Obesity: A Challenge to Esophagogastric Junction Integrity John E. Pandolfino, Hashem B. El–Serag, Qing Zhang, Nimeesh Shah, Sudip K. Ghosh, Peter J. Kahrilas  Gastroenterology  Volume 130, Issue 3, Pages 639-649 (March 2006) DOI: 10.1053/j.gastro.2005.12.016 Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 1 Solid-state manometric assembly with 36 sensors spaced at 1-cm intervals. Each pressure sensor consists of 12 radially dispersed sensing elements that are 2.5 mm in length. Sector pressures are averaged within each sensor making is circumferentially sensitive. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 2 Isocontour manometric plots of the EGJ of a patient with normal anatomy (A) and a patient with hiatal hernia (B). The isocontour representation provides an overview of regional differences in intraluminal pressure integrated over time. The on-screen pressure scale was color coded, but in this illustration a gray scale is used with each isocontour level representing a 5-mm Hg increment in pressure. High-pressure zones, such as the EGJ or the separated components of the EGJ, are easily recognized by sharp transitions in pressure. The exact pressure at any point on this spatiotemporal grid can be ascertained either using the isobaric contour tool or the point-and-click smart mouse tool of the ManoView software. The time of peak inspiration is identified by maximal augmentation of EGJ, intragastric, or crural diaphragm (CDi) pressure, depending on an individual’s anatomy. Expiratory pressures were measured midway between adjacent peak inspirations. The distal border of the LES and the proximal border of the CDi typically overlap; however, once separation occurs they can be distinguished by the sharp transitions in pressure levels as in (B). The axial separation between LESmax and CDimax was quantified by taking the midpoint of the 2 EGJ components and determining the distance between them using the manometric ports as a distance reference. When separation exceeded 3–4 cm, a well-defined hiatal hernia pressure not subject to the influence of the LES or crural diaphragm could be ascertained (B). Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 3 Mean intragastric and intraesophageal pressures during inspiratory and expiratory phases of respiration. ANOVA was used to compare the pressure values between the 3 subject groups. Gastric expiration pressure: obese subjects had significantly higher gastric pressures compared to overweight subjects (P < .0001) and normal BMI subjects (P < .0001), whereas overweight subjects had a significantly higher gastric pressure than normal subjects (P < .0001). Gastric inspiration pressure: obese subjects had significantly higher gastric pressures compared with overweight subjects (P < .0001) and normal BMI subjects (P < .0001) whereas overweight subjects had a significantly higher gastric pressure than normal subjects (P < .0001). Esophageal expiration pressure: obese subjects had significantly higher intraesophageal pressures compared to overweight subjects (P = .013) and normal BMI subjects (P < .0001), and overweight subjects had a significantly higher intraesophageal pressure than normal subjects (P = .002). Esophageal inspiration pressure: there was no statistically significant difference between the 3 groups. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 4 (A) Association between intragastric pressure and BMI during both respiratory phases. (B) Association between intragastric pressure and WC during both respiratory phases. *P < .0001 using Pearson correlation calculation. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 5 Mean GEPG during both respiratory phases. Expiratory: obese vs normal BMI, P < .001 using ANOVA. Inspiratory: obese vs normal BMI, P < .0001, obese vs overweight, P < .0001, normal BMI vs overweight, P = .01, using ANOVA. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 6 (A) Mean values for sphincter separation (B) Mean EGJmax pressure during both respiratory phases. Using ANOVA, there was a significant increase in sphincter separation when normal BMI subjects were compared to overweight subjects (P = .005) and obese subjects (P = .001). There was no statistical difference between the sphincter separation when overweight and obese subjects were compared (P = .80). There was also no significant difference in the basal LES pressure between the 3 groups during both respiratory phases. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 7 The association between LES pressure and sphincter separation during inspiration and expiration. *P < .05 using Pearson correlation calculation. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions

Figure 8 Spatial pressure variation plots of a patient with (A) normal EGJ anatomy, (B) an obese patient with clear separation but overlap between the LES and crural diaphragm, and (C) a patient with a large hiatal hernia. These plots depict pressure along the length of the EGJ as a function of time. Each vertical line represents the simultaneous pressure values along the EGJ at that specific time and each line is spaced every 0.2 seconds. (A) In the normal weight subject without hiatal hernia the locus of maximal inspiratory pressure augmentation indicative of the CDi is superimposed on the LES making the 2 indistinguishable (EGJmax indicated by dots). Nonetheless, there are 2 distinct zones to the EGJ; a proximal high-pressure zone and a subdiaphragmatic low-pressure zone. The subdiaphragmatic low-pressure zone is most evident during expiration and likely represents the sphincteric contribution of the gastric sling and clasp fibers. (B) In this obese subject, gastric pressure is clearly increased. Additionally, the morphology of the EGJ is altered such that there is a 2-cm separation between LESmax (proximal dots) and CDimax (distal dots). Note that the lumen surrounded by the crural diaphragm pressurizes to intragastric pressure with expiration significantly shortening the EGJ high-pressure zone analogous to what is seen with hiatal hernia. (C) This subject has complete separation of the LES and the CDi (5 cm) with no overlap between the 2 high-pressure zones. Note that expiratory LESmax was greater than inspiratory LESmax because inspiration had the paradoxical effect of subtracting from LES pressure, presumably because the sphincter resided within the thoracic space. Gastroenterology 2006 130, 639-649DOI: (10.1053/j.gastro.2005.12.016) Copyright © 2006 American Gastroenterological Association Terms and Conditions