and the absence of mucosal py breaks at endoscopy. Agreement 100%
A+, 12.5%; A, 75%; A-, 12.5% GRADE: not applicable
Statement #25
Epigastric pg pain p in older children and adolescents can be a major symptom of GERD. Agreement 100%
A+, 75%; A-, 25% GRADE: moderate
Statement #26
GERD in newborns and infants may y be associated with sleep disturbances. Agreement 87 87.5% 5%
A+, 25%; A, 25%; A-, 37.5%; D+, 12.5% GRADE: low
Statement #27
GERD in toddlers and children may y be associated with sleep disturbances. Agreement 100%
A+, 12.5%; A, 37.5%; A-, 50% GRADE: very low
Statement #28
GERD in adolescents may y be associated with sleep disturbances. Agreement 100%
A+, 62.5%; A-, 37.5% GRADE: very low
Statement #29
Physical exercise in toddlers and children may induce troublesome symptoms of GERD in individuals who have no or minimal symptoms at other times (exercise (exercise-induced reflux). Agreement 87.5%
A+, 12.5%; A-, 75%; D-, 12.5% GRADE: very low
Statement #30
Physical exercise in older children and adolescents may induce troublesome symptoms of GERD in individuals who have either no or minimal symptoms at other times (exercise (exercise-induced reflux) . Agreement 100%
A+ 25%; A A+, A, 25%; A A-, 50% GRADE: very low
Statement #31
When assessing GERD, GERD rumination should be distinguished from regurgitation. Agreement A t 100%
A+, 62.5%; A, 25%; A-, 12.5% GRADE: not applicable
Syndromes with Esophageal Injury
Esophageal
Extraesophageal
Statement #32
In pediatric patients, esophageal complications of GERD are reflux esophagitis esophagitis, hemorrhage, hemorrhage stricture, Barretts esophagus and rarely, adenocarcinoma. Agreement 100%
A+, 62.5%; A, 25%; A-, 12.5% GRADE: high
Statement #33
Insufficient data exist to recommend histology as a tool to diagnose or exclude GERD in children. Agreement 87.5%
A+, 37.5%; A, 25%; A-, 25%; D+, 12.5% GRADE: not applicable
Statement #34
A primary role for esophageal histology is to rule out other conditions in the differential diagnosis. Agreement 100%
A+, 37.5%; A, 50%; A-, 12.5% GRADE: high
Statement #35
Reflux esophagitis in pediatrics is defined endoscopically by visible breaks of the distal esophageal mucosa. Agreement 62.5%
A+, 50%; A-, 12.5%; D, 12.5%; D+, 25% GRADE: not applicable
Statement #36
When refluxreflux-related erosions are present at endoscopy the grade should be described endoscopy, according to one of the recognized classifications of erosive esophagitis. Agreement 100%
Statement #37
In otherwise healthy children, reflux esophagitis may not be chronic or recurrent following treatment. Agreement 100%
A+, 12.5%; A, 75%; A-, 12.5% GRADE: low
Statement #38
Reflux esophagitis in children with chronic neurologic impairment, impairment repaired esophageal atresia, hiatal hernia or chronic respiratory diseases is usually chronic and recurrent. Agreement 87.5%
A+, 12.5%; A, 62.5%; A-, 12.5%; D, 12.5% GRADE: moderate
Statement #39
Although GER symptom frequency and intensity in pediatrics correlate with the severity of mucosal injury, neither will accurately predict the severity of mucosal injury in the individual patient. Agreement 100%
A+ 12 5%; A 5%; A A+, 12.5%; A, 62 62.5%; A-, 25% GRADE: low
Statement #40
A reflux stricture is defined as a persistent luminal narrowing of the esophagus caused by GERD in pediatric patients. Agreement 100%
Statement #41
The characteristic symptom of a stricture in pediatrics is persistent troublesome dysphagia. Agreement 100%
A+, 37.5%; A, 50%; A-, 12.5% GRADE: high
Statement #42
Dysphagia in older children and adolescents is a perceived impairment of the passage of food from the mouth into the stomach. Agreement 100%
Statement #43
Troublesome dysphagia is present when older children and adolescents need to alter eating patterns or report food impaction. Agreement 100%
Statement #44
In the pediatric age group, Barrett's esophagus mainly occurs in individuals with hiatal hernia, hernia and in those with certain underlying disorders that predispose to severe GERD. Agreement 100%
A+, 25%; A, 62.5%; A-, 12.5% GRADE: low
Statement #45
The term Endoscopically Suspected Esophageal Metaplasia (ESEM) describes endoscopic findings consistent with Barretts esophagus that await histological confirmation. Agreement 100%
A+ 25%; A A+, A, 75% GRADE: not applicable
Statement #46
Documentation of esophogastric landmarks together with multiple biopsies are necessary to characterize endoscopically suspected esophageal metaplasia. Agreement 87.5%
A+, 12.5%; A, 62.5%; A, 12.5%; D-, 12.5% GRADE: moderate
Statement #47
When biopsies from endoscopically suspected esophageal metaplasia show columnar epithelium it should be called Barretts esophagus and the presence or absence of intestinal metaplasia specified. Agreement 100%
A+ 50%; A 5%; A 12 5% A+, A, 37 37.5%; A-, 12.5% GRADE: not applicable
Possible Associations
Esophageal
Extraesophageal
Statement # 48
Sandifers Sandifer s syndrome (torticollis) is a specific manifestation of GERD in pediatric patients. Agreement A t 100%
A+, 62.5%; A-, 37.5% GRADE: high
Statement #49
There is insufficient evidence that GERD causes or exacerbates sinusitis sinusitis, pulmonary fibrosis, pharyngitis and serous otitis media in the pediatric population. Agreement 100%
A, 100% GRADE: low
Statement #50
Chronic cough cough, chronic laryngitis, laryngitis hoarseness and asthma may be associated with GERD. Agreement A t 87.5% 87 5%
A+, 25%; A, 37.5%; A-, 25%; D-, 12.5% GRADE: very low
Statement #51
In the absence of heartburn or regurgitation, unexplained asthma is less likely to be related to GERD. Agreement 100%
A+, 12.5%; A, 75%; A-, 12.5% GRADE: low
Statement #52
Chronic cough, chronic laryngitis, hoarseness and asthma are multifactorial disease processes and acid reflux can be an aggravating cofactor. Agreement 87.5%
A+, 37.5%; A, 25%; A-, 25%; D-, 12.5 GRADE: very low
Statement #53
GERD may cause dental erosions in children. Agreement 100%
A+, 12.5%; A, 37.5%; A-, 50% GRADE: very low
Statement #54
There is an association between GERD and bronchopulmonary dysplasia in neonates and infants, but the causecause-and and-effect relationship is uncertain. Agreement 100%
A+, 25%; A, 50%; A-, 25% GRADE: low
Statement #55
In premature infants, a relationship between gastroesophageal reflux and pathologic apnea and/or bradycardia has not been established. Agreement 100%
A+, 37.5%; A, 50%; A-, 12.5% GRADE: high
Statement #56
Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants. Agreement 100%
A+, 37.5%; A, 37.5%; A-, 25% GRADE: moderate
Statement #57
When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature. Agreement 100%
A+, 25%; A, 25%; A-, 50% GRADE: moderate
Statement #58
A diagnosis of an acute lifelife-threatening event (ALTE) warrants consideration of causes other than gastroesophageal reflux. Agreement 100%
A+, 25%; A, 50%; A-, 25% GRADE: high
Statement #59
At present, no single diagnostic test can prove or exclude extraesophageal presentations of GERD in pediatrics. Agreement 100%
Summary

