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Han-Kwang YANG, Seong-Ho KONG, Yun-Suk SUH and Hyuk-Joon LEE ICG-ENHANCED NIR FLUORESCENCE IMAGING IN LAPAROSCOPIC GASTRIC CANCER SURGERY

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Page 1: ICG-EnhanCEd nIR FluoREsCEnCE ImaGInG In … · mans by the FDA since 1959 for cardiac and liver function tests. The tricarbon dye has an absorption maximum of ... Gastric cancer

Han-Kwang YANG, Seong-Ho KONG, Yun-Suk SUH and Hyuk-Joon LEE

ICG-EnhanCEd nIR FluoREsCEnCE ImaGInG

In laPaRosCoPIC GasTRIC CanCER suRGERY

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Page 3: ICG-EnhanCEd nIR FluoREsCEnCE ImaGInG In … · mans by the FDA since 1959 for cardiac and liver function tests. The tricarbon dye has an absorption maximum of ... Gastric cancer

ICG-Enhanced NIR Fluorescence Imaging in

LAPAROSCOPIC GASTRIC CANCER SURGERY

Han-Kwang YANG, Seong-Ho KONG, Yun-Suk SUH and Hyuk-Joon LEE

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine,

Seoul, Korea

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery4

ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

Han-Kwang Yang, Seong-Ho Kong, Yun-Suk Suh and Hyuk-Joon Lee

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Correspondence address:

Han-Kwang Yang Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine 101 Daehang-Ro, Jongno-Gu, Seoul 110-744, Korea Email: [email protected]

All rights reserved. 1st Edition © 2018 GmbH P.O. Box, 78503 Tuttlingen, Germany Phone: +49 (0) 74 61/1 45 90 Fax: +49 (0) 74 61/708-529 Email: [email protected]

No part of this publication may be translated, reprinted or reproduced, transmitted in any form or by any means, electronic or mechanical, now known or hereafter invent ed, including photocopying and recording, or utilized in any information storage or retrieval system without the prior written permission of the copyright holder.

Editions in languages other than English and German are in preparation. For up-to-date information, please contact

GmbH at the address shown above.

Design and Composing: GmbH, Germany

Printing and Binding: Straub Druck + Medien AG Max-Planck-Straße 17, 78713 Schramberg, Germany

03.18-2.0

ISBN 978-3-89756-937-9

Important notes:

Medical knowledge is ever changing. As new research and clinical experience broaden our knowledge, changes in treat ment 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 information that is complete and in accord with the standards accept ed at the time of publication. However, in view of the possibili ty of human error by the authors, editors, or publisher, or changes in medical knowledge, neither the authors, editors, publisher, nor any other party who has been involved in the preparation of this booklet, warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from use of such information. The information contained within this booklet is intended for use by doctors and other health care professionals. This 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.

Some of the product names, patents, and re gistered designs referred to in this booklet are in fact registered trademarks or proprietary names even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain.

The use of this booklet as well as any implementation of the information contained within explicitly takes place at the reader’s own risk. No liability shall be accepted and no guarantee is given for the work neither from the publisher or the editor nor from the author or any other party who has been involved in the preparation of this work. This particularly applies to the content, the timeliness, the correctness, the completeness as well as to the quality. Printing errors and omissions cannot be completely excluded. The publisher as well as the author or other copyright holders of this work disclaim any liability, particularly for any damages arising out of or associated with the use of the medical procedures mentioned within this booklet.

Any legal claims or claims for damages are excluded.

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 made clear that neither the publisher nor the author or other copyright holders of this booklet/book endorse in any way the content of said 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 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.

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5ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

Table of Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

1.1 Basic Concepts of ICG-Enhanced Fluorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2 SentinelLymphNodeDissectionwithICG-EnhancedNIR FluorescenceLymphangiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.1 Epidemiology and Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.2 Injection Sites and Timing of ICG Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3 Gastrointestinal Perfusion Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

4 Summary and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

5 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

The KARL STORZ OPAL1® Technology for ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery6

The Authors

Han-Kwang Yang, Seong-Ho Kong, Hyuk-Joon Lee and Yun-Suk Suh (left to right).

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery 7

Fig. 1.1  Schematic drawing demonstrating the principle of fluorescence.

– En

ergy

+

Excitation Energy loss / non-radiative energy transfer Emission

1 Introduction

1.1 Basic Concepts of ICG-Enhanced FluorescenceIn 1852, George Gabriel Stokes described the mineral Fluorite as emitting blue light following exposure to ul-traviolet light. He termed the phenomenon as ‘Fluores-cence’ and proposed that chemical compounds offering this property be called ‘Fluorophores’.21

The ability to emit fluorescence is very common in nature. The photosensitivity of delocalized electrons in aromatic ring structures is responsible for this. The absorbed light energy excites the delocalized electrons into a higher state of energy. When the electrons return to the ground state, the absorbed light energy is emitted as fluores-cence. The emitted fluorescence is lower in energy as the absorbed exciting light energy is partially lost as heat.19

The oldest known approved near-infrared (NIR) fluores-cent dye in medicine, indocyanine green (ICG), has been discovered as a chemical compound suited for use in NIR fluorescence-guided surgery.

