Surgery 172 (2022) S14eS20 Contents lists available at ScienceDirect Surgery journal homepage: www.elsevier.com/locate/surg Use of fluorescence imaging during lymphatic surgery: A Delphi survey of experts worldwide Fernando Dip, MDa,*, Nistor Alexandru, MD, PhDb, Miguel Amore, MDc, Corinne Becker, MDd, Jean-Paul Belgrado, PT, PhDe, Pierre Bourgeois, MD, PhDe, Edward I-Fei Chang, MD, PhDf, Isao Koshima, MDg, Gabriel Liberale, MD, PhDe, Jaume Masia, MD, PhDh, Peter Mortimer, MDi, Peter Neligan, MDj, Bernardo Nogueira Batista, MD, PhDk, Waldemar Olszewski, MDl, Sophia Alexia Salvia, MDm, Hiroo Suami, MD, PhDn, Sophie Vankerckhove, MSe, Takumi Yamamoto, MD, PhDo, Emanuele Lo Menzo, MD PhDp, Kevin P. White, MD PhDq, Raul J. Rosenthal, MDp a Hospital de Clínicas Jose de San Martín, Buenos Aires, Argentina b Universitatea de Medicina si Farmacie Victor Babes, Timisoara, Romania c Central Military Hospital, Buenos Aires, Argentina d AP-HP Ho ^pital Europeen Georges Pompidou, Paris, France e University of Brussels, Brussels, Belgium f MD Anderson Cancer Center, Houston, TX g Tottori University, Tottori, Japan h Department Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Spain i St. Georges University Hospital, London, UK j University of Washington, Seattle, WA k AC Camargo Cancer Center, Sa ~o Paulo, Brazil l Polish Academy of Sciences, Warsaw, Poland (Deceased) m Central Military Hospital, Buenos Aires, Argentina n Australian Lymphedema Education, Research and Treatment (ALERT), Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia o National Center for Global Health and Medicine, Tokyo, Japan p Cleveland Clinic Florida, Weston, FL q ScienceRight Research Consulting Services, London, Ontario, Canada a r t i c l e i n f o a b s t r a c t Article history: Background: Fluorescence imaging with indocyanine green is increasingly used during lymphedema Accepted 23 August 2022 patient management. However, to date, no guidelines exist on when it should and should not be used or how it should be performed. Our objective was to have an international panel of experts identify areas of consensus and nonconsensus in current attitudes and practices in fluorescence imaging with indoc- yanine green use during lymphedema surgery patient management. Methods: A 2-round Delphi study was conducted involving 18 experts in the use of fluorescence imaging during lymphatic surgery, all asked to vote on 49 statements on patient preparation and contraindica- tions (n ¼ 7 statements), indocyanine green dosing and administration (n ¼ 10), fluorescence imaging uses and potential advantages (n ¼ 16), and potential disadvantages and training needs (n ¼ 16). Results: Consensus ultimately was reached on 40/49 statements, including consistent consensus regarding the value of fluorescence imaging with indocyanine green in almost all facets of lymphedema patient management, including early detection, assessing disease extent, preoperative work-up, surgical planning, intraoperative guidance, monitoring short- and longer-term outcomes, quality control, and resident training. All experts felt it was very safe, while 94% felt it should be part of routine care and that This article is published as part of a supplement supported by the International * Reprint requests: Fernando Dip, MD, Department of Surgery, Hospital de Clínicas Society for Fluorescence Guided Surgery (ISFGS) with funding from Arthrex, Diag-  de San Martín, University of Buenos Aires, Buenos Aires, Argentina. Jose nostic Green, Intuitive, Medtronic, Olympus, Karl Storz Endoscopy, Stryker, and E-mail address: fernandodip@gmail.com (F. Dip); Richard Wolf. Twitter: @FernandoDDip https://doi.org/10.1016/j.surg.2022.08.026 0039-6060/© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). F. Dip et al. / Surgery 172 (2022) S14eS20 S15 indocyanine green was superior to colored dyes and ultrasound. Nonetheless, there also was consensus that limited high-quality evidence remains a barrier to its widespread use and that patients should still be provided with specific information and asked to sign specific consent for both fluorescence imaging and indocyanine green. Conclusion: Fluorescence imaging with or without indocyanine green appears to have several roles in lymphedema prevention, diagnosis, assessment, and treatment. © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction nonconsensus in the use of FI during lymphedema surgery. More specifically, this survey primarily