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Year : 2019  |  Volume : 56  |  Issue : 3  |  Page : 269-270
 

Diagnostic application of patent blue V in sentinel lymph node biopsy for breast cancer – Is it time for a change?


1 Department of Breast Surgery, Royal Wolverhampton Hospital, Wolverhampton, UK
2 Department of Allergy and Immunology, Heart of England NHS Foundation Trust, Birmingham, UK
3 Department of Allergy and Immunology, Heart of England NHS Foundation Trust; Birmingham Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, UK

Date of Web Publication19-Jul-2019

Correspondence Address:
Raghavan Vidya
Department of Breast Surgery, Royal Wolverhampton Hospital, Wolverhampton
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_139_18

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 » Abstract 


Sentinel lymph node biopsy (SLNB) was introduced in the 1990s, as a minimally invasive procedure for staging the axilla with less morbidity to the traditional axillary lymph node dissection and is now standard management of the axilla in the early breast cancer. SLNB using the combined technique of blue dye and radioisotope is currently the recommended method for lymphatic mapping, and studies have shown high identification rates (IR) (>95%) and low false-negative rates (FNR) 5–10%. However, there are several reports raising awareness regarding patent blue V dye-induced peri-operative anaphylaxis. The main aim of this article is to highlight the emergence of patent blue dye as a new allergen and present evidence regarding the utility of alternative safer methods of evaluation of early breast cancer without compromising IR.


Keywords: Allergy, blue dye, breast cancer, sentinel node


How to cite this article:
Vidya R, Athwal R, Huissoon AP, Baretto RL, Thirumala Krishna M. Diagnostic application of patent blue V in sentinel lymph node biopsy for breast cancer – Is it time for a change?. Indian J Cancer 2019;56:269-70

How to cite this URL:
Vidya R, Athwal R, Huissoon AP, Baretto RL, Thirumala Krishna M. Diagnostic application of patent blue V in sentinel lymph node biopsy for breast cancer – Is it time for a change?. Indian J Cancer [serial online] 2019 [cited 2019 Dec 12];56:269-70. Available from: http://www.indianjcancer.com/text.asp?2019/56/3/269/263026




The evaluation of axillary status in patients with invasive breast cancer is paramount for assessing prognosis and stratifying adjuvant therapy. Sentinel lymph node biopsy (SLNB) was introduced in the 1990s to stage the axilla when preoperatively negative (clinically and imaging). This is a minimally invasive procedure for staging the axilla, with lesser morbidity, and is now considered the best practice in the management of early breast cancer.

SLNB using a combination of patent blue V (PBV) (patent blue dye; also called triphenylmethane dye or E131) and radioisotope is the currently recommended method for lymphatic mapping, and studies have shown high identification rates >95% and low false-negative rates of 5–10%.[1] However, there are several reports raising awareness regarding PBV-induced peri-operative anaphylaxis.

The main aim of this article is to highlight the emergence of patent blue dye as a new allergen and present evidence regarding the utility of alternative safer methods of evaluation of early breast cancer without compromising identification rates.

Anaphylaxis during general anesthesia (GA) is a serious event leading to severe cardio and/or respiratory arrest. It often leads to abandonment of the procedure and admission to intensive care, thus delaying a lifesaving surgical treatment. A large study in France reported neuromuscular blocking agents, antibiotics, and latex as leading allergens responsible for anaphylaxis during GA with PBV listed as a rare culprit (0.6% of immunoglobulin E [IgE]-mediated anaphylaxis).[2] In the first multicenter UK study [3] and a subsequent report,[4] we highlighted the emergence of PBV as a culprit allergen in 5–8% cases of near-fatal IgE-mediated anaphylaxis during GA. Allergic reactions to PBV pose serious challenges to the anesthetists. It can induce refractory anaphylaxis requiring prolonged inotropic support and interfere with oxygen saturation measurement, thus potentially delaying the identification of early signs of anaphylaxis and delivery of prompt treatment, which is crucial for a favorable outcome. Another important feature of PBV-induced anaphylaxis is the time lag (~15–30 minutes; 60 minutes in some cases) between administration of the dye and manifestation of early allergic signs.[5]

A recent study has highlighted that anaphylaxis during GA is more common than previously estimated in the United Kingdom.[6] In a large survey undertaken in Yorkshire, United Kingdom, Savic et al. reported 1 in 2297 cases, although this figure could be much higher (1 in 353) since a significant number of cases with relatively less severe clinical manifestations are not referred for specialist evaluation.

Are there safer alternatives to patent blue dye and what are the identification rates with other techniques?

First, methylene blue dye is worth considering. It is rarely implicated in allergic reactions and has comparable identification rates to blue dye when either used singly or in combination with a radioisotope.[7] Methylene blue is a small molecule and considered less allergenic.