ICG is a drug which has been approved for use in hu-mans by the FDA since 1959 for cardiac and liver function tests. The tricarbon dye has an absorption maximum of λEx = 805 nm and an emission maximum of λEm = 835 nm. On account of the inherent property of ICG to emit light in the NIR spectral range (wavelength of 700–900 nm), dis-turbing effects of autofluorescence that may arise from the main blood components (hemoglobin and water) are virtually impossible. The tissue penetration depth of ICG/NIR-enhanced fluorescence ranges between 0.5 cm and 1 cm.1,16,17

(1) Intravenous injection of ICG.(2) ICG binds to plasma proteins.(3) Visualization of ICG in bloodstream

with the KARL STORZ OPAL1® technology for ICG/NIR imaging.

(4) Full HD camera system coupled to a Xenon cold light source equipped with a special filter required for ICG/NIR imaging.

Fig. 1.2 Principle of perfusion assessment with ICG/NIR imaging.

Most commonly, ICG is intravenously administered where it binds to plasma proteins (albumin) thereby re-maining in the bloodstream due to size exclusion. From the bloodstream, ICG is transported to the liver, where it is excreted via the bile into the duodenum. This exclusive excretion into bile makes it an ideal compound for delin-eation of the extra-hepatic biliary tree.

In addition to bile duct imaging, ICG can be used for per-fusion assessment as well as for visualization of lymph channels and lymph nodes.

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery8

2 Sentinel Lymph Node Dissection with ICG-Enhanced NIR Fluorescence Lymphangiography

2.1 Epidemiology and Background

Gastric cancer is the 5th most common cancer in the world according to GLOBOCAN 2012 data,7 and is ranked 3rd for the incidence of cancer-related mortality. Irrespective of the historical debate and ongoing controversy among experts in western and eastern countries, the use of lymph node dissection in gastric cancer surgery has gained widespread acceptance in the worldwide community of surgeons. In Asian countries, where a significant proportion of patients are diagnosed with early-stage gastric cancer through routine screening programs, NIR imaging tech-nology is considered a promising cutting-edge imaging solution for sentinel lymph node (SLN) mapping and dis-section.12,15 The emerging technique of ICG-enhanced NIR fluorescence imaging can be used effectively to tailor the extent of lymph node dissection to the individual patient, which in turn can help to reduce the rate of postoperative complications associated with extended lymphadenec-tomy. Additional benefits that can be derived from the new technique include preservation of organ function and improved quality of life. In Western countries, where most patients with gastric cancer are diagnosed at an advanced stage of the disease, and where many surgeons are not familiar with a more extended radical lymph node dissec-tion, ICG-enhanced NIR fluorescence lymphangiography is used as a safe tracer method that allows to improve the accuracy of detection and to enable a less radical lymph

node dissection. In conclusion, the use of this method is suited to improve intraoperative surgical staging and can ultimately lead to a better oncological outcome and a higher survival rate.

The use of ICG-enhanced fluorescence-guided lymph node mapping in gastric cancer surgery offers some advantages over other modalities employing radioisotopes (e.g., 99mTechnetium radiocolloid) and vital dye tracers (e.g. methylene blue, patent blue), which are currently known to provide the best sensitivity and specificity for sentinel lymph node mapping.20 ICG-enhanced NIR fluorescence imaging is a method that obviates the need to adhere to a specific safety protocol against the radiation hazards associated with the use of radioisotopes.

ICG-enhanced NIR fluorescence imaging for real-time detection of lymph nodes is superior to modalities using vital dyes in that it offers a higher tissue penetration depth and better signal-to-background ratio. However, in order to validate the accuracy of this new method, additional studies with a larger number of patients are needed prior to implementing it in routine clinical practice.11 In view of its good dispersion properties, ICG can also be used as a tracer to guide and evaluate extensive lymph node dissec-tion, especially in the D2 area and in some parts of the D1 region (Fig. 2.1).8

Fig. 2.1 The extent of lymphadenectomy after total (a) and distal (b) gastrectomy. The numbers correspond to the lymph node stations as defined in the Japanese Classification of Gastric Carcinoma.8 Dissection of the lymph nodes highlighted by blue squares corresponds to a D1 lymphadenectomy. When complemented by dissection of the nodes highlighted by orange squares, a D1+ lymphadenectomy is the result. Additional dissection of all nodes highlighted by red squares results in D2 lymphadenectomy.

a bTotal gastrectomy Distal gastrectomy

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9Sentinel Lymph Node Dissection with ICG-Enhanced NIR Fluorescence Lymphangiography

2.2 Injection Sites and Timing of ICG AdministrationICG can be administered either by submucosal injection under flexible gastroendoscopy or laparoscopic subse-rosal injection. The authors prefer the use of submucosal injection (with a 23-gauge endoscopic needle introduced through the flexible scope’s working channel) because during or after subserosal injection, there is an elevated risk of ICG leakage which can significantly compromise the goal of fluorescence guidance.

