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Response to Comment on “High Levels of 18F-FG Uptake in Aortic Aneurysm Wall are Associated with High Wall Stress”
Eur J Vasc Endovasc Surg (2010) 39, 795e798
CORRESPONDENCE Inflammatory Response to Aortic Aneurysm Intraluminal Thrombus may Cause Increased 18F-FDG Uptake at Sites not Associated with High Wall stress. Comment on “High Levels of 18F-FDG Uptake in Aortic Aneurysm Wall are Associated with High Wall Stress” Dear Editor, We read with great interest the paper by Xu et al. where they demonstrated in a small series of aortic aneurysms that predicted peak wall stress (PWS) regions coincided with the region of high uptake of FDP, suggestive of a focally accelerated metabolism attributed to inflammatory changes affecting the structural integrity of aneurysm wall.1 The authors suggest a potential causal relationship between high wall stress and accelerated metabolism. This study should be commended for being the first to investigate the possible conjugation of PWS sites with biochemical markers that have been proven to correlate with decreased wall strength.2 The simultaneous combination of the latter with PWS could give a more reliable prediction of rupture risk. However, it should be noted that in these aortic aneurysms, the PWS sites were located at the junction between the neck and the sac, where little if any amount of thrombus was present. It is known that the presence of thrombus is associated with cellular inflammatory changes in the aneurysm wall3 and local reduction of the wall strength.4 So, in aneurysms with a thick layer of ILT, stress values would be considerably reduced at the thrombus sites, where at the same time, the induced inflammatory reaction would cause an elevated uptake of FDP, thus, the site with elevated FDP uptake may not correspond to the location of PWS.
References 1 Xu XY, Borghi A, Nchimi A, Leung J, Gomez P, Cheng Z, et al. High levels of 18F-FDG uptake in aortic Aneurysm wall are associated with high wall stress. Eur J Vasc Endovasc Surg 2010;39:295e301. 2 Choke E, Cockerill G, Wilson WRW, Sayed S, Dawson J, Loftus I, et al. A review of biological factors implicated in abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg 2005;30:227e44. 3 Kazi M, Thyberg J, Religa P, Roy J, Eriksson P, Hedin U, et al. Influence of intraluminal thrombus on structural and cellular composition of abdominal aortic aneurysm wall. J Vasc Surg 2003;38:1283e92. 4 Wang DH, Makaroun MS, Nemoto EM, Oqawa S, Webster MW. Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening. J Vasc Surg 2001;34:291e9.
E. Georgakarakos Department of Vascular Surgery, University of Crete Medical School, Heraklion 711 10, Greece Department of Vascular Surgery, St. Bonifatius Hospital, Lingen, Germany C. Ioannou* T. Kostas A. Katsamouris Department of Vascular Surgery, University of Crete Medical School, Heraklion 711 10, Greece *Corresponding author. Tel.: þ30 2810 392 393, þ30 6976 697 696 (mobile); Fax: þ30 2810 542 063. E-mail address: [email protected] (C. Ioannou) Available online 19 March 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.02.020
Response to Comment on “High Levels of 18F-FG Uptake in Aortic Aneurysm Wall are Associated with High Wall Stress”
Dear Editor, Structural alterations in the wall of abdominal aortic aneurysms (AAA) are dependent on the production of proteases by resident vascular wall cells and by cells of the lymphomonocytic infiltrate. The involvement of intraluminal thrombus (ILT) in aneurysmal progression as a source of proteases has been suggested following our initial report of increased MMP-9 in ILT.1 ILT activities are initiated at the luminal interface by circulating blood, such as platelet activation and fibrin formation and progressively convey zymogens towards the aneurysm wall, thus participating in the extracellular matrix degradation.2 On the abluminal side, ILT may be completely degraded by fibrinolysis, resulting in a crescent sign that corresponds to ‘liquefaction’ or bleeding into ILT3 and is best appreciated in the arterial phase of the scan. Besides a reduction of aneurysmal wall stress, ILT can also lead to local hypoxia triggering a medial neovascularisation and inflammation. FDG uptake could therefore be explained by the presence
796
Correspondence
of inflammatory cells at the a) luminal side, b) abluminal side, c) internal part of the ILT (in case of fibrinolysis), and d) within the aortic wall without thrombus. In our cases,4 we consider the points raised by Georgakarakos et al. irrelevant since no ILT was observed, neither in the neck nor at the junction of the sac and the neck of this inflammatory AAA (patients 4 & 5). The apparent thickness of the wall is only due to the inflammatory nature of the lesion. The co-localisation of areas of high wall stress and elevated FDG uptake and their concordance with the sites of rupture in two cases as shown in our study also suggest that high wall stress and accelerated metabolism may act together to cause aortic aneurysm rupture.
