Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey.

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.

Assessing the development status of intraoperative fluorescence imaging for anatomy visualisation, using the IDEAL framework.

Objectives: Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: visualising anatomy, assessing tissue perfusion, identifying/localising cancer and mapping lymphatic systems. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging used to visualise anatomical structures using the IDEAL framework, a framework designed to describe the stages of innovation in surgery and other interventional procedures. Design: IDEAL staging based on a thorough literature review. Setting: All publications on intraoperative fluorescence imaging for visualising anatomical structures reported in PubMed through 2020 were identified for five surgical procedures: cholangiography, hepatic segmentation, lung segmentation, ureterography and parathyroid identification. Main outcome measures: The IDEAL stage of research evidence was determined for each of the five procedures using a previously described approach. Results: 225 articles (8427 cases) were selected for analysis. Current status of research evidence on fluorescence imaging was rated IDEAL stage 2a for ureterography and lung segmentation, IDEAL 2b for hepatic segmentation and IDEAL stage 3 for cholangiography and parathyroid identification. Enhanced tissue identification rates using fluorescence imaging relative to conventional white-light imaging have been documented for all five procedures by comparative studies including randomised controlled trials for cholangiography and parathyroid identification. Advantages of anatomy visualisation with fluorescence imaging for improving short-term and long-term postoperative outcomes also were demonstrated, especially for hepatobiliary surgery and (para)thyroidectomy. No adverse reactions associated with fluorescent agents were reported. Conclusions: Intraoperative fluorescence imaging can be used safely to enhance the identification of anatomical structures, which may lead to improved postoperative outcomes. Overviewing current research knowledge using the IDEAL framework aids in designing further studies to develop fluorescence imaging techniques into an essential intraoperative navigation tool in each surgical field.

Near-Infrared Fluorescence Imaging for the Intraoperative Detection of Endometriosis: A Pilot Study.

INTRODUCTION: Endometriosis surgery is associated with a high risk of reoperation due to an insufficient recognition of endometriotic lesions. Our aim was to explore the role of near-infrared fluorescence (NIRF) imaging for the visualization and identification of endometriotic lesions next to conventional white light (WL) laparoscopy. MATERIALS AND METHODS: Fifteen women scheduled for diagnostic laparoscopy in whom peritoneal endometriosis was suspected were included. Peritoneal exploration was performed in WL, followed by NIRF imaging after ICG administration. Biopsies of all the suspected lesions were taken for histological examination. Subjective evaluations of the equipment and NIRF imaging were also performed. RESULTS: Only 61% (44) of the biopsied lesions contained endometriosis. The positive predictive value (PPV) for the lesions found in WL was 64%. The PPV for the lesions found under NIRF was 69% and the PPV for the lesions found in both modes was 61%. The mean satisfaction of surgeons regarding the surgical procedure and equipment using both imaging modalities was 6.5 (p > 0.05) on a 10 item Likert scale and the mean satisfaction with the quality of the NIRF imaging was 7.4 (p > 0.05). CONCLUSION: In this study, the additional value of NIRF imaging, although feasible, was found to be limited for the intraoperative detection of endometriotic lesions.

Fluorescence-based cholangiography: preliminary results from the IHU-IRCAD-EAES EURO-FIGS registry.

INTRODUCTION: Near-infrared fluorescence cholangiography (NIRF-C) is a popular application of fluorescence image-guided surgery (FIGS). NIRF-C requires near-infrared optimized laparoscopes and the injection of a fluorophore, most frequently Indocyanine Green (ICG), to highlight the biliary anatomy. It is investigated as a tool to increase safety during cholecystectomy. The European registry on FIGS (EURO-FIGS: www.euro-figs.eu ) aims to obtain a snapshot of the current practices of FIGS across Europe. Data on NIRF-C are presented. METHODS: EURO-FIGS is a secured online database which collects anonymized data on surgical procedures performed using FIGS. Data collected for NIRF-C include gender, age, Body Mass Index (BMI), pathology, NIR device, ICG dose, ICG timing of administration before intraoperative visualization, visualization (Y/N) of biliary structures such as the cystic duct (CD), the common bile duct (CBD), the CD-CBD junction, the common hepatic duct (CHD), Visualization scores, adverse reactions to ICG, operative time, and surgical complications. RESULTS: Fifteen surgeons (12 European surgical centers) uploaded 314 cases of NIRF-C during cholecystectomy (cholelithiasis n = 249, cholecystitis n = 58, polyps n = 7), using 4 different NIR devices. ICG doses (mg/kg) varied largely (mean 0.28 ± 0.17, median 0.3, range: 0.02-0.62). Similarly, injection-to-visualization timing (minutes) varied largely (mean 217 ± 357; median 57), ranging from 1 min (direct intragallbladder injection in 2 cases) to 3120 min (n = 2 cases). Visualization scores before dissection were significantly correlated, at univariate analysis, with ICG timing (all structures), ICG dose (CD-CBD), device (CD and CD-CBD), surgeon (CD and CD-CBD), and pathology (CD and CD-CBD). BMI was not correlated. At multivariate analysis, pathology and timing remained significant factors affecting the visualization scores of all three structures, whereas ICG dose remained correlated with HD visualization only. CONCLUSIONS: The EURO-FIGS registry has confirmed a wide disparity in ICG dose and timing in NIRF-C. EURO-FIGS can represent a valuable tool to promote and monitor FIGS-related educational and consensus activities in Europe.