The typical working concentrations of the ICG solution prepared with commercially available lyophilized powder formulations are either 2.5 mg / mL or 5.0 mg / mL in sterile water, respectively, if the dilution is prepared as prescribed. In vitro studies performed by the authors have shown that the ICG fluorescence signal reaches its highest level of intensity at a final concentration of 0.05 mg / mL. In terms of injection volume, a bolus of 0.5– 1.0 mL should be prepared for each injection site , if ad-ministered 15–30 minutes prior to dissection. When ICG is injected at higher concentrations, some lymph nodes are prone to accumulate ICG which can lead to a focal reduction in fluorescence intensity during the initial post-injection period, a phenomen also known as ‘quenching’.

A fluorescent NIR signal will be noticeable once the dif-fusing ICG is diluted enough with the surrounding lymph fluid. In cases where ICG is administered at a higher concentration, the agent will be dispersed more widely into the soft tissue surrounding the lymph nodes. During the continuing course of the operation, the dye can leak and the resulting high intensity of the signal can interfere with detection of fluorescence from the lymph nodes.

ICG can remain in the lymph nodes and lymphatic network for several days, which is why injection of the dye 1–2 days before surgery can be used as an alter-native to intraoperative injection if the operating room is not equipped with a flexible endoscopy system.22 To date, no well-designed clinical trial has been conducted to compare intraoperative and preoperative injection techniques, however, preliminary evaluation suggests that intraoperative injection is associated with a higher probability to visualize the lymphatic channels between the injection site and the lymph nodes, which can offer additional visual information to trace and identify the draining lymph nodes.

Fig. 2.2  Near-infrared (NIR) fluorescence signals of indocyanine green (ICG) at different concentration levels.12

a. The in vivo NIR image of the small bowel in a pig shows bright signals in the lymph nodes with an ICG concentration of 0.1 mg/ml or higher. The signals were weak at first and then became brighter as ICG was diluted with 1 and 5 mg/ml ICG, however, as a result of the quenching effect (red arrows), a dark area remained in the center of the injection site.

b. The ex vivo NIR image demonstrates the resulting signal sizes at various injection sites / concentration levels in the porcine stomach. Note that 0.1 mg/ml is the optimal concentration level of ICG, with the smallest signal size at the injection site and a signal intensity sufficient to visual-ize lymphatic flows with the least quenching effect.

a b

b c

a

Fig. 2.3 In vitro color image (a) and in vitro NIR image (b) of ICG dye (values are in mg/ml) diluted in cryotubes.Macroscopic color image of the porcine stomach (c). An ICG concentration level of 0.1mg/ml seemed to be optimal because it was correlated with the smallest signal size at the injection site and good visualization of lymphatic flows with the least quenching effect.12

By courtesy of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. Original article: Kong S et al. (2015) 12.

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery10

2.2.1 Injection SitesThe decision as to which ICG injection site to choose is essentially made between two options according to the predefined purpose. A peritumoral site can be selected to detect lymph nodes that drain from the tumor. Alterna-tively, the injections can be placed along the lesser and greater curvatures to stain perigastric level-1 and level-2 nodes. For sentinel lymph node mapping, the surgeon may opt for peritumoral injections (4 or more injections placed around the tumor). Considering that the lymphatic pathway between the injection site and the lymph nodes often becomes visible, this should permit the first drain-ing sentinel nodes to be distinguished from other nodes (Fig. 2.4). Most commonly, the authors inject the ICG solution 15–30 minutes prior to the beginning of surgery,

thus the sentinel lymph node can be detected through ICG-enhanced NIR fluorescence imaging well within this time frame.

In cases where ICG-enhanced NIR fluorescence imaging is used to guide the surgeon during extensive lymph node dissection, one may choose to place several injections along the lesser and greater curvature allowing the dye to be dispersed more widely to the lymph nodes surround-ing the stomach; e.g., the prepyloric antrum, the angular notch, the cardia in the lesser curvature, the antrum, the lower body, and the midbody in the greater curvature, if a distal gastrectomy is planned.

Fig. 2.4  Sentinel lymph node detection with ICG-enhanced NIR fluorescence imaging 15–30 min after ICG injection.Laparoscopic image of the operative site taken during standard white light mode (a). Peritumoral submucosal injection of ICG was performed under  flexible endoscopy. Note the linear signal (arrowheads) (ICG/NIR mode, b) marking the lymphatic channels and the sentinel lymph nodes (arrow).

a b

Fig. 2.5 Lymph node station #8a (ICG/NIR mode, b), one of the level-2 stations, is clearly noticeable by NIR fluorescence after placing several injections of ICG solution along the lesser and greater curvature.

a b

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11Gastrointestinal Perfusion Assessment

Fig. 2.6 Infrapyloric area after pylorus-preserving gastrectomy. The nodular soft tissue mimicking a lymph node (arrowhead, a) without showing any signs of fluorescence was in fact confirmed to be adipose tissue. Conversely, some soft tissue which under white light mode is not identified as being of lymphatic type can be detected under ICG/NIR mode (arrow, b).

a b

ICG-enhanced NIR fluorescence imaging is helpful in differentiating lymph nodes from non-lymphatic soft tis-sues (Fig. 2.6), as well as in assessing the completeness of lymph node dissection.

