FLUORESCENCE CHOLANGIOGRAPHY the Advent of a New Era of Improved Visualization and Safety

FLUORESCENCE CHOLANGIOGRAPHY The Advent of a New Era of Improved Visualization and Safety

Fernando DIP, Luis SAROTTO, Laurents P. S. STASSEN, Rutger M. SCHOLS, and Raul J. ROSENTHAL

FLUORESCENCE CHOLANGIOGRAPHY The Advent of a New Era of Improved Visualization and Safety

Fernando DIP,1 Luis SAROTTO,2 Laurents P.S. STASSEN,3 Rutger M. SCHOLS4 and Raul J. ROSENTHAL5

1| MD, MAAC; Chief of Research Surgery, Oncological Surgical Division, Department of Surgery, Division of Surgical Research, University of Buenos Aires, Hospital de Clinicas José de San Martin, Buenos Aires, Argentina Affiliate Faculty, Section of Minimally Invasive Surgery, Department of General Surgery, Cleveland Clinic Florida, Weston, FL, USA 2| MD, PhD, MAAC; Chief of Surgery, Department of Gastroenterological Surgery Professor of Surgery, University of Buenos Aires, Hospital de Clinicas José de San Martin, Buenos Aires, Argentina 3| MD, PhD; Professor of Gastrointestinal Surgery, Chief of Surgical Training, Vice Chair, Department of Surgery, Maastricht University Medical Center Maastricht, The Netherlands 4| MD, PhD; Resident in Plastic, Reconstructive and Hand Surgery Maastricht University Medical Center Maastricht, The Netherlands 5| MD, FACS, FASMBS, Professor of Surgery and Chairman, Department of General Surgery, Director, The Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, FL, USA 4 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety Fernando Dip1, Luis Sarotto2, Laurents P.S. Stassen3, Rutger M. Schols4 and Raul J. Rosenthal5 1| MD, MAAC, Chief of Research Surgery, Oncological Surgical Division, Department of Surgery, Division of Surgical Research, University of Buenos Aires, Hospital de Clinicas José de San Martin, Buenos Aires, Argentina Affiliate Faculty, Section of Minimally Invasive Surgery, Department of General Surgery, Cleveland Clinic Florida, Weston, FL, USA 2| MD, PhD, MAAC; Chief of Surgery, Department of Gastroenterological Surgery Professor of Surgery, University of Buenos Aires, Hospital de Clinicas José de San Martin, Buenos Aires, Argentina 3| MD, PhD; Professor of Gastrointestinal Surgery, Chief of Surgical Training, Vice Chair, Department of Surgery, Maastricht University Medical Center Maastricht, The Netherlands 4| MD, PhD; Resident in Plastic, Reconstructive and Hand Surgery Maastricht University Medical Center Maastricht, The Netherlands 5| MD, FACS, FASMBS, Professor of Surgery and Chairman, Important notes: Department of General Surgery, Director, The Bariatric and Metabolic Institute, Medical knowledge is ever changing. As new research and clinical Cleveland Clinic Florida, Weston, FL, USA experience broaden our knowledge, changes in treatment and therapy may be required. The authors and editors of the material herein have consulted sources believed to be reliable in their efforts to provide Correspondence address of the first author: information that is complete and in accord with the standards Fernando Dip, MD, MAAC, accepted at the time of publication. However, in view of the possibility Chief of Research Surgery, Oncological Surgical Division, of human error by the authors, editors, or publisher, or changes Department of Surgery, Division of Surgical Research, in medical knowledge, neither the authors, editors, publisher, nor University of Buenos Aires, Hospital de Clinicas José de any other party who has been involved in the preparation of this San Martin, Buenos Aires, Argentina booklet, warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for Affiliate Faculty, Section of Minimally Invasive Surgery, any errors or omissions or for the results obtained from use of Department of General Surgery, Cleveland Clinic Florida, such information. The information contained within this booklet is Weston, FL, USA intended for use by doctors and other health care professionals. This Email: [email protected] material is not intended for use as a basis for treatment decisions, and is not a substitute for professional consultation and/or use of peer- reviewed medical literature. All rights reserved. 1st edition 2017 Some of the product names, patents, and registered designs referred © 2017 GmbH to in this booklet are in fact registered trademarks or proprietary names P.O. Box, 78503 Tuttlingen, Germany even though specific reference to this fact is not always made in the Phone: +49 (0) 74 61/1 45 90 text. Therefore, the appearance of a name without designation as Fax: +49 (0) 74 61/708-529 proprietary is not to be construed as a representation by the publisher E-mail: [email protected] that it is in the public domain. The use of this booklet as well as any implementation of the information No part of this publication may be translated, reprinted or contained within explicitly takes place at the reader’s own risk. No reproduced, transmitted in any form or by any means, electronic liability shall be accepted and no guarantee is given for the work or mechanical, now known or hereafter invented, including neither from the publisher or the editor nor from the author or any photocopying and recording, or utilized in any information storage other party who has been involved in the preparation of this work. This or retrieval system without the prior written permission of the particularly applies to the content, the timeliness, the correctness, the copyright holder. completeness as well as to the quality. Printing errors and omissions Editions in languages other than English and German are in prepa- cannot be completely excluded. The publisher as well as the author or other copyright holders of this work disclaim any liability, particularly for ration. For up-to-date information, please contact any damages arising out of or associated with the use of the medical GmbH at the address shown above. procedures mentioned within this booklet. Design and Composing: Any legal claims or claims for damages are excluded. GmbH, Germany In case any references are made in this booklet to any 3rd party publication(s) or links to any 3rd party websites are mentioned, it is Printing and Binding: made clear that neither the publisher nor the author or other copyright Straub Druck + Medien AG holders of this booklet/book endorse in any way the content of said Max-Planck-Straße 17, 78713 Schramberg, Germany publication(s) and/or web sites referred to or linked from this booklet