assessed (1) whether ICG fluo- Lymphedema is a potentially catastrophic condition, estimated rescence can be used to evaluate lymphedema; (2) how effective it to affect somewhere from 140 to 250 million people worldwide.1 is at various stages of lymphedema evolution and for what specific Untreated, symptoms range from mild limb heaviness to disfigur- purposes; (3) when it should and should not be used; and (4) the ing and often painful and/or disabling swelling.1 Both primary and technical performance of ICG fluorescence lymphography, in terms secondary forms of lymphedema existdthe former rare, occurring of ICG administration dose, route, and timing. in only ~1 in 100,000 patients2 and caused by congenital malfor- mations that impair lymph drainage. Secondary lymphedema, Methods which is much more common than its primary counterpart and, likely, markedly under-reported, stems from lymph vessel damage Study architecture acquired in various ways, including cancer, cancer treatment, trauma, parasitic infections, and obesity.3 The present study was a 2-stage, 2-round Delphi survey, Neither primary nor secondary lymphedema, once fully estab- adhering to published guidelines and coordinated by an interna- lished, is considered curable.3,4 However, various nonsurgical and tional, MD-PhDelevel expert in survey design. Since its emergence surgical techniques have been used to enhance sluggish lymphatic among the military after World War II as a means of reaching flow with variable success.1 Such treatments include multifaceted consensus on handling of the Cold War, Delphi studies have ach- decongestive physiotherapy4,5 and surgical procedures like lym- ieved considerable credence as a way to identify areas of consensus phaticovenular anastomosis (LVA),6e8 vascularized lymph node and nonconsensus among experts across a wide variety of health- transfer,8,9 lymphatic vessel free flaps,10 and vascularized omentum and nonehealth-related fields. lymphatic transplantation.11 Preventing secondary lymphedema The first stage of our survey was conducted in Buenos Aires, from ever starting and recognizing it early enough to slow its Argentina, during a special session at the 27th International progression and enhance its manageability are crucial to the Congress of Lymphology in September 2019. At this session, 10 management of many surgery patients, especially cancer patients internationally known experts in the use of FI during lymphedema who require extensive nodal resections involving either the axilla surgery participated in a 2-round Delphi survey. Because only 10 or groin.4,10,12 As with treating established lymphedema, various experts attended this meeting, and the study investigators had nonsurgical and surgical techniques have been proposed to prevent hoped for 15e20, a second-stage, an online (modified) Delphi the development or worsening of secondary lymphedema.10,12,13 survey was initiated a few months later, and all data from the in- Among the greatest challenges surgeons face when treating or person and online Delphi studies compiled. trying to prevent lymphedema is finding the vessels, which are often difficult to locate because lymph fluid is generally clear and contains few cells.14 In recent years, numerous articles have been Survey development published, including controlled trials, reporting the effectiveness of injecting indocyanine green (ICG) into vessels intraoperatively and After the above-noted ISFGS advisory board meeting in Frank- observing them under near-infrared light for a variety of clinical furt, Germany,24 e-mails were distributed to all advisory board purposes. Such purposes include identifying lymphatic vessels with members asking every member to provide a list of questions/issues high and low flow and locating collateral vessels in cancer patients they considered important pertaining to FI use during procedures requiring extensive node resections15,16; detecting early, asymp- within their surgical field. These suggestions then were screened tomatic decreases in lymphatic flow4; assessing lymphatic flow in and used to generate a series of Delphi surveys intended for dis- patients receiving nonoperative therapy17,18; quantifying lymphatic tribution among experts within each specific surgical field. For the contractility19; determining the need for surgical intervention18; lymphedema Delphi study, the final survey consisted of 7 questions guiding reparative surgical