Like a number of [tumors], [cutaneous] melanomas often spread through lymph channels to regional lymph nodes. Because of this tendency, elective lymph node dissection--removal of [lymph nodes] before there is clinical evidence of metastasis--has long been a standard treatment for patients with early [stage] cutaneous melanoma. While this procedure has not been proven to prolong survival, many surgeons believe that elective lymph node dissection in a patient with micrometastases can prolong the patient's life and in some cases cure the disease.
Until recently, however, this approach involved a catch-22: elective lymph node dissection could benefit only those patients with micrometastases, but determining whether a patient had micrometastases required a lymph node dissection. Thus, some patients underwent unnecessary surgery--a matter of concern because lymph node dissection is a major surgical procedure associated with a number of potential short- and long-term complications.
A cutting-edge approach being studied in [clinical trials] at The University of Texas M. D. Anderson [Cancer] Center offers a way around this dilemma. Using this new technique--intraoperative lymphatic mapping and sentinel node biopsy--surgeons can determine the disease status of an entire lymph node basin by identifying, removing, and examining a single special lymph node called the sentinel node.
The sentinel node is the first node that the dermal lymphatics around a tumor drain to. Studies have shown that the pathologic status of the sentinel node accurately predicts the status of all of the lymph nodes along that drainage pathway. In other words, if the sentinel node is free of [tumor], so are all of the other nodes, and formal [lymph] node dissection is not necessary.
"This procedure can help identify which patients are most likely to benefit from lymph node dissection and which patients probably would not benefit," said Merrick I. Ross, M.D., associate professor in the Department of Surgical [Oncology]. "It allows us to be more selective about performing [lymphadenectomy]."
When the drainage patterns are ambiguous, lymphoscintigraphy is used to identify the nodal basins at risk. This simple outpatient procedure is typically performed several days before the intraoperative lymphatic mapping and sentinel node [biopsy]. Lymphoscintigraphy begins with injection of a [radiolabeled] colloid into the skin adjacent to the [tumor]. Over the course of a few minutes, the colloid passes through the dermal lymphatics to one or more [lymph] node basins, where it is taken up by the macrophages in the lymph nodes. A scintillation camera is then used to document the path of the radiolabeled colloid through the [lymphatic system]. This is the same path that tumor [cells] would follow if they broke away from the primary lesion and entered the lymphatics.
"Lymphoscintigraphy doesn't tell us if there's tumor in these areas," said Ross, "but it does tell us that if tumor had traveled to a lymph node area, that's where tumor would most likely be." With this information in hand, the surgeon can plan the intraoperative lymphatic mapping.
About an hour before [surgery], the patient is taken to the nuclear medicine station, where technicians inject a radiolabeled colloid into the skin adjacent to the tumor. The next stop is the operating room, where the surgeon injects a blue vegetable dye called isosulfan blue near the tumor.
While the blue dye travels through the lymphatic system, the surgeon [scans] the skin over the nodal basin with a hand-held, portable gamma probe, looking for areas with high levels of radioactivity. These "hot" areas signal [lymph nodes] that have taken up the [radiolabeled] colloid; the hottest area corresponds to the sentinel node.
The surgeon makes a small [incision] directly over the sentinel node and inserts the gamma probe, which is covered with a [sterile] sheath. By moving the probe around, the surgeon can further pinpoint the area of high radioactivity. Within this region, the surgeon hunts for a blue-stained node--the sentinel node--and carefully dissects it.
How does the surgeon know that the blue-stained node in question is actually the sentinel node? "There's a time element involved," said Ross. "If you wait too long, the dye can pass through several nodes. We generally do the [biopsy] within 20 minutes after injecting the blue dye." The lymphatic channels connecting the nodes are also stained blue, so "once you find the node, you can trace back the lymphatic channels leading to it to make sure it's the first node--that there isn't a node before that one."
When surgeons at M. D. Anderson [Cancer] Center first performed intraoperative lymphatic mapping, they relied on the blue dye alone to localize the node. The gamma probe was introduced about one and a half years ago. "When we were using just the dye," said Ross, "we were confident between 85 and 90 percent of the time that the node we found was the sentinel node, because we were limited to visual inspection. Since we've been using the gamma probe, we almost never have a concern about not finding the appropriate [lymph] node."
With use of the gamma probe, said Ross, "we know where the sentinel node is going to be. This allows us to make a very small [incision] and also makes the operation much quicker."
After the sentinel node is removed, it is examined by a [pathologist]. If the node looks clinically suspicious, it is examined by frozen section. The results are available in a matter of minutes, and if the node contains [metastases], the surgeon can proceed with a formal lymph node dissection in the same operative setting. However, "if the node looks normal," said Ross, "we prefer to evaluate the [lymph nodes] by serial sectioning with permanent sections. It is more accurate, and we are less likely to miss [tumor]. We are looking for a small amount of microscopic disease, and you can sometimes lose important [tissue] when you do a frozen section." In this case, if the sentinel node contains micrometastases, the lymph node dissection is performed at a later date.
The new procedure may also allow better detection of micrometastatic disease. "There are patients who are thought to be [lymph] [node negative] who eventually have a [recurrence]," said Ross. "We think that a number of these patients are actually lymph node positive, but we missed the micrometastases because we weren't able to look at every lymph node carefully enough." With a traditional lymph node dissection, detailed examination of all the nodes removed is not feasible--the time and expense involved are prohibitive. However, with only one or two nodes to focus on, said Ross, "it is more feasible to perform very careful examination by using serial sectioning and immunohistologic studies," and thus the chances of detecting micrometastases are greater. The sentinel nodes are also thought to be the nodes most likely to harbor micrometastatic disease, so focusing on those nodes is the best strategy for detecting micrometastases.
Early detection of disease spread to [lymph nodes] is especially important now that alpha-interferon has been identified as an effective [adjuvant therapy] for patients with lymph node spread of [melanoma]. The earlier micrometastases in regional lymph nodes are identified, the earlier patients can receive this therapy.
Intraoperative lymphatic mapping can also be used for [melanomas] of the vulva and for other skin cancers that spread to lymph nodes--some of the adnexal tumors of the skin, Merkel [cell] tumors of the skin, and some of the more [aggressive] [squamous cell] [cancers]. "This technique," said Ross, "is applicable to essentially any [solid tumor] that has a predilection for lymph node [metastases]."
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REFERRALS. Readers who would like more information may write Dr. Ross, Department of Surgical [Oncology], Box 106, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, or call (713) 792-7217. To refer a patient, call the New Patient Referral Office at (800) 392-1611 or (713) 792-6161.