Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of... Summary Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage. A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters. Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described. Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery. INTRODUCTION Anastomotic leakage is a major complication after esophagectomy with gastric tube reconstruction, with a high morbidity and even mortality rate (4%).1 The development of poor blood perfusion is partially described to a lack of oxygen and nutrients, which are essential for cell metabolism. This is widely known as a contributing factor for anastomotic dehiscence.2 The gastric tube depends on the right gastric and right gastroepiploic arteries, which usually terminate before the anastomotic site at the gastric fundus and this area is therefore prone to decreased perfusion (Fig. 1). At present, perfusion is not quantitatively examined during surgery. If perfusion could be monitored and quantified, the surgeon could change the reconstructive design3–5 and the anesthesiologists might improve perfusion with medication or adapting fluid administration.6 Fig. 1 View largeDownload slide Esophagectomy with gastric tube reconstruction. Fig. 1 View largeDownload slide Esophagectomy with gastric tube reconstruction. Over the past decades, innovative optical techniques have been developed that use the interaction of light with tissue. Different optical techniques have been tested to monitor perfusion in gastric tube surgery (Table 2). The aim of this systematic review is to evaluate (1) technical background of optical modalities that are tested in gastric tube surgery, (2) quantitative parameters that are used to monitor (micro)vascularization at the anastomotic site, and (3) which parameters are the most predictive for anastomotic leakage. METHODS Methodology was developed from standard guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement7 and the Standards for the Reporting of Diagnostic accuracy studies (STARD) Statement.8 Search strategy and study selection A detailed electronic search was carried out on optical techniques and gastric tube surgery from the following databases: MEDLINE, Embase, and Pubmed (Table 1). No timeline limitation was applied to the search, so all articles published before October 26, 2017 were included for analysis. Table 1 Medline, Embase, and Pubmed electronic search strategies Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] View Large Table 1 Medline, Embase, and Pubmed electronic search strategies Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] View Large Table 2 Perfusion imaging methods Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No LDF, laser Doppler flowmetry; NIRS, near infrared spectroscopy; LSCI, laser speckle contrast imaging; IRT, infrared thermographic imaging; FI, fluorescence imaging; OCT, optical coherence tomography. View Large Table 2 Perfusion imaging methods Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No LDF, laser Doppler flowmetry; NIRS, near infrared spectroscopy; LSCI, laser speckle contrast imaging; IRT, infrared thermographic imaging; FI, fluorescence imaging; OCT, optical coherence tomography. View Large Abstracts of publications with potential relevance based on titles were analyzed and selected full text articles were reviewed for analysis and quality assessment by two authors (DMB, SMJ). Inclusion and exclusion criteria Inclusion criteria were perfusion or blood flow and use of optical techniques and gastric tube reconstruction as subject of study. Exclusion criteria were articles not available, articles not in English, study designs (reviews, case reports), and reviews. Endpoints Primary outcome was quantitative measurement of change in perfusion in gastric tube reconstruction; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters. Data extraction Data extraction on year of publication, study design, inclusion and exclusion criteria, type of technique (index test), reference standard, target condition, number of participants in each group, types of surgery, variables and outcomes (data on efficacy) was done by two reviewers (SMJ, DMB). In vivo studies were reviewed according to QUADAS-2 standards.9 Development of techniques was staged by IDEAL (Idea-Development-Exploration-Assessment-Long-term Study).10 Assessment of risk of bias Two reviewers (SMJ, DMB) independently assessed the quality of methodology by using the QUADAS-2 quality tool for assessing risk of bias.9 This includes patient selection, index test, reference standard, flow, and timing. A representative spectrum was defined as any cohort of patients or animals with esophageal cancer treated with esophagectomy and gastric tube reconstruction. Results Our search identified 953 articles. After removal of duplicates 577 unique articles were screened by title and abstract and 43 articles were selected based on the inclusion and exclusion criteria (Fig. 2). Eleven articles were excluded after reading full text for 3 reasons; cancer as subject of the study, trachea as subject of the study, no optical modality used. We included 32 articles for analyses on study quality and data extraction (Tables 3–5). After screening references for original articles, 1 article was added to our search (n = 33). Twelve articles studied laser Doppler flowmetry, 12 fluorescence imaging, and 1 fluorescence imaging & laser Doppler flowmetry, 3 studied spectroscopy & laser Doppler flowmetry, 3 laser speckle contrast imaging, and 1 laser speckle contrast imaging and thermographic imaging, 1 sidestream dark field microscopy and laser Doppler flowmetry and 0 articles on optical coherence tomography. Fig. 2 View largeDownload slide Flow diagram. Fig. 2 View largeDownload slide Flow diagram. Table 3 Details of the study characteristics in LDF studies Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND (ND = not done). View Large Table 3 Details of the study characteristics in LDF studies Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND (ND = not done). View Large Table 4 Details of study characteristics in NIRS studies Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND View Large Table 4 Details of study characteristics in NIRS studies Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND View Large Table 5 Details of study characteristics in LSCI, FI, and SDF studies Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND View Large Table 5 Details of study characteristics in LSCI, FI, and SDF studies Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND View Large Quality assessment All studies are in the initial phase of research, according to the IDEAL-stage (1–3) (Table 6). Quadas-2 analysis for diagnostic accuracy showed a level of bias, due to lack of a reference test to measure perfusion. Table 6 QUADAS-2 results and IDEAL-stage View Large Table 6 QUADAS-2 results and IDEAL-stage View Large Statistical analysis Due to the experimental set-up of studies, heterogeneity in outcome parameters and lack of randomized controlled trials, a meta-analysis could not be performed of the selected articles. Studies were evaluated on IDEAL-stage and quality (QUADAS-2) and an overview is given on optical techniques, working mechanism, measurement parameters and interpretation of parameters. OPTICAL