Skip to main content

Advertisement

SpringerLink
Log in

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy—a Prospective Validation Study in Early Breast Cancer

  • Surgery in Low and Middle Income Countries
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD).

Methods

Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared.

Results

The mean number of SLNs identified was 3.5 ± 1.8 (range 1–6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations.

Conclusions

SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lyman GH, Somerfield MR, Giuliano AE (2017) Sentinel lymph node biopsy for patients with early-stage breast cancer: 2016 American society of clinical oncology clinical practice guideline update summary. J Oncol Pract 13:196–198. https://doi.org/10.1200/JOP.2016.019992

    Article  PubMed  Google Scholar 

  2. Ho C, Argáez C (2019) Sentinel lymph node biopsy for the management of breast cancer: a review of guidelines [Internet]. Canadian Agency for Drugs and Technologies in Health, Ottawa, ON

    Google Scholar 

  3. Simmons R, Thevarajah S, Brennan MB et al (2003) Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization. Ann Surg Oncol 10:242–247. https://doi.org/10.1245/aso.2003.04.021

    Article  PubMed  Google Scholar 

  4. He P-S, Li F, Li G-H et al (2016) The combination of blue dye and radioisotope versus radioisotope alone during sentinel lymph node biopsy for breast cancer: a systematic review. BMC Cancer. https://doi.org/10.1186/s12885-016-2137-0

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pesek S, Ashikaga T, Krag LE, Krag D (2012) The false-negative rate of sentinel node biopsy in patients with breast cancer: a meta-analysis. World J Surg 36:2239–2251. https://doi.org/10.1007/s00268-012-1623-z

    Article  PubMed  PubMed Central  Google Scholar 

  6. Motomura K, Inaji H, Komoike Y et al (2001) Combination technique is superior to dye alone in identification of the sentinel node in breast cancer patients. J Surg Oncol 76:95–99. https://doi.org/10.1002/1096-9098(200102)76:2<95:aid-jso1018>3.0.co;2-d

    Article  CAS  PubMed  Google Scholar 

  7. Simsek O, Belli AK, Aydogan F et al (2018) Combination technique is superior to dye alone in identification of the sentinel lymph node in male breast cancer. Am Surg 84:1957–1960

    PubMed  Google Scholar 

  8. Mansel RE, Fallowfield L, Kissin M et al (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 98:599–609. https://doi.org/10.1093/jnci/djj158

    Article  PubMed  Google Scholar 

  9. Goyal A, Newcombe RG, Chhabra A et al (2006) Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer–results of the ALMANAC validation phase. Breast Cancer Res Treat 99:203–208. https://doi.org/10.1007/s10549-006-9192-1

    Article  PubMed  Google Scholar 

  10. Seenu V, Suhani S, Srivastava A et al (2019) Optimization of sentinel lymph node identification techniques in the Indian setting: a randomized clinical trial. Indian J Cancer 56:114. https://doi.org/10.4103/ijc.IJC_163_18

    Article  CAS  PubMed  Google Scholar 

  11. Nagaya T, Nakamura YA, Choyke PL, Kobayashi H (2017) Fluorescence-guided surgery. Front Oncol. https://doi.org/10.3389/fonc.2017.00314

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dan AG, Saha S, Monson KM et al (2004) 1% Lymphazurin vs 10% fluorescein for sentinel node mapping in colorectal tumors. Arch Surg 139:1180–1184. https://doi.org/10.1001/archsurg.139.11.1180

    Article  CAS  PubMed  Google Scholar 

  13. Fluorescein for lymphatic mapping and sentinel lymph node (SLN) Biopsy in patients with stage I and II malignant melanoma—study results—ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT00847522. Accessed 10 Apr 2020

  14. Srivastava A, Badwe RA, Prem A et al (2015) Abstract P2–01-31: Sentinel node mapping with fluorescein and comparison with methylene blue and technitium sulphur colloid in early breast cancer. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS14-P2-01-31

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kersey TW, Van Eyk J, Lannin DR et al (2001) Comparison of intradermal and subcutaneous injections in lymphatic mapping. J Surg Res 96:255–259. https://doi.org/10.1006/jsre.2000.6075

    Article  CAS  PubMed  Google Scholar 

  16. Agarwal G, Rajan S, Gambhir S et al (2016) A Comparative validation of primary surgical versus post-neo-adjuvant chemotherapy sentinel lymph node biopsy for stage III breast cancers. World J Surg 40:1583–1589. https://doi.org/10.1007/s00268-015-3222-2

    Article  PubMed  Google Scholar 

  17. Agarwal G, Rajan S, Mayilvaganan S et al (2018) Prospective randomized trial of use of in-house prepared low-cost radiopharmaceutical versus commercial radiopharmaceutical for sentinel lymph node biopsy in patients with early stage invasive breast cancer. World J Surg 42:1391–1395. https://doi.org/10.1007/s00268-018-4504-2

