Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2018

Open Access 01-10-2018 | Original Article

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes

Authors: G. H. KleinJan, E. van Werkhoven, N. S. van den Berg, M. B. Karakullukcu, H. J. M. A. A. Zijlmans, J. A. van der Hage, B. A. van de Wiel, T. Buckle, W. M. C. Klop, S. Horenblas, R. A. Valdés Olmos, H. G. van der Poel, F. W. B. van Leeuwen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2018

Login to get access

Abstract

Purpose

Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients.

Patients and methods

A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).

Results

A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22–78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced.

Conclusion

With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.
Appendix
Available only for authorised users
Literature
1.
go back to reference Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.CrossRefPubMed Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.CrossRefPubMed
2.
go back to reference Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.CrossRefPubMed Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.CrossRefPubMed
3.
4.
go back to reference Wit EMK, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, et al. Sentinel node procedure in prostate cancer: a systematic review to assess diagnostic accuracy. Eur Urol. 2017;71:596–605.CrossRefPubMed Wit EMK, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, et al. Sentinel node procedure in prostate cancer: a systematic review to assess diagnostic accuracy. Eur Urol. 2017;71:596–605.CrossRefPubMed
5.
go back to reference KleinJan GH, van den Berg NS, Brouwer OR, de Jong J, Acar C, Wit EM, et al. Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer. Eur Urol. 2014;66:991–8.CrossRefPubMed KleinJan GH, van den Berg NS, Brouwer OR, de Jong J, Acar C, Wit EM, et al. Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer. Eur Urol. 2014;66:991–8.CrossRefPubMed
6.
go back to reference Heller S, Zanzonico P. Nuclear probes and intraoperative gamma cameras. Semin Nucl Med. 2011;41:166–81.CrossRefPubMed Heller S, Zanzonico P. Nuclear probes and intraoperative gamma cameras. Semin Nucl Med. 2011;41:166–81.CrossRefPubMed
7.
8.
go back to reference Chao C, Wong SL, Edwards MJ, Ross MI, Reintgen DS, Noyes RD, et al. Sentinel lymph node biopsy for head and neck melanomas. Ann Surg Oncol. 2003;10:21–6.CrossRefPubMed Chao C, Wong SL, Edwards MJ, Ross MI, Reintgen DS, Noyes RD, et al. Sentinel lymph node biopsy for head and neck melanomas. Ann Surg Oncol. 2003;10:21–6.CrossRefPubMed
9.
go back to reference Motomura K, Inaji H, Komoike Y, Kasugai T, Noguchi S, Koyama H. Sentinel node biopsy guided by indocyanine green dye in breast cancer patients. Jpn J Clin Oncol. 1999;29:604–7.CrossRefPubMed Motomura K, Inaji H, Komoike Y, Kasugai T, Noguchi S, Koyama H. Sentinel node biopsy guided by indocyanine green dye in breast cancer patients. Jpn J Clin Oncol. 1999;29:604–7.CrossRefPubMed
10.
go back to reference KleinJan GH, Bunschoten A, van den Berg NS, Olmos RA, Klop WM, Horenblas S, et al. Fluorescence guided surgery and tracer-dose, fact or fiction? Eur J Nucl Med Mol Imaging. 2016;43:1857–67.CrossRefPubMedPubMedCentral KleinJan GH, Bunschoten A, van den Berg NS, Olmos RA, Klop WM, Horenblas S, et al. Fluorescence guided surgery and tracer-dose, fact or fiction? Eur J Nucl Med Mol Imaging. 2016;43:1857–67.CrossRefPubMedPubMedCentral
11.
go back to reference van Leeuwen FW, Hardwick JC, van Erkel AR. Luminescence-based imaging approaches in the field of interventional molecular imaging. Radiology. 2015;276:12–29.CrossRefPubMed van Leeuwen FW, Hardwick JC, van Erkel AR. Luminescence-based imaging approaches in the field of interventional molecular imaging. Radiology. 2015;276:12–29.CrossRefPubMed
12.