Optimizing Indocyanine Green Fluorescence Angiography in Reconstructive Flap Surgery: A Systematic Review and Ex Vivo Experiments.

Background. Indocyanine green angiography (ICGA) offers the potential to provide objective data for evaluating tissue perfusion of flaps and reduce the incidence of postoperative necrosis. Consensus on ICGA protocols and information on factors that have an influence on fluorescence intensity is lacking. The aim of this article is to provide a comprehensive insight of in vivo and ex vivo evaluation of factors influencing the fluorescence intensity when using ICGA during reconstructive flap surgery. Methods. A systematic literature search was conducted to provide a comprehensive overview of currently used ICGA protocols in reconstructive flap surgery. Additionally, ex vivo experiments were performed to further investigate the practical influence of potentially relevant factors. Results. Factors that are considered important in ICGA protocols, as well as factors that might influence fluorescence intensity are scarcely reported. The ex vivo experiments demonstrated that fluorescence intensity was significantly related to dose, working distance, angle, penetration depth, and ambient light. Conclusions. This study identified factors that significantly influence the fluorescence intensity of ICGA. Applying a weight-adjusted ICG dose seems preferable over a fixed dose, recommended working distances are advocated, and the imaging head during ICGA should be positioned in an angle of 60° to 90° without significantly influencing the fluorescence intensity. All of these factors should be considered and reported when using ICGA for tissue perfusion assessment during reconstructive flap surgery.

Technical Note: Are Currently Used Measurements of Fluorescence Intensity in Near Infrared Fluorescence Imaging During Laparoscopic Cholecystectomy Comparable?

Aims: To investigate whether different calculation methods to express fluorescence intensity (FI) as target-to-background (BG) ratio are comparable and which method(s) match with human perception. Materials and Methods: Comparison of three calculation methods from current literature (OsiriX®, ImageJ®, and Photoshop®) to objectify FI during laparoscopic cholecystectomy measured at the exact same locations within recorded images of two categories: ex vivo and in vivo. Currently applied formulas to present FI in relation to the BG signal are compared with the subjective assessment by the human observers. These three formulas are Signal contrast = (FI in fluorescence regions-FI in BG)/255; Target-to-background ratio = (FI of target-FI of BG)/FI of BG; Signal-to-background ratio = FI of cystic duct/FI of liver and Target-to-background ratio = (FI of target-noise)/(FI of BG-noise). Results: In our evaluation OsiriX and ImageJ provided similar results, whereas OsiriX values were structurally slightly lower compared with ImageJ. Values obtained through Photoshop were less evidently related to those obtained with OsiriX and ImageJ. The formula Target-to-background ratio = (FI of target-noise)/(FI of BG-noise) was less corresponding with human perception compared with the other used formulas. Conclusions: FI results based on measurements using the programs OsiriX and ImageJ are similar, allowing for comparison of results between these programs. Results using Photoshop differ significantly, making direct comparison impossible. This is an important finding when interpreting study results. We propose to report both target and BG FI in articles, so that proper interpretation between articles can be made.

Near-infrared fluorescence image-guidance in anastomotic colorectal cancer surgery and its relation to serum markers of anastomotic leakage: a clinical pilot study.

