Introduction

Contemporary parathyroid operations are successful: surgery for primary hyperparathyroidism has evolved to a procedure with a greater than 95% success rate and a complication rate of less than 2%. A favorable outcome depends on an accurate diagnosis, appropriate patient selection, and good operative technique. Use of adjunctive approaches such as radio-guided parathyroidectomy and intraoperative parathyroid hormone (PTH) measurements can facilitate success (see Chapter 63, Intraoperative PTH Montioring during Parathyroid Surgery).

Open bilateral exploration of the neck has largely given way to minimally invasive approaches. Minimally invasive parathyroidectomy is made possible by accurate pre- and intraoperative technetium-99 m (^99mTc) sestamibi localization of the overactive parathyroid gland(s), allowing for a small incision and a more targeted operation. It can be aided by intraoperative PTH measurement, which helps to rule out multigland disease demonstrating surgical cure. The benefits of minimally invasive parathyroidectomy include improved cosmesis, reduced postoperative pain, shorter hospitalization, and a quicker return to one’s preoperative activity level.

Radio-guided parathyroidectomy is to be viewed as a version of minimally invasive parathyroidectomy.¹^,² We believe that this is a useful adjunct, especially in difficult parathyroidectomies, that leads to an improved outcome with minimal added cost and morbidity (see Chapters 60, Minimally Invasive Single Gland Parathyroid Exploration, 61, Minimally Invasive Video-Assisted Parathyroidectomy, and 62, Local Anesthesia for Thyroid and Parathyroid Surgery).

Principles of Radio-Guided Parathyroid Surgery

Radio-guided parathyroidectomy is closely related to other radio-guided techniques used for breast cancer, malignant melanoma, thyroid cancer, and colon cancer.³^,⁴ A radiotracer is administered, which accumulates preferentially in the target tissue. Radio-guided techniques are used to localize specific tissue through the detection of radioactivity, theoretically minimizing dissection by a direct approach and decreasing overall operative time.

In the case of parathyroid tissue, ^99mTc-sestamibi is utilized. Because of increased mitochondrial density in hypercellular parathyroid glands, the hyperfunctional parathyroid tissue becomes “hot” relative to surrounding thyroid.²⁵ ^99mTc-sestamibi is not truly specific to parathyroid tissue, as it also accumulates in salivary, thyroid, and cardiac tissues, as well as some malignancies. This phenomenon was first described by Coakley in 1989 to preoperatively localize hyperactive parathyroid with ^99mTc-sestamibi imaging.⁵ This finding was then utilized in the operative setting by Martinez et al. in 1995.⁶ Their series of three pediatric patients was the first description in the literature of radio-guided parathyroid surgery.

Multiple surgeons have adopted and extended this technique to the spectrum of parathyroid diseases. This includes all variations of hyperparathyroidism, parathyroid cancer, and treatment of the pediatric patient. The specifics of the technique are discussed in more detail here.

Radio-Guided Parathyroidectomy

Preoperative Evaluation

Preoperatively, patients are evaluated and diagnosed in the manner standard to the institution at which they are being treated. Typically, this includes a history and physical exam, as well as serum calcium, serum PTH, and preoperative localization imaging (see Chapters 56, Primary Hyperparathyroidism: Pathophysiology, Surgical Indications, and Preoperative Workup, 57, Guide to Preoperative Parathyroid Localization Testing, and 58, Principles in Surgical Management of Primary Hyperparathyroidism).

Preoperative Localization

If the ^99mTc-sestamibi scan localizes a single parathyroid adenoma, a minimally invasive parathyroidectomy utilizing an intraoperative gamma probe would be feasible (see Chapter 57, Guide to Preoperative Parathyroid Localization Testing).⁷ It is important that surgeons review all preoperative imaging to localize abnormal glands, as other specialties may be more reluctant to commit to a diagnosis of localization.⁷ In patients with a negative ^99mTc-sestamibi scan, a cervical ultrasound is advised. The sensitivity of cervical ultrasound for the identification of parathyroid adenomas has been demonstrated to be between 70% and 80%.⁸^,⁹^,²⁹ This also has the advantage of assessing for synchronous thyroid disease.¹⁰ If the ultrasound also proves to be negative, the decision is presented to the patient. Further imaging with a CT scan may be pursued, or the parties may proceed to radio-guided parathyroidectomy with negative preoperative localization studies. If desired, a perioperative bilateral internal jugular venous sampling of parathyroid hormone for localization may be of some utility when all localization scans are negative.¹¹ We feel this test, generally reserved for reoperative cases, is rarely necessary.

Anesthesia and Other Operative Considerations

Minimally invasive parathyroidectomy can easily be performed under general endotracheal anesthesia. Either because of contraindications or patient preference, it can also be performed under local anesthesia with intravenous sedation. Initially described by LoGerfo,¹² utilization of local anesthesia with monitored anesthesia care (MAC) has been validated for parathyroidectomy. Snyder et al. have shown comparable operative results, clinical results, and patient satisfaction between local anesthesia with monitored anesthesia care and general anesthesia.¹³ MAC may include the use of laryngeal mask anesthesia.

