Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study
Guo et al. World Journal of Surgical Oncology
Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study
Jiajia Guo 0
Houpu Yang 0
0 Equal contributors Peking University People's Hospital Breast Center , NO 11, Xizhimen South Street, Xicheng District, Beijing 10044 , People's Republic of China
Background: Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy. Methods: A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated. Results: Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ2 = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis. Conclusions: The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods. Trial registration: ACTRN12612000109808. Retrospectively registered on 23 January 2012.
Breast neoplasm; Indocyanine green; Sentinel lymph node biopsy; Lymphography
Knowledge of the regional lymph node status is essential
to establishing staging and prognostic outcomes of
breast cancer. Axillary lymph node staging by sentinel
lymph node biopsy (SLNB) is a widely used method and
is now regarded as a standard of care in patients without
clinical evidence of axillary lymph node metastasis in
early breast cancer [
The existing standard SLNB method is a dual
technique involving the injection of a technetium-99m
(99mTc)-labeled nanocolloid and blue dye [
]. Despite the
reports of effectiveness and good safety data, the
involvement of radioisotopes creates logistical challenges,
including isotope handling and disposal, staff training,
and legislative requirements, as well as the reluctance of
patients and personnel to be exposed to radiation.
Constraints of radioisotopes have led to the development of
non-radioactive alternative methods. Quite a few
institutions have attempted to perform SLNB using blue dye
]. As an alternative dye tracer, methylene blue
(MB) does not have the restrictions of isosulfan blue and
patent blue, such as life-threatening anaphylaxis and
international shortage. The MB alone method has gained
widespread popularity worldwide, especially in
developing countries like China [
]. However, some
investigators maintained that the use of blue dye alone leads to
a lower SLN identification rate , which might draw
concerns about the potential adverse impact on
longterm prognosis [
SLNB with near-infrared (NIR) fluorescence imaging
using indocyanine green (ICG) was recently introduced
and was reported to be a highly sensitive method for
SLN detection [
]. In this method, ICG is injected,
and its progress through the lymphatic ducts to SLNs is
tracked using an excitation illumination system
combined with a high-sensitivity camera that detects the
emitted fluorescence. As NIR could be transcutaneously
detected similar to radioactive agents, the combination
of ICG and MB shows great potential as an alternative
to standard dual mapping methods [
we designed the present prospective study to evaluate
whether combining ICG and MB could improve the
SLN tracing performance in early breast cancer patients.
Between January 2010 and March 2013, a total of 198
consecutive patients (196 with unilateral cancers and 2
with bilateral disease) with early breast cancer, as
confirmed by core needle biopsy or open biopsy, and
clinically negative axillas were enrolled in the present study.
The present study was approved by the Ethical
Committee of Peking University People’s Hospital, Beijing and
was registered as the Australian and New Zealand
Clinical Trials Registry No 12612000109808. Patients
with tumors > 5 cm, clinically or radiologically
suspicious lymph nodes, inflammatory breast cancer, distant
metastatic tumor, previous axillary surgery, or
hypersensitivity to iodine or indocyanine green were excluded
from the study. Written informed consent was obtained
from all patients.
MB (Jizhou Pharmaceutical, Suzhou, China) was diluted
to a final concentration of 1% with saline from an
original concentration of 2%. The ICG (Dandong
Pharmaceutical, Jilin, China) agent used in this study included
iodine. Twenty-five milligrams of stock ICG powder was
dissolved in 10 ml of distilled water and was then diluted
to a final concentration of 0.05%. Immediately before
surgery, 1 ml of 1% MB was subdermally injected into
the periareolar region. Five minutes later, 1 ml of ICG
solution (1.25 mg) was intradermally injected into two
to four sites in the same periareolar area region. The
movement of the tracer in the periareolar region was
facilitated by massage. ICG fluorescence was stimulated
and detected by a hand-held fluorescence detector
(MingDe Medicine, China, elicitation wavelength of 780 nM
and acquisition wavelength of 735 nM). The lymphatic
drainage was traced by fluorescence navigation and
visualized on a monitor in real time. The fluorescent signal
was followed from the injection sites to the axilla
(occasionally to the intramammary region), and an incision
was made to start the SLNB where the fluorescence
disappeared. Fluorescent lymph nodes (ICG-positive) and/
or blue nodes (MB-positive) were localized and excised.