References 1 Sakalihasan N, Delvenne Ph, Nusgens B, Limet R, Lapie `re CM. Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms. J Vasc Surg 1996;24:127e33. 2 Fontaine V, Jacob MP, Houard X, Rossignol P, Plissonnier D, Angles-Cano E, Michel JB. Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms. Am J Pathol 2002;161:1701e10. 3 Roy J, Labruto F, Beckman MO, Danielson J, Johansson G, Swedenborg J. Bleeding into the intraluminal thrombus in abdominal aortic aneurysms is associated with rupture. J Vasc Surg Nov 2008;48(5):1108e13. 4 Xu XY, Borghi A, Nchimi A, Leung J, Gomez P, Cheng Z, et al. High levels of 18F-FDG uptake in aortic aneurysm wall are associated with high wall stress. Eur J Vasc Endovasc Surg 2010;39:295e301.
N. Sakalihasan* J.O. Defraigne Department of Thoracic and Cardiovascular, University of Lie`ge, Liege, Belgium *Corresponding author. E-mail address: [email protected] (N. Sakalihasan) X.Y. Xu Department of Chemical Engineering, Imperial College London, UK Available online 31 March 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.03.006
Comment on “The Influence of Wall Stress on AAA Growth and Biomarkers”
KEYWORDS Wall stress; Shear stress; Aneurysm expansion
Dear Editor, We read with great interest the article by Speelman et al., which combines information about wall stress and circulating biomarkers, related to AAA growth rate. The results suggested no correlation between stress values and biomarkers.1 Growth rate of the low stress group was significantly lower than that of the medium stress, despite the fact that this difference was not large between low and high stress groups. Stress is strongly influenced by the loading systolic pressure and the geometry of the AAA. So, the pressure steady state could actually not only unmask the effects of different geometry on stress values, but also its importance regarding other hemodynamic factors proven to influence the AAA expansion, especially in the early stages, where the amount of intraluminal thrombus could be negligible. Increased flow turbulence, depending on AAA geometry, results in increased stress values.2 The kinetic energy generated by turbulence increases wall and fluid shear stress distally. The increased fluid shear stress can result in further expansion and hence further turbulence, while wall shear stress is a mechanism for aneurysmal growth.2 This pattern provides an additional explanation theory of small AAA expansion, potentially applied in cases where neither differences in PWS nor biomarker values conjugate satisfactory with the different growth rates, like in the present study.
References 1 Speelman L, Hellenthal FA, Pulinx B, Bosboom EM, Breeuwer M, van Sambeek MR, et al. The influence of wall stress on AAA growth and biomarkers. Eur J Vasc Endovasc Surg 2010;39:410e6. 2 Khanafer KM, Bull JL, Upchurch Jr GR, Berguer R. Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions. Ann Vasc Surg 2007;21:67e74.
E. Georgakarakos Department of Vascular Surgery, University of Crete Medical School, 711 10 Heraklion, Greece St. Bonifatius Hospital, Lingen, Germany C.V. Ioannou* T. Kostas A.N. Katsamouris Department of Vascular Surgery, University of Crete Medical School, 711 10 Heraklion, Greece *Corresponding author. Tel.: þ30 2810 392 393, þ30 6976 697 696(mobile); fax: þ30 2810 542 063. E-mail address: [email protected] (C.V. Ioannou) Y. Papaharilaou Institute of Applied and Computational Mathematics, Foundation for Research and Technology-Hellas, Greece Available online 28 April 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.03.023
DOI of original article: 10.1016/j.ejvs.2009.12.021.
