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Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study

Elke Van Daele (UGent) , Yves Van Nieuwenhove (UGent) , Wim Ceelen (UGent) , Christian Vanhove (UGent) , Bart Braeckman (UGent) , Anne Hoorens (UGent) , Jurgen Van Limmen (UGent) , Oswald Varin (UGent) , Dirk Van de Putte (UGent) , Wouter Willaert (UGent) , et al.
(2018) MEDICINE. 97(38).
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Abstract
Introduction: The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft after esophageal reconstruction. Clinical judgment is unreliable in determining graft perfusion. Therefore, an objective, validated, and reproducible method is urgently needed. Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an emerging and promising modality. This study's objectives are to evaluate the feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion and to validate ICGA by comparison with hemodynamic parameters, blood and tissue expression of hypoxia-induced markers, and tissue mitochondrial respiration rates. And, second, to evaluate its ability to predict AL in patients after minimally invasive esophagectomy (MIE). Methods: Patients (N = 70) with resectable esophageal cancer will be recruited for standard MIE. ICGA will be performed after graft creation and thoracic pull-up. Dynamic digital images will be obtained starting after intravenous bolus administration of ICG. The resulting images will be subjected to curve analysis and to compartmental analysis based on the adiabatic approximation to tissue homogeneity kinetic model. The calculated perfusion parameters will be compared to intraoperative hemodynamic data to evaluate the effects of patient hemodynamics. To verify whether graft perfusion represents tissue oxygenation, ICGA perfusion parameters will be compared with systemic and serosa lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia-related markers and mitochondrial chain respiratory rate. Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict AL and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses. Discussion: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during MIE, potentially reducing the incidence of AL and its associated severe morbidity and mortality.
Keywords
anastomotic leakage, esophagectomy, indocyanine green angiography, near-infrared fluorescence imaging, oxygenation, perfusion, stomach graft, GASTRIC TUBE PERFUSION, ENHANCED REALITY, ANASTOMOTIC LEAKAGE, FACTOR 1-ALPHA, PREDICTORS, EXPRESSION, MORBIDITY, MORTALITY, CARCINOMA, SURVIVAL

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MLA
Van Daele, Elke et al. “Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery : Protocol for a Single-center Prospective Observational Study.” MEDICINE 97.38 (2018): n. pag. Print.
APA
Van Daele, E., Van Nieuwenhove, Y., Ceelen, W., Vanhove, C., Braeckman, B., Hoorens, A., Van Limmen, J., et al. (2018). Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study. MEDICINE, 97(38).
Chicago author-date
Van Daele, Elke, Yves Van Nieuwenhove, Wim Ceelen, Christian Vanhove, Bart Braeckman, Anne Hoorens, Jurgen Van Limmen, et al. 2018. “Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery : Protocol for a Single-center Prospective Observational Study.” Medicine 97 (38).
Chicago author-date (all authors)
Van Daele, Elke, Yves Van Nieuwenhove, Wim Ceelen, Christian Vanhove, Bart Braeckman, Anne Hoorens, Jurgen Van Limmen, Oswald Varin, Dirk Van de Putte, Wouter Willaert, and Piet Pattyn. 2018. “Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery : Protocol for a Single-center Prospective Observational Study.” Medicine 97 (38).
Vancouver
1.
Van Daele E, Van Nieuwenhove Y, Ceelen W, Vanhove C, Braeckman B, Hoorens A, et al. Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study. MEDICINE. 2018;97(38).
IEEE
[1]
E. Van Daele et al., “Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study,” MEDICINE, vol. 97, no. 38, 2018.
@article{8575222,
  abstract     = {Introduction: The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft after esophageal reconstruction. Clinical judgment is unreliable in determining graft perfusion. Therefore, an objective, validated, and reproducible method is urgently needed. Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an emerging and promising modality. This study's objectives are to evaluate the feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion and to validate ICGA by comparison with hemodynamic parameters, blood and tissue expression of hypoxia-induced markers, and tissue mitochondrial respiration rates. And, second, to evaluate its ability to predict AL in patients after minimally invasive esophagectomy (MIE). 
Methods: Patients (N = 70) with resectable esophageal cancer will be recruited for standard MIE. ICGA will be performed after graft creation and thoracic pull-up. Dynamic digital images will be obtained starting after intravenous bolus administration of ICG. The resulting images will be subjected to curve analysis and to compartmental analysis based on the adiabatic approximation to tissue homogeneity kinetic model. The calculated perfusion parameters will be compared to intraoperative hemodynamic data to evaluate the effects of patient hemodynamics. To verify whether graft perfusion represents tissue oxygenation, ICGA perfusion parameters will be compared with systemic and serosa lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia-related markers and mitochondrial chain respiratory rate. Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict AL and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses. 
Discussion: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during MIE, potentially reducing the incidence of AL and its associated severe morbidity and mortality.},
  articleno    = {e12073},
  author       = {Van Daele, Elke and Van Nieuwenhove, Yves and Ceelen, Wim and Vanhove, Christian and Braeckman, Bart and Hoorens, Anne and Van Limmen, Jurgen and Varin, Oswald and Van de Putte, Dirk and Willaert, Wouter and Pattyn, Piet},
  issn         = {0025-7974},
  journal      = {MEDICINE},
  keywords     = {anastomotic leakage,esophagectomy,indocyanine green angiography,near-infrared fluorescence imaging,oxygenation,perfusion,stomach graft,GASTRIC TUBE PERFUSION,ENHANCED REALITY,ANASTOMOTIC LEAKAGE,FACTOR 1-ALPHA,PREDICTORS,EXPRESSION,MORBIDITY,MORTALITY,CARCINOMA,SURVIVAL},
  language     = {eng},
  number       = {38},
  pages        = {6},
  title        = {Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery : protocol for a single-center prospective observational study},
  url          = {http://dx.doi.org/10.1097/md.0000000000012073},
  volume       = {97},
  year         = {2018},
}

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