and do not assume any form of liability for any factual inaccuracies or breaches of law which may occur therein. Thus, no liability shall 02.17–3 be accepted for content within the 3rd party publication(s) or 3rd party websites and no guarantee is given for any other work or any other websites at all. ISBN 978-3-89756-936-2 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety 5

Table of Contents

1 An Unresolved Problem: Bile Duct Injury �� 7 1.1. Current Methods for Bile Duct Visualization and Identification �� 8 1.1.1. Critical View of Safety Approach ...... 8 1.1.2. Intraoperative Cholangiography...... 8

2 NIR-Fluorescence: Seeing Beyond Human Vision �� 8 2.1. Basic Concepts of Fluorescence �� 8 2.2. Fluorescence Cholangiography: Technique �� 10 2.3. Cystic Duct and Common Hepatic Duct Visualization �� 10 2.4. Difficult Scenarios �� 11 2.5. Bile Duct Variability and Accessory Ducts �� 11 2.6. Why Routine Use of Fluorescence Cholangiography is Recommended �� 12 2.6.1. Feasible Without the Need for Cutting a Bile Duct...... 12 2.6.2. Cost-Effective...... 12 2.6.3. Expeditious / Not Time-Consuming ...... 12 2.6.4. Obviates the Use of X-Ray or Laser ...... 12 2.6.5. Effective Imaging Modality...... 12 2.6.6. The Role of Fluorescence Cholangiography in a Teaching Program . . . . 13 2.6.7. Fluorescence Cholangiography in Obese Patients ...... 13 2.6.8. Fluorescence Cholangiography and Bile Stones ...... 13