CORRESPONDENCE Inflammatory Response to Aortic Aneurysm Intraluminal Thrombus may Cause Increased 18F-FDG Uptake at Sites not Associated with High Wall stress. Comment on “High Levels of 18F-FDG Uptake in Aortic Aneurysm Wall are Associated with High Wall Stress” Dear Editor, We read with great interest the paper by Xu et al. where they demonstrated in a small series of aortic aneurysms that predicted peak wall stress (PWS) regions coincided with the region of high uptake of FDP, suggestive of a focally accelerated metabolism attributed to inflammatory changes affecting the structural integrity of aneurysm wall.1 The authors suggest a potential causal relationship between high wall stress and accelerated metabolism. This study should be commended for being the first to investigate the possible conjugation of PWS sites with biochemical markers that have been proven to correlate with decreased wall strength.2 The simultaneous combination of the latter with PWS could give a more reliable prediction of rupture risk. However, it should be noted that in these aortic aneurysms, the PWS sites were located at the junction between the neck and the sac, where little if any amount of thrombus was present. It is known that the presence of thrombus is associated with cellular inflammatory changes in the aneurysm wall3 and local reduction of the wall strength.4 So, in aneurysms with a thick layer of ILT, stress values would be considerably reduced at the thrombus sites, where at the same time, the induced inflammatory reaction would cause an elevated uptake of FDP, thus, the site with elevated FDP uptake may not correspond to the location of PWS.
References 1 Xu XY, Borghi A, Nchimi A, Leung J, Gomez P, Cheng Z, et al. High levels of 18F-FDG uptake in aortic Aneurysm wall are associated with high wall stress. Eur J Vasc Endovasc Surg 2010;39:295e301. 2 Choke E, Cockerill G, Wilson WRW, Sayed S, Dawson J, Loftus I, et al. A review of biological factors implicated in abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg 2005;30:227e44. 3 Kazi M, Thyberg J, Religa P, Roy J, Eriksson P, Hedin U, et al. Influence of intraluminal thrombus on structural and cellular composition of abdominal aortic aneurysm wall. J Vasc Surg 2003;38:1283e92. 4 Wang DH, Makaroun MS, Nemoto EM, Oqawa S, Webster MW. Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening. J Vasc Surg 2001;34:291e9.
E. Georgakarakos Department of Vascular Surgery, University of Crete Medical School, Heraklion 711 10, Greece Department of Vascular Surgery, St. Bonifatius Hospital, Lingen, Germany C. Ioannou* T. Kostas A. Katsamouris Department of Vascular Surgery, University of Crete Medical School, Heraklion 711 10, Greece *Corresponding author. Tel.: þ30 2810 392 393, þ30 6976 697 696 (mobile); Fax: þ30 2810 542 063. E-mail address: [email protected] (C. Ioannou) Available online 19 March 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.02.020
Response to Comment on “High Levels of 18F-FG Uptake in Aortic Aneurysm Wall are Associated with High Wall Stress”
Dear Editor, Structural alterations in the wall of abdominal aortic aneurysms (AAA) are dependent on the production of proteases by resident vascular wall cells and by cells of the lymphomonocytic infiltrate. The involvement of intraluminal thrombus (ILT) in aneurysmal progression as a source of proteases has been suggested following our initial report of increased MMP-9 in ILT.1 ILT activities are initiated at the luminal interface by circulating blood, such as platelet activation and fibrin formation and progressively convey zymogens towards the aneurysm wall, thus participating in the extracellular matrix degradation.2 On the abluminal side, ILT may be completely degraded by fibrinolysis, resulting in a crescent sign that corresponds to ‘liquefaction’ or bleeding into ILT3 and is best appreciated in the arterial phase of the scan. Besides a reduction of aneurysmal wall stress, ILT can also lead to local hypoxia triggering a medial neovascularisation and inflammation. FDG uptake could therefore be explained by the presence
796
Correspondence
of inflammatory cells at the a) luminal side, b) abluminal side, c) internal part of the ILT (in case of fibrinolysis), and d) within the aortic wall without thrombus. In our cases,4 we consider the points raised by Georgakarakos et al. irrelevant since no ILT was observed, neither in the neck nor at the junction of the sac and the neck of this inflammatory AAA (patients 4 & 5). The apparent thickness of the wall is only due to the inflammatory nature of the lesion. The co-localisation of areas of high wall stress and elevated FDG uptake and their concordance with the sites of rupture in two cases as shown in our study also suggest that high wall stress and accelerated metabolism may act together to cause aortic aneurysm rupture.