procedures like LVA; assessing lymph regarding each expert’s surgical practice, followed by 49 state- flow through anastomoses intraoperatively20; identifying ments to vote upon, divided into 4 modules: module 1, patient lymphatic leaks21,22; and assessing short-, intermediate-, and long- preparation and contraindications (n ¼ 7 statements); module 2, term outcomes.23 Despite its extensive use, however, because of its ICG dosing and administration (n ¼ 10); module 3, uses and po- relative novelty, there are no published guidelines regarding when, tential advantages of using FI during lymphedema surgery (n ¼ 16); why, and how to use fluorescence imaging (FI) for almost any of the and module 4, potential barriers and training issues (n ¼ 16). numerous indications for which it is currently used. It is for this Among these 49 statements, 34 had the binary response option reason that, in February 2019, at a quarterly meeting of the advisory agree/disagree and 15 multiple-choice options like selecting 1 of 4 board of the International Society of Fluorescence Guided Surgery ICG doses. (ISFGS) in Frankfurt, Germany, the board decided to conduct a se- During survey design, several approaches were adopted to ries of consensus surveys for the various indications where FI is reduce the acquiescence bias risk that the survey instrument itself used to aid in ultimately drafting procedure-specific consensus might influence responses via either the wording and/or order of its guidelines. The first of these studies to be initiated is presented statements and/or response options. This entailed including state- herein. Its main objective was to identify the areas of consensus and ments favorable, unfavorable, and neutral to FI and varying the S16 F. Dip et al. / Surgery 172 (2022) S14eS20 order of response options, sometimes listing the most FI-agreeable Table I option (eg, agree) first and sometimes last. Practice characteristics of the voting experts Practice characteristic Number Percentage Expert recruitment and data collection Region of practice (N ¼ 18) Asia-Pacific 3 16.7 The following eligibility criteria were used to select experts: (1) Europe 9 50.0 coauthorship of 1 published clinical study examining FI use dur- North America 2 11.1 Central and South America 4 22.2 ing lymphedema surgery; (2) or 10 years in surgical practice and 5 Nature of practice (N ¼ 18) years using FI during lymphedema surgery. Survey participants also Some university affiliation 15 83.3 had to (3) be acknowledged as an international expert by the ISFGS Nonacademic 3 16.7 advisory board, (4) be fluent in written English, (5) express will- Area of surgery (N ¼ 18) Plastic surgery 10 55.5 ingness to participate, and (6) express willingness to review and Oncology surgery 5 27.8 provide comments on the manuscript before its submission for Lymph surgery 3 16.7 publication. The potential experts were identified by word of Years performing lymphatic surgery (N ¼ 18), y mouth and by reviewing all published studies on FI for lymphe- <10 2 11.1 dema surgery to identify corresponding authors. This ultimately 10e20 7 38.9 >20 9 50.0 resulted in a list of 26 international experts spanning 5 continents Years performing fluorescence-guided surgery (N ¼18), y (ie, North America, Latin America, Europe, Asia, and Oceana). <5 5 27.8 5e10 6 33.3 Stage 1 >10 7 38.9 As stated earlier, 10 of these 26 experts attended the special Fluorescence-guided procedures per month (N ¼ 17)* <5 2 11.8 session in Buenos Aires, Argentina, at which a 2-round, traditional 5e10 6 35.3 Delphi survey was conducted. Voting was conducted electronically >10 9 52.9 on voters’ cell phones or any other handheld device, linked to the Percentage of lymph surgeries using indocyanine green polling software Slido (Bratislava, Slovakia), with statements dis- (N ¼ 18) <50% 8 44.4 played on a large screen in PowerPoint (Microsoft Corp, Redmond, 50% 10 55.6 WA). Before voting on each statement commenced, the voters were * Question left blank by 1 respondent. permitted to ask questions of clarity only, with voting permitted only after all questions of clarity were answered and the moderator announced the start of voting. From then, voters had 30 seconds to considered necessary for consensus/nonconsensus to be consid- vote before voting was blocked. Only statements for which ered valid. Although the small numbers provided no opportunity to consensus was not reached were re-presented