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Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery PDF
Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery PDF
DOI 10.1245/s10434-016-5432-8
1
Department of Surgery, University of Vermont College of Medicine, Burlington, VT; 2Department of Surgery, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA; 3Department of Surgery, Yale University, New Haven,
CT; 4Department of Surgery, Mayo Clinic, Rochester, MN; 5Department of Surgery, University of Arkansas, Little Rock,
AR; 6Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; 7Department of Surgery, Cedars-
Sinai Medical Center, Los Angeles, CA
TABLE 1 Checklist of key steps for the sentinel lymph node biopsy procedure in breast cancer
Consider SLNB for all invasive breast cancer and cases of DCIS undergoing mastectomy
Utilize dual tracer (blue dye and radiocolloid) to optimize identification and reduce false negative rates, especially following neoadjuvant
therapy, prior breast/axillary surgery, or in patients with elevated BMI
Consider IV prophylaxis if blue dye utilized
Inject blue dye around tumor periphery, at the palpable edge of the biopsy cavity, or into the subareolar plexus
Inject radiocolloid peritumorally, intradermally, or into the subareolar plexus
Avoid injection into the tumor itself or into a seroma cavity
Consider lower dose or subareolar injection for tumors located in the axillary tail
Breast massage can be performed
Remove any suspicious palpable nodes
SLNB sentinel lymph node biopsy, DCIS ductal carcinoma in situ, BMI body mass index, IV intravenous
axillary lymph node dissection (ALND), as has been per- 0.5 mCi is injected the day of the surgery, or 2.5 mCi is
formed for isosulfan blue. Methylene blue is also injected the day before as the half-life for technetium-99 m
associated with side effects, including skin necrosis and sulfur colloid is 6 h. As with blue dye injection, technetium
induration, as well as reports of pulmonary edema and should not be injected directly into the tumor or into a
central nervous system reactions in patients who take seroma cavity. The ‘10 % rule’ is a guideline referring to
serotonin-acting medications.21–23 Side effects can be removal of all SLNs with counts over 10 % of the most
potentially minimized by diluting the methylene blue (1:7 radioactive node.26 Surgeons should confirm ex vivo
dilution; 1.25 mg/mL—0.5 cc of methylene blue mixed counts to limit falsely positive counts due to in vivo scatter.
with 3.5 cc of normal saline).24 Despite these issues, All nodes that qualify as sentinel nodes should be removed,
methylene blue is widely used and has become the ‘de not just the hottest nodes. A median of two to three SLNs
facto’ standard in the US because of difficulties obtaining are removed.27 Suspicious palpable nodes should also be
Lymphazurin and the cost of generic 1 % isosulfan blue removed for evaluation as a lymph node replaced with
dye [available from a single manufacturer (Mylan)]. Of tumor is not likely to absorb technetium.
note, isosulfan blue can be made by a compounded phar-
macy (utilized by one of the authors when Lymphazurin
was in short supply). TROUBLESHOOTING GUIDE FOR SLNB
When performing SLNB using blue dye only it is
important not to inject the dye into the tumor itself because No uptake of radioactive tracer in the axilla This
the lymphatics can be occluded by tumor. It is also important problem is seen most often when the radiotracer is injected
not to inject into a seroma cavity following an excisional into the breast parenchyma alone. The use of a small der-
biopsy as the seroma itself does not contain lymphatic mal injection of tracer greatly enhances the activity that
channels. Pericavitary injection is preferred to a subareolar reaches the axillary nodes.28 Some surgeons use the dermal
technique when upper outer quadrant excisions have already injection technique exclusively as it leads to smaller areas
been performed as the scar can obstruct lymphatic drainage of radioactivity diffusion; however, it should be noted that
from the nipple-areolar complex to the axilla, leading to a extra-axillary sites of drainage are rarely identified if only
failure of mapping. Breast massage can be performed for intradermal injections are used.29
approximately 5 min to dilate the breast lymphatics. The In cases where there is difficulty finding a pre-incision
axillary fascia is entered through an axillary incision. Some hot spot with a gamma probe, there are some potential
surgeons prefer the incision at the inferior border of the remedies. First, be sure the gamma probe is functioning and
axillary hair and extend medially to the edge of the pectoralis set to the appropriate settings to maximize the sensitivity of
major muscle. A careful search is made for blue lymphatic the audio feedback. If there is still difficulty identifying the
channels leading to blue-stained lymph nodes. All blue hot spot, the next step is to inject blue dye to increase the
lymph nodes and any lymph nodes at the end of a blue SLN identification rate. Often an SLN can still be identified
lymphatic channel are removed and designated as SLNs.25 after an incision has been made and the gamma probe is
The dye-filled tract is dissected to the first blue lymph node. placed into the axilla. Therefore, proceed with an incision in
If possible, the tract is followed proximally to the tail of the the axilla and re-evaluate the nodes with the gamma probe.