TECHNIQUES Laser Doppler flowmetry Laser Doppler flowmetry (LDF) was first introduced by Sheperd and Riedel in 1982 and utilizes laser light to measure velocities of red blood cells by their Doppler shifts.11 LDF makes point measurements. Perfusion is measured in perfusion units, an arbitrary unit. In gastric tube surgery, LDF was studied the most widely. It is the oldest technique, developed in 1980. There were three animal studies (1 rat study n = 20, 2 pig studies n = 32), and nine prospective patients studies (n = 209) on LDF included in our analysis (Table 3). Studies were conducted between 1995 and 2013. Outcomes were change in blood flow in perfusion units (PU) in all studies and leakage in two.12–14 Four of 12 studies (n = 67) found a significant decrease in PU after vessel ligation of the stomach for gastric tube reconstruction. One study (n = 11) found a significant decrease of PU only in the fundus after stomach mobilization and not in the antrum.15 PU’s had a variety in amounts (23–1109) compared between studies, emphasizing the fact that this is an arbitrary parameter, and not an absolute parameter. Ikeda et al. (n = 43) evaluated the effect of tissue blood flow on the incidence of anastomotic leakage following esophagostomy with gastric tube reconstruction. He found that blood flow measured with LDF in patients with leakage was significantly lower (9.1 ± 2.0 mL/min/100 g) when compared to patients without leakage (13.7 ± 2.9 mL/min/100 g) (P < 0.01, unpaired t-test). To change the arbitrary unit of PU to this parameter of mL/min/100 g tissue, Ikeda et al. used the theory of Bonner (Physicist).16 However, Rajan et al. showed that Bonner and Nossal use assumptions for light scattering and Doppler shift in this theory, which are difficult to apply on human tissue.17 Miyazaki et al. (n = 44) compared intraoperative blood flow in PU between leakage and nonleakage groups.13 However, groups were not comparable due to unmatched group sizes (low power: n = 5 leakage patients, compared to n = 39 nonleakage patients). Postoperative blood flow was significantly lower in the leakage group after three days. Boyle et al. validated scanning laser Doppler flowmetry (2000) based on LDF (n = 16).18 They found a significant fall in gastric perfusion (PU) of 41% in all subjects after mobilization of the stomach. Also, a greater decrease of perfusion in the fundus (55%) compared to the antrum (25%) measured with scanning laser Doppler flowmetry was found. In general, LDF is able to measure perfusion in perfusion units with a significant lower amount of perfusion units in tissue with necrosis development compared to healthy tissue. Near infrared spectroscopy Near infrared spectroscopy (NIRS) is based on the absorption of laser light by tissue properties, and it was first described by MacMunn.19 The absorption spectrum of light is different for diverse chromophores in tissue. This could i.e. be used to measure oxygenated or deoxygenated hemoglobin. We found three articles on NIRS in gastric perfusion evaluation, of which one animal study of van Bommel et al. in pigs (n = 12), all using one type of optical device (Table 4). Outcome parameters were mucosal oxygen saturation (MOS) and hemoglobin concentration (Hbcon). Van Bommel et al. found no difference in MOS and Hbcon between nitro-glycerine and norepinephrine in a pig study.20 Buise et al. also evaluated the influence of nitro-glycerine on gastric tube microcirculation and found no difference in MOS between intervention with nitroglycerine and saline.21 Measured MOS decreased significantly in both groups after pulling up the gastric tube to the neck (91% to 63% in nitro-glycerine group, 86% to 51% in saline group). In general, NIRS is able to measure perfusion in mucosal oxygen saturation and hemoglobin concentration; however the predictive value of necrosis development is not described yet. Laser speckle (contrast) imaging The principle of speckle intensity fluctuations to measure skin perfusion is developed by many researchers using different techniques around 1970–1980.22,23 We found one animal study (n = 9 pigs) on laser speckle imaging (LSI) by Klijn et al.24 and three patients studies (n = 81). Klijn combined LSI and thermographic imaging to evaluate blood flow changes after increase of mean arterial blood pressure (MAP) from 50 to 110 during gastric tube surgery. An increasing MAP had no effect on perfusion at any location in the gastric tube measured by LSI and thermography. A decrease in PU (arbitrary units) was found between top and the base and medial side of the gastric tube, this difference however was not significant. Milstein et al. evaluated 11 patients using laser speckle contrast imaging (LSCI) intraoperatively. They found a high interrater reliability of blood flow measurements in laser speckle perfusion units (LSPU), with a progressive decrease of LSPU toward the fundus of the gastric tube.25 Ambrus et al. showed a decrease of LSPU toward the fundus after gastric pull-up of 25% in 25 patients.26 In another study of 45 patients, they used LSCI to investigate the influence of phenyl ephedrine on gastric microcirculation and they observed no difference between the group with phenyl ephedrine (n = 20) compared to the group without phenyl ephedrine (n = 25).27 In short, LSCI measures perfusion in perfusion units and a decrease of PU is observed toward the fundus intraoperatively. However, no predictive value for necrosis is found yet. Fluorescence imaging In fluorescence imaging (FI), a laser illuminates the tissue. An intrinsic or extrinsic fluorescent molecule is excited by this light from the ground state to a higher energy level. When the molecule returns to the ground state a photon is emitted with a lower energy (higher wavelength) than used for excitation. Filtering separates the emitted light from the excitation light, enabling discrimination between the two types of light. This creates an image with a high contrast. In the past years, there has been an exponential grow of FI studies, mostly qualitative.28 Twelve articles on FI were included all with use of indocyanine green (ICG) (n = 556). Different qualitative outcome measures were determined cognitively: detection of microcirculation, blood flow (good vs. sparse or absent), and blood flow routes. Rino et al. used FI to evaluate blood supply routes and found 66.7% located in the greater omentum and ‘splenic hiatal route’ (n = 22).29 Shimada et al. found that microcirculation detected by ICG does not necessarily provide enough blood flow to maintain a viable anastomosis.30 Kubota et al. also describe the possibility to observe venous perfusion with FI.31 However, they did not quantify this perfusion. Kumagai et al. measured enhancement of the route to the cranial branch in seconds and found no difference in ‘enhancement time’ between ‘good or ‘sparse or absent’ flow (P = 0.24).32 Yukaya et al. reported a quantitative assessment of blood flow with ICG in luminance over time, however no significant correlation was found.33 Hodari et al.34 described the decrease of anastomotic leakage incidence from 20% to 0% after the introduction of robotic-assisted esophagectomy with gastric tube reconstruction, using integrated FI (n = 54). Zehetner et al. correlated the distance of the point of demarcation assessed