Axillary Sentinel Lymph Node Biopsy

Selection of Optimal Dye for Intraoperative Lymphatic Mapping

The selection of an appropriate vital dye is critical for a successful procedure. The optimal dye for lymphatic mapping has been studied in an animal model. Three different dyes were investigated: Cyalume, a fluorescent dye; methylene blue, a water soluble dye; and isosulfan blue, a dye with selective avidity for the lymphatics. Cyalume readily identified the lymphatics but also stained the surrounding interstitial tissue creating a high background. Methylene blue proved to be unsatisfactory in the animal model because of poor uptake by the lymphatics. The success rate of methylene blue with radioisotope is reported to be equivalent to isosulfan blue with isotope. Isosulfan blue is conjugated to albumin, taken up by the lymphatics readily, and retained in the lymphatics and SN without leak into extralymphatic tissues. The more concentrated compound available outside of the United States is Patent Blue V, which has similar functional characteristics. Indigocarmine has been used successfully in Japan. It has a higher intralymphatic retention with a high degree of success. Indigocyanine green has also been used successfully. Evan's blue dye has been used for successful identification of axillary and internal mammary SNs.

Complications of Dye Injection

The safety and efficacy of isosulfan blue dye was first studied in a rat model and then investigated in 11 volunteers and 543 patients in the 1980s. Up to 15 mg of a 1% solution injected into the extremity resulted in a 97.4% success rate to identify the lymphatic vessels, with no adverse reactions and minimal allergic reactions in patients (≤1%). Isolated case reports of adverse reactions with blue dye including allergic urticaria and anaphylaxis have been reported, but this rate is extremely low. Data from the NSABP B-32 trial show 0.4% grade 1 and 2 allergic reactions and 0.2% grade 3 and 4 with no deaths. The data from the American College of Surgeons Oncology Group (ACOSOG) Z0010 trial show 0.1% anaphylaxis with isosulfan blue alone or in combination with radiocolloid, axillary wound complications in 1%, axillary seroma in 7.1%, and axillary hematoma in 1.4%. Hives covering the trunk and upper extremities, not associated with hypotension, resolve within 24 to 48 hours after administration of methylprednisolone and diphenhydramine. Management of hypotensive anaphylaxis includes discontinuation of anesthetic agents; administration of fluids; and epinephrine, diphenhydramine hydrochloride and corticosteroids. Intraoperative plasma histamine levels may be elevated at the time of reaction. Postoperative skin testing to isosulfan blue may be a useful test. The anaphylactic reaction seems to be an immunoglobulin E reaction and may occur as long as 30 minutes to one hour after injection. Intraoperatively, isosulfan blue can affect pulse oximetry. Although this is a pseudodesaturation with Pa o ₂ remaining normal, surgeons and anesthesiologists must investigate the clinical situation and the potential causes of desaturation. Relatively minor problems include transient staining of the epidermis that can take several weeks to several months to fade completely. There is a transient change in color of the urine and stool to a greenish hue. Although these are temporary events, unless patients are forewarned about what to expect this can cause a great deal of unnecessary distress.

In contrast to isosulfan blue, methylene blue has not been associated with anaphylactic reaction. Local reactions of skin erythema, superficial ulceration, or necrosis have been reported with intradermal injections. Partial skin loss usually responds to topical Silvadene therapy, with no need for surgical debridement. Methylene blue should not be injected intradermally or subdermally because of risk of skin ulceration.

Anesthetic Considerations

Sentinel lymphadenectomy is usually an outpatient procedure. Axillary exploration can be performed under general anesthesia, conscious sedation with local, or local anesthesia alone. SLND under local anesthesia requires expert surgeons, quick and precise surgery, and minimal use of electrocautery. Local anesthesia may not be appropriate for some patients.

Vital Dye Injection Technique

After adequate anesthesia, the patient is positioned at the edge of the operating room table with the arm extended at 90 degrees and prepped free. Five mL of 1% isosulfan blue is injected peritumorally or around the biopsy cavity in an arc toward the axilla. Successful SN identification has been reported when isosulfan dye is injected into sites other than breast parenchyma: subdermal, intradermal, intradermal periareolar, and subareolar. For palpable lesions, dye is injected into the breast parenchyma around the axillary side of the tumor. For mammographically or ultrasonographically detected lesions, dye is injected adjacent to the localization needles or with the use of ultrasound guidance. For tumors previously removed by excisional biopsy, dye is injected into the wall of the biopsy cavity on the axillary side but not into the cavity itself ( Figure 43-1-1 ). Dye injected into biopsy cavities or directly into the tumor does not gain access to the afferent lymphatics and therefore will not identify the sentinel node.

The average interval between dye injection and axillary incision is 5 minutes. The time can be modified for individual patients, such as in older patients or in those with a higher BMI. In the latter case, more time is required for dye to opacify the lymphatics. Dye transit time from primary to axilla is related to the location of the tumor, with shorter transit times for lesions in the axillary tail and longer ones for those in the lower inner quadrant. Typically 3 to 4 minutes and 7 to 10 minutes should be allowed for dye to travel, respectively, from lesions in these locations. This time delay often seems endless for the surgeon; therefore, strict monitoring of time is recommended. Disregard of this simple fact may contribute to the difficulties that some have had with the dye-directed technique. Improved blue node identification has been reported with breast or three-stage lymphatic massage.

Dissection Technique

SLND is performed prior to mastectomy or partial mastectomy. A 2- to 3-cm transverse incision is made 1 cm below the hair-bearing area of the axilla slightly anterior to the midaxillary line, preferably in a skin crease for improved cosmesis. Skin flaps are not developed for this procedure. The clavipectoral fascia is identified and incised. The arm is abducted to bring the axillary content outward into the operative field. Gentle blunt dissection is initiated at the margin of the pectoralis major in the zone containing the pectoral nodes, the most likely region to contain the SN. If no blue lymphatic is identified, attention is redirected to the known zones of nodal clustering (e.g., external mammary, central subscapular, subclavicular) in levels I and II. The SN is located in level I in 83% of cases, level II in 15.6%, and level III in 0.5%. The blue lymphatic trunk is followed to the SN and traced proximally and distally to locate other blue nodes ( Figure 43-1-2 ). Omission of this step can result in missing a more proximal or distal blue node and can be another reason for a false-negative SN. After removal of the SN, the axillary space is gently explored and palpated for suspicious, palpable nodes.These are removed and identified as suspicious. Disregard for palpable nodes has been the cause of false-negative SNs in several series. After all SNs are identified, they are sent for pathologic evaluation.