Reviewer ’s report  
Title: Comparison of the indocyanine green dye method versu s the combined method of indigo 
carmine blue dye with indocyanine green fluorescence imaging for sent inel lymph node biopsy 
in breast conservative therapy for stage ≤IIA breast cancer  
 
Version: 0 Date: 27 Feb 2018  
 
Reviewer: Benjamin Calhoun  
 
Reviewer's report:  
This is a well organized and well conducted study of over 200 patient's almost evenly spli t 
between 2 different methods of sentinel lymph node identification. One of the strength of the 
study is the experience of the surgeons and pathologists involved. It should be noted that one 
surgeon either performed and assisted in all of the sentinel lymp h node biopsy procedures, 
presumably providing some consistency in the technical performance. It should also be noted 
that there were no axillary lymph node recurrences in either group patients in this study. The 
goals and the methods of the study are clea r. The patients were appropriately selected for 
inclusion in the study. The results are clear and well presented. The study is relevant to 
contemporary practice and addresses an issue of great importance in providing care for breast 
cancer patients.  
 
Abstract, Conclusion, line 39: While it does seem likely that radiation exposure may be avoided, 
this study only compares fluorescent dye to a combination of fluorescent dye and conventional 
blue dye. This is not a head to head comparison of combined mixed  dye and florescence (CMF) 
and localization with a radioisotope.  
 
Introduction, line 26: The combination of a radioisotope and blue dye has been shown to be 
highly effective in the identification of sentinel lymph nodes. Is the radiation dose to the patie nt 
significant and harmful? Avoiding radiation exposure seems reasonable. Perhaps a more 
important point is that the fluorescent dye or CMF approach allow sentinel lymph node biopsy to 
be performed and facilities that do not have nuclear medicine. However facilities that use and 
approach with the fluorescent dye would need to purchase the appropriate equipment (PDE etc) 
to use this method.  
 
Introduction, line 51: Has florescence ICG been shown to be equivalent or superior to the 
combination of radioisotope and blue dye? The combination allows identification of sentinel 
lymph nodes that may not been identified with either the radioisotope or the blue dye alone.  
 
CMF method, page 6, line 13: The combination of fluorescent dye and blue dye appears to 
identify s entinel lymph nodes that may not be identified with either method by itself, similar to 
the combination of radioisotope and blue dye. The case referenced here suggests that blue dye 
alone is not the best option for sentinel lymph node identification. It ap pears that blue dye should 
be used in combination either with a radioisotope or a fluorescent dye for optimal sentinel lymph 
node identification.  
 
Methods, page 5, line 8: "herceptine score" should be changed to HER2 immunohistochemistry 
or HER2 FISH depen ding on which method was used  
 
Results, page 7, lines 49 -59: Based on these data it seems important to continue to use blue dye 
in any method for sentinel lymph node identification and this may be especially true for patients 
with sentinel lymph node metas tasis. The fact that 5 -6% of CMF cases required intraoperative 
PDE to detect sentinel lymph nodes seems to reinforce the idea that a combined dye approach is 
best. 
 
Discussion, page 8, line 17 -19: Has the fluorescence method been shown to be equivalent or 
superior to the combination of blue dye and a radioisotope? It seems that the "conventional" 
method is still a combination of blue dye and radioisotope. Should the authors be using the word 
"conventional" here? The same question could apply to line 48 on t he same page.  
 
Discussion, page 9, lines 17 -19: Expand the discussion and comparison of ICG -D, CMF, and 
accommodation of radioisotope and dye. How comparable are they? Are they essentially 
equivalent? Is there a method this still provides superior identifi cation of sentinel lymph nodes?  
Discussion, page 10, lines 1 -11: The gold standard would be a backup axillary dissection in cases 
with sentinel lymph node identification by CMF. However, this seems extreme and beyond the 
scope of this study. The authors c ould comment on the fact that none of these patients had 
backup axillary dissections and the false negative rate, especially for clinically occult 
microscopic disease, has not been definitively established.  
 
Table 3, Methods, and Results: What happened in the patients who did not have a sentinel lymph 
node identified with ICG -D or CMF? Did they have full axillary dissections? If so what were the 
pathologic findings in those cases? What were the clinical and pathologic features of the cases in 
which a sentin el lymph node was not identified? Age, BMI, prior breast or axillary surgery?  
 
Figure 1 provides an excellent illustration of the techniques used in this study.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an a dditional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I am able to assess the statistics  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
 
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