3 References �� 14 6 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

Contributing Authors

Fernando Dip, MD, MAAC Luis Sarotto,. MD, PhD, MAAC

Laurents PS Stassen, MD, PhD Rutger M. Schols, MD, PhD

Raul J. Rosenthal, MD, FACS, FASMBS An Unresolved Problem: Bile Duct Injury 7

1 An Unresolved Problem: Bile Duct Injury

Laparoscopic cholecystectomy is among the oldest Bile duct injury (BDI) is associated with significant morbidity, laparoscopic procedure in surgery, with the first reported and can effect relatively young patients who incur a cases dating back to the mid-1980s.21 Since then it has substantial loss in quality of life as a consequence of multiple become a common procedure with approximately 90% of re-hospitalizations and re-interventions needed to repair the cholecystectomies performed laparoscopically in Germany bile ducts.16, 36 and the United States alone.2 When bile duct injuries occur, surgeons and hospitals often Many advantages have accrued from the laparoscopic have to go through long and costly legal claims that usually approach as compared to the open procedure including favor the patients.35 earlier discharge of the patients, improved cosmetics, less abdominal pain and more rapid recovery.5 Nevertheless, Conventional intraoperative cholangiography (IOC) has been the minimally invasive approach has been associated with advocated to decrease the incidence of BDI, but has not shortcomings like a significant learning curve, loss of tactile gained worldwide acceptance nor has it been shown to feedback and increased risk of bile duct injury (BDI).17 reduce BDIs.14, 15, 19 Strict observance of the ‘Critical-View-of- Safety’ has been proposed as the most suitable technique Undoubtedly, the main concern with laparoscopic in order to prevent the occurrence of BDI, yet the incidence cholecystectomy is related to the associated increase of has not further decreased in the past decade,35 which is why BDI compared to that of the open surgery era (0.4 vs 0.2%).2 it became desirable that other techniques or precautionary Bile duct injury is a rare, but serious complication during this measures be adopted. Fluorescence Cholangiography (FC) procedure, which is most often due to misidentification of is such a technique. By enhancing the visualization of the the extra-hepatic bile duct anatomy.9 bile ducts in real time, accurate identification of the various structures is facilitated, which may help prevent injury. The The reported incidence is 0.3–0.7% of cases.2, 5, 17, 21 This technique requires no additional incisions and is easy to translates to approximately 3,000 injuries out of the reported apply.11 750,000 laparoscopic cholecystectomies performed in the US in 2008 alone.9

Fig. 1.1 Visual perceptual illusion is the cause of 97% of bile duct Fig. 1.2 A bile duct injury is a life-changing event for the patient.16, 36 injuries.9 Key to acronym: Endoscopic retrograde cholangiopancreatography (ERCP).

Fig. 1.3 Consequences after a bile duct injury.4, 8, 18, 20 8 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

1.1. Current Methods for Bile Duct Visualization and Identification

1.1.1. Critical View of Safety Approach The complete exposure of Calot’s triangle – which is freed bile duct prior to cutting any structure at all. Although this from all fatty and fibrous tissue, followed by mobilization of has been reported in the literature as a critical step toward the lowest part of the gall bladder from its bed – was initially improving the safety of laparoscopic cholecystectomy, its described in 1995 by Strasberg et al.34 who suggested this implementation in routine clinical practice has not lead to a preliminary step to be taken with the main objective of decrease in the rate of BDI.31–33 identifying the cystic artery, the cystic duct and the main

1.1.2. Intraoperative Cholangiography Intraoperative cholangiography (IOC) is a well-known IOC, because it is said to be time-consuming and prone to technique that is used to demonstrate integrity of intra- and the risk of misinterpretation of fluoroscopic images, so as extra-hepatic bile ducts. For this purpose, a catheter has to to explain that – despite the use of this modality – bile duct be placed inside the bile ducts and with the administration injuries have not decreased.3, 27, 28 of iodine and application of fluoroscopy, anatomical images from the relevant region are obtained.29 Up to now, no real-time intraoperative method has been 7 The routine and selective use of IOC is still under debate. shown to be useful to identify the extra-hepatic biliary Proponents of the technique state that – given proper anatomy during a laparoscopic cholecystectomy before interpretation of the intraoperative fluoroscopic image – IOC clipping or cutting a bile duct structure. is capable of decreasing the severity of BDI and allows identification of bile duct stones. This brochure describes a novel technique that is based on the combined use of indocyanine green (ICG) – a Others find it challenging to cope with IOC, because it fluorescent dye administered IV – and near-infrared (NIR) is said to be time-consuming and prone to the risk of light allowing the surgeon to obtain additional information misinterpretation of fluoroscopic images, so as to explain regarding biliary anatomy in real time during a laparoscopic that – despite the use of this modality – bile duct injuries procedure. have not decreased. Others find it challenging to cope with