Then, the axilla was inspected for residual fluorescent or
blue nodes. The excised nodes were categorized as
fluorescent+/blue+, fluorescent+/blue-, or fluorescent−/blue
+. All removed nodes were sent for histological
examination following an institutional standard protocol.
Patients with positive SLNs underwent axillary clearance,
and benign axillas were spared.
Adverse events, including skin lesions, allergic
reactions and any other complication considered to be
caused by the tracers, were recorded in indicated cases
according to patients’ complaint, physical examination,
and imaging tests.
Study design and statistical analysis
The trial was composed to evaluate whether the ICG +
MB modality was superior to MB alone in terms of its
ability to detect SLNs.
The detection rate was calculated by the number of
successful mappings divided by the total number of
mapping cases performed for each modality. To estimate
the number of samples, we assumed a detection rate of
85% for the control method (dye alone) [
] and set δ at
5%. We found that 200 procedures were needed to
demonstrate superiority between the two methods with a
power of 80% and a significance (α) of 5%. The
calculation was performed by using PASS 11 software (NCSS,
LLC. Kaysville, Utah, USA).
For statistical analysis, SAS software (version 9.2) was
used. A chi-square test was used to compare the
detection rates. To compare the median number of SLNs
between groups, a non-parametric Mann-Whitney U test
Patient and tumor characteristics are shown in Table 1.
Transcutaneous fluorescent lymphography was visible in
184 breasts. A routine incision used in dye-guided SLNB
in the armpit was made in the other 16 procedures.
When the skin and subdermal fat were incised,
fluorescent lymph nodes could be successfully detected in 194
axillas, including 15 cases with no visible fluorescent
flow in the skin (Fig. 1).
Nodal identification performance
The detection rates of the tracer agents are shown in
Table 2. The overall SLN detection rates for the ICG
and dual methods were 97 and 99.5%, respectively, while
the detection rate for dye alone was 89% (χ2 = 26.2,
p < 0.001). The difference between the ICG + MB
tracing modality and MB alone was therefore 10.5%. The
95% confidence interval (CI) for this difference was 6.1
to 14.9%. Since this CI does not include the superiority
margin of 5%, we are powered to reject the null
hypothesis and conclude that the combination of ICG and MB
is superior to MB alone.
An age ≥ 50, a BMI ≥ 25, an outer upper quadrant
tumor and a larger tumor size were associated with a
reduced detection rate for the MB alone method but not
for the ICG or combination method.
A total of 616 SLNs were detected by one or both
methods. The median numbers of SLNs detected by the
ICG (fluorescent−/blue−), MB alone (fluorescent−/blue
+), and the combination methods (fluorescent+/blue+)
were 3 (range 1–8), 2 (range 1–6), and 3 (range 1–8),
respectively. The median numbers of SLNs identified by
the ICG and combination methods were significantly
higher than those identified by MB alone (p < 0.001).
Fifty-eight nodes out of 616 SLNs contained
metastases. Twenty nodes were fluorescent, 4 were blue, and 34
were double-positive (Table 3), and the numbers of
axillary nodes diagnosed by each modality were 10, 2, and
32, respectively. Hence, 22.7% positive axillas would have
been missed if the dye only method had been the sole
method used in this cohort.
No acute or chronic allergic reactions were observed in
this study. A total of 148 patients reported colored urine,
most of which disappeared in 24 h. Twenty-three
patients (23/82) who received breast-conserving therapy
reported temporary skin staining, which was a
complication of both ICG and MB, and only five patients had
permanent tattooing (we defined “permanent” as skin
pigmentation ≥ 6 months), which was due to the
injection of MB. Although palpable subcutaneous nodules,
probably due to fat necrosis at the injection sites, were
reported in nine patients, no patient needed a diagnostic
biopsy, and there were no reports of skin necrosis.
