Indocyanine green is superior to blue colorimetric method for identifying sentinel lymph nodes during laparoscopic surgery for uterine malignancies: a pilot study

Aim: The objective of this study was to compare indocyanine green (ICG) and blue colorimetric methods for detection of sentinel lymph nodes (SLN) during laparoscopic surgery for uterine malignancies. Materials and Methods: Over a two years and 3months period, laparoscopic surgery was performed on 16 cases of uterine malignancies using near infrared (NIR) fluorescence imaging of ICG tracer uptake to direct SLN biopsy (NIR-FI-SLNB). ICG was injected into the uterine cervix prior to surgery. For comparison of detection efficacy, blue dye used for traditional colorimetric method was injected concurrently into 14 of these 16 cases. After pneumoperitoneum, we opened the retroperitoneum to laparoscopically identify the SLN. After biopsy of the SLN, a systemic pelvic lymph node dissection was performed. Results: Using ICG, we were able to identify SLN in 15/16 cases (93.7%), and achieved bilateral pelvic mapping in 12/16 (75%). With the blue dye, we were also able to identify SLN in only 64.3% of the 14 cases so tested, and bilateral pelvic mapping in only 14.3%. There were no intraoperative complications during any of the procedures. For conducting a laparoscopic bilateral SLN biopsy, we found that use of ICG was significantly superior to the blue colorimetric method (14.3% vs. 75%, p = 0.0009). Conclusions: These pilot data provide suggestive evidence that the laparoscopic NIR fluorescence imaging for SLN biopsy provide superior efficacy, compared to the traditional blue colorimetric method, without additional complications.

Indocyanine green; Sentinel lymph node; Near-infrared fluorescence imaging; Blue dye.

[1] Gortzak-Uzan L., Jumenez W., Nofech-Mozes S., Ismiil N., Khalifa M. A., Dube V., et al.: “Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: is it time to change the gold standard ?” Gynecol. Oncol., 2010, 116, 28.

[2] Boudenwijin E.S., van der Vorst J.R., Gaarenstroom K.N., Peters A.A., Verbeek F.P., de Kroon C.D., et al.: “Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer”. Gynecol. Oncol., 2012, 127, 126.

[3] Verheijen R.H., Pijpers R., van Diest P.J., Burger C.W., Buist M.R., Kenemans P.: “Sentinel node detection in cervical cancer”. Obstet. Gynecol., 2000, 96, 135.

[4] Dargent D., Martin X., Mathevet P.: “Laparoscopic assessment of the sentinel lymph node in early stage cervical cancer”. Gynecol. Oncol., 2000, 79, 411.

[5] Malur S., Krause N., Kohler C., Schneider A.: “Sentinel lymph node detection in patients with cervical cancer”. Gynecol. Oncol., 2001, 80, 254.

[6] Lantzsch T., Wolters M., Grimm J., Mende T., Buchmann J., Sliutz G., et al.: “Sentinel node procedure in Ib cervical cancer: a preliminary series”. Br. J. Cancer, 2001, 85, 791.

[7] Van Dam P.A., Hauspy J., Vanderheyden T., Sonnemans H., Spaepen A., Eggenstein G., et al.: “Intraoperative sentinel node identification with technetium-99m-labeled nanocolloid in patients with cancer of the uterine cervix: a feasibility study”. Int. J. Gynecol. Cancer, 2003, 13, 182.

[8] Niikura H., Okamura C., Akahira J., Takano T., Ito K., Okamura K., et al.: “Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue”. Gynecol. Oncol., 2004, 94, 528.

[9] Diaz J.P., Gemignani M.L., Pandit-Taskar N., Park K.J., Murray M.P., Chi D.S., et al.: “Sentinel lymph node biopsy in the management of early-stage cervical carcinoma”. Gynecol. Oncol., 2011, 120, 347.