by FI of the gastric tube towards the anastomosis with leakage and found a significant correlation: the longer this distance the higher risk of anastomotic leakage.35 Also, Koyanagi et al. found a significant difference in anastomotic leakage development based on ICG stream. They divided patients into two groups based on the ICG fluorescence stream: a simultaneous group where the blood stream was fast and a delayed group where the blood stream was slow (n = 40). In the delayed group, 7 patients developed anastomotic leakage, whereas 0 patients developed leakage in the simultaneous group.36 Kitagawa et al. showed in a retrospective study (n = 72) that FI was associated with postoperative endoscopic assessment of the anastomosis after gastric tube reconstruction. In the group that used FI for line marking, only 6.5% anastomotic leakage occurred, compared to 15.4% in the group without FI.37 Ohi et al. showed a correlation between a surgical intervention in case of low perfusion area and the development of anastomotic leakage. They described FI depicted low flow as an independent risk factor for the development of anastomotic leakage (P = 0.0057).38 Finally, Schlottmann and Patti imaged gastric tube perfusion using FI in 5 patients. In 2 of the 5 patients (40%) low FI intensity was visible in the fundus of the gastric tube and a surgical intervention was made. They describe that there was no anastomotic leakage in this group of patients.39 In short, FI is able to measure the quality of perfusion. No quantitative parameter is described yet. However, with FI the length of the demarcation to the anastomosis seems a predictive value for necrosis intraoperatively. Sidestream dark field microscopy In sidestream dark field (SDF), imaging tissue is illuminated by green light emitting diodes (LEDs). Hemoglobin in red blood cells is absorbing this 530 nm light, producing a high contrast compared to surrounding tissue. To image movement of flowing RBSs, light is pulsed stroboscopically into the tissue and is detected with a camera.40 We found one article on SDF imaging in gastric tube surgery.41 However, instead of gastric tissue SDF was performed sublingually to calculate microvascular parameters like vessel density and blood flow velocity. Sublingual microvascular flow significantly increased in patients after stroke volume-guided fluid therapy and dopexamine. In short, based upon these findings, SDF is able to measure microvascular flow. However, intraoperative prediction of necrosis is not yet described. Optical coherence tomography Optical coherence tomography (OCT) is an imaging method that was developed in 1991 by Fuijimoto.42 It is the optical equivalent of ultrasound, except instead of sound near infrared light waves are shined into the tissue. Light intensity changes are caused by differences in backscattered light and measured in an interferometer, which allows for the depth resolved visualization of tissue layers. With OCT, it is possible to image tissue in real time, in high-resolution and in depth and potentially blood flow could be imaged by this technique. OCT is able to image the internal lumen of the esophagus during gastroscopy, as described by multiple studies.43,44 Additionally, perfusion could be measured by OCT in different tissues.45,46 However, in our analysis, we did not find any article on OCT imaging of perfusion in gastric tube surgery. OCT could potentially measure perfusion in related parameters. However, no studies are there to proof this and show the relation between these parameters and the prediction of necrosis development. DISCUSSION This systematic review describes the current literature on optical techniques and their (quantitative) parameters to measure perfusion and predict anastomotic leakage in gastric tube reconstruction after esophagostomy. The techniques differ in terms of field of view, resolution, and perfusion parameter. Recommendations for the intraoperative use of optical techniques (Scanning) laser Doppler flowmetry Advantages of LDF are the real-time, noninvasive imaging in a relatively easy and fast way. Disadvantages are the inaccuracy of Doppler-shift measurements in angled movements, point measurements missing important information due to heterogeneity of capillary network and misinterpretation of parameters due to overlying vessels. Although articles show a relation between drop in perfusion units and development of anastomotic leakage, surgeons should understand this relative change of color within the image is arbitrary and therefore sensitive for misinterpretation. Near infrared spectroscopy Advantages of this technique are the small probe and the ability to monitor perfusion during and postsurgery. Disadvantages are the sensitivity for patient movements, which could influence the outcome during monitoring, the use of point measurements and the probing of overlying vessels, which results in misinterpretation due to probing of underlying arteries instead of the subsurface capillaries. Articles show variance in MOS before and after gastric pull up, but also between antrum and fundus of healthy gastric tissue. In surgery tissue will always be deoxygenated due to the operation; therefor predication of necrosis with NIRS becomes difficult. Laser speckle (contrast) imaging The advantage of LSCI is the directly available color-coded images. Moreover, speckle is more sensitive for motion than Doppler shift and does not relate to angle motions. The disadvantage is the parameter (perfusion units), which is arbitrary and therefore difficult to compare. Articles show the feasibility of LSCI diagnostics during surgery and a significant decrease of the quantitative parameter LSPU towards the fundus. Correlation of this parameter to patient outcome has not been showed yet and would improve the value of this technique in the clinical setting. Fluorescence imaging Advantages of FI are the visual movie of influx of perfusion in real-time during surgery. It is very easy to interpret, however studies use qualitative parameters, which is a disadvantage. Although the correlation between the distance of ICG demarcation to the fundus and the patient outcome in terms of anastomotic leakage is described, a quantitative parameter is needed to determine perfusion problems intraoperatively on the spot. Luminance over time could be a useful parameter, but the significant correlation with anastomotic leakage development is not proven yet. At the moment, studies focus on the development of FI to a quantitative imaging technique, for example in the PERFECT trial for colorectal cancer (NCT02626091). Sidestream dark field microscopy Advantages of SDF are the real-time visualization of RBCs in the capillaries; to see movement means that there is flow. Moreover, flow can be measured in a quantitative parameter (mm/second, vessel density and vessel diameter). Disadvantages are the contact that you have to make with tissue. Therefore patient movement by breathing or heartbeats will influence the image and artifacts can occur due to pressure. The validation of this quantitative parameter needs to be done, before we can adjust measurements to the clinic. Optical coherence tomography This technique is the only optical depth-resolved imaging system that is able to make a cross-sectional image in millimeters. Advantages