3 Gastrointestinal Perfusion Assessment

The occurrence of anastomotic leakage – a major complication after gastric cancer surgery – has been ob-served in 0.7% to 2.2% of cases. Postoperative anasto-motic leakage has a significant impact on the patient’s life because it is associated with prolonged hospital stay, more reoperations and higher mortality rates, which ultimately poses a major economic burden on the health system.9,10,14

In order to decrease the risk of anastomotic leakage, adequate tissue perfusion has been identified as a major factor contributing to the success of intestinal anastomosis.2 The penetration depth of ICG-enhanced

NIR fluorescence (not only through blood but also tissue) ranges between 0.5 cm and 1 cm.1,16,17 Several studies in-vestigating the efficacy of fluorescence-guided perfusion control during colorectal anastomosis surgery confirmed that the technique has a great potential to reduce the rate of anastomotic leakage, if applied on a routine basis.5,6

Real-time ICG-enhanced NIR fluorescence imaging can be used effectively to evaluate blood perfusion of gastrointestinal tract anastomosis after radical cancer surgery.3,4 The following scoring system (Table  3.1) has been proposed to evaluate the perfusion status.18

Score 1 2 3 4 5

Clinical assessment (using standard white

light endoscopy)

Dusky appearing bowel

Patchy appearing bowel

Bowel appearing pink, but no pulsatility or bleeding cut edges

Bowel appearing pink, pulsatility of

mesenteric vessels, and bleeding cut

edges, but clinical concern regarding

viability

Bowel appearing pink, pulsatility of

mesenteric vessels, bleeding from cut

edge of bowel

Fluorescence No uptake Patchy fluorescenceSignificantly 

hypofluorescent, but homogenous

Somewhat hypofluorescent 

compared to other segments

Iso-fluorescent to all other segments

Table 3.1 Scoring system for assessment of anastomotic perfusion as proposed by Sherwinter DA et. al. 2013.18

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery12

Vascular diffusion of ICG into the anatomical area of interest occurs rapidly following IV infusion ( approx. 10 – 30 sec. up to 4 – 5 min., depending on dosage) and the fluorescence visualization remains stable for several minutes. The residual fluorescence diminishes within 10–15 min. which is addressed with the administration of a second dose of ICG, if desired. Taking into account the extremely low contraindication rate and a maximum recommended daily dosage of 2–5 mg/kg, multiple dose administration of ICG is extremely safe and effective when required.

The amount of ICG administered via a peripheral vein can be 2.5 – 5.0 mg, which is similar to that used for evaluation

of gastric conduit perfusion in Ivor-Lewis eso-phagectomy.13 Higher concentration levels of ICG can be used safely, e.g., 0.2 mg / kg, as used in colorectal surgery or even up to 0.5 mg / kg. Systemically injected ICG initially causes the liver to appear very bright. Therefore, the hepatic background fluorescence around the area of interest should be masked by using some material such as gauze pledgets as a cover.

It should be noted that ICG eventually spreads to poorly perfused areas, which is why perfusion assessment is better done within a few minutes post-injection.

Fig. 3.1  Use of ICG-enhanced NIR fluorescence for perfusion assessment of gastroduodenal anastomosis after distal gastrectomy. Intraoperative views taken directly after (a), at 4 min. (b) and at 5 min. (c) after IV injection of ICG dye.

a b c

Fig. 3.2 Gross visualization under white light mode (a) and ICG/NIR mode (b) after ICG uptake following laparoscopic distal gastrectomy with gastroduo-denostomy. The gross perfusion score of the duodenum is 4 while that of the stomach is 5. The ICG/NIR perfusion score of the duodenum is 5 whereas that of the stomach is 4. There are no signs of a perfusion defect. The patient had no anastomosis-related postoperative complication.

a b

Fig. 3.3 Gross visualization under white light mode (a) and ICG/NIR mode (b) after ICG uptake following laparoscopic total gastrectomy with Roux-en Y esophagojejunostomy. The gross perfusion score of the esophagus is 5, which is also given to the jejunum. The ICG/NIR perfusion score of the esophagus is 4 and the same applies to the jejunum. There are no signs of a perfusion defect. The patient had no anastomosis-related postoperative complication.

a b

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13Summary and Discussion

Even though, to date, the efficacy of ICG-enhanced NIR fluorescence imaging for perfusion assessment of the staple line and surrounding region with a scoring system has not been sufficiently validated by clinical trials, the method provides additional subjective information and therefore has the potential to improve postoperative out-comes through early detection of anastomotic leakage.

Fig. 3.4 Gross visualization under white light mode (a) and ICG/NIR mode (b) after ICG uptake following laparoscopic distal gastrectomy with gastroduo-denostomy. The gross perfusion score of the duodenum is 4 and that of the stomach is 5. The ICG/NIR perfusion score of the duodenum is 4 and that of the stomach is 3. Note the focal perfusion defect around the gastroduodenostomy (white arrow). The patient had postoperative anastomotic leakage.

a b

4 Summary and Discussion

ICG-enhanced NIR fluorescence-guided imaging is a new method that offers a high signal-to-background ratio and deeper penetration depth as compared to vital dyes. It is recommended for use as an alternative option in gastric cancer surgery for lymph node mapping. Sentinel lymph nodes as well as lymphatic channels between the tumor and the nodes can be identified after peritumoral injec-tion of the ICG dye. Several injections placed along the lesser and greater curvature of the stomach can be used to disperse the agent more widely to the lymph nodes in the D1 and D2 area. Such a course of action is believed to be helpful in complete D2 dissection and to enable

a well-tailored lymph node dissection during function-preserving surgery. Intravenous injection of ICG allows to visualize the perfusion around the anastomosis, which can provide additional information about its patency and integrity. The authors believe that this novel technique will be very helpful to surgeons who are not familiar with D2 lymph node dissection. Apart from that, experienced surgeons may also draw specific advantages from the use of ICG-enhanced fluorescence NIR imaging, particu-larly regarding accuracy and completeness of surgery as well as in terms of safety.