Second, the use of radioisotope alone to avoid the blue-dye complications and problems with blue dye obscuring the surgical field has been studied. A randomized control trial demonstrated no advantage for dual agents in SLNB detection.[8] Although a recent systematic review showed a high identification rate for the combined approach (radioisotope and blue dye), there was no statistical significance post-neoadjuvant chemotherapy and it did not reduce false-negative rate in comparison to radioisotope alone. The use of radioisotope presents logistic challenges with respect to health and safety issues related to radiation.

Third, SLNB can also be performed by employing superparamagnetic iron oxide (SPIO) magnetic tracer injected into the breast and the use of a handheld magnetometer for detection during the procedure. The first trial to assess this method showed noninferiority in comparison to standard dual tracer. Several clinical trials have since evaluated this technique and a meta-analysis by Zada et al. showed identification rate of 97.1%, concluding that the magnetic technique was noninferior to the standard technique and a low false-negative rate at 8.4%.[9] These studies did report adverse reactions.

Fourth, there is increasing evidence to support the use of indocyanine green (ICG) fluorescence for SLN detection in early breast cancer. The near-infrared fluorescence imaging system utilizes the characteristic spectrum of ICG and imaging visualizes lymphatic flow and allows direct detection of axillary SLN. ICG appears to be safe with fewer allergic reactions (0.01% vs. 0.07–2.7% for blue dye). A systematic review of 12 studies assessed the diagnostic utility of ICG for SLN detection compared to radioisotope alone and showed no significance differences highlighting the former as an useful alternative.[10]

In conclusion, patent blue dye carries a real risk of triggering near-fatal refractory anaphylaxis during GA albeit in a small proportion of patients and is best avoided. Recent evidence favors alternative approaches for SLNB in breast cancer including SPIO, methylene blue, or ICG ± radioisotope without compromising identification rates. In conclusion, there are exciting novel alternatives to replace patent blue dye for sentinel node biopsy localization.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Ashikaga T, et al. National surgical adjuvant breast and bowel project. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: Results from the NSABP B-32 randomised phase III trial. Lancet Oncol 2007;8:881-8.  Back to cited text no. 1
    
2.
Mertes PM, Alla F, Tréchot P, Auroy Y, Jougla E; Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques. Anaphylaxis during anesthesia in France: An 8-year national survey. J Allergy Clin Immunol 2011;128:366-73.  Back to cited text no. 2
    
3.
Krishna MT, York M, Chin T, Gnanakumaran G, Heslegrave J, Derbridge C, et al. Multi-centre retrospective analysis of anaphylaxis during general anaesthesia in the United Kingdom: Aetiology and diagnostic performance of acute serum tryptase. Clin Exp Immunol 2014;178:399-404.  Back to cited text no. 3
    
4.
Baretto, RL, Beck S, Heslegrave J, Melchior C, Mohamed O, Ekbote A, et al. Validation of International consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective. Allergy 2017;72:2031-4.  Back to cited text no. 4
    
5.
Mertes PM, Malinovsky JM, Mouton-Faivre C, Bonnet-Boyer MC, Benhaijoub A, Lavaud F, et al. Anaphylaxis to dyes during the perioperative period: Reports of 14 clinical cases. J Allergy Clin Immunol2008;122:348-52.  Back to cited text no. 5
    
6.
Savic, LC, Kaura V, Yusaf M, Hammond-Jones AM, Jackson R, Howell S, et al. Incidence of suspected perioperative anaphylaxis: A multicenter snapshot study. J Allergy Clin Immunol Pract2015;3:454-5e1.  Back to cited text no. 6
    
7.
Simmons R, Thevarajah S, Brennan MB, Christos P, Osborne M. Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization. Ann Surg Oncol 2003;10:242-7.  Back to cited text no. 7
    
8.
O'Reilly EA, Prichard RS, Al Azawi D, Aucharaz N, Kelly G, Evoy D, et al. The value of isosulfan blue dye in addition to isotope scanning in the identification of the sentinel lymph node in breast cancer patients with a positive lymphoscintigraphy: A randomized controlled trial. Ann Surg 2015;262:243-8.  Back to cited text no. 8
    
9.
Zada A, Peek M, Ahmed M, Anninga B, Baker R, Kusakabe M, et al. Meta-analysis of sentinel lymph node biopsy in breast cancer using the magnetic technique. Br J Surg2016;103:1409-9.  Back to cited text no. 9
    
10.
Sugie T, Ikeda T, Kawaguchi A, Shimizu A, Toi M. Sentinel lymph node biopsy using indocyanine green fluorescence in early-stage breast cancer: A meta-analysis. Int J Clin Oncol 2016;22:11-7.  Back to cited text no. 10
    



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