OBJECTIVE: Near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) might help reduce anastomotic leakage (AL) after colorectal surgery. This pilot study aims to analyze whether a relation exists between measured fluorescence intensity (FI) and postoperative inflammatory markers of AL, C-reactive protein (CRP), Intestinal fatty-acid binding protein (I-FABP), and calprotectin, to AL, in order to evaluate the potential of FI to objectively predict AL. METHODS: Patients scheduled for anastomotic colorectal cancer surgery were eligible for inclusion in this prospective pilot study. During surgery, at three time points (after bowel devascularization; before actual transection; after completion of anastomosis) a bolus of 0.2 mg/kg ICG was administered intravenously for assessment of bowel perfusion. FI was scored in scale from 1 to 5 based on the operating surgeon's judgment (1 = no fluorescence visible, 5 = maximum fluorescent signal). The complete surgical procedure was digitally recorded. These recordings were used to measure FI postoperatively using OsiriX imaging software. Serum CRP, I-FABP, and calprotectin values were determined before surgery and on day 1, 3, and 5 postoperative; furthermore, the occurrence of AL was recorded. RESULTS: Thirty patients (n = 19 males; mean age 67 years; mean BMI 27.2) undergoing either laparoscopic or robotic anastomotic colorectal surgery were included. Indication for surgery was rectal-(n = 10), rectosigmoid-(n = 2), sigmoid-(n = 10), or more proximal colon carcinomas (n = 8). Five patients (16.7%) developed AL (n = 2 (6.6%) grade C according to the definition of the International Study group of Rectal Cancer). In patients with AL, the maximum fluorescence score was given less often (P = 0.02) and a lower FI compared to background FI was measured at 1st assessment (P = 0.039). However, no relation between FI and postoperative inflammatory parameters could be found. CONCLUSION: Both subjective and measured FI seem to be related to AL. In this study, no relation between FI and inflammatory serum markers could yet be found.

Near-infrared fluorescence laparoscopy of the ureter with three preclinical dyes in a pig model.

BACKGROUND: Ureteric injury is reported to occur in 1-7.6% of colorectal surgeries. To reduce the incidence of ureteral injury, it is essential to identify the ureters. The use of near-infrared fluorescence (NIRF) imaging with intravenously administered dyes might be of added value for ureteral visualization during laparoscopy. The aim of this study is to assess the performance of three preclinical dyes; IRDye® 800BK, IRDye® 800NOS and IRDye® 800CW, for near-infrared fluorescence laparoscopy of the ureter in pigs. METHODS: In three female Dutch landrace pigs, the new dyes were evaluated. In each pig, 1 dye was tested using a 6-mg intravenous dose in a concentration of 1 mg/ml. Imaging was performed in fluorescence mode and white light mode with a laparoscopic imaging system. In order to further evaluate the dyes, an ex vivo imaging experiment was performed, in which 8 decreasing concentrations per dye, diluted in PBS, were evaluated in a transparent test tube with NIRF mode at a distance of 1, 5 and 10 cm from the laparoscope. RESULTS: All three dyes were effective in allowing the identification of the ureter with NIRF imaging. The ureter became fluorescent after 35, 45 and 10 min, respectively, for IRDye® 800BK, IRDye® 800NOS and IRDye® 800CW with a maximum target-to-background ratio (TBR) of 2.14, 0.66 and 1.44, respectively. In the ex vivo imaging experiment, all three dyes produced a strong fluorescence signal at all concentrations and all distances evaluated. CONCLUSIONS: Intravenous administration of the preclinical dyes IRDye® 800CW, IRDye® 800 BK and IRDye® 800NOS facilitated successful identification of the anatomical course of the ureter in living pig models. The highest measured TBR occurred with the use of IRDye® 800BK. Ex vivo, a correlation was observed between the fluorescence intensities of the signal with the concentration of the dye and with the distance to the object.

Feasibility of indocyanine green fluorescence imaging for intraoperative identification of parathyroid glands during thyroid surgery.

BACKGROUND: This study assessed the feasibility of near-infrared fluorescence imaging with indocyanine green (ICG) to identify the parathyroid glands (PGs) intraoperatively and to assess their perfusion after thyroid resection. METHODS: Patients undergoing elective thyroidectomy were enrolled in this prospective study. An intravenous bolus of 7.5 mg ICG was administered twice: the first bolus to identify the PGs before resection of the thyroid and the second to assess vascularization of the PGs after resection. RESULTS: A total of 30 operations in 26 patients were included. In 17 surgeries (56.7%), fluorescence imaging was of added value, especially to confirm the presence of a suspected PG. No intraoperative or postoperative complications occurred because of the use of ICG. CONCLUSION: Near-infrared fluorescence imaging with the use of ICG for intraoperative identification of the PGs and the assessment of its vascularization is feasible and safe and can provide more certainty about the location of the PGs.