breast to ensure that the identified lymph node is the most This is especially true in patients with higher BMI. Another
proximal lymph node and thus the sentinel node. Care must technique involves injecting fluid into the site of the tech-
be taken to identify proximal blue nodes because the dye netium injection, using 10–40 mL of sterile saline or local
transit time is rapid and blue staining of distal, non-sentinel anesthetic. This increases the interstitial pressures, which
axillary lymph nodes is not uncommon.3 Failure to consider forces more tracer into the lymphatic channels. It is rec-
the node at the end of a blue lymphatic channel as a sentinel ommended to perform gentle massage at the injection site,
node whether or not the node itself appears blue, and failure after which the pre-incision hot spot is reassessed with the
to remove the most proximal blue lymph node(s), are the two gamma probe. This process may be repeated as needed if a
most common technical errors. Suspicious palpable nodes hot spot is still not identified.
should also be removed for evaluation as a lymph node Under circumstances of prior breast/axillary surgery or
replaced with tumor is not likely to take up the localizing dye. prior radiation therapy, lymphatic channels may be dis-
rupted, causing alternate drainage pathways to be formed.
Radiocolloid Method In these situations, a lymphoscintigraphy can be used
preoperatively to identify the appropriate drainage basin.
Radioactive tracer may be injected peritumorally, Using dual tracer with radiocolloid and blue dye can also
intradermally, or into the subareolar plexus. There is be considered. It is also important to palpate the axilla and
ongoing debate about the best site for injection. Typically, resect any palpable abnormal nodes as SLNs.
3462 T. A. James et al.
No uptake of radioactive
tracer inthe axilla
No
No
Intraoperative ultrasound may help identify nodes. If all to be sure that all of the ‘hottest’ nodes have been removed.
else fails, the default option is to proceed to ALND or If the remaining bed counts are uniform, with no ‘discreet’
axillary sampling; however, first consider how important areas of greater radioactivity found, and the bed count
the nodal staging information is and the likelihood of nodal remains over 10 %, then the surgeon need not remove any
positivity. For instance, not identifying an SLN in a T1a other nodes unless they are suspicious by palpation. Data
low-grade, estrogen receptor (ER) ? , human epidermal indicate that once four or five SLNs have been resected, the
growth factor receptor 2 (HER2) tumor in an older woman value of additional SLNs is extremely low.30,31 Some have
may not require an ALND. Figure 1 depicts the algorithm reported that taking three SLNs is sufficient,32 but this has
for troubleshooting no uptake of radioactive tracer. been controversial.33 Additional details for addressing this
Cannot achieve a residual bed count below 10 % of the situation are presented in Fig. 2.
most radioactive node In the event a surgeon is confronted Overlap between injection site and axilla (i.e., cannot
with a ‘high residual bed count’ in the axilla, it is important isolate sentinel node) The problem of overlap of the
Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery 3463
Consider
contacting the
nuclear medicine No Are you using unfiltered
department to use radioactive colloid?