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery14

5 References

1. ALANDER JT, KAARTINEN I, LAAKSO A, PATILA T, SPILLMANN T, TuCHIN VV et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012;2012:940585.

2. BONI L, DAVID G, DIONIGI G, RAuSEI S, CASSINOTTI E, FINGERHuT A. Indocyanine green-enhanced fluorescence to assess bowel perfusion during laparoscopic colorectal resection. Surg Endosc 2016;30(7):2736–42.

3. DIANA M, AGNuS V, HALVAX P, LIu Y, DALLEMAGNE B, SCHLAGOWSKI A et al. Intraoperative fluorescence-based enhanced reality laparoscopic real-time imaging to assess bowel perfusion at the anastomotic site in an experimental model. Br J Surg 2015;102(2):e169-76.

4. DIANA M, NOLL E, DIEMuNSCH P, DALLEMAGNE B, BENAHMED MA, AGNuS V et al. Enhanced-reality video fluorescence: a real-time assessment of intestinal viability. Ann Surg 2014;259(4):700–7.

5. FRATTINI F, LAVAZZA M, MANGANO A, AMICO F, RAuSEI S, ROVERA F et al. Indocyanine green-enhanced fluorescence in laparoscopic sleeve gastrectomy. Obes Surg 2015;25(5):949–50.

6. HAMMOND J, LIM S, WAN Y, GAO X, PATKAR A. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes. J Gastrointest Surg 2014;18(6):1176–85.

7. IARC – INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. GLOBOCAN 2012 (Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012). [14, Sept 2017]; Available from: http://globocan.iarc.fr.

8. JAPANESE GASTRIC CANCER ASSOCIATION. Japanese Gastric Cancer Treatment Guidelines 2014 (ver. 4). Gastric Cancer 2017;20(1):1–19.

9. KIM MC, KIM W, KIM HH, RYu SW, RYu SY, SONG KY et al. Risk factors associated with complication following laparoscopy-assisted gastrectomy for gastric cancer: a large-scale korean multicenter study. Ann Surg Oncol 2008;15(10):2692–700.

10. KIM W, KIM H, HAN S, KIM M, HYuNG WJ, RYu SW et al. Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01). Ann Surg 2016;263(1):28–35.

11. KITAGAWA Y, TAKEuCHI H, TAKAGI Y, NATSuGOE S, TERASHIMA M, MuRAKAMI N et al. Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan. J Clin Oncol 2013;31(29):3704–10.

12. KONG S, NOH Y, SuH Y, PARK HS, LEE H, KANG KW et al. Evaluation of the novel near-infrared fluorescence tracers pullulan polymer nanogel and indocyanine green/gamma-glutamic acid complex for sentinel lymph node navigation surgery in large animal models. Gastric Cancer 2015;18(1):55–64.

13. KOYANAGI K, OZAWA S, OGuMA J, KAZuNO A, YAMAZAKI Y, NINOMIYA Y et al. Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy. Medicine (Baltimore) 2016;95(30):e4386.

14. LEE K, LEE H, YANG J, OH S, BARD S, SuH Y et al. Risk factors associated with complication following gastrectomy for gastric cancer: retrospective analysis of prospectively collected data based on the Clavien-Dindo system. J Gastrointest Surg 2014;18(7):1269–77.

15. OH C, WON Y, JuNG K, KONG H, CHO H, LEE J et al. Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2013. Cancer Res Treat 2016;48(2):436–50.

16. SCHAAFSMA BE, MIEOG JSD, HuTTEMAN M, VAN DER VORST, JOOST R, KuPPEN PJK, LOWIK, CLEMENS W G M et al. The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol 2011;104(3):323–32.

17. SCHOLS RM, BOuVY ND, VAN DAM RM, STASSEN LPS. Advanced intraoperative imaging methods for laparoscopic anatomy navigation: an overview. Surg Endosc 2013;27(6):1851–9.

18. SHERWINTER DA, GALLAGHER J, DONKAR T. Intra-operative transanal near infrared imaging of colorectal anastomotic perfusion: a feasibility study. Colorectal Dis 2013;15(1):91–6.

19. SKOOG DA, HOLLER FJ, CROuCH SR. Principles of instrumental analysis. 6th ed. Belmont, Calif.: Thomson Brooks/Cole; 2007. (ISBN No. 9780495125709).

