Die not yet cast for lymphazurin and methylene blue dye

Key clinical point: Contrary to prior studies, lymph node positivity was higher with lymphazurin than methylene blue in patients with early breast cancer.

Major finding: Nodal positivity was 14.93% with lymphazurin vs. 8.85% with methylene blue (P less than .001).

Data source: Prospective study in 651 patients undergoing lymphatic mapping for breast cancer.

Disclosures: Dr. Patel and Dr. Throckmorton reported having no relevant conflicts.




CHICAGO – Two commonly used dyes produced mixed results in sentinel lymph node mapping of early stage breast cancer in what was described as the highest-powered study to date.

The average number of sentinel lymph nodes identified per person was significantly higher with 1% methylene blue dye than with 1% lymphazurin (2.89 vs. 2.22; P less than .001).

Dr. Vaishali Patel

Dr. Vaishali Patel

Although there is extensive support for methylene blue as a safe and efficacious alternative to lymphazurin, this finding on the number of sentinel nodes identified is not replicated in any other study, Dr. Vaishali Patel said at the annual clinical congress of the American College of Surgeons. The study was conducted at the McLaren Flint (Mich.) Medical Center. Dr. Sukamal Saha was principal investigator.

On the other hand, lymphazurin identified significantly more additional lymph nodes than methylene blue (mean 4.48 vs. 2.84; P less than .001).

Nodal positivity was also significantly higher with lymphazurin than methylene blue (14.93% vs. 8.85%; P less than .001), which also has not been reported in other trials.

“We think this does offer a true comparison between the two dyes,” Dr. Patel of Detroit Medical Center Sinai-Grace Hospital said. “The volume of dye and technique were consistent for all 651 patients. … with one surgeon performing the injections and one surgeon performing the procedures.” The 651 consecutive patients were randomly assigned based on agent availability to a preoperative injection of lymphazurin (half intraparenchymal and half subareolar in the upper outer quadrant) or an intraoperative injection of methylene blue over 5 minutes (3 ccs intraparenchymal, 1 cc subareolar, and 1 cc intradermal).

The lymphazurin and methylene blue groups were also similar in number (298 patients vs. 353 patients), age (mean 61.6 years vs. 63.5 years), and T stage (in situ 12% vs. 17.8%; T1 64% vs. 65%; T2 23% vs. 17.5%).

In contrast, three smaller, well-established studies that came to different conclusions used four different surgeons and novel techniques to inject their radiocolloid and supervised residents for lymphatic mapping, she noted.

The radiocolloid lymphazurin first demonstrated superiority over methylene blue in 1990, but alternatives continue to be investigated due to frequent nonavailability and a host of adverse events including blue hives, blue discoloration or tattooing, and anaphylaxis.

Lymphazurin also costs 10-12 times more than methylene blue, which was reflected in the study in an average per patient cost of $815 vs. $75 for methylene blue, Dr. Patel said.

The American Society of Breast Surgeons, however, recommends dual-agent mapping using blue dye and a radioisotope in breast cancer to further improve the success in identifying the sentinel lymph nodes. The improvement is likely because of the dual mechanism at play: radiocolloids become entrapped within the lymph node, whereas certain blue dyes bind to interstitial albumin and are taken up by lymphatics, she explained.

The higher number of sentinel lymph nodes in the methylene blue group may be due to its particle size, which is smaller, weighs less, and diffused faster, Dr. Patel suggested.

The higher number of additional lymph nodes captured with lymphazurin may be because of the higher frequency of nodal dissection in this group than in the methylene blue group (25% vs. 16%).

The finding of greater nodal positivity in the lymphazurin group may be related to mechanism of action or the high percentage of patients with T1 disease enrolled in the study. Still, nodal positivity was higher with lymphazurin than methylene blue regardless of T stage, she said.

The lymphazurin group had higher rates than the methylene blue group of pseudohypoxemia (10% vs. 0%; P less than .0001), but blue hives (1.34% vs. 0%; P = .043) and anaphylaxis (.67% vs. 0%; P = .20) were kept in check. Patients were premedicated and early in the series, the surgeon began excising the area of injected blue skin during the primary surgery, Dr. Patel observed.

Despite being diluted, methylene blue was associated with higher rates of seroma (3.4% vs. 1.7%; P = .005) and skin necrosis (2.55% vs. 9%; P = .005).

Discussant Dr. Alyssa Throckmorton of Baptist Memorial Health Care in Memphis pointed out that more recent data show radiocolloid mapping alone is comparable to dual-agent mapping, suggesting that blue dye may not be needed. That said, there have been national shortages of methylene blue as well as lymphazurin.

“I think in surgeons who are going to use blue dye, with the way drug shortages have become in the last few years, you are going to have to be facile and familiar with both types of dye if you are going to use that as part of your clinical practice,” she said.

Next Article:

   Comments ()