2 NIR-Fluorescence: Seeing Beyond Human Vision

2.1. Basic Concepts of Fluorescence In 1852, George Gabriel Stokes described the mineral The oldest known approved near-infrared (NIR) fluorescent Fluorite as emitting blue light following exposure to ultraviolet dye in medicine, indocyanine green (ICG), has been light. He termed the phenomenon as ‘Fluorescence’ and discovered as a chemical compound suited for use in NIR proposed that chemical compounds offering this property to fluorescence cholangiography. be called ‘Fluorophores’.37 ICG is a drug which has been approved for use in humans by The ability to emit fluorescence is very common in nature. the FDA since 1959 for cardiac and liver function tests. The The photosensitivity of delocalized electrons in aromatic tricarbon dye has an absorption maximum of λ Ex = 805 nm ring structures is responsible for this. The absorbed light and an emission maximum of λ Em = 835 nm. On account of energy excites the delocalized electrons into a higher state the inherent property of ICG to emit light in the NIR spectral of energy. When the electrons return to the ground state, range, disturbing effects of autofluorescence that may arise the absorbed light energy is emitted as fluorescence. The from the main blood components (hemoglobin and water) emitted fluorescence is lower in energy as the absorbed are virtually impossible. This results in a tissue detection exciting light energy is partially lost as heat.30 depth for NIR fluorescence of up to 1 cm.1 NIR-Fluorescence: Seeing Beyond Human Vision 9 – Energy +

Excitation Energy loss / non-radiative energy transfer Emission Fig. 2.1 Principle of fluorescence.

Most commonly, ICG is intravenously administered where it it an ideal compound for delineation of the extra-hepatic binds to plasma proteins (albumin) thereby remaining in the biliary tree. bloodstream due to size exclusion. From the bloodstream, In addition to bile duct imaging, ICG can be used for ICG is transported to the liver, where it is excreted via the bile perfusion assessment and for the visualization of lymph into the duodenum. This exclusive excretion into bile makes channels and lymph nodes.

(1) Intravenous injection of ICG (2) ICG binds to plasma proteins (3) Visualization of ICG in bloodstream with the KARL STORZ NIR/ICG System (4) NIR/ICG light source

Fig. 2.2 Principle of perfusion assessment with ICG. 10 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

2.2. Fluorescence Cholangiography: Technique The procedure begins with the intravenous administration Once the gallbladder is retracted, Calot’s triangle is of 0.05 mg/kg of indocyanine green, ideally performed illuminated using a special xenon light source that allows preoperatively when the IV line is placed, which allows at the use of both white light (WL) and NIR light. Switching or least 45 minutes prior to the surgery for it to be excreted ‘toggling’ between these two modes is easily done using a from the liver and into the bile. Alternatively, if preoperative foot pedal operated by the surgeon. Using this combination administration is not possible or was missed, the ICG can be of WL and NIR imaging, the biliary ducts can be identified administered directly after induction of anesthesia, but this through the non-dissected tissue even earlier than in WL will result in a less optimal viewing of the biliary anatomy due mode alone.25 to residual ICG remaining in the liver.

2.3. Cystic Duct and Common Hepatic Duct Visualization Fluorescent cholangiography is the first method that can the use of this technology allows vital structures – which be used in real time during a laparoscopic cholecystectomy otherwise could not be identified with standard xenon white in order to improve endoscopic visualization and facilitate light alone – to be visualized by ICG-enhanced fluorescence, identification of the extra-hepatic bile ducts. Accordingly, guiding the surgeon during dissection.25, 26

a b Figs. 2.3 Visualization of biliary structures through fat. Note the technique of ‘toggling’ between white light mode (WL) (a) and near-infrared (NIR) mode (b), which may be used as determined by surgeon’s preferences or by individual circumstances. NIR-Fluorescence: Seeing Beyond Human Vision 11

a b Figs. 2.4 Visualization of biliary structures through blood and inflammation. Intraoperative views taken with white light mode (a) and NIR mode (b).

2.4. Difficult Scenarios Correct identification of the extra-hepatic bile duct is that is seemingly ‘easy to do’ can turn into an unexpected one of the main concerns of any surgeon undertaking a nightmare. laparoscopic cholecystectomy. Preoperative workup of the patient includes laboratory tests, hepatobiliary ultrasound In these situations, structures of the Calot’s triangle are and, in some cases, MR imaging. Usually, these tests are difficult to see. When blood or fat covers the bile structures, capable of predicting the complexity of a planned laparo- Fluorescence cholangiography can be used efficiently to scopic cholecystectomy, but occasionally, a procedure clarify the location of the ducts.