are the high-resolution, high-contrast, and real-time imaging ability. Disadvantages are the postprocessing that is needed to measure perfusion in a linear parameter. If OCT would be able to create measurements in quantitative parameters of mL/minutes/gram, it would be very promising to use this technique in gastric tube surgery. Limitations Our results show that there is lack of understanding of quantitative parameters and little consensus on which technique to use. Due to a missing gold standard in perfusion measurements, diagnostic accuracy at this stage cannot be tested and therefor overall quality of literature according to QUADAS-2 is medium. Moreover, selected studies use optical techniques as a method to test an intervention, which makes it difficult to evaluate the optical technique itself. This is caused by the gap between the biomedical engineering and the clinic, the misinterpretation of quantitative parameters by clinicians and the force of companies to get their device into the clinic. Almost all studies are in the initial phase of human research according to IDEAL-stage for surgical innovation. Human studies are needed to evaluate quantitative parameters of techniques and their ability to predict anastomotic leakage. Because of the heterogeneity in parameters, a meta-analysis could not be conducted and overall appraisable on quantification is complicated. Although this is a limitation of our study, understanding of techniques and parameters are important for the evaluation and set-up of further studies. Variability of parameters makes it hard to evaluate different techniques. We need studies with the same outcome variables and a gold standard to test diagnostic accuracy in perfusion monitoring. Techniques are in an initial phase; 1–3 stage of IDEAL. Moreover, validation of techniques is needed, by using a reference test or a standard laboratory setting (phantom study), to evaluate measured parameters before we can implement new modalities in the clinic. This systematic review shows a lack in validation of optical techniques and parameters. Advice for perfusion monitoring A quantitative parameter is needed to objectify perfusion during surgery. The ideal perfusion parameter would be mL/minutes/gram. Future prospective studies need to validate quantitative parameters using a gold standard or a standard setting (phantom study). Furthermore, techniques have to be tested at the same time point during surgery to compare modalities and their parameters. CONCLUSIONS Optical techniques are valuable for perfusion evaluation in gastric tube surgery, giving their real-time, high-resolution, and high-contrast measurements. LSCI and FI give a real-time wide field overview of perfusion, unfortunately they both lack in terms of quantitative parameters. LDF and LSCI use arbitrary perfusion units, and are therefore difficult in interpretation. Moreover, point measurements (LDF) should not be the first choice in perfusion evaluation, taking vascular heterogeneity into account. SDF and OCT have great potential in perfusion diagnostics, but patient studies are needed. Future prospective studies need to determine a threshold value for quantitative parameters to predict anastomotic failure. Disclosures Drs. Jansen, Dr. de Bruin, Dr. van Berge Henegouwen, Dr. Strackee, Dr. Veelo, and Dr. Gisbertz have no conflicts of interest or financial ties to disclose. Dr. van Leeuwen reports grants from ZON-MW, non-financial support from Quest innovations, other from PA imaging BV, grants and nonfinancial support from Lionix, grants and nonfinancial support from Xiophotonics, grants and nonfinancial support from Ninepoint, outside the submitted work. In addition, Dr. van Leeuwen has a patent Combined Raman Spectroscopy-Optical Coherence Tomography (RS-OCT) System and Applications of the Same issued, a patent Common detector for combined Raman spectroscopy-optical coherence tomography issued, a patent Arthroscopic Instrument assembly, and method of localizing musculoskeletal structure during athroscopic surgery issued, a patent flow cytometry method for determination of size and refractive index of substantially spherical single particles and calibration method suitable for use with such a flow cytometry method pending, a patent high wavenumber Raman spectroscopy and applications of same pending, and a patent Common-Path Integrated Low Coherence Interferometry System and Method Therefor pending. ACKNOWLEDGMENTS Authors would like to thank Faridi van Etten of the Dutch Cochrane Centre & Medical Library AMC for her contribution to this paper and Inge Kos for the illustrations. 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Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diseases of the Esophagus Oxford University Press

Optical techniques for perfusion monitoring of the gastric tube after esophagectomy: a review of technologies and thresholds

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© The Authors 2018. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.
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Abstract

Summary Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage. A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters. Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described. Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery. INTRODUCTION Anastomotic leakage is a major complication after esophagectomy with gastric tube reconstruction, with a high morbidity and even mortality rate (4%).1 The development of poor blood perfusion is partially described to a lack of oxygen and nutrients, which are essential for cell metabolism. This is widely known as a contributing factor for anastomotic dehiscence.2 The gastric tube depends on the right gastric and right gastroepiploic arteries, which usually terminate before the anastomotic site at the gastric fundus and this area is therefore prone to decreased perfusion (Fig. 1). At present, perfusion is not quantitatively examined during surgery. If perfusion could be monitored and quantified, the surgeon could change the reconstructive design3–5 and the anesthesiologists might improve perfusion with medication or adapting fluid administration.6 Fig. 1 View largeDownload slide Esophagectomy with gastric tube reconstruction. Fig. 1 View largeDownload slide Esophagectomy with gastric tube reconstruction. Over the past decades, innovative optical techniques have been developed that use the interaction of light with tissue. Different optical techniques have been tested to monitor perfusion in gastric tube surgery (Table 2). The aim of this systematic review is to evaluate (1) technical background of optical modalities that are tested in gastric tube surgery, (2) quantitative parameters that are used to monitor (micro)vascularization at the anastomotic site, and (3) which parameters are the most predictive for anastomotic leakage. METHODS Methodology was developed from standard guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement7 and the Standards for the Reporting of Diagnostic accuracy studies (STARD) Statement.8 Search strategy and study selection A detailed electronic search was carried out on optical techniques and gastric tube surgery from the following databases: MEDLINE, Embase, and Pubmed (Table 1). No timeline limitation was applied to