[10] Pelosi E., Arena V., Baudino B., Bellò M., Gargiulo T., Giusti M., et al.: “Preliminary study of sentinel node identification with 99mTc colloid and blue dye in patients with endometrial cancer”. Tumori, 2002, 88, S9.

[11] Frumovitz M., Bodurka D.C., Broaddus R.R., Coleman R.L., Sood A.K., Gershenson D.M., et al.: “Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer”. Gynecol. Oncol., 2007, 104, 100.

[12] Lelievre L., Camatte S., Le Frere-Belda M.A., Kerrou K., Froissart M., Taurelle R., et al.: “Sentinel lymph node biopsy in cervical and endometrial cancers: a feasibility study”. Bull. Cancer, 2004, 91, 379.

[13] Holub Z., Jabor A., Kliment L.: “Comparison of two procedures for sentinel lymph node detection in patients with endometrial cancer: a pilot study”. Eur. J. Gynaecol. Oncol., 2002, 23, 53.

[14] Abu Rustum N.R., Gomez J.D., Alektiar K.M., Soslow R.A., Hensley M.L., Leitao Jr. M.M., et al.: “The incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes”. Gynecol. Oncol., 2009, 115, 236.

[15] Cibula D., Abu-Rustum N.R., Dusek L., Zikán M., Zaal A., Sevcik L., et al.: “Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer”. Gynecol. Oncol., 2012, 124, 496.

[16] Cormier B., Diaz J.P., Shih K., Sampson R.M., Sonoda Y., Park K.J., et al.: “Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer”. Gynecol. Oncol., 2011, 122, 275.

[17] Khoury-Collado F., Abu-Rustum N.R.: “Lymphatic mapping in endometrial cancer: a literature review of current techniques and results”. Int. J. Gynecol. Cancer, 2008, 18, 1163.

[18] Khoury-Collado F., Glaser G.E., Zivanovic O., Sonoda Y., Levine D.A., Chi D.S., et al.: “Improving sentinel lymph node detection rates in endometrial cancer: how many cases are needed?” Gynecol. Oncol., 2009, 115, 453.

[19] Rossi E.C, Ivanova A., Boggess J.F.: “Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: A feasibility study”. Gynecol. Oncol., 2012, 124, 78.

[20] Holloway R.W., Bravo R.A., Rakowski J.A., James J.A., Jeppson C.N., Ingersoll S.B., et al.: “Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging: a comparison of colorimetric and fluorescence imaging”. Gynecol. Oncol., 2012, 126, 25.

[21] Sinno A.K., Fader A.N., Roche K.L., Giuntoli R.L. 2nd, Tanner E.J., et al.: “A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial can-cer”. Gynecol. Oncol., 2014, 134, 181.

[22] How J., Gotlieb W.H., Press J.Z., Abitbol J., Pelmus M., Ferenczy A., et al.: “Comparing indocyanine green, technetium, and blue dye for sentinel lymph node mapping in endometrial cancer”. Gynecol. Oncol., 2015, 137, 436.

[23] Buda A., Di Martino G., Vecchione F., Bussi B., Dell’Anna T., Palazzi S., et al.: “Optimizing strategies for sentinel lymph node mapping in early-stage cervical cancer and endometrial cancer: Comparison of real-time fluorescence with indocyanine green and methylene blue”. Int. J. Gynecol., 2015, 25, 1513.

[24] Tanaka T., Terai Y., Ashihara K., Tsunetoh S., Akagi H., Yamada T., et al.: “The detection of sentinel lymph nodes in laparoscopic surgery for uterine cervical cancer using 99m-technetium-tin colloid, indocyanine green, and blue dye”. J. Gynecol. Cancer, 2017, 28, e3.

[25] Eriksson A.G., Beavis A., Soslow R.A., Zhou Q., Abu-Rustum N.R., Gardner G.J., et al.: “A comparison of detection of sentinel lymph nodes using indocyanine green and near-infrared fluorescence imag-ing versus blue dye during robotic surgery in uterine cancer”. Int. J. Gynecol. Cancer, 2017, 27, 743.