2.5. Bile Duct Variability and Accessory Ducts Some authors report up to 2% of iatrogenic bile leaks On account of their small diameter (typically 1–2 mm), after laparoscopic cholecystectomy, which is linked to an intraoperative identification of accessory ducts is very increase in the associated rate of morbidity.23 Unnoticed difficult during a laparoscopic procedure. The vast majority iatrogenic injuries to small subvesical or Luschka ducts are of these minor bile duct injuries go unnoticed during laparo- among the major factors contributing to postoperative com- scopic procedures. plications after laparoscopic cholecystetomies.13, 31 In 1753, Antoine Ferrein (1693–1769), a human anatomist, was the Based on initial experience from surgeons using fluores- first to report on the presence of bile ducts within the left cence cholangiography on a routine basis, a detection rate lateral or triangular ligament of the liver. These ducts were of up to 7% of Luschka ducts has been reported. Once the later described by Weber in 1842 as ‘aberrant biliary ducts’ ducts are recognized, they can be clipped to avoid further located outside the hepatic parenchyma.22, 31 In an attempt leaks. Fluorescence imaging of even small ducts may allow to elicit their course and drainage pathway, detailed stud- the surgeon to avoid Type-A bile duct injuries. ies were undertaken by Luschka in 1863, who called them ‘accessory’ instead of ‘aberrant’ ducts. Accessory ducts are present in 20–50% of the overall population.6

a b Figs. 2.5 Bifurcation of hepatic ducts. In this case, the hepatic ducts cannot be identified using standard white light endoscopy (a). Once the light source is switched to NIR/ICG mode (b), the hepatic ducts can be visualized. 12 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

2.6. Why Routine Use of Fluorescence Cholangiography is Recommended

2.6.1. Feasible Without the Need for Cutting a Bile Duct Fluorescence cholangiography can be performed without any incision in the bile duct. This is a main advantage of the technique, because unlike IOC, it can be performed in patients in whom the bile duct is friable. Trying to cannulate the cystic duct in order to perform an IOC in a patient suffering from severe cholecystitis or in the case of a short cystic duct, may provoke an injury.11

Initial studies show significant differences in feasibility rate between IOC and FC. One study concluded that FC was feasible on all patients in the trial, whereas IOC was feasible in only 93%.11

Fig. 2.6 Main reasons for using fluorescence cholangiography (FC) on a routine basis.

2.6.2. Cost-Effective 2.6.4. Obviates the Use of X-Ray or Laser One of the surgeon’s main concerns with a new technology The use of X-ray in the OR is time-consuming and associated is related to cost. According to published data, cost with well-known risks for the OR staff. Fluorescence cholan- effectiveness has been demonstrated using FC as a routine giography uses NIR light produced by a xenon light source precautionary measure. The rate of toxicity of ICG is less equipped with a specific filter. Unlike with the use of laser than 0.003%3 and the overall cost of the dye administered devices, which may necessitate a prior risk assessment throughout the procedure is low. In 2014, costs for a FC by a laser safety commissioner, FC obviates the need for were estimated between US$14 (cost of actual volume of additional safety measures. ICG used) and US$100 (cost per vial).24 Additionally, FC has been shown to be far less expensive than IOC once the equipment is part of the medical armamentarium in the OR.12 2.6.5. Effective Imaging Modality FC works as a complement to traditional white light laparo 2.6.3. Expeditious / Not Time-Consuming scopy which helps the surgeon to more distinctly visualize the bile ducts. Fluorescence cholangiography is not time-consuming and is significantly faster when compared to IOC. The average time to perform an FC is less than one minute, whereas the average IOC takes over seven minutes.12 NIR-Fluorescence: Seeing Beyond Human Vision 13

2.6.6. The Role of Fluorescence Cholangiography in a Teaching Program

Considering that a laparoscopic approach is the current White light NIR mode P Value mainstay of care in the majority of cholecystectomy patients, mode it has in turn changed the way surgery is taught in residency programs. Undoubtedly, the control that a surgeon can Cystic duct 40% 99% 0.0001 have over a resident is reduced compared to open surgery. Common hepatic duct 35% 96% 0.0001 Instructions on where to proceed with dissection can be Cystic-common hepatic challenging because verbal communication is inherently 24% 95.5% 0.0001 prone to misunderstanding and observer-dependent duct junction interpretation of visual information. Table 2.1 Percentage of extra-hepatic duct visualization with white light (WL) and near-infrared (NIR) light.23 Fluorescence cholangiography has been shown to be a very useful tool for surgeons who are in charge of teaching residents, in that it considerably facilitates proper identification of vulnverable biliary structures as compared to white light visualization alone.