20. TAJIMA Y, MuRAKAMI M, YAMAZAKI K, MASuDA Y, KATO M, SATO A et al. Sen-tinel node mapping guided by indocyanine green fluorescence imaging during laparoscopic surgery in gastric cancer. Ann Surg Oncol 2010;17(7):1787–93.

21. WILSON DB. Kelvin and stokes: A comparative study in Victorian physics. Bristol: Hilger; 1987. (ISBN No. 0852745265).

22. YOSHIDA M, KuBOTA K, KuRODA J, OHTA K, NAKAMuRA T, SAITO J et al. Indocyanine green injection for detecting sentinel nodes using color fluorescence camera in the laparoscopy-assisted gastrectomy. J Gastroenterol Hepatol 2012;27 Suppl 3:29–33.

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15ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

The KARL STORZ OPAL1® Technology for ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery16

OPAL1® Technology for NIR/ICGbased on IMAGE1 S™ camera system

1 IMAGE1 S™ l brilliant FULL HD image quality l NIR / ICG fluorescence in standard mode

or SPECTRA A* mode

2 NIR/ICG telescope and camera head l 3-chip FULL HD camera head

with high resolution, optimal NIR light sensitivity

l telescopes for optimal fluorescence excitation and detection; can be used for white light and fluorescence modes

l telescopes with various lengths and diameters

3 D-LIGHT P light source (Xenon light source) l best daylight spectrum in

white light and fluorescence modes l no additional security measures

(vs. Laser) l with enhanced background display

4 Footswitch l fast switch between white light and

fluorescence mode

5 Autoclavable fiber optic light cable l optimal light transmission in the

white light and NIR spectral range

* SPECTRA A: Not for sale in the U.S.

1

2

3

4

5

It is recommended to check the suitability of the product for the intended procedure prior to use.

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17ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

OPAL1® Technology for NIR/ICGbased on IMAGE1 S™ camera system

Camera system

Camera control unit

Light source

Camera head

Light cables

Telescopes

Open surgery

D-LIGHT P/ 20 1337 01-1 Spare lamp: 20 1330 28lamp modul: 20 1337 25

H3-Z FI TH 102

VITOM® II ICG 20 9160 25 AGA

Accessories:28272 UGN/CN

28272 HC28172 HR/HM

Fiber Optic Light Cables 495 NAC/NCSC/TIP/NCS/VIT

HOPKINS® Telescope 26003 ACA/BCA/AGA/BGA

26046 ACA/BCA

IMAGE1 S CONNECT™ TC 200

IMAGE1 S™ H3-LINK TC 300

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery18

26003 BCA 1 x HOPKINS® Forward-Oblique Telescope 30°, enlarged view, diameter 10 mm, length 31 cm, autoclavable, for indocyanine green (ICG), fiber optic light transmission incorporated, for use with Fiber Optic Light Cable 495 NCSC, Fluid Light Cable 495 FQ/FR and Cold Light Fountain D-LIGHT P SCB 20133701-1, color code: red

alternatively:

26046 BCA 1 x HOPKINS® Forward-Oblique Telescope 30°, enlarged view, diameter 5 mm, length 29 cm, autoclavable, for indocyanine green (ICG), fiber optic light transmission incorporated, color code: red

495 NCSC 1 x Fiber Optic Light Cable, with straight connector, extremely heat-resistant, with safety lock, diameter 4.8 mm, length 250 cm

30160 GYG 3 x Trocar, with conical tip, with LUER-Lock connector for insufflation, size 6 mm, working length 10 cm, color code: black,

including: Cannula

Trocar only Valve Seal

30103 GYG 1 x Trocar, with conical tip, with LUER-Lock connector for insufflation, size 11 mm, working length 10 cm, color code: green,

including: Cannula

Trocar only Valve Seal

30108 GZG 1 x Trocar, with pyramidal tip, with LUER-Lock connector for insufflation, size 13.5 mm, working length 10 cm, color code: blue,

including: Cannula

Trocar only Valve Seal

30141 RS 1 x Reducer, to reduce from 11 to 5 mm

30142 RS 1 x Reducer, to reduce from 13.5 mm to 5 mm

33351 CC 2 x CLICKLINE CROCE-OLMI Grasping Forceps, rotating, with connector pin for unipolar coagulation, size 5 mm, length 36 cm, atraumatic, fenestrated, curved, single action jaws,

including: Plastic Handle, without ratchet,

with larger contact area Outer Tube, insulated Forceps Insert

33352 C 2 x CLICKLINE Bowel Grasper, rotating, with connector pin for unipolar coagulation, size 5 mm, length 36 cm, fenestrated, double action jaws,

including: Plastic Handle, with MANHES style ratchet,

with larger contact area Outer Tube, insulated Forceps Insert

33351 ML 1 x CLICKLINE KELLY Dissecting and Grasping Forceps, rotating, with connector pin for unipolar coagulation, size 5 mm, length 36 cm, long, double action jaws,

including: Plastic Handle, without ratchet,

with larger contact area Outer Tube, insulated Forceps Insert

34310 MA-D 1 x CLICKLINE Scissors Insert, with Outer Sheath, curved, double action jaws, spoon-shaped jaws, length of blades 17 mm, size 5 mm, length 36 cm, sterile, for single use, package of 10