Local anesthesia is accomplished with the use of a superficial cervical block. This is achieved by injecting approximately 30 mL of 1% lidocaine posterior and deep to the sternocleidomastoid muscle and along the anterior border of the muscle. A local field block is achieved with subcutaneous administration of the local anesthetic. This provides adequate anesthesia for most patients, and this is particularly advantageous because of the decreased use of postoperative IV opioid analgesia and antiemetics.

In cases of known bilateral disease, local anesthetic can be extended to the opposite side. This also applies to patients who are shown to have multigland disease intraoperatively. If local anesthesia has been chosen, conversion to general anesthesia should not be delayed in case of complications, unexpected findings, or patient discomfort (see Chapter 62, Local Anesthesia for Thyroid and Parathyroid Surgery).

Equipment

We utilize an 11-mm collimated gamma probe, the Neoprobe 2000 (Neoprobe Corporation; Dublin, Ohio). Other gamma probes are available such as the Navigator (RMD Instruments; Watertown, Massachusetts) and C-Trak (Care Wise Medical Products; Morgan Hill, California). Gamma probes are commonly utilized in breast and melanoma surgery, so such a probe is likely to be available in the operating room in most institutions.

Radiotracer Injection

Basic Principles

For intraoperative gamma detection, a 10 mCi dose of ^99mTc-sestamibi is given on the day of surgery. Because some patients with primary hyperparathyroidism have previously received a 20 mCi dose of ^99mTc-sestamibi for preoperative localization, we usually do not perform surgery within 3 days to allow complete wash out. Therefore, patients with primary hyperparathyroidism will typically have two ^99mTc-sestamibi injections: the diagnostic scan injection a few weeks before surgery and the second injection, which takes place on the day of surgery, for intraoperative localization.

Radio-guided resection is also feasible for patients with secondary and tertiary hyperparathyroidism.¹⁷ Because of the high likelihood of multigland disease, preoperative ^99mTc-sestamibi scans are typically not obtained for these patients unless there is suspicion of ectopic disease. They have a lower sensitivity and specificity for localization of multigland disease.²⁹ Thus, patients with secondary or tertiary hyperparathyroidism will get only one dose of ^99mTc-sestamibi the day of surgery for intraoperative localization.

Protocol

As the success of radio-guided parathyroidectomy depends on the differential washout of ^99mTc-sestamibi from the thyroid and parathyroid glands, several protocols have been put forth to optimize gamma probe sensitivity and specificity. At our respective institutions, we utilize two different protocols for intraoperative gamma probe–directed surgery, described later.

Protocol 1: Wisconsin

On the day of surgery, patients are injected intravenously with 10 mCi ^99mTc-sestamibi approximately 1 to 2 hours before surgery.³ An important consideration is that ^99mTc decays with an approximate half-life of 6 hours. It has been shown that intraoperative gamma probe localization is most successful within a very narrow time window of 1 to 3 hours after radiotracer injection.¹^,¹⁵ In our series, the median time from injection to surgery was 90 minutes, with a range from 30 to 420 minutes. Despite this large range, intraoperative radio-guided localization was successful in all cases. More consistent protocols are recommended, but these data suggest that an additional injection or procedure cancellation are not required if delays occur.¹⁶

Alternatively, a same-day protocol can be pursued with a full dose of 20 mCi ^99mTc-sestamibi in the nuclear medicine department on the day of surgery; scintigraphy for localization is performed at 20 minutes and 2 hours postinjection.¹⁷ Gamma probe–directed minimally invasive parathyroidectomy was performed approximately 3 hours following initial radiotracer injection. This protocol is advantageous in that it offers a same-day experience for the patient. At our institutions, this is occasionally utilized for patients who live some distance away or for patients with hypercalcemic crisis requiring urgent operative intervention.

Background Counts

The localization of hyperfunctioning parathyroid tissue by radioguidance is based on the detection of radiotracer counts above background counts. ^99mTc-sestamibi washes out of the thyroid gland faster than hyperfunctioning parathyroid tissue. Consequently, an enlarged parathyroid gland should have higher counts than the thyroid. The background counts are based on thyroid gland activity and is set based on the thyroid isthmus (see figure 64-1). Therefore, our first step intraoperatively is to place the gamma probe on the thyroid isthmus to determine background counts (see Figure 64-1).

Figure 64-1 Background counts. The gamma probe is placed over the thyroid isthmus to measure the background counts.

A small 1- to 3-cm central incision is made, regardless of the presumed side of the lesion. The incision is placed in a skin fold just under the cricoid cartilage. One advantage to this approach is its familiarity to general surgeons. Moreover, this facilitates exploration of the opposite side of the neck if necessary. A lateral approach is best utilized in the reoperative neck. The most commonly missed adenomas are the superior glands, which are easier and more directly approached laterally.

