The National Cancer Institute Bulletin for this week describes the important clinical trials presented at ASCO in Chicago.
These were summarized by Dr. William Wood:
"These are practice-changing results. And it’s also interesting to see scientific hypotheses proven, even if it’s only the null hypothesis."
Go to this link to read the news:
http://www.cancer.gov/ncicancerbulletin/062910/page6
Below is a summary from the Tree of Medicine capturing the world's literature on blue dye complications in breast cancer patients.
Sentinel Node and Breast Cancer
Complications
Dye Related
David Krag, M.D.
SD Ireland Professor of Surgical Oncology
University of Vermont, College of Medicine
David.Krag@uvm.edu
Summary based on 68 Articles
Earliest PMID 10873370
Most recent PMID 20140704
Introduction:
Dyes are commonly injected into the breast for sentinel node surgery to trace the movement of lymph in breast cancer patients. The number of different dyes used for this procedure is expanding and includes isosulfan blue, patent blue, methylene blue, indocyanine green, and indigocarmine green. These dyes all have the potential to cause immediate life-threatening complications. In addition, particular dyes may cause additional complications unrelated to allergic events. The surgeon must be prepared to immediately treat anaphylactic complications and be aware of nonallergic complications related to the dye they choose to use.
Allergic reactions:
Severity: The allergic reactions can be severe, with unstable vital signs, bronchospasm, and complete cardiovascular collapse. Treatment for this life threatening complication needs to be immediate: vigorous resuscitation, including protection of airway; antihistamines; steroids; fluid resuscitation; oxygen; and medications to support blood pressure.
Timing: Most allergic reactions occur within 5 to 15 minutes of injection but delayed reactions or “biphasic” reactions have occurred hours after injection.
Incidence: The incidence of allergic reactions appears to be different for different dyes. A portion of these are reactions will be anaphylactic. By far the largest experience has been with isosulfan blue and patent blue; these two dyes are similar in their risk (about 1% to 2%). The incidence of these allergic reactions is based on observation of thousands of cases. Methlyene blue, indocyanine green, and indigocarmine green appear to have a lower risk of allergic response. However, the reported experience with these dyes in the breast cancer sentinel node literature is based on hundreds, not thousands of cases.
Prevention: Medications have been used to prevent allergic reactions to blue dyes. The medications include a glucocorticoid, diphenhydramine, and famotadine administered shortly before injection of blue dye. This may reduce severity of allergic reactions but it may also increase wound complications.
Screening for allergy: Several detailed analyses have been performed on patients in whom allergic reactions have been observed. Most of these patients demonstrate positive skin tests. Since reactions to skin tests occur rapidly, these tests could be considered in a preoperative setting. Although there is merit for performing preoperative skin testing, it is not a guarantee that an allergic response will not occur. While prior allergy to dyes is important to elicit, there is little association between dye allergies and drugs such as antibiotics.
Local tissue reactions:
Staining of tissues: Prolonged staining of skin is possible and skin staining visible at 18 months has been observed in 41% of patent blue cases with intradermal injection. Long term or permanent staining should be considered a possibility with any dye.
Inflammation and necrosis:
Most reports on tissue reactions are associated with methylene blue. This dye has properties that can lead to toxic effects. For example it is oxidized forming formaldehyde and deaminization oxidation products. It can also cause vasospasm through inhibition of nitric oxide and it can destroy nerve endings. Risk of symptoms is increased with superficial injections; intense erythema, ulceration, and necrosis have been observed. Fat necrosis has been observed deeper in the breast. Grade 4 capsular contraction with blue staining of the implant has also been observed, as has wound dehiscence.
Skin necrosis has also been reported with subdermal patent blue.
Local tissue reactions with indocyanine green and indigocarmine green have not been reported in the breast cancer sentinel node literature.
Interference with ductoscopy:
Subareoloar blue dye injection has been reported to interfere with adequate duct visualization during ductoscopy.
Genotoxicity of dyes:
Breast cells were exposed to dyes in vitro at clinically relevant doses to assess genotoxic damage. Patent blue and methylene blue stimulated DNA strand breaks and increased levels of oxidative DNA lesions. Indigocarmine did not. In these experiments, dye exposure was of short duration. Residual dye in cancer patients will last much longer and exposure may last for months to years. These in vitro experiments warrant further attention.
Interference with pulse oximetry:
Patent blue and isosulfan blue have both been reported to interfere with pulse oximetry. Pulse oximetry values are typically reduced by 5% to 10%; complete failure of pulse oximetry readings has also been reported. The reduction occurs promptly and may last at least as long as 3 hours. Arterial blood gas determinations concomitant with pulse oximetry have confirmed that the pulse oximetry readings are erroneous and that patient blood is not truly desaturated by these dyes.
Adverse effects on immunocytochemistry:
Methylene blue has been reported to decrease immunostaining of estrogen and progesterone receptors. Patent blue and indocyanine green did not interfere with these immunoassays.
Adverse effects on serum studies:
Patent blue was spiked into blood samples at clinically relevant levels and was observed to interfere with Roche Modular serum indices. Chemical analysis was not affected but lipaemic index, hemolysis, and icteric indices were affected.