Optimizing the image of fluorescence cholangiography using ICG: a systematic review and ex vivo experiments.

BACKGROUND: Though often only briefly described in the literature, there are clearly factors that have an influence on the fluorescence intensity, and thereby the usefulness of the technique. This article aims to provide an overview of the factors influencing the fluorescence intensity of fluorescence imaging with Indocyanine green, primarily focussed on NIRF guided cholangiography. METHODS: A systematic search was conducted to gain an overview of currently used methods in NIRF imaging in laparoscopic cholecystectomies. Relevant literature was searched to gain advice on what methods to use. Ex vivo experiments were performed to assess various factors that influence fluorescence intensity and whether the found clinical advices can be confirmed. RESULTS: ICG is currently the most widely applied fluorescent dye. Optimal ICG concentration lies between 0.00195 and 0.025 mg/ml, and this dose should be given as early as achievable-but maximum 24 h-before surgery. When holding the laparoscope closer and perpendicular to the dye, the signal is most intense. In patients with a higher BMI and/or cholecystitis, fluorescence intensity is lower, but NIRF seems to be more helpful. There are differences between various marketed fluorescence systems. Also, no uniform method to assess fluorescence intensity is available yet. CONCLUSIONS: This study identified and discussed several factors that influence the signal of fluorescence cholangiography. These factors should be taken into account when using NIRF cholangiography. Also, surgeons should be aware of new dyes and clinical systems, in order to benefit most from the potential of NIRF imaging.

Lacunar implementation of the critical view of safety technique for laparoscopic cholecystectomy: Results of a nationwide survey.

BACKGROUND: Bile duct injury remains a dilemma in laparoscopic cholecystectomy, with an incidence still higher than in conventional cholecystectomy. The Critical View of Safety technique is used as one of the important operating technique to reduce bile duct injury incidence. The objective of this study was to determine current practices in laparoscopic cholecystectomy and the use of the Critical View of Safety technique among surgeons and residents in surgical training. METHODS: We conducted an electronic survey among all affiliated members of the Association of Surgeons of the Netherlands containing questions regarding the current practice of laparoscopic cholecystectomy, essential steps of the Critical View of Safety technique, reasons for conversion to open cholecystectomy, and the use of other safety techniques. RESULTS: The response rate was 37% (766/2,055). In the study, 610 completed surveys were analyzed. Of the respondents, 410 (67.2%) were surgeons and 200 (32.8%) were residents in surgical training. Furthermore, 98.2% of the respondents indicated incorporating the Critical View of Safety technique into current practice. However, only 72% of respondents performed the essential steps of the Critical View of Safety technique frequently. Subsequently, half of respondents were able to identify the corresponding steps of the Critical View of Safety technique, and only 16.9% were able to distinguish these adequately from possible harmful steps. Furthermore, 74.9% selected ≥1 possible harmful steps as part of this technique. Residents significantly performed and selected the essential steps of the Critical View of Safety technique more often than surgeons. Intraoperative cholangiography, intraoperative ultrasound, and fluorescence cholangiography are seldom used. Bail-out techniques such as subtotal cholecystectomy, fundus first dissection, and leaving the gallbladder in situ are familiar to the majority of respondents. CONCLUSION: Responses indicate that practically all Dutch surgeons and residents claim to use the Critical View of Safety technique. The majority of surgeons and residents are unable to discern correctly the essential steps of the Critical View of Safety technique from actions not part of the technique and even potentially harmful. Residents' current knowledge regarding the Critical View of Safety technique is superior to those of surgeons.

Near-Infrared Fluorescence Imaging for Real-Time Intraoperative Guidance in Anastomotic Colorectal Surgery: A Systematic Review of Literature.