2.6.7. Fluorescence Cholangiography in Obese Patients In recent years, obesity has become a global problem. Occasionally, surgical treatment of obese patients can pose a challenge when proper visualization of structures of interest is obscured by fatty tissue.

The feasibility of fluorescence cholangiography and visualization of anatomical key structures has been analyzed on the basis of various groups of patients treated by laparoscopic cholecystectomies. Even though it is well known that penetration of NIR light may be reduced by fat, no significant differences nor differences in the visualization of cystic duct, common bile duct, and accessory duct were noted between the obese and non-obese groups (p-value 0.09, 0.16, and 0.66, respectively).10

Fig. 2.7 Unlike IOC, FC is feasible in obese patients. 2.6.8. Fluorescence Cholangiography and Bile Stones Fluorescence cholangiography has been shown to be very effective in visualizing extra-hepatic biliary structures. In the presence of lithiasis, however, calculi may accumulate in the bile ducts, surrounded by bile. So far, no studies have demonstrated the visualization of bile stones using fluorescence cholangiography, and as such, it should be considered a complementary modality to IOC if preoperative laboratory results suggest the presence of bile stones.2 14 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

3 References

1. ALANDER JT, KAARTINEN I, LAAKSO A, PATILA T, 11. DIP F, ROY M, LO MENZO E, SIMPFENDORFER C, SPILLMANN T, TUCHIN VV ET AL. A review SZOMSTEIN S, ROSENTHAL RJ. Routine use of of indocyanine green fluorescent imaging in fluorescent incisionless cholangiography as a new surgery. Int J Biomed Imaging 2012;2012:940585. imaging modality during laparoscopic cholecystectomy. doi:10.1155/2012/940585. Surg Endosc 2015;29(6):1621–6. doi:10.1007/ s00464-014-3853-7. 2. BERCI G, HUNTER J, MORGENSTERN L, ARREGUI M, BRUNT M, CARROLL B ET AL. Laparoscopic 12. DIP FD, ASBUN D, ROSALES-VELDERRAIN A, cholecystectomy: first, do no harm; second, take care LO MENZO E, SIMPFENDORFER CH, SZOMSTEIN S of bile duct stones. Surg Endosc 2013;27(4):1051–4. ET AL. Cost analysis and effectiveness comparing doi:10.1007/s00464-012-2767-5. the routine use of intraoperative fluorescent cholangiography with fluoroscopic cholangiogram in 3. BUDDINGH KT, WEERSMA RK, SAVENIJE RA, patients undergoing laparoscopic cholecystectomy. VAN DAM GM, NIEUWENHUIJS VB. Lower rate of Surg Endosc 2014;28(6):1838–43. doi:10.1007/ major bile duct injury and increased intraoperative s00464-013-3394-5. management of common bile duct stones after implementation of routine intraoperative 13. DOUMENC B, BOUTROS M, DEGREMONT R, cholangiography. J Am Coll Surg 2011;213(2):267–74. BOURAS AF. Biliary leakage from gallbladder bed after doi:10.1016/j.jamcollsurg.2011.03.004. cholecystectomy: Luschka duct or hepaticocholecystic duct? Morphologie 2016;100(328):36–40. doi:10.1016/ 4. CARROLL BJ, BIRTH M, PHILLIPS EH. Common bile j.morpho.2015.08.003. duct injuries during laparoscopic cholecystectomy that result in litigation. Surg Endosc 1998;12(4):310-3; 14. FLUM DR, DELLINGER EP, CHEADLE A, CHAN L, discussion 314. KOEPSELL T. Intraoperative cholangiography and risk of common bile duct injury during cholecystectomy. 5. CASTALDO P, CHIAVELLATI L, DI GIULIO E, JAMA 2003;289(13):1639–44. doi:10.1001/ SCHIFFINO L, STIPA F, ZIPARO V ET AL. Laparoscopic jama.289.13.1639. cholecystectomy. The beginning of a new era. Recenti 15. FLUM DR, KOEPSELL T, HEAGERTY P, SINANAN M, Prog Med 1992;83(7-8):429–36. DELLINGER EP. Common bile duct injury during 6. CHAMPETIER J, DAVIN JL, LETOUBLON C, laparoscopic cholecystectomy and the use of LABORDE Y, YVER R, COUSSET F. Choleperitoneum intraoperative cholangiography: adverse outcome or following perforation of the liver. The role of the vasa preventable error? Arch Surg 2001;136(11):1287–92. aberrantia. Ann Chir 1982;36(4):312. 16. GOSSAGE JA, FORSHAW MJ. Prevalence and 7. CIULLA A, AGNELLO G, TOMASELLO G, outcome of litigation claims in England after CASTRONOVO G, MAIORANA A, GENOVA G. laparoscopic cholecystectomy. The intraoperative cholangiography during Int J Clin Pract 2010;64(13):1832–5. doi:10.1111/ videolaparoscopic cholecystectomy. What is its role? j.1742-1241.2009.02200.x. Results of a non randomized study. Ann Ital Chir 17. HALBERT C, ALTIERI MS, YANG J, MENG Z, CHEN H, 2007;78(2):85–9. TALAMINI M ET AL. Long-term outcomes of patients 8. DAGEFORDE LA, LANDMAN MP, FEURER ID, with common bile duct injury following laparoscopic POULOSE B, PINSON CW, MOORE DE. cholecystectomy. Surg Endosc 2016. doi:10.1007/ A cost-effectiveness analysis of early vs late s00464-016-4745-9. reconstruction of iatrogenic bile duct injuries. 18. LO NIGRO C, GERACI G, SCIUTO A, LI VF, SCIUME C, J Am Coll Surg 2012;214(6):919–27. doi:10.1016/ MODICA G. Bile leaks after videolaparoscopic j.jamcollsurg.2012.01.054. cholecystectomy: duct of Luschka. Endoscopic 9. DEKKER SW, HUGH TB. Laparoscopic bile duct injury: treatment in a single centre and brief literature review on understanding the psychology and heuristics of the current management. Ann Ital Chir 2012;83(4):303–12. error. ANZ J Surg 2008;78(12):1109–14. doi:10.1111/ 19. MASSARWEH NN, FLUM. Role of intraoperative j.1445-2197.2008.04761.x. cholangiography in avoiding bile duct injury. 10. DIP F, NGUYEN D, MONTORFANO L, NOSTE ME, J Am Coll Surg 2007;204(4):656–64. doi:10.1016/ LO MENZO E, SIMPFENDORFER C ET AL. Accuracy j.jamcollsurg.2007.01.038. of Near Infrared-Guided Surgery in Morbidly Obese 20. MCLEAN TR. Risk management observations from Subjects Undergoing Laparoscopic Cholecystectomy. litigation involving laparoscopic cholecystectomy. Arch Obes Surg 2016;26(3):525–30. Surg 2006;141(7):643-8; discussion 648. doi:10.1001/ doi:10.1007/s11695-015-1781-9. archsurg.141.7.643. Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety 15