This was a prospective study to assess whether the
addition of the promising ICG method to the widely
used MB dye method improved the SLN identification
performance in patients with early breast cancer. We
conclude that the detection rate of the fluorescence and
dye combination was significantly higher than that of
the MB dye alone (99.5 vs. 89%). This result is consistent
with previous studies [
Detection rate (%)
The high identification rate and accurate diagnosis
performance of the ICG + MB modality provide the
possibility of a non-radioactive alternative method for dual
tracing of SLNs. It would be fairly attractive to abandon
the use of radioactive agents, especially in institutes
where radioisotopes are not readily available. Ballardini
B. from the European Institute of Oncology reported a
trial comparing ICG with a 99mTc-labeled radiotracer in
134 patients. This equivalently designed study was
powered to demonstrate that the ICG method yielded a high
detection rate of SLNs that was not inferior to that of
]. Although Ahemd M. subsequently
criticized the absence of a standard dual mapping technique
in Ballardini B’s study [
], replacing the radiotracer with
ICG showed promise. A recent meta-analysis performed
by Sugie T. [
] confirmed this assumption. Since the
current study was designed as a superiority trial with δ
set at 5%, we can draw the conclusion from the positive
results that the combined use of ICG and MB is more
effective than dye alone, as we observed an increase in
the detection rate by 10.5%, or in other words, a 5%
improvement, which is comparable to the difference
between standard radioisotope included method and dye
]. Although there were few studies that
compared the identification performance of ICG with
standard radiotracer and dye combination method directly,
the combined use of ICG and dye is deemed to be the
most likely alternative to the current standard.
In addition to the detection performance
improvement, ICG may bring accuracy benefits. First and
foremost, the extreme sensitivity of ICG contributed to the
harvest of extra SLNs that were undetected by the dye.
In the current study, the median number of the SLNs
detected by ICG + MB was 3, which was greater than
that of SLNs detected by MB alone. Similar results were
also found in previous studies [
18, 21, 27, 28
]. Results of
two meta-analyses revealed that acceptably more SLNs
(three to four nodes) were related to a higher detection
rate and a more accurate prognosis, whereas only one
SLN was found to not adequately represent the axillary
]. Since ICG detected more SLNs, we
speculated that the higher sensitivity of ICG was due to its
higher visibility via the high-resolution near-infrared
equipment in contrast with the perception of dye uptake
via the naked eye and that this higher visibility might
improve the detection rate of positive nodes. As a
consequence, identification of additional positive SLNs missed
by the dye method may elevate the accuracy of the
biopsy procedure. The present trial demonstrated that
adding ICG to MB tracing might contribute to avoiding
a false-negative assessment of the axillary status in
22.7% of patients. However, the potential benefits should
be confirmed by randomized trials.
As reported before, ICG-guided SLNB had several
limitations. For example, the tissue penetration capacity of
NIR fluorescence is lower than that of gamma rays. One
concern is that the limitation of penetration distance of
ICG based tracing would result in worse performance in
obese patients. Though no axillary skin compression
technique used in the current study which was reported
by Kitai [
], we found no significant difference between
obese patients (BMI ≥ 25) and non-obese patients.
