Skip to main content
Top
Published in: Techniques in Coloproctology 12/2019

Open Access 01-12-2019 | Metastasis | Original Article

Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis

Authors: M. Ankersmit, H. J. Bonjer, G. Hannink, L. J. Schoonmade, M. H. G. M. van der Pas, W. J. H. J. Meijerink

Published in: Techniques in Coloproctology | Issue 12/2019

Login to get access

Abstract

Background

Near-infrared (NIR) fluorescence imaging has the potential to overcome the current drawbacks of sentinel lymph node mapping (SLNM) in colon cancer. Our aim was to provide an overview of current SLNM performance and of factors influencing successful sentinel lymph node (SLN) identification using NIR fluorescence imaging in colon cancer.

Methods

A systematic review and meta-analysis was conducted to identify currently used methods and results. Additionally, we performed a single-center study using indocyanine green (ICG) as SLNM dye in colon cancer patients scheduled for a laparoscopic colectomy. SLNs were analyzed with conventional hematoxylin-and-eosin staining and additionally with serial sectioning and immunohistochemistry (extended histopathological assessment). A true-positive procedure was defined as a tumor-positive SLN either by conventional hematoxylin-and-eosin staining or by extended histopathological assessment, independently of regional lymph node status. SLN procedures were determined to be true negatives if SLNs and regional lymph nodes revealed no metastases after conventional and advanced histopathology. SLN procedures yielding tumor-negative SLNs in combination with tumor-positive regional lymph nodes were classified as false negatives. Sensitivity, negative predictive value and detection rate were calculated.

Results

This systematic review and meta-analysis included 8 studies describing 227 SLN procedures. A pooled sensitivity of 0.63 (95% CI 0.51–0.74), negative predictive value 0.81 (95% CI 0.73–0.86) and detection rate of 0.94 (95% CI 0.85–0.97) were found. Upstaging as a result of extended histopathological assessment was 0.15 (95% CI 0.07–0.25). In our single-center study, we included 30 patients. Five false-negative SLNs were identified, resulting in a sensitivity of 44% and negative predictive value of 80%, with a detection rate of 89.7%. Eight patients had lymph node metastases, in three cases detected after extended pathological assessment, resulting in an upstaging of 13% (3 of 23 patients with negative nodes by conventional hematoxylin and eosin staining).

