Howard Hampel, MD, PhD; Neena S. Abraham, MD, MSc(Epi); Hashem B. El-Serag, MD, MPH
Acknowledgments: The authors thank Loralee Capistrano, MPH, and Jennifer R. Kramer, PhD, for their help in using STATA.
Grant Support: Dr. El-Serag is a recipient of the Department of Veterans Affairs Health Services Research and Development Advanced Career Development Award (RCD00-013-2).
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Hashem B. El-Serag, MD, MPH, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX 77030; e-mail, email@example.com.
Current Author Addresses: Drs. Hampel, Abraham, and El-Serag: Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX 77030.
The association of body mass index and gastroesophageal reflux disease (GERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear.
To conduct a systematic review and meta-analysis to estimate the magnitude and determinants of an association between obesity and GERD symptoms, erosive esophagitis, Barrett esophagus, and adenocarcinoma of the esophagus and of the gastric cardia.
MEDLINE search between 1966 and October 2004 for published full studies.
Studies that provided risk estimates and met criteria on defining exposure and reporting outcomes and sample size.
Two investigators independently performed standardized search and data abstraction. Unadjusted and adjusted odds ratios for individual outcomes were obtained or calculated for each study and were pooled by using a random-effects model.
Nine studies examined the association of body mass index (BMI) with GERD symptoms. Six of these studies found statistically significant associations. Six of 7 studies found significant associations of BMI with erosive esophagitis, 6 of 7 found significant associations with esophageal adenocarcinoma, and 4 of 6 found significant associations with gastric cardia adenocarcinoma. In data from 8 studies, there was a trend toward a dose–response relationship with an increase in the pooled adjusted odds ratios for GERD symptoms of 1.43 (95% CI, 1.158 to 1.774) for BMI of 25 kg/m2 to 30 kg/m2 and 1.94 (CI, 1.468 to 2.566) for BMI greater than 30 kg/m2. Similarly, the pooled adjusted odds ratios for esophageal adenocarcinoma for BMI of 25 kg/m2 to 30 kg/m2 and BMI greater than 30 kg/m2 were 1.52 (CI, 1.147 to 2.009) and 2.78 (CI, 1.850 to 4.164), respectively.
Heterogeneity in the findings was present, although it was mostly in the magnitude of statistically significant positive associations. No studies in this review examined the association between Barrett esophagus and obesity.
Obesity is associated with a statistically significant increase in the risk for GERD symptoms, erosive esophagitis, and esophageal adenocarcinoma. The risk for these disorders seems to progressively increase with increasing weight.
Table 1. Characteristics of 9 Studies of Body Mass Index and Symptoms of Gastroesophageal Reflux Disease
Adjusted odds ratios for the association of overweight (body mass index 25 kg/m2 to 30 kg/m2) and gastroesophageal reflux disease symptoms (top) and for the association between obesity (body mass index > 30 kg/m2) and gastroesophageal reflux disease symptoms (bottom).
Table 2. Characteristics of 5 Studies of Obesity and Erosive Esophagitis
Adjusted odds ratios from cross-sectional and case–control studies examining the association between overweight or obesity (body mass index ≥25 kg/m2) and erosive esophagitis.
Table 3. Characteristics of 9 Studies of Body Mass Index and Esophageal Adenocarcinoma or Adenocarcinoma of the Gastric Cardia
Adjusted odds ratios from case–control studies examining the association between overweight (body mass index ≥25 kg/m2) and adenocarcinoma of the esophagus (top) and the association between obesity (body mass index >30 kg/m2) and esophageal adenocarcinoma (bottom).
Unadjusted odds ratios (95% CIs) for the risk for gastroesophageal reflux disease (GERD) symptoms among overweight (top) and obese (bottom) versus normal-weight individuals.
Unadjusted odds ratios (95% CIs) from cross-sectional and case–control studies examining the risk for erosive esophagitis among overweight (body mass index [BMI] ≥ 25 kg/m2) versus normal-weight (BMI < 25 kg/m2) individuals.
Unadjusted odds ratios (95% CIs) from case–control studies examining the association between overweight or obesity (body mass index [BMI] ≥25 kg/m2) and adenocarcinoma of the esophagus or gastric cardia.
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Douglas J Sprung
Florida Hospital, Orlando,Fl
August 14, 2005
The Obese Refluxer- Nothing New Under the Sun
The meta-analysis by Hampel et al ( 1) was immensely impressive. Yet, it has amazed me over the past 3 decades, how much energy has gone into the debate as to whether or not obesity causes gastroesophageal reflux. As a medical student at Duke in the 1970's I learned that obesity was commonly associated with reflux symptoms by spending time at the Rice Diet program in Durham,NC. Dr Kempner would bring over one obese patient after another and he would discuss their symptoms and medical issues, including hypertension, diabetes,heart failure,gallstones,arthritis and reflux symptoms. After a few weeks on the program,without any antacids or proton- pump inhibitors,the reflux symptoms were resolved in most of the patients ,as their oral intake and weight had dramatically reduced. Those observations were published in the 1960's, and quite frankly the conclusions drawn from this extensive meta-analysis could have been garnered by simply speaking to any of the successful dieter's at the Rice House or other diet centers around the country. It is an academic shame that so much time,effort and grant money had to be spent to this end. As far as Barrett's esophagus(BE) and adenocarcinoma go, we have not found a significant association with obesity in our community private practice. 1/9 patients with incident adenocarcinoma within BE was obese. Very few patients with BE (long segment) were obese.Whereas obesity is correlated with reflux symptoms, Barrett's esophagus and its complications were not in our community.
1.Hampel H,Abraham N,El-Serag HB. Meta-Analysis: Obesity and the Risk for Gastroesophageal Reflux Disease and its Complications. Ann INtern Med. 2005;143:199-211. 2.Sprung DJ,Sprung GM. Barrett's Esophagus In Our Community Over the Past 12 Years. Amer Journal Gastro. Vol 98,No 9,supp 2003; S-1.
SENIOR RESIDENT IN INTERNAL MEDICINE,JIPMER,PONDICHERRY.
August 24, 2005
Malnutrition and molecular basis of esophageal adenocarcinoma
Malnutrition either as over and undernutrition can result in deficiency of trace elements such as zinc which can lead to Cyclin D1 overexpression and p53 deficiency,which increases cell proliferation.Further zinc deficiency has been found to dysregulate p16ink4a-cyclin D1/Cdk4-Rb pathway,thereby promoting esophageal tumors.Many other genes and gene products such as TGF-Ã¡,EGF,COX- 2,FAS,VEGF,Telomerase are also commonly linked to both esophageal and colonic adenocarcinoma in obese individuals.Whether these can be targeted as a therapeutic option needs further research and large scale studies.Role of aspirin as COX-2 inhibitor in regulating apoptosis appears theoritically as a promising drug as in prevention of colonic adenocarcinoma in patients with familial adenomatous polyposis.
Hampel H, Abraham NS, El-Serag HB. Meta-Analysis: Obesity and the Risk for Gastroesophageal Reflux Disease and Its Complications. Ann Intern Med. 2005;143:199–211. doi: 10.7326/0003-4819-143-3-200508020-00006
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Published: Ann Intern Med. 2005;143(3):199-211.
Esophageal Disorders, Gastroenterology/Hepatology, Gastroesophageal Reflux Disease, Obesity, Peptic Disease.
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