According to Grischke’s research, there was no difference
in the detection rate when a cut-off of BMI ≥ 30, or ≥ 35
were used, whereas detection with ICG was only difficult
in patients when BMI > 40 [
]. As shown by our study,
patients with very high BMI were rare in China. Hence,
this limitation would not be an obstacle to the clinical
use of ICG. Fluorescence quenching effect was another
point regarding the efficacy of ICG navigation. It was
reported that the ICG exhibited intense quenching (i.e.,
Detected positive nodes
reduction of fluorescence emission) as its concentration
was increased. Based on their results of a small cohort,
Mieog recommended an injection dose of 0.62 mg as an
optimal dose for ICG [
]. However, several studies that
reported varied doses (between 0·625 and 15 mg in a
volume of between 1 and 5 ml) yielded similarly high
detection rates [
]. There was no consensus on the
optimal dose of ICG. Based on the lymphatic visibility, we
chose 1.25 mg in 1 ml as our injection dose. The
excellent navigation performance indicated that this dose was
clinically acceptable. Adverse effects such as sensitive
reaction and skin lesion are the primary concerns
regarding the safety of dye-based mapping [
]. In this
cohort, we found no allergic cases. Interstitial use in
lymph mapping rather than intravenous injection may
be the main cause of the fewer instances of allergic
reaction. Moreover, absence of an allergic reaction may be
due to the exclusion of iodine hypersensitive patients.
The main dermal complications included temporary skin
staining, permanent tattooing, and subcutaneous
nodules at the injection sites. Although these skin
complications may lead to certain degrees of anxiety in stressed
patients, these complications would be acceptable to
most patients. The relatively good safety results were
similar to results from previous meta-analyses [
The current study had two shortcomings. First, we did
not compare the ICG + MB method to the 99mTc + MB
method. However, the excellent performance of this dual
mapping method might be indirectly confirmed by a
superiority test at 5%. Furthermore, regardless of the
benefits of self-controlled design, including elimination of
individual variation, decreased sample size, and good
statistical efficiency, confounding bias may occur. In this
setting, after all fluorescent nodes have been detected,
surgeons might tend to end the procedure rather than
work so hard to search for more blue nodes. This might
result in an underestimation of the efficacy of MB and
an overestimation of the performance difference.
In summary, this study reveals a high detection rate of
ICG and the superiority of combining ICG fluorescence
with blue dye in early breast cancer detection strategies. It
is proposed that a combination of ICG fluorescence and
blue dye (MB) method can be used in centers where
radioactive agents are unavailable. Furthermore, for the
excellent performance of this novel dual tracing modality,
a better non-radioactive substitute for the combination of
radioisotope and blue dye beckons.
The lymphatic navigation by ICG fluorescence detects
SLNs at a high detection rate and improves the mapping
performance when added to the dye method. The novel
ICG + MB dual tracing modality, without involvement
of radioactive isotopes, exhibits great potential as an
alternative to traditional standard mapping methods.
99mTc: Technetium-99m; BMI: Body mass index; CI: Confidence interval;
ICG: Indocyanine green; MB: Methylene blue; NIR: Near-infrared; SLN: Sentinel
lymph node; SLNB: Sentinel lymph node biopsy
This study was sponsored by the Capital Medical Development Scientific
Research Fund (2014-2-4083). The funding body did not participate in the
design of the study; the collection, analysis, and interpretation of data; or the
writing of the manuscript.
Availability of data and materials
Please contact the corresponding author for data requests.
JG participated in the study design and coordination and participated in the
data analysis. HY participated in the study design, data collection, and data
analysis and participated in drafting the manuscript. Shu Wang conceived
the study and participated in its design and coordination. YC, ML, FX, PL, BZ,
FT, LC, HL, and SW participated in the clinical study implementation and
data collection. All authors read and approved the final manuscript.
Ethics approval and consent to participate
This study was approved by the Ethical Committee of Peking University
People’s Hospital, Beijing. Written informed consent from all patients was
obtained before the operation. No individual data were contained in this
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
1. Lyman GH , Somerfield MR , Giuliano AE . 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 . 2017 ; 13 : 196 - 8 .
2. Giammarile F , Alazraki N , Aarsvold JN , Audisio RA , Glass E , Grant SF , Kunikowska J , Leidenius M , Moncayo VM , Uren RF , et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer . Eur J Nucl Med Mol I . 2013 ; 40 : 1932 - 47 .