Conclusions

Several anatomical and technical difficulties make SLNM with NIR fluorescence imaging in colon cancer particularly challenging when compared to other types of cancer. As a consequence, reports of SLNM accuracy vary widely. Future studies should try to standardize the SLNM procedure and focus on early-stage colon tumors, validation of tracer composition, injection mode and improvement of real-time optical guidance.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A, Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer I (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://doi.org/10.1056/nejmoa032709 CrossRef Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A, Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer I (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351. https://​doi.​org/​10.​1056/​nejmoa032709 CrossRef
5.
go back to reference Sloothaak DA, Sahami S, van der Zaag-Loonen HJ, van der Zaag ES, Tanis PJ, Bemelman WA, Buskens CJ (2014) The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: a systematic review and meta-analysis. Eur J Surg Oncol 40(3):263–269. https://doi.org/10.1016/j.ejso.2013.12.002 CrossRefPubMed Sloothaak DA, Sahami S, van der Zaag-Loonen HJ, van der Zaag ES, Tanis PJ, Bemelman WA, Buskens CJ (2014) The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: a systematic review and meta-analysis. Eur J Surg Oncol 40(3):263–269. https://​doi.​org/​10.​1016/​j.​ejso.​2013.​12.​002 CrossRefPubMed
12.
go back to reference Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, Liefers GJ, Choi HS, Gibbs-Strauss SL, Putter H, Gioux S, Kuppen PJ, Ashitate Y, Lowik CW, Smit VT, Oketokoun R, Ngo LH, van de Velde CJ, Frangioni JV, Vahrmeijer AL (2011) Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer. Ann Surg Oncol 18(9):2483–2491. https://doi.org/10.1245/s10434-011-1566-x CrossRefPubMedPubMedCentral Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, Liefers GJ, Choi HS, Gibbs-Strauss SL, Putter H, Gioux S, Kuppen PJ, Ashitate Y, Lowik CW, Smit VT, Oketokoun R, Ngo LH, van de Velde CJ, Frangioni JV, Vahrmeijer AL (2011) Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer. Ann Surg Oncol 18(9):2483–2491. https://​doi.​org/​10.​1245/​s10434-011-1566-x CrossRefPubMedPubMedCentral
19.
go back to reference Hermanek P, Hutter RV, Sobin LH, Wittekind C (1999) International union against cancer. Classification of isolated tumor cells and micrometastasis. Cancer 86(12):2668–2673CrossRef Hermanek P, Hutter RV, Sobin LH, Wittekind C (1999) International union against cancer. Classification of isolated tumor cells and micrometastasis. Cancer 86(12):2668–2673CrossRef
20.
go back to reference Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M (2017) Sentinel lymph node mapping with isosulfan blue or indocyanine green in colon cancer shows comparable results and identifies patients with decreased survival: a prospective single-center trial. World J Surg 41(9):2378–2386. https://doi.org/10.1007/s00268-017-4051-2 CrossRefPubMed Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M (2017) Sentinel lymph node mapping with isosulfan blue or indocyanine green in colon cancer shows comparable results and identifies patients with decreased survival: a prospective single-center trial. World J Surg 41(9):2378–2386. https://​doi.​org/​10.​1007/​s00268-017-4051-2 CrossRefPubMed
24.
26.
go back to reference Hutteman M, Choi HS, Mieog JS, van der Vorst JR, Ashitate Y, Kuppen PJ, van Groningen MC, Lowik CW, Smit VT, van de Velde CJ, Frangioni JV, Vahrmeijer AL (2011) Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light. Ann Surg Oncol 18(4):1006–1014. https://doi.org/10.1245/s10434-010-1426-0 CrossRefPubMed Hutteman M, Choi HS, Mieog JS, van der Vorst JR, Ashitate Y, Kuppen PJ, van Groningen MC, Lowik CW, Smit VT, van de Velde CJ, Frangioni JV, Vahrmeijer AL (2011) Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light. Ann Surg Oncol 18(4):1006–1014. https://​doi.​org/​10.​1245/​s10434-010-1426-0 CrossRefPubMed
28.
go back to reference van der Pas MH, Ankersmit M, Stockmann HB, Silvis R, van Grieken NC, Bril H, Meijerink WJ (2013) Laparoscopic sentinel lymph node identification in patients with colon carcinoma using a near-infrared dye: description of a new technique and feasibility study. J Laparoendosc Adv Surg Tech A 23(4):367–371. https://doi.org/10.1089/lap.2012.0407 CrossRefPubMed van der Pas MH, Ankersmit M, Stockmann HB, Silvis R, van Grieken NC, Bril H, Meijerink WJ (2013) Laparoscopic sentinel lymph node identification in patients with colon carcinoma using a near-infrared dye: description of a new technique and feasibility study. J Laparoendosc Adv Surg Tech A 23(4):367–371. https://​doi.​org/​10.​1089/​lap.​2012.​0407 CrossRefPubMed
29.