unfiltered
Yes
radioactive colloid*
Angle gamma probe
Are you properly interrogating the No away from injection
axilla to reduce shine-through? site; consider using
collimator
Yes
Remove any node
No Is the bed count uniform with
with a count >10%
of the hottest no discrete hotter areas?
node
Yes
No Remove any
Have you palpated the axilla? suspicious palpable
If the previous steps lymph nodes
Yes
are completed and
the surgeon is still No Have 5 or more sentinel lymph
concerned, consider
nodes already been removed?
axillary ultrasound
to locate any lymph
Yes
nodes
It is uncommon that a
change in nodal status
will occur with
additional lymph node
resection
FIG. 2 Cannot achieve a residual bed count below 10 % of the most nodes. However, these smaller particles rapidly pass through sentinel
radioactive node. * Consideration for future patients. The larger nodes and label second and third echelon nodes in the basin. This
particles in the unfiltered solution are trapped better by the sentinel greatly complicates the surgeon’s ability to identify and remove only
lymph nodes. Filtered radioactive colloid is best when performing true sentinel nodes
lymphoscintigrams as it quickly identifies the first draining lymph
injection site diffusion zone with the axillary nodes is often to go to extra-axillary sites. The use of small volumes
an issue with tumors located in the upper outer quadrant limits the size of the diffusion zone, facilitating identifi-
and axillary tail of the breast. Utilizing a subareolar cation of the axillary hot spots. Both of these solutions
injection technique as opposed to a peritumoral injection require the surgeon to anticipate the problem prior to
increases the distance between injection site and axilla, injection. Additional potential solutions are illustrated in
minimizing the potential for overlap. There are an abun- Fig. 3.
dance of data in support of this technique.34 A second Radioactive node identified in the internal mammary site
potential solution to this problem is to limit the volume of Surgeons have debated the utility of dissecting nodes from
injection as much as possible. For tumors located in the the internal mammary (IM) chain, given the relative lack of
upper outer quadrant/axillary tail, this may be a good sit- familiarity with the procedure and the associated potential
uation in which to use small-volume intradermal injections risks (e.g. pneumothorax, bleeding). Current evidence
alone as it would be rare for lymphatic drainage in this area indicates that the prognostic significance of sentinel nodes
3464 T. A. James et al.
Overlap between
injection site and axilla
(i.e. cannot isolate
sentinel lymph node)
No
FIG. 3 Overlap between injection site and axilla (i.e., cannot isolate the sentinel lymph node). Note this problem may be anticipated for tumors
in the upper outer quadrant and avoided by using a subareolar injection or by limiting the injection volume
in the IM chain is similar to sentinel nodes in the axilla.35 is also critical since the surgeon cannot rely on a gamma
Other reports demonstrate the incidence of isolated positive probe signal to identify the location of the sentinel node.
IM nodes (i.e., without concurrent positive axillary SLNs) The incision should be made at the inferior border of the
to be low.36 Therefore, evidence suggests that the status of axillary hair and extend medially to the edge of the pec-
the axillary SLNs also reflect the status of the IM nodes in toralis major muscle instead of being centered within the
the vast majority of cases. Removal of the IM nodes may axilla.
not change treatment, particularly if radiation oncologists In patients with very large breasts, or those over the age
treat IM nodes in patients with positive axillary nodes.37 of 65 years where failure to map is slightly more frequent,
Many of the authors do not routinely evaluate the IM chain the surgeon can consider increasing the injection volume.39
with the gamma probe, unless the IM node(s) appears A volume of 8–10 cc of blue dye can be used depending on
enlarged or abnormal on preoperative imaging [e.g. ultra- the breast size.
sound or magnetic resonance imaging (MRI)]. The Finally, a common error with the blue dye technique
procedure for identifying and removing sentinel nodes in when an SLN is easily identified immediately beneath the
the IM chain has been previously described.38 incision is failure to actively search for other SLNs. Failure
General troubleshooting techniques for blue dye alone to search for additional blue nodes contributes to a high
The most common cause for a lack of blue dye uptake in false negative identification rate. Since the majority of
the axilla is extensive tumor infiltration. Therefore, the sentinel nodes are in close proximity to one another, it is
surgeon should always palpate the axilla carefully and not necessary to open the entire axilla to search for addi-
remove any palpable suspicious nodes. Incision placement tional nodes.
Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery 3465
DISCUSSION 8. Johnson JM, Orr RK, Moline SR. Institutional learning curve for
sentinel node biopsy at a community teaching hospital. Am Surg.
2001;67(11):1030–1033.
Sentinel lymph node biopsy has gained widespread 9. Moonka R, Hunter JA, Cray WK, Duncan M, Wechter DG. A
acceptance as the primary means of axillary staging for comparison of rates of lymph node metastases between patients
patients with clinically node-negative invasive breast can- undergoing sentinel and axillary lymphadenectomy. Am J Surg.
cer. Many surgeons have obtained appropriate training and 2002;183(5):558–561.
10. Kiluk JV, Ly QP, Meade T, et al. Axillary recurrence rate fol-
experience in the procedure and have reached an ideal level lowing negative sentinel node biopsy for invasive breast cancer:
of proficiency performing the technique. However, some long-term follow-up. Ann Surg Oncol. 2011;18(Suppl 3):S339–
variation in technical performance remains, and practical S342.
guidance can help success rates of SLNB, especially when 11. Krag D, Weaver D, Ashikaga T, et al. The sentinel node in breast
cancer–a multicenter validation study. N Engl J Med. 1998;
first commencing with the procedure in practice or when 339(14):941–946.
encountering unusual or difficult circumstances. 12. Cox CE, Salud CJ, Cantor A, et al. Learning curves for breast
Troubleshooting has long been used in industries such as cancer sentinel lymph node mapping based on surgical volume
engineering, computer science, and mechanics. The appli- analysis. J Am Coll Surg. 2001;193(6):593–600.
13. Stitzenberg KB, Chang Y, Louie R, Groves JS, Durham D, Fraher
cation of this process to a surgical procedure is a relatively EF. Improving our understanding of the surgical oncology
novel endeavor. The techniques outlined in this guide offer workforce. Ann Surg. 2014;259(3):556–562.
a concise and practical approach to addressing problems 14. Cady B, Falkenberry SS, Chung MA. The surgeon’s role in
with SLNB (compiling ‘tips’ learned through years of outcome in contemporary breast cancer. Surg Oncol Clin N Am.
2000;9(1):119–132.
collective experience). The information presented is 15. Newman LA. Locoregional control of breast cancer: surgical
intended to provide a logical, systematic approach to technique does matter. Ann Surg Oncol. 2004;11(1):11–13.
problem solving, thereby enhancing the success rate of 16. Schwartz GF, Giuliano AE, Veronesi U; Consensus Conference
SLNB. Committee. Proceedings of the Consensus Conference on the role
of sentinel lymph node biopsy in carcinoma of the breast, April
19–22, 2001, Philadelphia, Pennsylvania. Cancer. 2002;94(10):
ACKNOWLEDGMENT The authors would like to thank Nancy 2542–2551
Bianchi from the Dana Medical Library at the University of Vermont 17. Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph
for her contribution to the literature review. node surgery after neoadjuvant chemotherapy in patients with
node-positive breast cancer: the ACOSOG Z1071 (Alliance)
FUNDING SOURCES None. clinical trial. JAMA. 2013;310(14):1455–1461.
18. Raut CP, Hunt KK, Akins JS, et al. Incidence of anaphylactoid
DISCLOSURES None. reactions to isosulfan blue dye during breast carcinoma lymphatic
mapping in patients treated with preoperative prophylaxis: results
of a surgical prospective clinical practice protocol. Cancer.
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