21. PERISSAT J, COLLET, BELLIARD R. Gallstones: 29. SIRINEK KR, SCHWESINGER WH. Has intraoperative laparoscopic treatment, intracorporeal lithotripsy cholangiography during laparoscopic cholecystectomy followed by cholecystostomy or cholecystectomy – become obsolete in the era of preoperative endoscopic a personal technique. Endoscopy 1989;21 Suppl retrograde and magnetic resonance cholangiopan- 1:373–4. doi:10.1055/s-2007-1012994. creatography? J Am Coll Surg 2015;220(4):522–8. 22. POIRIER P, CHARPY A. Traité d'anatomie humaine. doi:10.1016/j.jamcollsurg.2014.12.043. Masson, Paris, 1912(Tome 4, Fasc. 1.):187–9. 30. SKOOG DA, HOLLER FJ, CROUCH SR. Principles of 23. ROY M, DIP F, NGUYEN D, SIMPFENDORFER CH, instrumental analysis. 6th ed. Belmont, Calif.: Thomson MENZO EL, SZOMSTEIN S ET AL. Fluorescent Brooks/Cole; 2007. (ISBN No. 9780495125709). incisionless cholangiography as a teaching tool for 31. SPANOS CP, SYRAKOS T. Bile leaks from the duct of identification of Calot's triangle. Surg Endosc 2016. Luschka (subvesical duct): a review. doi:10.1007/s00464-016-5250-x. Langenbecks Arch Surg 2006;391(5):441–7. 24. SAVADER SJ, LILLEMOE KD, PRESCOTT CA, doi:10.1007/s00423-006-0078-9. WINICK AB, VENBRUX AC, LUND GB ET AL. Laparoscopic cholecystectomy-related bile duct 32. STRASBERG SM. Avoidance of biliary injury during injuries: a health and financial disaster. Ann Surg laparoscopic cholecystectomy. 1997;225(3):268–73. J Hepatobiliary Pancreat Surg 2002;9(5):543–7. doi:10.1007/s005340200071. 25. SCHOLS RM, BOUVY ND, MASCLEE AA, VAN DAM RM, DEJONG CH, STASSEN LP. 33. STRASBERG SM. Error traps and vasculo-biliary injury Fluorescence cholangiography during laparoscopic in laparoscopic and open cholecystectomy. cholecystectomy: a feasibility study on early biliary J Hepatobiliary Pancreat Surg 2008;15(3):284–92. tract delineation. Surg Endosc 2013;27(5):1530–6. doi:10.1007/s00534-007-1267-9. doi:10.1007/s00464-012-2635-3. 34. STRASBERG SM, HERTL M, SOPER NJ. An analysis 26. SCHOLS RM, BOUVY ND, VAN DAM RM, of the problem of biliary injury during laparoscopic MASCLEE AA, DEJONG CH, STASSEN LP. cholecystectomy. J Am Coll Surg 1995;180(1):101–25. Combined vascular and biliary fluorescence imaging 35. TORNQVIST B, STROMBERG C, AKRE O, in laparoscopic cholecystectomy. Surg Endosc ENOCHSSON L, NILSSON M. Selective intraoperative 2013;27(12):4511–7. doi:10.1007/s00464-013-3100-7. cholangiography and risk of bile duct injury during 27. SHEFFIELD KM, HAN Y, KUO YF, TOWNSEND CM JR, cholecystectomy. Br J Surg 2015;102(8):952–8. GOODWIN JS, RIALL TS. Variation in the use of doi:10.1002/bjs.9832. intraoperative cholangiography during cholecystectomy. J Am Coll Surg 2012;214(4):668-79; discussion 679-81. 36. VERDONK RC, LOZANO MF, VAN DEN BAP, GOUW AS. doi:10.1016/j.jamcollsurg.2011.12.033. Bile ductal injury and ductular reaction are frequent phenomena with different significance in autoimmune 28. SHEFFIELD KM, RIALL TS, HAN Y, KUO YF, hepatitis. Liver Int 2016. doi:10.1111/liv.13083. TOWNSEND CM JR, GOODWIN JS. Association between cholecystectomy with vs without intraoperative 37. WILSON DB. Kelvin and stokes: A comparative study cholangiography and risk of common duct injury. JAMA in Victorian physics. Bristol: Hilger; 1987. (ISBN No. 2013;310(8):812–20. doi:10.1001/jama.2013.276205. 0852745265). 16 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

