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

Surgical Endoscopy, Oct 2017

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.

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

Near-infrared fluorescence laparoscopy of the cystic duct and cystic artery: first experience with two new preclinical dyes in a pig model Jacqueline van den Bos 1 Mahdi Al-Taher 1 Shu Gi Hsien 1 Nicole D. Bouvy 1 Laurents P. S. Stassen 1 0 Jacqueline van den Bos 1 NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University , Maastricht , The Netherlands 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. Fluorescent dyes; Near-infrared fluorescence imaging; Biliary anatomy; Laparoscopic cholecystectomy; Fluorescent cholangiography - Laparoscopic cholecystectomy is standard care for symptomatic gallbladder stones or acute cholecystitis, and is one of the most commonly performed surgical procedures in the Western hemisphere. The reported incidence of bile duct injuries in laparoscopic surgery is 0.4–1.4% [1, 2]. Such injuries are associated with increased morbidity, reduced survival, impaired quality of life and have economic consequences for society [2, 3]. Anatomical variations of the biliary ducts or vascular system are not uncommon and represent operative challenges and looming sources for operative complications [3, 4]. Therefore, enhanced intraoperative visualisation of the biliary anatomy is needed to reduce the incidence of bile duct injuries. Near-infrared fluorescence (NIRF) imaging is a promising technique for real-time delineation of the perioperative anatomy. Among other applications, it is used for visualisation of the extra-hepatic bile ducts and the cystic artery in laparoscopic cholecystectomy, and visualisation of the ureter in colorectal, urological and gynaecological surgery [5–7]. In the clinical setting, ICG is the dye used for bile duct imaging, with reasonable visualisation results that makes clinical use possible. Both the extra-hepatic bile ducts and the cystic artery can be identified [8]. Subjectively however, imaging of the target is not optimal in all patients. Better contrast between target and background is expected to increase the usefulness of the technique. Adaptation in the equipment and its characteristics is one way to address this issue. Alteration in the dye or its use is another. One such alteration is the suggestion to inject the dye a day before surgery [9]. However, due to usually performed same-day admission, this is undesirable from a logistic standpoint. Applying another fluorescent dye is a further possibility. IRDye® 800CW (LICOR Biotechnology, Lincoln, United States) is an experimental dye, which in combination with laparoscopic imaging allows intraoperative visualisation of crucial anatomical structures. In a previous animal experiment, performed by our group, this dye was compared to ICG for imaging of the extra-hepatic bile ducts and the cystic artery in the pig. The main results were an earlier visualisation of the cystic duct, when using IRDye® CW-800 and a higher target-to-background ratio for the cystic artery [10]. This is in line with two other studies and makes this new dye promising for future clinical use [10–12]. However, a major disadvantage of IRDye® CW-800 is its cost, which is almost tenfold that of ICG. Therefore, more affordable alternatives are needed. Recently, the manufacturer of IRDye® 800CW developed two new preclinical dyes, IRDye® 800BK and IRDye® (...truncated)


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Jacqueline van den Bos, Mahdi Al-Taher, Shu Gi Hsien, Nicole D. Bouvy. Near-infrared fluorescence laparoscopy of the cystic duct and cystic artery: first experience with two new preclinical dyes in a pig model, Surgical Endoscopy, 2017, pp. 1-6, DOI: 10.1007/s00464-017-5450-z