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Introduction to Lymphatic Mapping Introduction to Lymphatic Mapping Cancer Staging When a patient is given the diagnosis of cancer, one of the first questions to be answered is whether the cancer has spread from the primary site (breast, colon, lung, etc.), or if it is still contained in that area. The answer to that question will have implications in the prognosis of the patient and the treatment prescribed. Determining whether a tumor has spread, or evaluating the extent of the cancer throughout the body, is called “staging.” There are multiple ways to analyze whether the tumor has spread, or “metastasized” from the primary site. The size of the tumor, for example, might give clues as to the likelihood of metastasis. But for most solid tumors, the most powerful indicator of metastatic spread is the presence or absence of cancer cells in the regional lymph nodes. The lymphatic system can be thought of as a secondary circulatory system (the primary circulatory system being the arterial-venous system). The lymphatic system collects fluid which escapes from the cells, arteries, and veins, and returns the fluid, called “lymph”, back to the heart. The lymph nodes serve as filters in the lymphatic system, that filter any foreign bodies from the lymph before it returns to the heart. These foreign bodies may be bacteria, viruses, etc., or even cancer cells. As tumors secrete fluid, and also shed cells (metastasize), the lymphatic system is a likely reservoir for those fluids and cancer cells to deposit. Thus, if the lymph nodes in the area of the tumor can be localized, surgically removed, and evaluated by pathology to determine if there are any cancer cells trapped there, the extent of the spread of the cancer can be determined. This is the most common method used to gain cancer staging information. Axillary Lymph Node Dissection (ALND) The technique of surgically removing the lymph nodes in the area of the tumor is a traumatic procedure, however. It is performed under anesthesia, and associated with a high degree of post-operative complications. Typical complications include the following: Rate Complication 40% Acute Lymphedema – the accumulation of lymphatic fluid in the tissues, causing swelling. This condition subsides over time. 5% 40% Chronic Lymphedema – a prolonged permanent condition of lymphedema. Paresthesia of arm – loss of sensation or movement due to nerve damage. 10% Seroma formation – a pocket of serum, caused by lymphatic drainage into an excision cavity. A Seroma must be surgically drained. 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com Introduction to Lymphatic Mapping Sentinel Lymph Node Biopsy (SLNB) First reported in 1977, a revised method of obtaining this staging information has been developed, and has gained broad acceptance in the surgical community. This method involves localization of the lymph node that is first in the lymph node chain to receive lymphatic drainage from a primary tumor site. This first draining node is referred to as the “sentinel” lymph node (SLN), and it has been found to be a highly accurate indicator of the metastatic involvement of the entire lymph node basin in which it is situated. In short, if the Sentinel Node doesn’t contain cancer, then the rest of the lymph nodes are also negative for cancer. What this means is that instead of removing all of the lymph nodes (10-15) in the lymphatic basin in the area of the tumor, only the Sentinel Node is necessary to remove. The localization, excision, and pathologic evaluation of the sentinel node for the purpose of gaining cancer staging information is called “Sentinel Lymph Node Biopsy, or “Intraoperative Lymphatic Mapping” (ILM). In theory, the histology of SLN should be highly predictive of the remainder of the lymphatic basin, a theory which has been proven clinically for melanoma and breast cancer. This procedure is beneficial in that it replaces full nodal dissection for a majority of patients, thus avoiding the complications associated with it. Typically in a full axillary dissection, 10-25 nodes are removed and analyzed. With SLNB, 1-3 sentinel nodes will be excised and analyzed, thereby greatly reducing or eliminating the complications associated with full dissection. The first technique investigated to localize the SLN involved the injection of a blue dye, Lyphazurin 1% blue dye, around the tumor site. The dye flows into the lymphatic basin which receives lymphatic drainage from the tumor, and the nodes are stained blue. The surgeon then proceeds to carefully dissect the nodal basin, and visually identify blue-stained lymphatic vessels. These lymphatic vessels are followed to the SLN, the first blue node in the lymphatic chain from the tumor. The SLN is then excised, and its histologic status is determined by pathology. Although this method has been used successfully by several researchers, its success varies with the experience level of the surgeon, and can result in a procedure which approaches the invasive level of a full dissection of the nodal basin. Success rates in finding the SLN by the blue dye technique alone vary from 65% to 93%. The second technique introduced a radiocolloid (Tc99m Sulfur Colloid) as the agent injected around the tumor. This radioactive tracer flows into the lymphatics in the same manner as the blue dye, and deposits into the SLN. The advantage to this method is that a gamma detection probe is utilized to detect and mark the SLN at the skin (pre-incision) and also intra-operatively. This method allows a small incision to be used, unlike the blue dye, when visual search for nodes is necessary. Once localized, the SLN is excised and its histologic status determined. It has been documented that the best results in SLN identification are obtained when the radiocolloid and blue dye are used together. Since there is a chance that some of the nodes will stain blue, but not be “hot” by radiocolloid, or may be “hot” but not blue, many surgeons find that the use of both agents increases their incidence of correctly identifying the SLN. 