go back to reference Brouwer OR, Buckle T, Vermeeren L, Klop WM, Balm AJ, van der Poel HG, et al. Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation study using lymphoscintigraphy and SPECT/CT. J Nucl Med. 2012;53:1034–40.CrossRefPubMed Brouwer OR, Buckle T, Vermeeren L, Klop WM, Balm AJ, van der Poel HG, et al. Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation study using lymphoscintigraphy and SPECT/CT. J Nucl Med. 2012;53:1034–40.CrossRefPubMed
13.
go back to reference Brouwer OR, van den Berg NS, Matheron HM, van der Poel HG, van Rhijn BW, Bex A, et al. A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol. 2014;65:600–9.CrossRefPubMed Brouwer OR, van den Berg NS, Matheron HM, van der Poel HG, van Rhijn BW, Bex A, et al. A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye. Eur Urol. 2014;65:600–9.CrossRefPubMed
14.
go back to reference Matheron HM, van den Berg NS, Brouwer OR, Kleinjan GH, van Driel WJ, Trum JW, et al. Multimodal surgical guidance towards the sentinel node in vulvar cancer. Gynecol Oncol. 2013;131:720–5.CrossRefPubMed Matheron HM, van den Berg NS, Brouwer OR, Kleinjan GH, van Driel WJ, Trum JW, et al. Multimodal surgical guidance towards the sentinel node in vulvar cancer. Gynecol Oncol. 2013;131:720–5.CrossRefPubMed
15.
go back to reference van den Berg NS, Brouwer OR, Klop WM, Karakullukcu B, Zuur CL, Tan IB, et al. Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid. Eur J Nucl Med Mol Imaging. 2012;39:1128–36.CrossRefPubMed van den Berg NS, Brouwer OR, Klop WM, Karakullukcu B, Zuur CL, Tan IB, et al. Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid. Eur J Nucl Med Mol Imaging. 2012;39:1128–36.CrossRefPubMed
16.
go back to reference van den Berg NS, Brouwer OR, Schaafsma BE, Matheron HM, Klop WM, Balm AJ, et al. Multimodal surgical guidance during sentinel node biopsy for melanoma: combined gamma tracing and fluorescence imaging of the sentinel node through use of the hybrid tracer indocyanine green-(99m)Tc-Nanocolloid. Radiology. 2015;275:521–9.CrossRefPubMed van den Berg NS, Brouwer OR, Schaafsma BE, Matheron HM, Klop WM, Balm AJ, et al. Multimodal surgical guidance during sentinel node biopsy for melanoma: combined gamma tracing and fluorescence imaging of the sentinel node through use of the hybrid tracer indocyanine green-(99m)Tc-Nanocolloid. Radiology. 2015;275:521–9.CrossRefPubMed
17.
go back to reference Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.CrossRefPubMed Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–96.CrossRefPubMed
18.
go back to reference Nieweg OE, Estourgie SH. What is a sentinel node and what is a false-negative sentinel node? Ann Surg Oncol. 2004;11:169S–73S.CrossRefPubMed Nieweg OE, Estourgie SH. What is a sentinel node and what is a false-negative sentinel node? Ann Surg Oncol. 2004;11:169S–73S.CrossRefPubMed
19.
go back to reference Harrel FE. Regression modeling strategies with applications to linear models, survival analysis and logistic regression. Spinger International Publishing; 2001. Harrel FE. Regression modeling strategies with applications to linear models, survival analysis and logistic regression. Spinger International Publishing; 2001.
20.
go back to reference Valsecchi ME, Silbermins D, de Rosa N, Wong SL, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. J Clin Oncol. 2011;29:1479–87.CrossRefPubMed Valsecchi ME, Silbermins D, de Rosa N, Wong SL, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma: a meta-analysis. J Clin Oncol. 2011;29:1479–87.CrossRefPubMed
21.
go back to reference Flach GB, Bloemena E, Klop WM, van Es RJ, Schepman KP, Hoekstra OS, et al. Sentinel lymph node biopsy in clinically N0 T1-T2 staged oral cancer: the Dutch multicenter trial. Oral Oncol. 2014;50:1020–4.CrossRefPubMed Flach GB, Bloemena E, Klop WM, van Es RJ, Schepman KP, Hoekstra OS, et al. Sentinel lymph node biopsy in clinically N0 T1-T2 staged oral cancer: the Dutch multicenter trial. Oral Oncol. 2014;50:1020–4.CrossRefPubMed