3. Eser M , Kement M , Kaptanoglu L , Gecer M , Abamor E , Tutal F , Balin S , Kurt N , Uzun H. A prospective comparative study to assess the contribution of radioisotope tracer method to dye-only method in the detection of sentinel lymph node in breast cancer . BMC Surg . 2013 ; 13 : 13 .
4. Radovanovic Z , Golubovic A , Plzak A , Stojiljkovic B , Radovanovic D. Blue dye versus combined blue dye-radioactive tracer technique in detection of sentinel lymph node in breast cancer . Eur J Surg Oncol . 2004 ; 30 : 913 - 7 .
5. Meyer-Rochow GY , Martin RC , Harman CR . Sentinel node biopsy in breast cancer: validation study and comparison of blue dye alone with triple modality localization . ANZ J Surg . 2003 ; 73 : 815 - 8 .
6. Ang CH , Tan MY , Teo C , Seah DW , Chen JC , Chan MY , Tan EY . Blue dye is sufficient for sentinel lymph node biopsy in breast cancer . Br J Surg . 2014 ; 101 : 383 - 9 .
7. Zaazou M , Mahran K , Merhem I. Sentinel lymph node biopsy using methylene blue dye in early breast cancer . Is it truly reliable? Egypt J Surg . 2010 ; 29 : 132 - 6 .
8. Mathelin C , Croce S , Brasse D , Gairard B , Gharbi M , Andriamisandratsoa N , Bekaert V , Francis Z , Guyonnet JL , Huss D , et al. Methylene blue dye, an accurate dye for sentinel lymph node identification in early breast cancer . Anticancer Res . 2009 ; 29 : 4119 - 25 .
9. Zakaria S , Hoskin TL , Degnim AC . Safety and technical success of methylene blue dye for lymphatic mapping in breast cancer . Am J Surg . 2008 ; 196 : 228 - 33 .
10. Varghese P , Abdelrahman A , Akberali S , Mostafa A , Gattuso J , Carpenter R . Methylene blue dye: a safe and effective alternative for sentinel lymph node localisation . Eur J Surg Oncol . 2007 ; 33 : 1134 .
11. Blessing WD , Stolier AJ , Teng SC , Bolton JS , Fuhrman GM . A comparison of methylene blue and lymphazurin in breast cancer sentinel node mapping . Am J Surg . 2002 ; 184 : 341 - 5 .
12. Hung WK , Chan CM , Ying M , Chong SF , Mak KL , Yip AW . Randomized clinical trial comparing blue dye with combined dye and isotope for sentinel lymph node biopsy in breast cancer . Br J Surg . 2005 ; 92 : 1494 - 7 .
13. Niebling MG , Pleijhuis RG , Bastiaannet E , Brouwers AH , van Dam GM , Hoekstra HJ . A systematic review and meta-analyses of sentinel lymph node identification in breast cancer and melanoma, a plea for tracer mapping . Eur J Surg Oncol . 2016 ; 42 : 466 - 73 .
14. Ahmed M , Purushotham AD , Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review . Lancet Oncol . 2014 ; 15 : e351 - 62 .
15. Tagaya N , Yamazaki R , Nakagawa A , Abe A , Hamada K , Kubota K , Oyama T. Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer . Am J Surg . 2008 ; 195 : 850 - 3 .
16. Kitai T , Inomoto T , Miwa M , Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer . Breast Cancer . 2005 ; 12 : 211 - 5 .
17. Chiu CC . Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence ( Br J Surg 2009 ; 96 : 1289 - 1294 ). Br J Surg . 2010 ; 97 : 455 - 6 .
18. Murawa D , Hirche C , Dresel S , Hunerbein M. Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence . Br J Surg . 2009 ; 96 : 1289 - 94 .
19. Xiong L , Gazyakan E , Yang W , Engel H , Hunerbein M , Kneser U , Hirche C. Indocyanine green fluorescence-guided sentinel node biopsy: a metaanalysis on detection rate and diagnostic performance . Eur J Surg Oncol . 2014 ; 40 : 843 - 9 .