go back to reference Nagata K, Endo S, Hidaka E, Tanaka J, Kudo SE, Shiokawa A (2006) Laparoscopic sentinel node mapping for colorectal cancer using infrared ray laparoscopy. Anticancer Res 26(3B):2307–2311PubMed Nagata K, Endo S, Hidaka E, Tanaka J, Kudo SE, Shiokawa A (2006) Laparoscopic sentinel node mapping for colorectal cancer using infrared ray laparoscopy. Anticancer Res 26(3B):2307–2311PubMed
31.
go back to reference Cahill RA, Anderson M, Wang LM, Lindsey I, Cunningham C, Mortensen NJ (2012) Near-infrared (NIR) laparoscopy for intraoperative lymphatic road-mapping and sentinel node identification during definitive surgical resection of early-stage colorectal neoplasia. Surg Endosc 26(1):197–204. https://doi.org/10.1007/s00464-011-1854-3 CrossRef Cahill RA, Anderson M, Wang LM, Lindsey I, Cunningham C, Mortensen NJ (2012) Near-infrared (NIR) laparoscopy for intraoperative lymphatic road-mapping and sentinel node identification during definitive surgical resection of early-stage colorectal neoplasia. Surg Endosc 26(1):197–204. https://​doi.​org/​10.​1007/​s00464-011-1854-3 CrossRef
36.
go back to reference Chand M, Keller DS, Joshi HM, Devoto L, Rodriguez-Justo M, Cohen R (2018) Feasibility of fluorescence lymph node imaging in colon cancer: FLICC. Tech Coloproctol 22(4):271-277CrossRef Chand M, Keller DS, Joshi HM, Devoto L, Rodriguez-Justo M, Cohen R (2018) Feasibility of fluorescence lymph node imaging in colon cancer: FLICC. Tech Coloproctol 22(4):271-277CrossRef
37.
go back to reference Backes Y, Elias SG, Bhoelan BS, Groen JN, van Bergeijk J, Seerden TCJ, Pullens HJM, Spanier BWM, Geesing JMJ, Kessels K, Kerkhof M, Siersema PD, de Vos Tot Nederveen Cappel WH, van Lelyveld N, Wolfhagen FHJ, Ter Borg F, Offerhaus GJA, Lacle MM, Moons LMG, Dutch TCRCWG (2017) The prognostic value of lymph node yield in the earliest stage of colorectal cancer: a multicenter cohort study. BMC Med 15(1):129. https://doi.org/10.1186/s12916-017-0892-7 CrossRefPubMedPubMedCentral Backes Y, Elias SG, Bhoelan BS, Groen JN, van Bergeijk J, Seerden TCJ, Pullens HJM, Spanier BWM, Geesing JMJ, Kessels K, Kerkhof M, Siersema PD, de Vos Tot Nederveen Cappel WH, van Lelyveld N, Wolfhagen FHJ, Ter Borg F, Offerhaus GJA, Lacle MM, Moons LMG, Dutch TCRCWG (2017) The prognostic value of lymph node yield in the earliest stage of colorectal cancer: a multicenter cohort study. BMC Med 15(1):129. https://​doi.​org/​10.​1186/​s12916-017-0892-7 CrossRefPubMedPubMedCentral
42.
go back to reference Hutteman M, Mieog JS, van der Vorst JR, Liefers GJ, Putter H, Lowik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL (2011) Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat 127(1):163–170. https://doi.org/10.1007/s10549-011-1419-0 CrossRefPubMedPubMedCentral Hutteman M, Mieog JS, van der Vorst JR, Liefers GJ, Putter H, Lowik CW, Frangioni JV, van de Velde CJ, Vahrmeijer AL (2011) Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat 127(1):163–170. https://​doi.​org/​10.​1007/​s10549-011-1419-0 CrossRefPubMedPubMedCentral
44.
go back to reference Cahill RA (2007) What’s wrong with sentinel node mapping in colon cancer? World J Gastroenterol 13(47):6291–6294CrossRef Cahill RA (2007) What’s wrong with sentinel node mapping in colon cancer? World J Gastroenterol 13(47):6291–6294CrossRef
46.
go back to reference Bembenek AE, Rosenberg R, Wagler E, Gretschel S, Sendler A, Siewert JR, Nahrig J, Witzigmann H, Hauss J, Knorr C, Dimmler A, Grone J, Buhr HJ, Haier J, Herbst H, Tepel J, Siphos B, Kleespies A, Koenigsrainer A, Stoecklein NH, Horstmann O, Grutzmann R, Imdahl A, Svoboda D, Wittekind C, Schneider W, Wernecke KD, Schlag PM (2007) Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial. Ann Surg 245(6):858–863. https://doi.org/10.1097/01.sla.0000250428.46656.7e CrossRefPubMedPubMedCentral Bembenek AE, Rosenberg R, Wagler E, Gretschel S, Sendler A, Siewert JR, Nahrig J, Witzigmann H, Hauss J, Knorr C, Dimmler A, Grone J, Buhr HJ, Haier J, Herbst H, Tepel J, Siphos B, Kleespies A, Koenigsrainer A, Stoecklein NH, Horstmann O, Grutzmann R, Imdahl A, Svoboda D, Wittekind C, Schneider W, Wernecke KD, Schlag PM (2007) Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial. Ann Surg 245(6):858–863. https://​doi.​org/​10.​1097/​01.​sla.​0000250428.​46656.​7e CrossRefPubMedPubMedCentral
Metadata
Title
Near-infrared fluorescence imaging for sentinel lymph node identification in colon cancer: a prospective single-center study and systematic review with meta-analysis
Authors
M. Ankersmit
H. J. Bonjer
G. Hannink
L. J. Schoonmade
M. H. G. M. van der Pas
W. J. H. J. Meijerink
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Techniques in Coloproctology / Issue 12/2019
Print ISSN: 1123-6337
Electronic ISSN: 1128-045X
DOI
https://doi.org/10.1007/s10151-019-02107-6

Other articles of this Issue 12/2019

Techniques in Coloproctology 12/2019 Go to the issue