Robotic Sentinel Lymph Node Dissection
Ahmed Nazer
Walter Gotlieb
Susie Lau
GENERAL PRINCIPLES
Endometrial cancer is the most common gynecologic cancer. The International Federation of Gynecology and Obstetrics (FIGO, 1988) adopted lymph node (LN) assessment as part of endometrial cancer staging, to determine prognosis and tailored adjuvant treatment. Over the years, the need for routine LN dissection was called to question, especially with the increased associated morbidity. Subsequently, large randomized clinical trials failed to demonstrate a therapeutic benefit from routine LN dissection.
Sentinel lymph node (SLN) sampling is proposed as an alternative to complete lymphadenectomy that balances the need to obtain adequate information regarding the extent of LN involvement while minimizing the adverse events associated with routine LN dissection.
The Concept of Sentinel Lymph Node
Thomas Bartholin first described the lymphatic system in 1653 and the existence of a sentinel node in penile lymphatic drainage was first observed by Cabanas in 1977. Using colloidal gold and cutaneous lymphoscintigraphy, Don Morton in 1977 introduced the concept of preoperative lymphatic mapping to identify lymphatic drainage of primary malignant melanomas and developed the technique of intraoperative mapping to identify the first echelon of LNs draining the primary melanoma.
The SLN was defined as the first LN that receives lymphatic drainage from the primary tumor and thus any metastasis to the lymphatic chain will first affect the SLN. Lymphatic mapping and SLN sampling have been well-studied, and have become the standard of care in solid tumors. SLN sampling was first introduced by Dr. Don Morton at UCLA for melanoma of the skin and cancer of the breast. Later on, gynecologic oncology has adopted this concept, and extensive research is ongoing in lymphatic mapping in vulvar, cervical, and endometrial cancers.
Sentinel Lymph Node Mapping in Gynecologic Malignancies
Implementing a new practice to replace a standard-of-care procedure requires careful assessment of many factors including, but not limited to, its safety, sensitivity, and specificity in detecting the disease, and both positive (PPV) and negative predictive values (NPV).
Definitions
Sensitivity: Patients with positive SLN divided by all patients with positive nodes (true-positive tests/all positive patients).
NPV: Patients with negative SLN.
Divided by all patients without a positive SLN.
True-negative tests/true-negative + false-negative tests.
False-negative rate: Metastatic patients without a positive SLN divided by all patients with positive nodes (false-negative tests/false-negative + true-positive tests).
Detection rate: Proportion of patients with at least one SLN detected.
Burke et al. had published the first feasibility report on lymphatic mapping for patients with endometrial cancer in 1996. Since then, many studies on SLN mapping have been performed using different dyes, either alone or in combination, and using various injection sites. SLN mapping has now been studied for more than 20 years, and based on the groundbreaking work performed at Memorial Sloan Kettering, it is becoming the standard of care for the treatment of endometrial cancer.
IMAGING AND OTHER DIAGNOSTICS
MRI
The diagnostic accuracy of magnetic resonance imaging (MRI) in LN metastasis remains low, with sensitivity around 40%, specificity and NPV around 90%.
SPECT/CT
In a prospective study (Pandit-Taskar et al.), planar lymphoscintigraphy localized SLN 75% in endometrial cancer patients while SPECT/CT localized SLN in all patients. In other studies, the detection rate of SLN with preoperative SPECT/CT varied between 77% and 89%.
Tracer
Many types of dyes and tracers can be used in SLN mapping, and vary in detection rate, availability, cost, and side effects.
Blue Dye
Blue-colored dyes including isosulfan blue, patent blue, and methylene blue have been used since the 1960s in lymphangiography. It is both inexpensive and widely available in most hospitals.
Detection time: Patent blue is detected in the lymphatic channels within 4 minutes after cervical injection and lasts for up to 180 minutes.
Detection rate: Between 45% and 80%, this rate can be increased when blue dye is injected with other tracers such as 99mTc. Studies on the learning curve for SLN mapping suggested that 30 cases are required per surgeon to reach optimal detection rate.
Adverse reactions: Allergic reactions vary from localized swelling and pruritus to severe reactions, including anaphylactic shock. In breast cancer, 0.9% of patients (out of 7,917) injected with patent blue experienced adverse reactions, and 0.06% experienced a severe reaction. Adverse reactions with isosulfan blue dye were observed in 1.42% (119/8,372) of patients and 0.44% (37/8372) were severe. These allergic reactions need to be differentiated with a transient drop in oxygen saturation as measured by pulse oximetry, due to the blue color of the dye taken up in the bloodstream.
Indocyanine Green
Indocyanine green (ICG) is a tricarbocyanine, negatively charged ion that belongs to the large family of cyanine dyes. ICG dye was developed for near-infrared (NIR) photography and was approved for clinical use in 1956. It has been used to assess liver function and for retinal angiography. It is transported by a plasma protein called glutathione S-transferase and extracted by the liver into bilious secretions.
Detection time: Same as blue dyes.
Detection rate: SLN detection rate using ICG dye ranges between 80% and 100%, and it has shown higher bilateral detection rate compared to blue dye and technetium-99m. In a recent multicentric prospective study (Jewell et al., 2017), the SLN detection rate during robotic staging for endometrial cancer using ICG dye reached 95%, with bilateral pelvic mapping in 79%.
Adverse reactions: Minimal side effects to ICG have been reported in the gynecologic oncology literature; however, cases of anaphylaxis and other mild to moderate reactions (skin rash, nausea, hypotension, tachycardia, and pulmonary edema) have been reported during cardiac catheterization or liver function test. The risk was higher in patients with ESRD.
Radioactive Tracer (Technetium-99m)
Technetium is an artificial element obtained by the radioactive decay of molybdenum. It was first introduced to medicine in 1964 for thyroid imaging and it became widely acceptable in LN mapping because of its relatively low cost, ease of preparation, and low radiation burden to the patients due to its short half-life. Preoperative injection of 99Tc microsulfur colloid has been used prior to the surgical procedure, followed by lymphoscintigraphy preoperatively in order to orient the surgeon to the SLN’s location. Intraoperative 99Tc can be identified through a gamma probe.
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