33151 1 x CLICKLINE Plastic Handle, without ratchet, with larger contact area at the finger ring, with connector pin for unipolar coagulation

37370 DL 1 x Coagulating and Dissecting Electrode, with channel, L-shaped size 5 mm, length 36 cm, for use with suction and irrigation handles

30810 1 x Handle, for suction and irrigation, autoclavable, for use with 5 mm coagulation suction tubes and 3 and 5 mm suction and irrigation tubes

alternatively:37113 A 1 x Handle, pistol grip, with clamping valve,

for suction and irrigation, autoclavable

30173 LAR 1 x Dismantling KOH Needle Holder, ergonomic axial handle with disengageable ratchet, ratchet release on right side, left curved jaws, with tungsten carbide insert ø 5 mm, length 33 cm

including: Insert Outer tube Handle

26173 AM 1 x BERCI Fascial Closure Instrument, for subcutaneous ligature of trocar incisions, size 2.8 mm, length 17 cm

30623 UR 1 x CUSCHIERI Retractor, size 10 mm, length 36 cm

including: Insert Outer Sheath Handle

Recommended Instrument Set

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19ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

HOPKINS® Telescopes

26003 BCA

26003 BCA HOPKINS® Forward-Oblique Telescope 30°, enlarged view, diameter 10 mm, length 31 cm, autoclavable, for indocyanine green (ICG), fiber optic light transmission incorporated, for use with Fiber Optic Light Cable 495 NCSC, Fluid Light Cable 495 FQ/FR and Cold Light Fountain D-LIGHT P SCB 20133701-1, color code: red

26046 BCA HOPKINS® Forward-Oblique Telescope 30°, enlarged view, diameter 5 mm, length 29 cm, autoclavable, for indocyanine green (ICG), fiber optic light transmission incorporated, color code: red

26046 BCA

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery20

The New Trocar Generation from KARL STORZThe new trocar generation combines single-use and reusable components. In line with the KARL  STORZ company philosophy, the cannulas and trocars were designed with reusable components in mind. The valve seal is intended for single use.

Special Features:## Ergonomic shape of the trocar ensures safe and comfortable handling during placement of the trocar

## One-piece sealing system for single use## Minimal friction between the valve seal and the instrument## Considerably reduced weight and good balance thanks to the newly designed plastic trocar housing

## Color coding for clear identification of different sizes## Available in the sizes 2.5 mm – 13.5 mm

Trocars and AccessoriesSize 6 mm, 11 mm, 13.5 mm

30103 GYG Trocar, with conical tip, with LUER-Lock connector for insufflation, size 11 mm, working length 10 cm, color code: green

including: CannulaTrocar onlyValve Seal

30160 GYG Trocar, with conical tip, with LUER-Lock connector for insufflation, size 6 mm, working length 10 cm, color code: blackincluding:CannulaTrocar onlyValve Seal

30141 RS Reducer, to reduce from 11 to 5 mm

30142 RS Reducer, to reduce from 13.5 mm to 5 mm

30108 GZG Trocar, with pyramidal tip, with LUER-Lock connector for insufflation, size 13.5 mm, working length 10 cm, color code: blue

including: CannulaTrocar onlyValve Seal

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21ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

Single-use ScissorsCLICKLINE – rotating, dismantling

Operating instruments, length 36 cm, for use with trocars size 6 mm

Size 5 mm

## Compatible with all handles from the CLICKLINE series (without ratchet)

## Packaging## Cost-effective solution: “single-use meets reusable”

Special Features: ## Scissor blades are always sharp and/or optimal cutting effect

## Sterile packed for immediate use in the OR## Proven scissor blade design

34310 MA-D

34310 MA-D CLICKLINE Scissors Insert with Outer Sheath, curved, double action jaws, spoon-shaped jaws, size 5 mm, length 36 cm, sterile, for single use, package of 10

34310 MS-D CLICKLINE METZENBAUM Scissors Insert with Outer Sheath, curved, double action jaws, size 5 mm, length 36 cm, sterile, for single use, package of 10

unipolar

Each scissors insert with outer sheath, including 3 patient labels, are sterile packed in an individual blister pack.

The single-use scissors are delivered in packages of 10 in a dispenser box with instructions for use.

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery22

Dissecting and Grasping ForcepsCLICKLINE – rotating, dismantling, insulated, with connector pin for unipolar coagulation

unipolar

Size 5 mm

Operating instruments, length 36 cm

Length

36 cm

Handle

33151 33152 33153 33156

Working Insert

CLICKLINE Forceps Insert, CROCE-OLMI grasping forceps, single action jaws, atraumatic, fenestrated, curved

33310 CC 33351 CC 33352 CC 33353 CC 33356 CC

Complete Instrument

27

CLICKLINE Forceps Insert, KELLY dissecting and grasping forceps, double action jaws, long

33310 ML 33351 ML 33352 ML 33353 ML 33356 ML

22

CLICKLINE Forceps Insert, bowel grasper, double action jaws, fenestrated

33310 C 33351 C 33352 C 33353 C 33356 C

37

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23ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

KOH Macro Needle Holder, size 5 mm, dismantling, consisting of:

## Handle## Outer sheath## Working insert

Cleaning and sterilization are gaining increasing importance for KARL STORZ as a manufacturer of surgical instruments.Similar to all our surgical instruments, the cleaning and hygiene of our needle holders also play an important

role. Our KOH macro needle holders feature consistent effectiveness and precision, with significantly improved cleaning results achieved by dismantling the instrument. The handle, outer sheath and inner part can be cleaned and sterilized separately for perfect results.