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com Introduction to Lymphatic Mapping Nuclear Medicine 101 Nuclear Medicine is a scientific and clinical discipline of medicine which utilizes radiopharmaceuticals, chemical substances which contain a radioactive component (radionuclide) within its structure and are suitable for human use. These radiopharmaceuticals are used in the diagnosis and/or treatment of disease. In the detection of disease, nuclear medicine technologists administer radiopharmaceuticals to patients and obtain images of the bio-distribution of these tracers. The images are captured by scintillation detectors, commonly called gamma cameras. Unlike an X-ray or CT scan, in which X-rays are transmitted through the patient to the film plate, nuclear medicine images are formed by the radiation emanating from the patient after the injection of the radiopharmaceutical. The gamma camera captures the emitted radiation, and the resulting images describe the organs in which the tracer has localized. Nuclear medicine is unique in that the obtained information describes the function of organs, while the other imaging modalities (X-ray, CT, MRI, Ultrasound, etc.) only depict the physical structure of organs. These functional studies are interpreted by a radiologist. A radiologist who has achieved certification in nuclear medicine is called a nuclear medicine physician. 85-90% of all nuclear medicine procedures utilize Technetium-99m (Tc99m) as the radioactive component of their associated radiopharmaceuticals. Tc99m is considered an optimum tracer for most procedures due to its half life (6 hrs), which is short enough to limit exposure to the patient, yet long enough to permit flexible scan scheduling. Another advantage is its gamma energy (140 keV), which is energetic enough to penetrate tissue, yet readily captured by the camera detector. The preparation of radiopharmaceuticals involves combining Tc99m with a chemical “carrier” which dictates which organs the tracer will localize to. The nuclear medicine staff typically will be responsible for procurement, preparation and injection of the radiopharmaceutical (Tc99m Sulfur Colloid) as well as any lymphoscintigraphy (imaging of the lymphatic flow). 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com Introduction to Lymphatic Mapping Principles of Radioactive Decay Radioactive decay is the spontaneous process by which an unstable atomic nucleus transforms into another, more stable nucleus. During this transition, the unstable nucleus emits particles and/or gamma rays. These photons, or “gamma rays”, have characteristic energies, measured in keV, or kilo electron volts. Each radionuclide can be identified by its peak energy. The illustration on the right shows the 140 keV gamma ray given off by Tc99m. In this example, we see that Tc99m emits the majority of its gamma rays around the 140 keV energy level. We also note that there are a significant number of radioactive counts falling in the 40-120 keV range. These counts represent “scattered” gamma rays, which are those protons which have lost some of their original 140 keV energy due to collisions with tissue before leaving the body. All radionuclides also have a characteristic lifetime, measured in half-lives. A half-life is defined as the time required for a radionuclide to decay to half its initial activity level. Radionuclides are identified by these two criteria. For Example, Technetium 99 (Tc99m) is the radio nuclide used in the SLNB procedure, as well as most Nuclear Medicine scans. Its characteristics can be described by the energy of its emitted gamma rays (140 keV), as well as its half-life (6-hours). These two defining characteristics make Tc99 an ideal radionuclide for diagnostic scanning, since its energy level is high enough to be detected outside the body, and its half-life is short enough to spare the patient excessive radiation exposure. 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com Introduction to Lymphatic Mapping Glossary ALND Axillary Lymph Node Dissection, the removal of all the lymph nodes in the axillary region, as part of breast cancer treatment Colloid A suspension of particles in a carrier medium (liquid) Ex vivo Outside the body FDG-18 Flourine-18 De-oxyglucose Formalin Preservative fluid used to store pathologic specimens Gamma A form of radiation. Other forms include microwave, radio wave, and light Half-life The length of time required for radioactive material to decay to ½ it’s initial activity In situ In place Interparenchymal Between the essential and distinctive tissue of an organ or an abnormal growth as distinguished from its supportive framework Intradermal Within or between the layers of skin keV Kilo electron volts, unit of measurement of gamma ray energy Lymph-edema The accumulation of lymphatic fluid in the tissues, causes swelling Lymphoscintigraphy Nuclear medicine imaging of lymphatic drainage mCi Millicurie, unit of measurement of radiation, 1/1000 curie Micron 1/1000 mm, sulfur colloid particles range in size from .05-1.0 micron nm Nanometer, 1/1000 micron Parenchyma The functioning tissue of an organ Paresthesia Lack of sensation, can be caused by nerve damage during axillary dissection PET Positron Emission Tomography Photopeak The graphical representation of the energy of the gamma emissions of a radionuclide Radiocolloid A colloid tagged with a radionuclide for the purpose of diagnostic imaging Radionuclide The radioactive form of an element 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com Introduction to Lymphatic Mapping Radiopharmaceutical A tracer used in nuclear medicine, composed of a radioactive component tagged to a chemical component which localizes to the organ of interest Scintillation Production of light photons by a crystal Seroma A pocket of serum, caused by lymphatic drainage into an excision cavity. Must be surgically aspirated SLN Sentinel Lymph Node, The first lymph node to receive lymphatic drainage from a tumor Staging Determining the extent of tumor spread Subdermal Under the skin (injection) TC-99m Technetium-99 uCi Microcurie, 1/1000 mCi VAT Video Assisted Technique 44 Hunt Street, Watertown, MA 02472 I Phone: 617.668.6900 I Fax: 617.926.9743 [email protected] I www.dynasilproducts.com