Finding the Hyperfunctioning Gland: In Vivo Counts

Once the incision is made and the sternohyoid and sternothyroid muscles are retracted, the gamma probe is inserted into the skin incision directly over the presumed location of the adenoma (Figure 64-2). Intraoperative scanning is performed looking for radionuclide counts greater than background in order to localize abnormal parathyroid glands. It is crucial to position the probe at different angles to triangulate counts to ensure specificity. The counts obtained by scanning on the identified enlarged parathyroid gland in situ are recorded as in vivo counts and expressed as a percentage of the background counts.

Figure 64-2 In vivo counts. Once the incision is made and the sternohyoid and sternothyroid muscles are retracted, the gamma probe is inserted into the skin incision directly over the presumed location of the adenoma. Parathyroid tissue is identified with values that are 150% of the background after allowing the probe to rest for 2 to 3 seconds.

An in vivo-to-background percentage higher than 150% strongly suggests the presence of a parathyroid adenoma.¹⁵ In more than 180 enlarged parathyroid glands, a mean in vivo count of 150% of background was demonstrated;¹⁸ moreover, all hyperfunctioning glands had in vivo counts that were greater than background. The neck is routinely scanned during the dissection to determine the trajectory to the hyperfunctioning parathyroid gland, minimizing the amount the tissue dissected.

Removal of the Parathyroid Gland: Ex Vivo Counts and the “20% Rule”

After excision of the enlarged parathyroid, the tissue is placed on top of the gamma probe while directed away from the patient to determine ex vivo counts (Figure 64-3). Ex vivo counts are also expressed as a percentage of background counts. If the ex vivo parathyroid count is greater than 20% of background, the tissue is identified as parathyroid adenoma (i.e., the “20% rule”).¹² In an earlier study of 180 resected parathyroid glands, 179 had ex vivo counts greater than 20% of background. Importantly, no fragments of fat, thyroid, or lymph node had counts greater than 20% of background, emphasizing the specificity of the cutoff.¹⁹^–²¹ Thus, the 20% rule functions quite well overall.

Figure 64-3 Ex vivo counts. The excised parathyroid gland is placed on top of the gamma probe while directed away from the patient to determine ex vivo counts. If the ex vivo parathyroid count is greater than 20% of the background, the tissue is identified as parathyroid.

We have found that the mean ex vivo counts tend to be higher in parathyroid adenomas when compared to hyperplastic glands. However, although the mean ex vivo counts differ between the adenomatous and hyperplastic glands, there is significant overlap in the distribution of ex vivo counts within these two groups. Although an ex vivo count greater than 20% of background confirms resection of parathyroid tissue, the exact ex vivo count is not specific enough to predict the etiology of hyperparathyroidism.

Once the intraoperative PTH level has fallen 50% below baseline, the surgical field is thoroughly examined for any signs of bleeding. Bovie cautery and forceps are used to achieve hemostasis. The strap muscles are closed with a running 2-0 Vicryl suture, and the platysma is reapproximated with a running 3-0 Vicryl suture. To decrease postoperative analgesic use, between 20 and 30 mL of 0.25% Marcaine (1:200,000 bupivacaine:epinephrine) is injected into the surrounding tissues prior to skin closure. The skin is closed with a subcuticular 5-0 Prolene.

Protocol 2: Arkansas

After the induction of either endotracheal or laryngeal mask airway (LMA) anesthesia, the neck is extended with a roll placed between the shoulders, and the head is placed on a circular headrest.²² A 2-cm horizontal incision is created in the midline halfway between the cricoid and the sternal notch. Subcutaneous electrocautery dissection is performed, undermining in all directions, and the subcutaneous fat is grabbed with a forceps. This subcutaneous fat is removed off of the strap muscles. The adipose tissue is reserved as a radiation count negative control. A Gelpe retractor is then used to expose the surgical site, the handle placed opposite the side of the anticipated adenoma.

The strap muscles are identified and divided in the midline raphe. Next, the strap muscles are undermined with cautery in a medial to lateral direction, arching over the anterior surface of the thyroid without injuring its capsule. The strap muscles are retracted with the surgeon’s retractor of choice. A Kitner dissector is used to retract the thyroid lobe medially while a second dissector pushes laterally to open up the tracheoesophageal grove. Blunt dissection is performed until the adenoma is identified. Two parathyroid glands can be identified in a unilateral exploration. This approach is repeated on the opposite side if indicated. Hemostasis is maintained with bipolar cautery forceps. It is also used for division of small blood vessels.

Care is taken to lift the adenoma out of the wound with forceps while not damaging its capsule and potentially spilling its contents. As the adenoma is lifted, blunt spreading and bipolar cautery are used to dissect away adjacent tissue and the parathyroid pedicle. Hemostasis is obtained, the wound is irrigated, a piece of Surgicel is placed in the tracheoesophageal groove, and skin edges are reapproximated in two layers. The time from incision to gland identification ranges from 5 to 20 minutes; a routine procedure is completed in less than 30 minutes. Patients are discharged the same day with rare exceptions.

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