2005

Percutaneous Ethanol Injection to Treat Recurrent Differentiated Thyroid Cancer

Points to Remember

• Papillary thyroid cancer is the most common malignant tumor of the endocrine system.
• Up to 20% of patients with papillary thyroid cancer develop recurrent metastatic adenopathy after initial surgical treatment.
• Ultrasonographically guided percutaneous ethanol injection (PEI) is a useful alternative to surgery, radiation, and radioiodine therapy in selected patients with limited nodal disease from papillary thyroid carcinoma.
• PEI is effective, safe, and relatively inexpensive.

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the endocrine system. In the United States, an estimated 19,500 new cases of thyroid cancer are diagnosed each year, and more than 80% are PTC. PTC typically has a benign course. Five-year survival is nearly 100% for patients with pTNM stage I and II disease, and the 10-year cause-specific survival for all stages is 93%. Near-total thyroidectomy with wide excision of affected regional nodes, often followed by remnant ablation with radioactive iodine, is the most common primary treatment. In a large Mayo Clinic study, 38% of patients had metastatically involved nodes at the time of operation. Despite the extent of initial neck node dissection, residual or recurrent metastatic adenopathy is common and is seen in 10% to 20% of PTC patients during clinical and ultrasonographic follow-up (Figure 1).

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Several treatment options are typically available for PTC patients with recurrent metastatic lymphadenopathy. One is radioiodine therapy, although the success of this technique has been variable in the treatment of metastatic adenopathy. Given the indolent nature of the disease, "watchful waiting" is an option for some patients, including elderly patients, those who are poor surgical candidates, or those who are considered to be at "low risk." Many younger patients in whom radioiodine therapy has failed or who had pTNM stage III disease at initial operation are usually subjected to further neck exploration and metastatic lymph node resection. However, surgery may be an overaggressive treatment approach in some patients. Surgery is also more difficult in patients who have had previous neck dissection or external beam irradiation, and there may be a limit to how many surgical reexplorations can be safely attempted. These disadvantages highlight the need for a less invasive method for treating patients with limited nodal metastases.

Treatment Technique

The technique of percutaneous ethanol injection (PEI) for the treatment of metastatic neck lymph nodes is based on a procedure that has been used at Mayo Clinic since 1988 to treat selected patients with benign parathyroid adenomas. Before the procedure, each lymph node is measured in 3 dimensions and color Doppler ultrasonography is performed to document baseline size and nodal perfusion. A conventional 3-cm, 25-gauge needle is attached to a tuberculin syringe containing up to 1 mL of 95% ethanol. Patients receive local anesthesia with 1% lidocaine before the procedure.

The needle is placed into the lymph node under ultrasonographic guidance. A free-hand technique is used to allow fine-needle positioning, which is required for complete treatment. Each node is punctured and injected in multiple sites. As the ethanol is injected, the injected portion of the node becomes intensely echogenic from the formation of microbubbles of gas. The needle is then repositioned, and small amounts (0.05-0.1 mL) of ethanol are injected in multiple sites within the node (average total amount of ethanol injected into a single node is 0.4 mL) (Figure 2).

The number of treatment sessions varies between 1 and 4, with an average of 2. Patients with 1 or 2 small nodes can be treated in 1 session. Patients with larger nodes or with nodes in locations that are difficult to inject are treated with multiple sessions. Treated patients receive routine clinical and ultrasonographic follow-up, typically every 3 to 6 months. Patients who show evidence of residual nodal perfusion on color Doppler ultrasonography are retreated.

Patient Selection and Outcomes

Patient selection requires biopsy-proven metastatic PTC in cervical lymph nodes identified by ultrasonography, and the nodes must be technically amenable to PEI. Often these nodes are single or few in number and located in the lateral neck, but selected nodes in the central compartment can be treated as well. Most patients are either poor surgical candidates or prefer not to have further surgery and have not responded in the past to radioiodine therapy.

More than 90 patients have been treated with this technique at Mayo Clinic. Our initial results from the first 14 patients were published (AJR Am J Roentgenol 2002; 178:699-704). In these 14 patients, 29 nodes were treated with PEI. The treated malignant nodes in this series were detected an average of 4.4 years after initial surgery. The patients had previously received a mean radioiodine dose of 204 mCi. They had undergone an average of 2.1 operations (range, 1-4), and 3 patients also had received external beam irradiation. At a mean follow-up of 18 months, 27 of 29 nodes had significantly decreased in size (Figure 3). The average decrease in node volume was 95%.

Advantages of PEI

In the management of metastatic cervical lymph nodes from PTC, the advantages of PEI over conventional therapy options are several. PEI is far less invasive than surgical neck exploration and can be repeated many times without increasing technical difficulty. It is less expensive than radioiodine therapy and substantially less expensive than surgical neck exploration. PEI has minimal morbidity and is done on an outpatient basis, and the treated patient can resume normal activities almost immediately. Patients avoid the morbidity, hospitalization, and general anesthesia required for neck exploration. PEI appears to be more effective than radioiodine therapy without the systemic symptoms of hypothyroidism or the sometimes required hospitalization. It gives endocrinologists an inexpensive, effective, low-morbidity option for patients who might otherwise be considered for "watchful waiting." Reexploration and radioiodine therapy are still the most appropriate management options for patients with widely metastatic adenopathy.