20. McMasters KM , Tuttle TM , Carlson DJ , Brown CM , Noyes RD , Glaser RL , Vennekotter DJ , Turk PS , Tate PS , Sardi A . Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multiinstitutional practice when optimal technique is used . J Clin Oncol . 2000 ; 18 : 2560 - 6 .
21. Sugie T , Sawada T , Tagaya N , Kinoshita T , Yamagami K , Suwa H , Ikeda T , Yoshimura K , Niimi M , Shimizu A , Toi M. Comparison of the indocyanine green fluorescence and blue dye methods in detection of sentinel lymph nodes in early-stage breast cancer . Ann Surg Oncol . 2013 ; 20 : 2213 - 8 .
22. Hirano A , Kamimura M , Ogura K , Kim N , Hattori A , Setoguchi Y , Okubo F , Inoue H , Miyamoto R , Kinoshita J , et al. A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients . Ann Surg Oncol . 2012 ; 19 : 4112 - 6 .
23. Ballardini B , Santoro L , Sangalli C , Gentilini O , Renne G , Lissidini G , Pagani GM , Toesca A , Blundo C , Del Castillo A , et al. The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: a concordance and validation study . Eur J Surg Oncol . 2013 ; 39 : 1332 - 6 .
24. Ahmed M , Douek M. What is the clinical relevance of discordance between radioisotope alone and indocynanine green in sentinel lymph node biopsy for breast cancer ? Eur J Surg Oncol . 2014 ; 40 : 786 .
25. 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 . 2017 ; 22 : 11 - 7 .
26. O Hea BJ , Hill AD , El-Shirbiny AM , Yeh SD , Rosen PP , Coit DG , Borgen PI , Cody HS 3rd. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center . J Am Coll Surg . 1998 ; 186 : 423 - 7 .
27. Hojo T , Nagao T , Kikuyama M , Akashi S , Kinoshita T . Evaluation of sentinel node biopsy by combined fluorescent and dye method and lymph flow for breast cancer . Breast . 2010 ; 19 : 210 - 3 .
28. Hirche C , Murawa D , Mohr Z , Kneif S , Hunerbein M. ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer . Breast Cancer Res Treat . 2010 ; 121 : 373 - 8 .
29. Yi M , Meric-Bernstam F , Ross MI , Akins JS , Hwang RF , Lucci A , Kuerer HM , Babiera GV , Gilcrease MZ , Hunt KK . How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer ? CancerAm Cancer Soc . 2008 ; 113 : 30 - 7 .
30. Ban EJ , Lee JS , Koo JS , Park S , Kim SI , Park BW . How many sentinel lymph nodes are enough for accurate axillary staging in t1-2 breast cancer ? J Breast Cancer . 2011 ; 14 : 296 - 300 .
31. Kitai T , Kawashima M. Transcutaneous detection and direct approach to the sentinel node using axillary compression technique in ICG fluorescencenavigated sentinel node biopsy for breast cancer . Breast Cancer . 2012 ; 19 : 343 - 8 .
32. Grischke EM , Röhm C , Hahn M , Helms G , Brucker S , Wallwiener D. ICG fluorescence technique for the detection of sentinel lymph nodes in breast cancer: results of a prospective open-label clinical trial . Geburtsh Frauenheilk . 2015 ; 75 : 935 - 40 .
33. Mieog JSD , Troyan SL , Hutteman M , Donohoe KJ , van der Vorst JR , Stockdale A , Liefers G , Choi HS , Gibbs-Strauss SL , Putter H , et al. Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer . Ann Surg Oncol . 2011 ; 18 : 2483 - 91 .
34. Wolf S , Arend O , Schulte K , Reim M. Severe anaphylactic reaction after indocyanine green fluorescence angiography . Am J Ophthalmol . 1992 ; 114 : 638 - 9 .
35. Stradling B , Aranha G , Gabram S. Adverse skin lesions after methylene blue injections for sentinel lymph node localization . Am J Surg . 2002 ; 184 : 350 - 2 .