in round 2, after inferentially compare stage 1 and 2 voters, we nonetheless which all voting was terminated. Immediately before voting on compared the overall level of consensus (ie, the proportion of each statement in round 2, the results of round 1 were displayed for statements for which consensus was reached) between the 2 stages all voters to see. and counted all statements, whereupon the majority selection between the 2 groups differed (ie, the majority in stage 1 selected Stage 2 1 response option, whereas the majority in stage 2 selected Once the decision was made to seek further voters, an e-mail another). was sent to the 16 experts on our initial list of 26 who did not attend Also, given that round 2 was completed for stage 1 (Argentina the special session in Buenos Aires, Argentina, asking them to in-person) before round 1 even could be initiated in stage 2 (on- participate in the survey and providing a link to the online survey line), there were 5 instances when compiling round 1 data from the application SurveyMonkey (Momentive, San Mateo, CA) with 2 stages resulted in a statement on which consensus reached in follow-up e-mails sent to all nonrespondents once weekly for 3 stage 1 no longer satisfied our consensus criteria when data from weeks, followed by an e-mail or telephone call from the primary the 2 stages were combined. To correct for this, simultaneously project co-ordinator (F. Dip) to anyone who had not yet responded. with participants in stage 2 being sent their round 2 surveys, all For stage 2, round 1 was considered complete within 1 week of the stage 1 participants were e-mailed a link to a supplementary round above-noted telephone calls. At that point, round 1 data were 2B survey containing these 5 statements, along with the compiled compiled from stages 1 and 2 and analyzed to determine which round 1 results, to have them vote on each of these 5 statements statements had and had not consensus reached. As in stage 1, only again. For each of these 5 statements, the earlier stage 1, round 2 statements for which adequate consensus was not reached were results were replaced in analysis with the later round 2B results. included in round 2, when the same e-mail, telephone, and data For quality control, all data were analyzed using both the Sur- collection termination protocol used for round 1 was repeated. As veyMonkey intrinsic data-analysis tool and Windows Excel, version in stage 1, for each statement in stage 2, round 2 voters were pro- 16.0 (Microsoft Corp). vided with the percentage of participants who had selected each response option in round 1. Results Data analysis Among the 18 survey participants, a majority (n ¼ 10) practiced The percentage of consensus was defined as agreement between in Europe (Belgium ¼ 4 and 1 each from France, Italy, Poland, responders, not agreement with any given statement, and was Romania, Spain, and the United Kingdom), whereas 3 each came calculated as the number of voters choosing the most commonly from Asia-Pacific (Japan ¼ 2 and Australia ¼1) and Latin America selected response option divided by the total number of experts (Brazil ¼ 2 and Argentina ¼ 1) and 2 from North America (USA ¼ 2). who voted on that particular statement, with 70% consensus The vast majority had university-affiliated practices. Among the considered “consensus reached.” The percentage participation also experts were 10 plastic surgeons, 5 cancer surgeons, and 3 was calculated for each statement, with 80% participation specializing in lymphatic surgery. Further panel characteristics are F. Dip et al. / Surgery 172 (2022) S14eS20 S17 Table II Regarding FI uses and advantages (Table V), all areas of non- Overall summary of results consensus pertained to timing, including how long to wait after Number Percentage lymphatic surgery, how long to wait after SLN resection to perform Total number of statements 49 follow-up ICG lymphography, and whether fluorescent lymphog- Consensus reached 40 81.6 raphy should be performed before any radioisotope is given. No consensus reached 9 18.4 Conversely, there was unanimous agreement that FI can be used to Consensus reached in first round* 34 85.0 plan lymphatic treatment and strong consensus that it should be Consensus reached in second round* 6 15.0 part of routine surgical practice. There also was consensus that FI 100% consensus reached* 4 10.0 90%e99% consensus reached* 7 17.5 was useful for virtually every listed