PURPOSE: The aims of this review are to determine the feasibility of near-infrared fluorescence (NIRF) angiography in anastomotic colorectal surgery and to determine the effectiveness of the technique in improving imaging and quantification of vascularization, thereby aiding in decision making as to where to establish the anastomosis. METHODS: A systematic literature search of PubMed and EMBASE was conducted. Searching through the reference lists of selected articles identified additional studies. All English language articles presenting original patient data regarding intraoperative NIRF angiography were included without restriction of type of study, except for case reports, technical notes, and video vignettes. The intervention consisted of intraoperative NIRF angiography during anastomotic colorectal surgery to assess perfusion of the colon, sigmoid, and/or rectum. Primary outcome parameters included ease of use, added surgical time, complications related to the technique, and costs. Other relevant outcomes were whether this technique changed intraoperative decision making, whether effort was taken by the authors to quantify the signal and the incidence of postoperative complications. RESULTS: Ten studies were included. Eight of these studies make a statement about the ease of use. In none of the studies complications due to the use of the technique occurred. The technique changed the resection margin in 10.8% of all NIRF cases. The anastomotic leak rate was 3.5% in the NIRF group and 7.4% in the group with conventional imaging. Two of the included studies used an objective quantification of the fluorescence signal and perfusion, using ROIs (Hamamatsu Photonics) and IC-Calc® respectively. CONCLUSIONS: Although the feasibility of the technique seems to be agreed on by all current research, large clinical trials are mandatory to further evaluate the added value of the technique.

IRCAD recommendation on safe laparoscopic cholecystectomy.

An expert recommendation conference was conducted to identify factors associated with adverse events during laparoscopic cholecystectomy (LC) with the goal of deriving expert recommendations for the reduction of biliary and vascular injury. Nineteen hepato-pancreato-biliary (HPB) surgeons from high-volume surgery centers in six countries comprised the Research Institute Against Cancer of the Digestive System (IRCAD) Recommendations Group. Systematic search of PubMed, Cochrane, and Embase was conducted. Using nominal group technique, structured group meetings were held to identify key items for safer LC. Consensus was achieved when 80% of respondents ranked an item as 1 or 2 (Likert scale 1-4). Seventy-one IRCAD HPB course participants assessed the expert recommendations which were compared to responses of 37 general surgery course participants. The IRCAD recommendations were structured in seven statements. The key topics included exposure of the operative field, appropriate use of energy device and establishment of the critical view of safety (CVS), systematic preoperative imaging, cholangiogram and alternative techniques, role of partial and dome-down (fundus-first) cholecystectomy. Highest consensus was achieved on the importance of the CVS as well as dome-down technique and partial cholecystectomy as alternative techniques. The put forward IRCAD recommendations may help to promote safe surgical practice of LC and initiate specific training to avoid adverse events.

Near-infrared fluorescence laparoscopy of the cystic duct and cystic artery: first experience with two new preclinical dyes in a pig model.

BACKGROUND: Imaging techniques that enhance visualisation of the anatomy may help prevent bile duct injury. Near-Infrared Fluorescence Imaging is such a technique. Previous experiments with ICG have shown that illumination of the extra-hepatic bile ducts is feasible. Yet, there is room for improvement in the visualisation of the target as compared to the background. Experiments with IRDye® 800CW show promising results. However, this dye is too expensive for routine clinical use. The aim of this study is to test the first applicability of two newly developed preclinical dyes regarding intraoperative imaging of the cystic duct and cystic artery, compared with IRDye® 800CW. METHODS: Laparoscopic cholecystectomy was performed in three pigs, using a laparoscopic fluorescence imaging system. Each pig received 6 mg of one of the fluorescent dyes (1 mg/mL; IRDye® 800CW, IRDye® 800BK or IRDye® 800NOS) by intravenous injection. Intraoperative recognition of the biliary system and cystic artery was registered at set time points. All procedures were digitally recorded, and the target to background ratio (TBR) was determined to assess the fluorescence signal. RESULTS: With all three fluorescent dyes, the cystic artery was directly visualised. For the visualisation of the cystic duct, 15, 34 and 30 min were needed using IRDye® 800BK, IRDye® 800NOS and IRDye® 800CW, respectively. The maximum TBR of the cystic duct was the highest with IRDye® 800NOS (4.20) after 36 min, compared to 2.45 for IRDye® 800BK and 2.15 for IRDye® 800CW, both after 45 min. There were no adverse events. CONCLUSION: IRDye® 800BK and IRDye® 800NOS seem to be good alternatives for IRDye® 800CW for the visualisation of the cystic duct and cystic artery in pigs.

Is Single-Port Laparoscopy More Precise and Faster with the Robot?