A global definition of GERD in infants, children and adolescents has been developed. The definition clarifies the role of histology in the diagnosis of GERD, details symptoms associated with the disease, and id ifi f identifies future research h priorities. i ii Critical feedback is now being sought from pediatric gastroenterologists, t t l i t and d other th i interested t t d parties. ti The consensus statements should prove useful for the development of clinical practice guidelines and in the establishment of high quality clinical trials to answer unresolved issues in the field.

GERD in Pediatric Patients2009

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GERD in Pediatric Patients2009

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Philip M.

Yes, a significant financial interest as follows

Research Support Speakers Bureau Stockholder Other

Vakil N et al. Am J Gastroenterol 2006;101:190020

Montreal Definition of GERD

Vakil N et al. Am J Gastroenterol 2006;101:190020

Lindstone et al, 2002. www.is.njit.edu/pubs/delphibook/

Consensus Group Selection

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Consensus Group Selection

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Systematic Literature Searches & Grades of Evidence

Grade Working Group. BMJ 2004;328:14904

For the first (electronic) vote 62 statements were presented:

76% 67% 66% 98%

2 Montreal Definition statements; 29 revised Montreal Definition statements; 28 new statements

The Global Definition

Typical reflux syndrome

Reflux esophagitis Reflux stricture Barretts esophagus Ad Adenocarcinoma i

However, this definition is complicated by unreliable symptom reporting by:

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Symptomatic Syndromes & y p Purported p to be due to GERD Symptoms

Typical reflux syndrome

Reflux esophagitis Reflux stricture Barretts esophagus Ad Adenocarcinoma i

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Typical Reflux Syndrome

Definition of GERD in Pediatric Patients

Syndromes with esophageal injury

Typical reflux syndrome

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Syndromes with Esophageal Injury

Typical reflux syndrome

Reflux esophagitis Reflux stricture Barretts esophagus Ad Adenocarcinoma i

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95

Sherman et al. Am J Gastroenterol 2009;104:1278-95