the search, so all articles published before October 26, 2017 were included for analysis. Table 1 Medline, Embase, and Pubmed electronic search strategies Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] View Large Table 1 Medline, Embase, and Pubmed electronic search strategies Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] Search strategy ‘Digestive System Surgical Procedures’[Mesh:NoExp] OR ‘Esophagectomy’[Mesh] OR ‘Esophageal Neoplasms’[Mesh] OR (reconstructive[tiab] AND surgery[ti]) OR esophagus surgery[tiab] OR oesophagus surgery[tiab] OR esophageal surgery [tiab] OR oesophageal surgery[tiab] OR esophageal resection[tiab] OR oesophageal resection[tiab] OR oesophagus resection[tiab] OR cardia cancer[tiab] OR cardia carcinoma[tiab] OR esophagectom*[tiab] OR oesophagectom*[tiab] OR esophageal reconstruct*[tiab] OR oesophageal reconstruct*[tiab] OR gastrointestinal surgery[tiab] OR Gastric Tube*[tiab] OR Gastric conduit*[tiab] OR Gastric Reconstruct*[tiab] OR esophagogastrostomy reconstruct*[tiab] OR oesophagogastrostomy reconstruct*[tiab] OR esophagus cancer*[tiab] OR oesophagus cancer*[tiab] OR esophageal neoplasm*[tiab] OR oesophageal neoplasm*[tiab] OR cancer esophagus[tiab] OR esophagus neoplasm*[tiab] OR esophageal cancer*[tiab] OR oesophageal cancer*[tiab] OR esophagus neoplasm*[tiab] AND ‘Tomography, Optical Coherence’[Mesh] OR ‘Indocyanine Green’[Mesh] OR "Laser-Doppler Flowmetry"[Mesh] OR OCT[tiab] OR Optical Coherence Tomography [tiab] OR Indocyanine green[tiab] OR ICG[tiab] OR Sidestream dark field[tiab] OR SDF[tiab] OR Laser speckle[tiab] OR Speckle contrast [tiab] OR LSI[tiab] OR LSCI[tiab] OR Laser-Doppler Flowmetry[tiab] OR Laser Doppler Imaging[tiab] OR LDI[tiab] OR doppler laser flowmetry[tiab] OR laser doppler velocimetry[tiab] OR velocimetry laser doppler[tiab] OR laser doppler velocimetry[tiab] OR doppler laser flowmetry [tiab] AND ‘Blood Flow Velocity’[Mesh] OR ‘Perfusion Imaging’[Mesh:NoExp] OR ‘blood supply’ [Subheading] OR perfusion[tiab] OR blood flow[tiab] OR blood supply[tiab] View Large Table 2 Perfusion imaging methods Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No LDF, laser Doppler flowmetry; NIRS, near infrared spectroscopy; LSCI, laser speckle contrast imaging; IRT, infrared thermographic imaging; FI, fluorescence imaging; OCT, optical coherence tomography. View Large Table 2 Perfusion imaging methods Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No Perfusion imaging methods Optical imaging method Optical principle Imaging resolution Physiology assessment Maximal imaging depth Dye administration? LDF Scattering – Perfusion in (perfusion units) 0.5 mm No NIRS Absorption – Oxygenation mm? No LSCI Scattering 10 μm Perfusion in (Flux) 1 mm No IRT Scattering 1.2 mm Temperature 2 mm No FI Fluorescence 0.45 mm Perfusion in blood flow routes 1 cm ICG, MB … OCT Scattering 1–15 μm Perfusion in speckle decorrelation 2–3 μm No LDF, laser Doppler flowmetry; NIRS, near infrared spectroscopy; LSCI, laser speckle contrast imaging; IRT, infrared thermographic imaging; FI, fluorescence imaging; OCT, optical coherence tomography. View Large Abstracts of publications with potential relevance based on titles were analyzed and selected full text articles were reviewed for analysis and quality assessment by two authors (DMB, SMJ). Inclusion and exclusion criteria Inclusion criteria were perfusion or blood flow and use of optical techniques and gastric tube reconstruction as subject of study. Exclusion criteria were articles not available, articles not in English, study designs (reviews, case reports), and reviews. Endpoints Primary outcome was quantitative measurement of change in perfusion in gastric tube reconstruction; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters. Data extraction Data extraction on year of publication, study design, inclusion and exclusion criteria, type of technique (index test), reference standard, target condition, number of participants in each group, types of surgery, variables and outcomes (data on efficacy) was done by two reviewers (SMJ, DMB). In vivo studies were reviewed according to QUADAS-2 standards.9 Development of techniques was staged by IDEAL (Idea-Development-Exploration-Assessment-Long-term Study).10 Assessment of risk of bias Two reviewers (SMJ, DMB) independently assessed the quality of methodology by using the QUADAS-2 quality tool for assessing risk of bias.9 This includes patient selection, index test, reference standard, flow, and timing. A representative spectrum was defined as any cohort of patients or animals with esophageal cancer treated with esophagectomy and gastric tube reconstruction. Results Our search identified 953 articles. After removal of duplicates 577 unique articles were screened by title and abstract and 43 articles were selected based on the inclusion and exclusion criteria (Fig. 2). Eleven articles were excluded after reading full text for 3 reasons; cancer as subject of the study, trachea as subject of the study, no optical modality used. We included 32 articles for analyses on study quality and data extraction (Tables 3–5). After screening references for original articles, 1 article was added to our search (n = 33). Twelve articles studied laser Doppler flowmetry, 12 fluorescence imaging, and 1 fluorescence imaging & laser Doppler flowmetry, 3 studied spectroscopy & laser Doppler flowmetry, 3 laser speckle contrast imaging, and 1 laser speckle contrast imaging and thermographic imaging, 1 sidestream dark field microscopy and laser Doppler flowmetry and 0 articles on optical coherence tomography. Fig. 2 View largeDownload slide Flow diagram. Fig. 2 View largeDownload slide Flow diagram. Table 3 Details of the study characteristics in LDF studies Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND (ND = not done). View Large Table 3 Details of the study characteristics in LDF studies Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND Study characteristics (laser Doppler flowmetry) Author Year Study design PTN Outcome Significant difference in perfusion? Predicting necrosis? Predicting anastomotic leakage? Urschel 1995 Animal study 20 Perfusion units Yes ND ND Schilling 1996 Cohort study 11 Perfusion Units Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units, Phi Yes ND ND Boyle 1998 Cohort study 16 Perfusion Units Yes ND ND Boyle 2000 Cohort study 10 Perfusion Units Excellent correlation between LDF & SLDF of 0.955 CC (P < 0.01) ND ND Ikeda 2001 Cohort study 43 mL/minutes/100 g Yes ND Yes Schroder 2002 Animal study 17 Perfusion units, ptO2 in mm/Hg Yes ND ND Miyazaki 2002 Clinical trial 44 Perfusion units No ND Yes Tobari 2005 Animal study 15 Perfusion units Yes Yes ND Michelet 2007 Cohort study 27 Perfusion units Yes ND No (n = 1) Al-Rawi 2008 Cohort study 12 Perfusion units Yes ND ND Pathak 2013 Cohort study 10 Perfusion units Yes ND ND (ND = not done). View Large Table 4 Details of study characteristics in NIRS studies Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND View Large Table 4 Details of study characteristics in NIRS studies Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND Study characteristics (near infrared reflectance spectroscopy) Buise 2006 Randomized controlled trial 32 Perfusion Units, μHbSO2, μHbcon No ND No (n = 7) Bludau 2008 Cohort study 18 Perfusion inits, MOS, SO2 