References 1 Sakalihasan N, Delvenne Ph, Nusgens B, Limet R, Lapie `re CM. Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms. J Vasc Surg 1996;24:127e33. 2 Fontaine V, Jacob MP, Houard X, Rossignol P, Plissonnier D, Angles-Cano E, Michel JB. Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms. Am J Pathol 2002;161:1701e10. 3 Roy J, Labruto F, Beckman MO, Danielson J, Johansson G, Swedenborg J. Bleeding into the intraluminal thrombus in abdominal aortic aneurysms is associated with rupture. J Vasc Surg Nov 2008;48(5):1108e13. 4 Xu XY, Borghi A, Nchimi A, Leung J, Gomez P, Cheng Z, et al. High levels of 18F-FDG uptake in aortic aneurysm wall are associated with high wall stress. Eur J Vasc Endovasc Surg 2010;39:295e301.
N. Sakalihasan* J.O. Defraigne Department of Thoracic and Cardiovascular, University of Lie`ge, Liege, Belgium *Corresponding author. E-mail address: [email protected] (N. Sakalihasan) X.Y. Xu Department of Chemical Engineering, Imperial College London, UK Available online 31 March 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.03.006
Comment on “The Influence of Wall Stress on AAA Growth and Biomarkers”
KEYWORDS Wall stress; Shear stress; Aneurysm expansion
Dear Editor, We read with great interest the article by Speelman et al., which combines information about wall stress and circulating biomarkers, related to AAA growth rate. The results suggested no correlation between stress values and biomarkers.1 Growth rate of the low stress group was significantly lower than that of the medium stress, despite the fact that this difference was not large between low and high stress groups. Stress is strongly influenced by the loading systolic pressure and the geometry of the AAA. So, the pressure steady state could actually not only unmask the effects of different geometry on stress values, but also its importance regarding other hemodynamic factors proven to influence the AAA expansion, especially in the early stages, where the amount of intraluminal thrombus could be negligible. Increased flow turbulence, depending on AAA geometry, results in increased stress values.2 The kinetic energy generated by turbulence increases wall and fluid shear stress distally. The increased fluid shear stress can result in further expansion and hence further turbulence, while wall shear stress is a mechanism for aneurysmal growth.2 This pattern provides an additional explanation theory of small AAA expansion, potentially applied in cases where neither differences in PWS nor biomarker values conjugate satisfactory with the different growth rates, like in the present study.
References 1 Speelman L, Hellenthal FA, Pulinx B, Bosboom EM, Breeuwer M, van Sambeek MR, et al. The influence of wall stress on AAA growth and biomarkers. Eur J Vasc Endovasc Surg 2010;39:410e6. 2 Khanafer KM, Bull JL, Upchurch Jr GR, Berguer R. Turbulence significantly increases pressure and fluid shear stress in an aortic aneurysm model under resting and exercise flow conditions. Ann Vasc Surg 2007;21:67e74.
E. Georgakarakos Department of Vascular Surgery, University of Crete Medical School, 711 10 Heraklion, Greece St. Bonifatius Hospital, Lingen, Germany C.V. Ioannou* T. Kostas A.N. Katsamouris Department of Vascular Surgery, University of Crete Medical School, 711 10 Heraklion, Greece *Corresponding author. Tel.: þ30 2810 392 393, þ30 6976 697 696(mobile); fax: þ30 2810 542 063. E-mail address: [email protected] (C.V. Ioannou) Y. Papaharilaou Institute of Applied and Computational Mathematics, Foundation for Research and Technology-Hellas, Greece Available online 28 April 2010 ª 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejvs.2010.03.023
DOI of original article: 10.1016/j.ejvs.2009.12.021.