indication, both diagnostic and 80%e89% consensus reached* 17 42.5 therapeutic, including early detection of lymphedema in cancer 70%e79% consensus reached* 12 30.0 patients, irrespective of whether they had or not had chemo- and/ Statements agreed with (total) 30 61.2 or radiotherapy; preoperative work-up; visualizing both lymph Statements disagreed with (total) 4 8.2 Statements agreed with (consensus) 29 59.2 vessels and SLNs; treating and monitoring outcomes for lymphatic Statements disagreed with (consensus) 2 4.1 disorders; and quality control. There was 83% consensus that ICG Statements worded favorably to FI/ICG 22 44.9 use should be part of the algorithm for assessing patients for Statements worded unfavorably to FI/ICG 11 22.4 lymphedema. Nonjudgmental statements 16 32.7 When asked to compare ICG, colored dyes, and ultrasound in their Average consensus 77.1% Minimum/maximum consensus 36.4%e100% effectiveness aiding visualization during lymphatic surgery, 94.4% Minimum when consensus reached* 70.6% selected ICG as best (Table VI). There again was consensus regarding FI, fluorescence imaging; ICG, indocyanine green. the usefulness of FI for various general purposes, including strong * Percent among statements wherein consensus was reached. consensus supporting its use visualizing lymphatic structures, enhancing patient outcomes, and training surgical residents. There summarized in Table I. Among the 8 nonparticipants, 3 were from also was consensus that nonsurgical residents should also learn North America (all USA), 3 from Europe (Belgium, Finland, and about FI and that its noninvasiveness, ability to reduce complica- Italy), and 2 from Asia-Pacific (Australia and Japan). tions, and low cost are advantages. On the other hand, barriers to its Of the 49 statements on which the experts were asked to vote, use include the need for repeat dosing, the limited availability of 22 were worded in a way favorable to using FI, whereas 27 were equipment and adequate training, and the lack of published high- worded either unfavorably or neutrally (Table II). A consensus of quality data. Most, but just short of 70%, disagreed that failed fluo- 70% was reached on 40 of the 49 statements, 34 in the first round rescence and inadequate nursing training administering ICG are and 6 in the second. Strong consensus (90%) was reached on 11 limitations. No consensus was achieved on the number of cases statements (100% for 4), whereas 17 achieved moderate (80.0%e needed for surgeons to overcome the learning curve, although, 89.9%) and 12 weaker (70.0%e79.9%) consensus. combining response options, 85% voted for >10 cases. Tables III through VI summarize results for each of the 49 Comparing the 2 expert panelsdthose completing the survey in statements. The overall level of consensus for module 1 (patient person and those completing it onlinedjust 10 instances (out of 49 preparation and contraindications) was much higher (91.9%) than statements) were identified where consensus was reached in 1 for any of the other 3 modules, with module 3 (potential uses and panel and not the other. However, for only 1 statement did a ma- advantages) a distant second, at 77.4%, followed by module 4 (po- jority on 1 panel vote for 1 response option whereas a majority in tential barriers and training issues), with 73.3%, and module 2 (ICG the other voted for another, and this pertained to how long sur- dosing and administration), with 72.8% consensus. geons should wait before repeating the same procedure using ICG At least moderate-level consensus was achieved for each of the (the majority in 1 group selecting 3 months and the other >3 7 statements on patient preparation and contraindications against months, with a clear majority in both groups believing that 3 using FI (Table III), including completely unanimous consensus on 3 months were necessary). statements, with 100% of the experts agreeing that intraoperative fluorescence guidance should be considered safe, but also that Discussion patients still should be provided with information specifically about FI and asked about any allergy to iodine preoperatively. In An exponentially growing body of literature is reporting the addition, 83.3% disagreed that ICG can be used subcutaneously in value of intraoperative FI across a very broad range of surgical fields iodine-allergic patients. and scenarios,25 including plastic26e31 and vascular surgery,32,33 Regarding ICG dose and