in % PU no, MOS yes ND ND van Bommel 2010 Animal study 12 Perfusion units, μHbcon, μHbSO2 PU yes, μHbcon yes, μHbSO2 no ND ND View Large Table 5 Details of study characteristics in LSCI, FI, and SDF studies Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND View Large Table 5 Details of study characteristics in LSCI, FI, and SDF studies Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND Study characteristics Laser speckle contrast imaging Klijn 2009 Animal study 9 Flux, celcius Yes ND ND Milstein 2016 Cohort study 11 Laser speckle perfusion units Yes ND ND Ambrus 2017 Cohort study 25 Laser Yes ND ND Speckle perfusion units Ambrus 2017 Cohort 45 Laser Yes ND ND Speckle perfusion units Fluorescence imaging Shimada 2011 Cohort study 40 ICG detection ND ND No (n = 3) Kubota 2013 Cohort study 5 Blood flow: good versus sparse ND ND ND (n = 0) Kumagai 2013 Cohort study 20 Blood flow: good versus sparse No No (n = 3) ND (n = 0) Rino 2014 Cohort study 33 Blood flow routes ND ND No (n = 5) Zehetner 2014 Cohort study 150 Perfusion: Good versus less robust Yes ND Yes (n = 24) Campbell 2015 Retrospective study 90 Anastomotic leakage Yes Yes Yes Yukaya 2015 Cohort study 27 Arterial blood flow & venous return Yes No No (n = 9) Koyanagi 2016 Cohort 40 Blood flow: simultaneous versus delayed Yes No Yes (n = 7) Kitagawa 2017 Retrospective cohort 45 Linemarking Yes Yes ND (n = 0) Ohi 2017 Retrospective cohort 120 Blood flow: rapid, slow, low Yes Yes Yes (P = 0.0057) Schlottmann 2017 Cohort 5 Blood flow Yes ND ND Sidestream darkfield microscopy Jhanji 2010 Randomized controlled trial 135 Vessel density, Blood flow: present, intermittent or absent, perfused vessel density, microvascular flow index (MFI) Yes ND ND View Large Quality assessment All studies are in the initial phase of research, according to the IDEAL-stage (1–3) (Table 6). Quadas-2 analysis for diagnostic accuracy showed a level of bias, due to lack of a reference test to measure perfusion. Table 6 QUADAS-2 results and IDEAL-stage View Large Table 6 QUADAS-2 results and IDEAL-stage View Large Statistical analysis Due to the experimental set-up of studies, heterogeneity in outcome parameters and lack of randomized controlled trials, a meta-analysis could not be performed of the selected articles. Studies were evaluated on IDEAL-stage and quality (QUADAS-2) and an overview is given on optical techniques, working mechanism, measurement parameters and interpretation of parameters. OPTICAL TECHNIQUES Laser Doppler flowmetry Laser Doppler flowmetry (LDF) was first introduced by Sheperd and Riedel in 1982 and utilizes laser light to measure velocities of red blood cells by their Doppler shifts.11 LDF makes point measurements. Perfusion is measured in perfusion units, an arbitrary unit. In gastric tube surgery, LDF was studied the most widely. It is the oldest technique, developed in 1980. There were three animal studies (1 rat study n = 20, 2 pig studies n = 32), and nine prospective patients studies (n = 209) on LDF included in our analysis (Table 3). Studies were conducted between 1995 and 2013. Outcomes were change in blood flow in perfusion units (PU) in all studies and leakage in two.12–14 Four of 12 studies (n = 67) found a significant decrease in PU after vessel ligation of the stomach for gastric tube reconstruction. One study (n = 11) found a significant decrease of PU only in the fundus after stomach mobilization and not in the antrum.15 PU’s had a variety in amounts (23–1109) compared between studies, emphasizing the fact that this is an arbitrary parameter, and not an absolute parameter. Ikeda et al. (n = 43) evaluated the effect of tissue blood flow on the incidence of anastomotic leakage following esophagostomy with gastric tube reconstruction. He found that blood flow measured with LDF in patients with leakage was significantly lower (9.1 ± 2.0 mL/min/100 g) when compared to patients without leakage (13.7 ± 2.9 mL/min/100 g) (P < 0.01, unpaired t-test). To change the arbitrary unit of PU to this parameter of mL/min/100 g tissue, Ikeda et al. used the theory of Bonner (Physicist).16 However, Rajan et al. showed that Bonner and Nossal use assumptions for light scattering and Doppler shift in this theory, which are difficult to apply on human tissue.17 Miyazaki et al. (n = 44) compared intraoperative blood flow in PU between leakage and nonleakage groups.13 However, groups were not comparable due to unmatched group sizes (low power: n = 5 leakage patients, compared to n = 39 nonleakage patients). Postoperative blood flow was significantly lower in the leakage group after three days. Boyle et al. validated scanning laser Doppler flowmetry (2000) based on LDF (n = 16).18 They found a significant fall in gastric perfusion (PU) of 41% in all subjects after mobilization of the stomach. Also, a greater decrease of perfusion in the fundus (55%) compared to the antrum (25%) measured with scanning laser Doppler flowmetry was found. In general, LDF is able to measure perfusion in perfusion units with a significant lower amount of perfusion units in tissue with necrosis development compared to healthy tissue. Near infrared spectroscopy Near infrared spectroscopy (NIRS) is based on the absorption of laser light by tissue properties, and it was first described by MacMunn.19 The absorption spectrum of light is different for diverse chromophores in tissue. This could i.e. be used to measure oxygenated or deoxygenated hemoglobin. We found three articles on NIRS in gastric perfusion evaluation, of which one animal study of van Bommel et al. in pigs (n = 12), all using one type of optical device (Table 4). Outcome parameters were mucosal oxygen saturation (MOS) and hemoglobin concentration (Hbcon). Van Bommel et al. found no difference in MOS and Hbcon between nitro-glycerine and norepinephrine in a pig study.20 Buise et al. also evaluated the influence of nitro-glycerine on gastric tube microcirculation and found no difference in MOS between intervention with nitroglycerine and saline.21 Measured MOS decreased significantly in both groups after pulling up the gastric tube to the neck (91% to 63% in nitro-glycerine group, 86% to 51% in saline group). In general, NIRS is able to measure perfusion in mucosal oxygen saturation and hemoglobin concentration; however the predictive value of necrosis development is not described yet. Laser speckle (contrast) imaging The principle of speckle intensity fluctuations to measure skin perfusion is developed by many researchers using different techniques around 1970–1980.22,23 We found one animal study (n = 9 pigs) on laser speckle imaging (LSI) by Klijn et al.24 and three patients studies (n = 81). Klijn combined LSI and thermographic imaging to evaluate blood flow changes after increase of mean arterial blood pressure (MAP) from 50 to 110 during gastric tube surgery. An increasing MAP had no effect on perfusion at any location in the gastric tube measured by LSI and thermography. A decrease in PU (arbitrary units) was found between top and the base and medial side of the gastric tube, this difference however was not significant. Milstein et al. evaluated 11 patients using laser speckle contrast imaging (LSCI) intraoperatively. They found a high interrater reliability of blood flow measurements in laser speckle perfusion units (LSPU), with