    Article  PubMed  Google Scholar 

  18. Li J, Chen X, Qi M, Li Y (2018) Sentinel lymph node biopsy mapped with methylene blue dye alone in patients with breast cancer: a systematic review and meta-analysis. PLoS ONE 13:e0204364. https://doi.org/10.1371/journal.pone.0204364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Parmar V, Hawaldar R, Nadkarni MS, Badwe RA (2009) Low axillary sampling in clinically node-negative operable breast cancer. Natl Med J India 22:234–236

    CAS  PubMed  Google Scholar 

  20. Tandon P (2010) Regulatory requirements for designing PET–CT facility in India. Indian J Nucl Med IJNM Off J Soc Nucl Med India 25:39–43. https://doi.org/10.4103/0972-3919.72684

    Article  Google Scholar 

  21. Sharma AR (2018) Nuclear medicine in India: a historical journey. Indian J Nucl Med 33:5. https://doi.org/10.4103/0972-3919.245053

    Article  Google Scholar 

  22. Agarwal G, Ramakant P, Forgach ERS et al (2009) Breast cancer care in developing countries. World J Surg 33:2069–2076. https://doi.org/10.1007/s00268-009-0150-z

    Article  PubMed  Google Scholar 

  23. Ushadevi JS, Rajaraman R, Subbaih S (2017) Assessment of sentinel nodes with methylene blue dye in carcinoma breast is feasible? A Pilot Study 5:5

    Google Scholar 

  24. Rao JS, Ramesh R (2019) Peri-areolar administration of methylene blue dye as an independent, cost effective and reliable technique for sentinel lymph node biopsy in early breast cancer. Clin Oncol 4:4

    Google Scholar 

  25. Agarwal G, Gambhir S, Kheruka S et al (2005) Low-cost sentinel node studies in breast cancer with indigenous blue dye & 99mTc-Antimony colloid (The 105th Annual Congress of Japan Surgical Society). J Jpn Surg Soc 106:580

    Google Scholar 

  26. Goyal A (2018) New technologies for sentinel lymph node detection. Breast Care 13:349–353. https://doi.org/10.1159/000492436

    Article  PubMed  PubMed Central  Google Scholar 

  27. Goonawardena J, Yong C, Law M (2020) Use of indocyanine green fluorescence compared to radioisotope for sentinel lymph node biopsy in early-stage breast cancer: systematic review and meta-analysis. Am J Surg. https://doi.org/10.1016/j.amjsurg.2020.02.001

    Article  PubMed  Google Scholar 

  28. Guo J, Yang H, Wang S et al (2017) Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study. World J Surg Oncol. https://doi.org/10.1186/s12957-017-1264-7

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mok CW, Tan S-M, Zheng Q, Shi L (2019) Network meta-analysis of novel and conventional sentinel lymph node biopsy techniques in breast cancer. BJS Open 3:445–452. https://doi.org/10.1002/bjs5.50157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Srivasatava A, Suresh J, Ranjan P et al (2018) Abstract PD203: sentinel lymph node mapping with dual tracer combination: fluorescent fluorescein with methylene blue compared to radio active sulphur colloid with methylene blue: a randomised comparison. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS17-PD2-03

    Article  Google Scholar 

  31. Chang YW, Lee HY, Lee CM et al (2020) Sentinel lymph node detection using fluorescein and blue light-emitting diodes in patients with breast carcinoma: A single-center prospective study. Asian J Surg 43:220–226. https://doi.org/10.1016/j.asjsur.2019.03.005

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This prospective study was partly supported from a MCh student research grant from the Indian Council of Medical Research. The authors would like to acknowledge help from the Resident Surgeons of the Department of Endocrine and Breast Surgery, SGPGIMS, Lucknow; and Professor Anurag Srivastava of the All India Institute of Medical Sciences, New Delhi, for his inputs relating the methodology of the study and for critically reviewing this manuscript.

Author information

Author notes

  1. Ramya C Valiveru and Gaurav Agarwal are joint first authors, having contributed equally.

Authors and Affiliations

  1. Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebareli Road, Lucknow, Uttar Pradesh, 226014, India

    Ramya C. Valiveru, Gaurav Agarwal, Sabaretnam Mayilvaganan, Gyan Chand, Anjali Mishra, Amit Agarwal & Saroj K. Mishra

  2. Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India

    Vinita Agrawal

  3. Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India

    Sanjay Gambhir

Authors
  1. Ramya C. Valiveru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaurav Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vinita Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sanjay Gambhir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sabaretnam Mayilvaganan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gyan Chand
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anjali Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amit Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Saroj K. Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gaurav Agarwal.

Ethics declarations

Conflict of interest

None.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Ethical approval

The study was approved by the Institute Ethics Committee, SGPGIMS, Lucknow, India on 3rd April 2018. (IEC code: 2018-36-MCh-102).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This work was awarded the Breast Surgery International (BSI) Best poster award at the World Congress of Surgery, Krakow, Poland, in August 2019.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Valiveru, R.C., Agarwal, G., Agrawal, V. et al. Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy—a Prospective Validation Study in Early Breast Cancer. World J Surg 44, 3417–3422 (2020). https://doi.org/10.1007/s00268-020-05631-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-020-05631-x

Search

Navigation