administration (Table IV), consensus largely for the purpose of assessing tissue perfusion. Similarly, its was reached that both when ICG is administered during the pro- multidimensional value is steadily being revealed for early detection cedure and how long surgeons must wait after ICG administration of lymphedema as well as its diagnostic confirmation, pretreatment before using near-infrared light are important, as is the concen- planning, therapeutic management, and post-treatment outcomes tration, but not the dose, of ICG (60% considered the actual dose of monitoring among patients managed both surgically1,6e13,15,18,34e47 ICG important, whereas 33% voted that the level of importance is and nonsurgically.4,5,16,18,48,49 In 2015, the Australian Lymphedema situation-dependent). There was strong consensus regarding the Education Research and Treatment (ALERT) program adopted the minimum effective dose to give to visualize lymph vessels and use of FI with ICG, and now uses it for virtually all aspects of lym- weak consensus regarding the optimum dose, but no consensus on phedema patient care.18 In 2019, the German-Speaking Society for the dose for sentinel lymph node (SLN) localization. For SLN Microsurgery of Peripheral Nerves and Vessels published consensus localization, 0.2 mL (at 5 mg/mL ¼ 1 mg) was the dose most recommendations for lympho-reconstructive microsurgery for commonly selected (by 40% of the experts), with 67.6% agreeing secondary lymphedema and concluded that that the use of FI with that the dose should be 0.5 mL (2.5 mg). There similarly was no ICG during preplanning is “inevitable.”50 consensus regarding how long surgeons should wait before per- In a systematic review of the literature, published by Abbaci forming the same lymphatic surgery procedure using ICG a second et al,12 investigators analyzing 33 studies regarding the effective- time; although, combining response options, 77.0% voted for a ness of ICG imaging in breast cancer patients for the purposes of duration of 3 months. axillary reverse mapping, lymphography, and upper-limb S18 F. Dip et al. / Surgery 172 (2022) S14eS20 Table III Module 1: patient preparation and contraindications to fluorescence imaging and/or indocyanine green Statement No. of votes Response No. of rounds % Consensus In general, the use of fluorescence-guidance during surgery should be considered very safe. 18 Agree 1 100.0 Patients undergoing a procedure using fluorescence technology should be provided specific information 18 Agree 1 100.0 about it before undergoing the procedure. Before being administered ICG, patients should be asked if they are allergic to iodine. 18 Agree 1 100.0 Patients undergoing a procedure using ICG should be provided specific information about the drug 18 Agree 1 88.9 before undergoing the procedure Patients undergoing a procedure using fluorescence technology should generally be asked to give 18 Agree 1 83.3 informed written consent for it to be used. Patients undergoing a procedure using ICG should generally be asked to give informed written consent 18 Agree 1 83.3 for it to be used. If a patient reports being allergic to iodine, ICG can still be used subcutaneously. 17 Disagree 1 82.4 ICG, indocyanine green. Table IV Module 2: indocyanine green dosing and administration Statement No. of votes Response No. of rounds % Consensus Consensus reached In general, the length of time one waits after administering ICG to view the anatomy 17 Important 1 94.1 under near-infrared light is important, unimportant, or depends on the situation. The minimum effective dose of ICG for fluorescence imaging for lymphatic vessel 17 0.1e0.2 mL 1 94.1 visualization is… (2.5 mg/mL) In general, the timing of ICG administration is important, unimportant, or depends on 17 Important 1 88.2 the situation. The maximum number of fluorescent lymphography procedures that should be 15 <10 2 86.7 performed annually in a patient to evaluate lymphedema progression is… It is important to repeat ICG lymphography after a surgical procedure. 15 Agree 2 73.3 The optimal dose of ICG to give to evaluate lymph vessels is… 15 0.2 mL 2 73.3 (2.5 mg/mL) In general, the concentration of ICG that is administered is important, unimportant, or 18 Important 1 72.2 depends on the situation. No consensus reached In general, the dose of ICG that is administered is important, important, unimportant, or 15 Important 2 60.0 depends on the situation. Before the same procedure is performed a second time with ICG, one should wait… 13 >3 mo 2 46.2 The optimal dose of ICG to give to evaluate lymph nodes is… 15 0.2 mL 2 40.0 ICG, indocyanine green. Table V Module 3: potential advantages and uses of fluorescence imaging with indocyanine green Statement No. of votes Response No. of rounds % Consensus Consensus reached ICG can be used to plan lymphatic treatment. 