a progressive decrease of LSPU toward the fundus of the gastric tube.25 Ambrus et al. showed a decrease of LSPU toward the fundus after gastric pull-up of 25% in 25 patients.26 In another study of 45 patients, they used LSCI to investigate the influence of phenyl ephedrine on gastric microcirculation and they observed no difference between the group with phenyl ephedrine (n = 20) compared to the group without phenyl ephedrine (n = 25).27 In short, LSCI measures perfusion in perfusion units and a decrease of PU is observed toward the fundus intraoperatively. However, no predictive value for necrosis is found yet. Fluorescence imaging In fluorescence imaging (FI), a laser illuminates the tissue. An intrinsic or extrinsic fluorescent molecule is excited by this light from the ground state to a higher energy level. When the molecule returns to the ground state a photon is emitted with a lower energy (higher wavelength) than used for excitation. Filtering separates the emitted light from the excitation light, enabling discrimination between the two types of light. This creates an image with a high contrast. In the past years, there has been an exponential grow of FI studies, mostly qualitative.28 Twelve articles on FI were included all with use of indocyanine green (ICG) (n = 556). Different qualitative outcome measures were determined cognitively: detection of microcirculation, blood flow (good vs. sparse or absent), and blood flow routes. Rino et al. used FI to evaluate blood supply routes and found 66.7% located in the greater omentum and ‘splenic hiatal route’ (n = 22).29 Shimada et al. found that microcirculation detected by ICG does not necessarily provide enough blood flow to maintain a viable anastomosis.30 Kubota et al. also describe the possibility to observe venous perfusion with FI.31 However, they did not quantify this perfusion. Kumagai et al. measured enhancement of the route to the cranial branch in seconds and found no difference in ‘enhancement time’ between ‘good or ‘sparse or absent’ flow (P = 0.24).32 Yukaya et al. reported a quantitative assessment of blood flow with ICG in luminance over time, however no significant correlation was found.33 Hodari et al.34 described the decrease of anastomotic leakage incidence from 20% to 0% after the introduction of robotic-assisted esophagectomy with gastric tube reconstruction, using integrated FI (n = 54). Zehetner et al. correlated the distance of the point of demarcation assessed by FI of the gastric tube towards the anastomosis with leakage and found a significant correlation: the longer this distance the higher risk of anastomotic leakage.35 Also, Koyanagi et al. found a significant difference in anastomotic leakage development based on ICG stream. They divided patients into two groups based on the ICG fluorescence stream: a simultaneous group where the blood stream was fast and a delayed group where the blood stream was slow (n = 40). In the delayed group, 7 patients developed anastomotic leakage, whereas 0 patients developed leakage in the simultaneous group.36 Kitagawa et al. showed in a retrospective study (n = 72) that FI was associated with postoperative endoscopic assessment of the anastomosis after gastric tube reconstruction. In the group that used FI for line marking, only 6.5% anastomotic leakage occurred, compared to 15.4% in the group without FI.37 Ohi et al. showed a correlation between a surgical intervention in case of low perfusion area and the development of anastomotic leakage. They described FI depicted low flow as an independent risk factor for the development of anastomotic leakage (P = 0.0057).38 Finally, Schlottmann and Patti imaged gastric tube perfusion using FI in 5 patients. In 2 of the 5 patients (40%) low FI intensity was visible in the fundus of the gastric tube and a surgical intervention was made. They describe that there was no anastomotic leakage in this group of patients.39 In short, FI is able to measure the quality of perfusion. No quantitative parameter is described yet. However, with FI the length of the demarcation to the anastomosis seems a predictive value for necrosis intraoperatively. Sidestream dark field microscopy In sidestream dark field (SDF), imaging tissue is illuminated by green light emitting diodes (LEDs). Hemoglobin in red blood cells is absorbing this 530 nm light, producing a high contrast compared to surrounding tissue. To image movement of flowing RBSs, light is pulsed stroboscopically into the tissue and is detected with a camera.40 We found one article on SDF imaging in gastric tube surgery.41 However, instead of gastric tissue SDF was performed sublingually to calculate microvascular parameters like vessel density and blood flow velocity. Sublingual microvascular flow significantly increased in patients after stroke volume-guided fluid therapy and dopexamine. In short, based upon these findings, SDF is able to measure microvascular flow. However, intraoperative prediction of necrosis is not yet described. Optical coherence tomography Optical coherence tomography (OCT) is an imaging method that was developed in 1991 by Fuijimoto.42 It is the optical equivalent of ultrasound, except instead of sound near infrared light waves are shined into the tissue. Light intensity changes are caused by differences in backscattered light and measured in an interferometer, which allows for the depth resolved visualization of tissue layers. With OCT, it is possible to image tissue in real time, in high-resolution and in depth and potentially blood flow could be imaged by this technique. OCT is able to image the internal lumen of the esophagus during gastroscopy, as described by multiple studies.43,44 Additionally, perfusion could be measured by OCT in different tissues.45,46 However, in our analysis, we did not find any article on OCT imaging of perfusion in gastric tube surgery. OCT could potentially measure perfusion in related parameters. However, no studies are there to proof this and show the relation between these parameters and the prediction of necrosis development. DISCUSSION This systematic review describes the current literature on optical techniques and their (quantitative) parameters to measure perfusion and predict anastomotic leakage in gastric tube reconstruction after esophagostomy. The techniques differ in terms of field of view, resolution, and perfusion parameter. Recommendations for the intraoperative use of optical techniques (Scanning) laser Doppler flowmetry Advantages of LDF are the real-time, noninvasive imaging in a relatively easy and fast way. Disadvantages are the inaccuracy of Doppler-shift measurements in angled movements, point measurements missing important information due to heterogeneity of capillary network and misinterpretation of parameters due to overlying vessels. Although articles show a relation between drop in perfusion units and development of anastomotic leakage, surgeons should understand this relative change of color within the image is arbitrary and therefore sensitive for misinterpretation. Near infrared spectroscopy Advantages of this technique are the small probe and the ability to monitor perfusion during and postsurgery. Disadvantages are the sensitivity for patient movements, which could influence the outcome during monitoring, the use of point measurements and