## With tungsten carbide inserts## Environmentally correct: In the event of damage, only the component with the defect needs to be replaced

## User-friendly and ergonomic handling

## Can be disassembled into three separate components## Fully autoclavable## Cleaning connector## Choice of six different handles and three different working inserts

The reusable dismantling design offers the user the following benefits:

KOH Macro Needle Holdersdismantling

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery24

30173 PR Handle, pistol-shaped, with disengageable ratchet, ratchet position right

Handles and Outer SheathsKOH Macro Needle Holders, dismantling

30173 AR Handle, axial, with disengageable ratchet, ratchet position right

30173 AL Handle, axial, with disengageable ratchet, ratchet position left

30173 AO Handle, axial, with disengageable ratchet, ratchet position on top

Handles, axial and pistol-shaped, with disengageable ratchet

30173 PL Handle, pistol-shaped, with disengageable ratchet, ratchet position left

30173 PO Handle, pistol-shaped, with disengageable ratchet, ratchet position on top

30173 A

Metal Outer SheathsSize 5 mm

30173 A Metal Outer Sheath, with LUER-Lock connector for cleaning, size 5 mm, length 33 cm

30178 A Same, length 43 cm

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25ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

KOH Macro Needle Holdersdismantling

Handle

30173 AR 30173 AL 30173 AO

Complete Instrument

30173 RAR 30173 RAL 30173 RAO

30178 RAR 30178 RAL 30178 RAO

KOH Macro Needle Holder, jaws curved to right, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 R

30178 R

Working Insert

43 cm

Length

33 cm

30173 LAR 30173 LAL 30173 LAO

30178 LAR 30178 LAL 30178 LAO

KOH Macro Needle Holder, jaws curved to left, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 L

30178 L

30173 FAR 30173 FAL 30173 FAO

30178 FAR 30178 FAL 30178 FAO

KOH Macro Needle Holder, straight jaws, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 F

30178 F

30173 GAR 30173 GAL 30173 GAO

KOH Macro Assistant Needle Holder, straight jaws

30173 G

Single action jaws

Size 5 mm

Operating instruments, lengths 33 and 43 cm, with axial handle for use with trocars size 6 mm

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery26

KOH Macro Needle Holdersdismantling

Handle

30173 PR 30173 PL 30173 PO

Complete Instrument

30173 RPR 30173 RPL 30173 RPO

30178 RPR 30178 RPL 30178 RPO

KOH Macro Needle Holder, jaws curved to right, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 R

30178 R

Working Insert

Length

30173 LPR 30173 LPL 30173 LPO

30178 LPR 30178 LPL 30178 LPO

KOH Macro Needle Holder, jaws curved to left, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 L

30178 L

30173 FPR 30173 FPL 30173 FPO

30178 FPR 30178 FPL 30178 FPO

KOH Macro Needle Holder, straight jaws, with tungsten carbide inserts, for use with suture material size 0/0 – 7/0

30173 F

30178 F

Single action jaws

43 cm

33 cm

Size 5 mm

Operating instruments, lengths 33 and 43 cm, with axial handle for use with trocars size 6 mm

30173 GPR 30173 GPL 30173 GPO

KOH Macro Assistant Needle Holder, straight jaws

30173 G

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27ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

CUSCHIERI Liver RetractorSize 5 and 10 mm

Special Features:## Automatic retraction of the liver for extended periods of time

## Also suitable for simple, atraumatic manipulation of other anatomical structures

## Easy dismantling for cleaning purpose

30623 UR

30623 UR CUSCHIERI Retractor, size 10 mm, length 36 cm

30623 U

30623 U CUSCHIERI Retractor, size 5 mm, length 36 cm

30623 URL CUSCHIERI Retractor, large contact surface, size 10 mm, length 36 cm

30623 URL

Multiple puncture approachOperating instrument, length 36 cm,for use with trocars size 6 mm

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery28

BERCI Fascial Closure Instrumentfor subcutaneous fascial closure

26173 AM BERCI Fascial Closure Instrument, for subcutaneous ligature of trocar incisions, size 2.8 mm, length 17 cm, for closure of trocar incision wounds

26173 AM

Coagulation and Dissection Electrodes with Suction and Irrigation Channel

37370 DL Coagulating and Dissecting Electrode, with channel, L-shaped size 5 mm, length 36 cm, for use with suction and irrigation handles

30810 Handle, for suction and irrigation, autoclavable, for use with 5 mm coagulation suction tubes and 3 and 5 mm suction and irrigation tubes

37113 A Handle, pistol grip, with clamping valve, for suction and irrigation, autoclavable

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29ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery

Notes:

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ICG-Enhanced NIR Fluorescence Imaging in Laparoscopic Gastric Cancer Surgery30

Notes:

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with the compliments of

KARL STORZ — ENDOSKOPE