18 Agree 1 100.0 Fluorescence imaging, with and without ICG, should be part of routine surgical practice. 15 Agree 2 93.3 Fluorescence imaging, with and without ICG, is useful for surgical quality control. 17 Agree 1 88.2 ICG needs to be considered for the preoperative work-up of lymph surgery patients. 17 Agree 1 88.2 In general, fluorescence imaging is an important tool for the visualization of lymphatic vessels. 18 Agree 1 83.3 The use of ICG to evaluate lymphatic vessels should be included in the algorithm for assessing 18 Agree 1 83.3 patients. In general, fluorescence imaging is an important tool for the visualization of sentinel lymph nodes. 17 Agree 1 82.4 ICG is useful as a diagnostic tool to evaluate the treatment of lymphatic disorders. 17 Agree 1 82.4 ICG is important to detect early evidence of lymphedema after sentinel lymph node identification. 17 Agree 1 82.4 ICG is important to detect early lymphatic changes after sentinel lymph node identification in 17 Agree 1 82.4 patients receiving chemo- or radiation therapy for cancer. ICG should be used to evaluate syndromes associated with lymphatic dysfunction. 15 Agree 1 80.0 ICG is useful for following up the noninvasive treatment of lymphedema. 18 Agree 1 77.8 Considering the diagnosis and treatment of lymphatic disorders, it is important to perform 17 Both 1 70.6 fluorescent lymphography for… (diagnosis, treatment, or both). No consensus reached It is appropriate to perform ICG lymphography after surgery on the lymph vessels. 13 After 3 mo 2 53.8 Fluorescent lymphography should be performed before any radioisotope study to evaluate the 14 Agree 2 50.0 lymphatic vessels. Postoperatively, initial fluorescent lymphography after sentinel lymph node resection is appropriate 15 >3 mo 2 40.0 at roughly… ICG, indocyanine green. F. Dip et al. / Surgery 172 (2022) S14eS20 S19 Table VI Module 4: potential barriers and training issues Statement No. of votes Response No. of rounds % Consensus Consensus reached Fluorescence imaging technology has the potential to significantly enhance patient outcomes. 17 Agree 1 94.1 The most effective visualization tool during lymphatic surgery is... (ICG, colored dyes, ultrasound) 17 ICG 1 94.1 Fluorescent lymphography is useful for training residents. 17 Agree 1 94.1 Increased visualization of lymphatic structures is an advantage of using fluorescent lymphography. 16 Agree 1 93.8 The noninvasiveness of the procedure is an advantage of using fluorescent lymphography. 16 Agree 1 87.5 The need for repeat dosing is one of the most common problems experienced during fluorescence 15 Disagree 1 80.0 imaging. Decreased risk of complications is an advantage of using fluorescent lymphography. 16 Agree 1 75.0 Equipment/technology unavailability is one of the most common problems experienced during 16 Agree 1 75.0 fluorescence imaging. Limited high-quality scientific data is one of the most common problems experienced during 16 Agree 1 75.0 fluorescence imaging. Unfamiliarity with the procedure is one of the most common problems experienced during 16 Agree 1 75.0 fluorescence imaging. Cost-effectiveness is an advantage of using fluorescent lymphography. 11 Agree 2 72.7 Exposure of physician trainees to fluorescent imaging should begin during… (medical school, 11 Residency 2 72.7 residency). Not just surgical residents but also residents in other nonsurgical fields should learn about 11 Agree 1 72.7 fluorescence imaging. No consensus reached Inadequate nurse training is one of the most common problems experienced during fluorescence 11 Disagree 2 63.6 imaging. Failure of fluorescence due to inadequate dosing or faulty technique is one of the most common 11 Disagree 2 63.6 problems experienced during fluorescence imaging. The number of cases needed to overcome the learning curve is… 13 11e25 2 38.5 ICG, indocyanine green. supermicrosurgery concluded that, although high-quality evidence In the present study, the overall level of consensus achieved was, at proving the efficacy of FI with ICG over standard clinical techniques 