OPAL1® Technology for NIR / ICG

1 IMAGE1 S™ l FULL HD image quality l NIR / ICG fluorescence

2 NIR/ICG telescope and camera head l 3-chip FULL HD camera head with high resolution and NIR light sensitivity l telescope for fluorescence excitation and 2 5 detection; can be used both in white light mode and in fluorescence mode l telescopes available in various lengths and diameters 1 3 D-LIGHT P light source (Xenon light source) 3 l daylight spectrum; white light and fluorescence modes l no additional security measures l with enhanced background display

4 Footswitch l fast switch between white light and fluorescence mode

5 Autoclavable fiber optic light cable 4

Basic equipment cart: Not for sale in the U.S.

It is recommended to check the suitability of the product for the intended procedure prior to use. Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety 17

OPAL1® Technology for NIR / ICG

IMAGE1 S™ System

™

Camera system IMAGE1 S CONNECT TC200

NIR / ICG

IMAGE1 S™ H3-LINK Camera CCU TC300

Light source D-LIGHT P 20 1337 01-1

IMAGE1 S™ H3-Z FI

Camera head TH102

Light cable Fiber Optic Light Cable 495NAC /NCSC /TIP /NCS / VIT

HOPKINS® Telescope 26003ACA / BCA

Telescopes 26046ACA / BCA

® VITOM II ICG 20 9160 25AGA 28272UGN / CN 28272HC VITOM 28172HR / HM 18 Fluorescence Cholangiography – The Advent of a New Era of Improved Visualization and Safety

Notes: with the compliments of KARL STORZ — ENDOSKOPE