BACKGROUND: Single-port laparoscopy is a step forward toward nearly scar less surgery. Concern has been raised that single-incision laparoscopic surgery (SILS) is technically more challenging because of the lack of triangulation and the clashing of instruments. Robotic single-incision laparoscopic surgery (RSILS) in chopstick setting might overcome these problems. This study evaluated the outcome in time and errors of two tasks of the Fundamentals of Laparoscopic Surgery on a dry platform, in two settings: SILS versus RSILS. METHODS: Nine experienced laparoscopic surgeons performed two tasks: peg transfer and a suturing task, on a standard box trainer. All participants practiced each task three times in both settings: SILS and a RSILS setting. The assessment scores (time and errors) were recorded. RESULTS: For the first task of peg transfer, RSILS was significantly better in time (124 versus 230 seconds, P = .0004) and errors (0.80 errors versus 2.60 errors, P = .024) at the first run, compared to the SILS setting. At the third and final run, RSILS still proved to be significantly better in errors (0.10 errors versus 0.80 errors, P = .025) compared to the SILS group. RSILS was faster in the third run, but not significant (116 versus 157 seconds, P = .08). For the second task, a suturing task, only 3 participants of the SILS group were able to perform this task within the set time frame of 600 seconds. There was no significant difference in time in the three runs between SILS and RSILS for the 3 participants that fulfilled both tasks within the 600 seconds. CONCLUSIONS: This study shows that robotic single-port surgery seems easier, faster, and more precise to perform basis tasks of the Fundamentals of laparoscopic surgery. For the more complex task of suturing, only the single-port robotic setting enabled all participants to fulfill this task, within the set time frame.

Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy versus conventional laparoscopic cholecystectomy (FALCON trial): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Misidentification of the extrahepatic bile duct anatomy during laparoscopic cholecystectomy (LC) is the main cause of bile duct injury. Easier intraoperative recognition of the biliary anatomy may be accomplished by using near-infrared fluorescence (NIRF) imaging after an intravenous injection of indocyanine green (ICG). Promising results were reported for successful intraoperative identification of the extrahepatic bile ducts compared to conventional laparoscopic imaging. However, routine use of ICG fluorescence laparoscopy has not gained wide clinical acceptance yet due to a lack of high-quality clinical data. Therefore, this multicentre randomised clinical study was designed to assess the potential added value of the NIRF imaging technique during LC. METHODS AND ANALYSIS: A multicentre, randomised controlled clinical trial will be carried out to assess the use of NIRF imaging in LC. In total, 308 patients scheduled for an elective LC will be included. These patients will be randomised into a NIRF imaging laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. The primary end point is time to 'critical view of safety' (CVS). Secondary end points are 'time to identification of the cystic duct (CD), of the common bile duct, the transition of CD in the gallbladder and the transition of the cystic artery in the gallbladder, these all during dissection of CVS'; 'total surgical time'; 'intraoperative bile leakage from the gallbladder or cystic duct'; 'bile duct injury'; 'postoperative length of stay', 'complications due to the injected ICG'; 'conversion to open cholecystectomy'; 'postoperative complications (until 90 days postoperatively)' and 'cost-minimisation'. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethical Committee of Maastricht University Medical Center/Maastricht University; the trial has been registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT02558556.

Fluorescence Ureteral Visualization in Human Laparoscopic Colorectal Surgery Using Methylene Blue.

BACKGROUND: Ureteral injury during laparoscopic surgery is rare, but when it occurs, it can be a serious problem. Near-infrared fluorescence (NIRF) with methylene blue (MB) administration is a promising technique for easier and potentially earlier intraoperative visualization of the ureter. Aim of this prospective study was to assess the feasibility of NIRF imaging of the ureter during laparoscopic colorectal surgery, using MB. METHODS: Patients undergoing laparoscopic colorectal surgery were included and received intravenous injection of MB preoperatively. The ureter was visualized using a laparoscope, which offered both conventional and fluorescence imaging. Intraoperative recognition of the ureter was registered. The precision of ureter distinction with MB imaging was compared to the conventional laparoscopic view. RESULTS: Ten patients were included. All procedures were initially performed using a laparoscopic approach. Dose per injection ranged between 0.125 mg/kg and 1.0 mg/kg bodyweight. There were no adverse effects attributable to MB administration. The ureter was successfully detected in five patients, with highest contrast between ureter and surrounding tissue at an administered dose of 0.75-1.0 mg/kg. The fluorescent signal was only picked up after the ureter was already visible in the conventional white light mode. CONCLUSION: Ureteral fluorescence imaging using MB proved to be safe and feasible. However, the present technique does not provide practical advantage over conventional laparoscopic imaging for identification of the ureter during laparoscopic colorectal surgery. Future research is necessary to explore more extensive dose finding, alternative fluorescent dyes, or improvement of the imaging system to make this application clinically beneficial.