77.1%, far from 100%, suggesting that our results did not reflect a clique remains inadequate, its potential as a real-time, multidimensional of like-minded individuals agreeing with each other. Consensus also imaging technique not requiring a radiolabeled probe is great. was reached on numerous items agreeing on the limitations of FI, Our panel of 18 international experts arrived at much the same including the need for further supportive empirical data. We would conclusion; consensus was reached that limited high-quality evi- argue that such findings indicate a well-selected panel of experts. We dence remains a barrier to the widespread use of this technology also had experts from 11 countries spanning 5 continents and a largely and that patients should be given specific information about and academic panel with extensive surgical experience, all meeting asked to sign specific consent forms both for FI and ICG. On the stringent expert selection criteria, who largely were identified other hand, there was consistent consensus regarding the value of through their publication history, rather than via personal contacts. FI and/or ICG for virtually every clinical scenario in which their use Hence, despite a clear need for further controlled trials to report might be considered during lymphedema patient management, the extent to which and ways in which FI, with or without ICG, is including preoperative work-up, surgical planning, visualizing both effective as a means to manage lymphedema patients, this rela- lymph vessels and SLNs intraoperatively, intraoperative surgical tively new technology appears to have several roles in lymphedema guidance, monitoring outcomes, quality control, and resident prevention, diagnosis, assessment, and treatment. training. There also was near-unanimous consensus that FI with ICG use should be part of both routine practice and any algorithm Funding/Support assessing individuals for lymphatic disease and that FI with ICG is superior to either using colored dyes or ultrasound, and unanimous Diagnostic Green, Intuitive, Medtronic, Olympus, Karl Storz, and agreement that intraoperative FI should be considered “very safe.” Stryker each provided unrestricted grants for the ISFGS advisory Delphi studies have inescapable limitations, primarily due to board meeting, Frankfurt, Germany, September 8, 2019, during their being opinion rather than data based. This article, for example, which the Delphi consensus was discussed. Diagnostic Green also summarized the opinions of experts who all use FI in their practice funded accommodations and meals. Diagnostic Green, Medtronic, and have an academic/clinical interest in fluorescence. As such, the Karl Storz, Stryker, Arthrex, and Richard Wolf provided additional results presented herein should not be used to replace well- financial support to ISFGS for this publication. designed clinical trials to ultimately determine whether a given patient management approach is effective. Such opinions none- Conflict of interest/Disclosure theless have numerous uses and advantages that even the most robustly designed randomized clinical trials lack. Among these Raul Rosenthal: consulting fees from Medtronics, Arthrex, Diag- advantages are the Delphi technique’s ability to permit those most nostic Green and Ethicon. Advisory Board Member Axon Imaging qualified to interpret the literature in their field to do so, especially Technologies. Stock Holder: Hechtech / Medicad Simulation, Germany. when published data conflict, to provide their views regarding the All other authors have no conflicts of interests or disclosures to report. patient management approach of interest’s limitations and need for further development and validation, and to potentially provide Acknowledgements detailed instructions in how to perform this new technique or technology. Among critics’ concerns is the potential for bias, the Fernando Dip, Emanuele Lo Menzo, Jaime Masia, Kevin White, assumption that expert panels inherently consist of like-minded and Raul Rosenthal are members of the ISFGS Advisory Board. None individuals. of the industry sponsors were actively involved in any process of S20 F. Dip et al. / Surgery 172 (2022) S14eS20 the Delphi consensus or drafting, review, or revision of the manu- 25. Zelken JA, Tufaro AP. Current trends and emerging future of indocyanine green usage in surgery and oncology: an update. 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