22.
go back to reference Pezier T, Nixon IJ, Gurney B, Schilling C, Hussain K, Lyons AJ, et al. Sentinel lymph node biopsy for T1/T2 oral cavity squamous cell carcinoma--a prospective case series. Ann Surg Oncol. 2012;19:3528–33.CrossRefPubMed Pezier T, Nixon IJ, Gurney B, Schilling C, Hussain K, Lyons AJ, et al. Sentinel lymph node biopsy for T1/T2 oral cavity squamous cell carcinoma--a prospective case series. Ann Surg Oncol. 2012;19:3528–33.CrossRefPubMed
23.
go back to reference Tanis PJ, Lont AP, Meinhardt W, Olmos RA, Nieweg OE, Horenblas S. Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique. J Urol. 2002;168:76–80.CrossRefPubMed Tanis PJ, Lont AP, Meinhardt W, Olmos RA, Nieweg OE, Horenblas S. Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique. J Urol. 2002;168:76–80.CrossRefPubMed
24.
go back to reference Van der Zee AG, Oonk MH, De Hullu JA, Ansink AC, Vergote I, Verheijen RH, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol. 2008;26:884–9.CrossRefPubMed Van der Zee AG, Oonk MH, De Hullu JA, Ansink AC, Vergote I, Verheijen RH, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol. 2008;26:884–9.CrossRefPubMed
25.
go back to reference Manny TB, Patel M, Hemal AK. Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol. 2014;65:1162–8.CrossRefPubMed Manny TB, Patel M, Hemal AK. Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol. 2014;65:1162–8.CrossRefPubMed
26.
go back to reference van den Berg NS, Miwa M, KleinJan GH, Sato T, Maeda Y, van Akkooi AC, et al. (Near-infrared) fluorescence-guided surgery under ambient light conditions: a next step to embedment of the technology in clinical routine. Ann Surg Oncol. 2016;23:2586–95.CrossRefPubMedPubMedCentral van den Berg NS, Miwa M, KleinJan GH, Sato T, Maeda Y, van Akkooi AC, et al. (Near-infrared) fluorescence-guided surgery under ambient light conditions: a next step to embedment of the technology in clinical routine. Ann Surg Oncol. 2016;23:2586–95.CrossRefPubMedPubMedCentral
27.
go back to reference van der Ploeg IM, Madu MF, van der Hage JA, Wouters MW, Klop WM, van der Hiel B, et al. Blue dye can be safely omitted in most sentinel node procedures for melanoma. Melanoma Res. 2016;26:464–8.CrossRefPubMed van der Ploeg IM, Madu MF, van der Hage JA, Wouters MW, Klop WM, van der Hiel B, et al. Blue dye can be safely omitted in most sentinel node procedures for melanoma. Melanoma Res. 2016;26:464–8.CrossRefPubMed
28.
go back to reference Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242:302–11, discussion 11–13PubMedPubMedCentral Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242:302–11, discussion 11–13PubMedPubMedCentral
29.
go back to reference Buckle T, Brouwer OR, Valdes Olmos RA, van der Poel HG, van Leeuwen FW. Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients. J Nucl Med. 2012;53:1026–33.CrossRefPubMed Buckle T, Brouwer OR, Valdes Olmos RA, van der Poel HG, van Leeuwen FW. Relationship between intraprostatic tracer deposits and sentinel lymph node mapping in prostate cancer patients. J Nucl Med. 2012;53:1026–33.CrossRefPubMed
30.
go back to reference Karim RZ, Scolyer RA, Li W, Yee VS, McKinnon JG, Li LX, et al. False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology. Ann Surg. 2008;247:1003–10.CrossRefPubMed Karim RZ, Scolyer RA, Li W, Yee VS, McKinnon JG, Li LX, et al. False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology. Ann Surg. 2008;247:1003–10.CrossRefPubMed
Metadata
Title
The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes
Authors
G. H. KleinJan
E. van Werkhoven
N. S. van den Berg
M. B. Karakullukcu
H. J. M. A. A. Zijlmans
J. A. van der Hage
B. A. van de Wiel
T. Buckle
W. M. C. Klop
S. Horenblas
R. A. Valdés Olmos
H. G. van der Poel
F. W. B. van Leeuwen
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4028-x

Other articles of this Issue 11/2018

European Journal of Nuclear Medicine and Molecular Imaging 11/2018 Go to the issue