the probing of overlying vessels, which results in misinterpretation due to probing of underlying arteries instead of the subsurface capillaries. Articles show variance in MOS before and after gastric pull up, but also between antrum and fundus of healthy gastric tissue. In surgery tissue will always be deoxygenated due to the operation; therefor predication of necrosis with NIRS becomes difficult. Laser speckle (contrast) imaging The advantage of LSCI is the directly available color-coded images. Moreover, speckle is more sensitive for motion than Doppler shift and does not relate to angle motions. The disadvantage is the parameter (perfusion units), which is arbitrary and therefore difficult to compare. Articles show the feasibility of LSCI diagnostics during surgery and a significant decrease of the quantitative parameter LSPU towards the fundus. Correlation of this parameter to patient outcome has not been showed yet and would improve the value of this technique in the clinical setting. Fluorescence imaging Advantages of FI are the visual movie of influx of perfusion in real-time during surgery. It is very easy to interpret, however studies use qualitative parameters, which is a disadvantage. Although the correlation between the distance of ICG demarcation to the fundus and the patient outcome in terms of anastomotic leakage is described, a quantitative parameter is needed to determine perfusion problems intraoperatively on the spot. Luminance over time could be a useful parameter, but the significant correlation with anastomotic leakage development is not proven yet. At the moment, studies focus on the development of FI to a quantitative imaging technique, for example in the PERFECT trial for colorectal cancer (NCT02626091). Sidestream dark field microscopy Advantages of SDF are the real-time visualization of RBCs in the capillaries; to see movement means that there is flow. Moreover, flow can be measured in a quantitative parameter (mm/second, vessel density and vessel diameter). Disadvantages are the contact that you have to make with tissue. Therefore patient movement by breathing or heartbeats will influence the image and artifacts can occur due to pressure. The validation of this quantitative parameter needs to be done, before we can adjust measurements to the clinic. Optical coherence tomography This technique is the only optical depth-resolved imaging system that is able to make a cross-sectional image in millimeters. Advantages are the high-resolution, high-contrast, and real-time imaging ability. Disadvantages are the postprocessing that is needed to measure perfusion in a linear parameter. If OCT would be able to create measurements in quantitative parameters of mL/minutes/gram, it would be very promising to use this technique in gastric tube surgery. Limitations Our results show that there is lack of understanding of quantitative parameters and little consensus on which technique to use. Due to a missing gold standard in perfusion measurements, diagnostic accuracy at this stage cannot be tested and therefor overall quality of literature according to QUADAS-2 is medium. Moreover, selected studies use optical techniques as a method to test an intervention, which makes it difficult to evaluate the optical technique itself. This is caused by the gap between the biomedical engineering and the clinic, the misinterpretation of quantitative parameters by clinicians and the force of companies to get their device into the clinic. Almost all studies are in the initial phase of human research according to IDEAL-stage for surgical innovation. Human studies are needed to evaluate quantitative parameters of techniques and their ability to predict anastomotic leakage. Because of the heterogeneity in parameters, a meta-analysis could not be conducted and overall appraisable on quantification is complicated. Although this is a limitation of our study, understanding of techniques and parameters are important for the evaluation and set-up of further studies. Variability of parameters makes it hard to evaluate different techniques. We need studies with the same outcome variables and a gold standard to test diagnostic accuracy in perfusion monitoring. Techniques are in an initial phase; 1–3 stage of IDEAL. Moreover, validation of techniques is needed, by using a reference test or a standard laboratory setting (phantom study), to evaluate measured parameters before we can implement new modalities in the clinic. This systematic review shows a lack in validation of optical techniques and parameters. Advice for perfusion monitoring A quantitative parameter is needed to objectify perfusion during surgery. The ideal perfusion parameter would be mL/minutes/gram. Future prospective studies need to validate quantitative parameters using a gold standard or a standard setting (phantom study). Furthermore, techniques have to be tested at the same time point during surgery to compare modalities and their parameters. CONCLUSIONS Optical techniques are valuable for perfusion evaluation in gastric tube surgery, giving their real-time, high-resolution, and high-contrast measurements. LSCI and FI give a real-time wide field overview of perfusion, unfortunately they both lack in terms of quantitative parameters. LDF and LSCI use arbitrary perfusion units, and are therefore difficult in interpretation. Moreover, point measurements (LDF) should not be the first choice in perfusion evaluation, taking vascular heterogeneity into account. SDF and OCT have great potential in perfusion diagnostics, but patient studies are needed. Future prospective studies need to determine a threshold value for quantitative parameters to predict anastomotic failure. Disclosures Drs. Jansen, Dr. de Bruin, Dr. van Berge Henegouwen, Dr. Strackee, Dr. Veelo, and Dr. Gisbertz have no conflicts of interest or financial ties to disclose. Dr. van Leeuwen reports grants from ZON-MW, non-financial support from Quest innovations, other from PA imaging BV, grants and nonfinancial support from Lionix, grants and nonfinancial support from Xiophotonics, grants and nonfinancial support from Ninepoint, outside the submitted work. In addition, Dr. van Leeuwen has a patent Combined Raman Spectroscopy-Optical Coherence Tomography (RS-OCT) System and Applications of the Same issued, a patent Common detector for combined Raman spectroscopy-optical coherence tomography issued, a patent Arthroscopic Instrument assembly, and method of localizing musculoskeletal structure during athroscopic surgery issued, a patent flow cytometry method for determination of size and refractive index of substantially spherical single particles and calibration method suitable for use with such a flow cytometry method pending, a patent high wavenumber Raman spectroscopy and applications of same pending, and a patent Common-Path Integrated Low Coherence Interferometry System and Method Therefor pending. ACKNOWLEDGMENTS Authors would like to thank Faridi van Etten of the Dutch Cochrane Centre & Medical Library AMC for her contribution to this paper and Inge Kos for the illustrations. 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Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Diseases of the EsophagusOxford University Press

Published: Apr 26, 2018

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