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Minimally Invasive Surgery of the Parathyroid

Sections Minimally Invasive Surgery of the Parathyroid
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Overview

Background

In the past, parathyroidectomy primarily involved an open procedure with a neck incision, not unlike that used for a thyroidectomy. This procedure required the inspection of all 4 parathyroid glands, with removal of the offending gland or glands. Its major indication was for primary hyperparathyroidism, with usually the largest parathyroid being the suspected cause resulting in its subsequent removal. Eventually, intraoperative physiologic studies improved the likelihood that the offending gland or glands were removed. Concurrently, there has been a push for less invasive procedures, with goals of decreased operative and recovery times, better cosmesis, and decreased complications.

This article discusses minimally procedures for parathyroidectomy (MIP), focusing on minimally invasive parathyroidectomy (MIP).

Embryology/Anatomy

The parathyroid glands are derived from the third and fourth pharyngeal pouches. The inferior parathyroids come from the third pharyngeal pouch and follow the descent of the thymus until they rest on the dorsal surface of the thyroid, usually in a plane anterior to the superior parathyroids. In contrast, the superior parathyroids develop from the fourth branchial arch and descend into the neck with the thyroid gland. The inferior thyroid artery usually provides the vascular supply for both the superior and inferior parathyroid glands, although 20% of superior parathyroids may be supplied solely by the superior thyroid artery.^[1] In general, the superior parathyroid glands lie in a vertical plane posterior to the recurrent laryngeal nerve, whereas the inferior parathyroid glands are anterior to this nerve. The superior parathyroid glands are generally found 1 cm superior to the intersection of the inferior thyroid artery and the recurrent laryngeal nerve.

There are usually 2 glands on each side of the thyroid, although 3–7% of the population may have an accessory or supernumerary parathyroid gland, and 3–6% may have fewer than 4 glands. The glands may occasionally descend incompletely or too far and can lie in aberrant locations, including the mediastinum, the bifurcation of the carotids, or in the retroesophageal or retropharyngeal regions. In addition, the relative increased path of descent of the inferior parathyroid glands tend to have a more variable location than the superior parathyroids. Overall, the most common location of aberrant parathyroid glands is in the anterior mediastinum.

Of the possible aberrant locations in which parathyroid glands are found, intrathyroidal parathyroid glands have been described, although there is some controversy surrounding their existence. Some state that these parathyroids are not indeed within the thyroid parenchyma itself but are instead within the thyroid capsule. Others describe true intrathyroidal parathyroids with an incidence of 0.5–3%.^[1]

Indications

The main indication for a parathyroidectomy is primary hyperparathyroidism. Classically, these patients are referred to an otolaryngologist's practice by either a primary care physician or endocrinologist for surgical intervention.

Classically, patients are described as having signs and symptoms following the mnemonic “bones, stones, groans, and psychiatric overtones”—including skeletal complications (pathologic fractures, osteitis fibrosa cystic, osteoporosis), renal disease (nephrolithiasis, nephrocalcinosis, diabetes insipidus, renal failure), gastrointestinal symptoms (constipation, nausea, vomiting), and psychiatric (mood swings, depression, psychosis) and central nervous system (lethargy, ataxia, delirium) manifestations.^[1]

However, in modern times the vast majority of patients present with subtle symptoms of fatigue, emotional lability, poor sleep, mental fogginess, and "aches and pains" together with elevated serum calcium and parathyroid hormone (PTH).^[2]

For these patients with so-called asymptomatic hyperparathyroidism, surgery is indicated when it falls within surgical guidelines by meeting criteria based on the National Institutes of Health (NIH) indications:

Serum calcium concentration of 1.0 mg/dl or more above the upper limit of normal
T-score at the hip, lumbar spine, or distal radius less than -2.5 or previous vertebral fracture
eGFR less than 60 mL/min, 24-hour urinary calcium > 400 mg/day, nephrolithiasis, or nephrocalcinosis
Age younger than 50 years ^[3]

Contraindications

In the past, radiation exposure to the head and neck has been a listed contraindication to MIP, secondary to the increased risk of multiglandular disease and the possibility of coexisting thyroid cancer.^[4] However, a prospective cohort study by Rahbari et al to determine the effectiveness of MIP showed no significant differences between concurrent thyroid diseases, the incidence of multiglandular parathyroid disease, or the eventual operation chosen between the cohort that had a history of head and neck radiation and the cohort that had no exposure to radiation.^[5]

It is important to distinguish patients with familial hypocalciuric hypercalcemia from patients with true primary hyperparathyroidism, as the first group would not benefit from a parathyroidectomy. A 24-hour urine calcium accomplishes this.

Procedure planning

As part of the preoperative planning for MIP, it is essential to localize the offending parathyroid gland. At the authors’ institution, patients may undergo an ultrasound and fused SPECT/CT scan or 4-dimensional CT of the neck.

A meta-analysis by Cheung et al compared various imaging studies to aid with localization. It determined that SPECT had a pooled sensitivity and positive predictive value of 78.9% and 90.7%, respectively, based on 9 studies (range of sensitivities between 61.4% and 100% in analyzed studies). For patients with radiotracer localization to one gland, MIP should be offered, with the caution that a parathyroid exploration may still be necessary based on intraoperative findings.^[6]

Aside from using a radioactive tracer, ultrasound is commonly used to identify parathyroid adenomas, although its use is subject to operator technique and interpretation. Sensitivities ranged from 48.3% to 96.2% in the studies analyzed in the meta-analysis by Cheung et al. The pooled sensitivity and positive predictive value for ultrasound based on 19 studies were 76.1% and 93.2%, respectively.^[6]

Miyabe described 3-dimensional ultrasonography, which provides coronal images similar to a surgeon’s view. This technique resulted in a lower operative time when compared with traditional 2-dimensional ultrasonography.^[7]

Another novel approach described by D'Agostino et al used a 3-dimensional rendering of a CT scan that is then referenced intraoperatively to aid in localization. This process requires that the patient has a CT scan performed preoperatively with neck extension. The rendered scan is then overlaid over a visual image of the patient’s neck in the operating room. A separate technician assists with manipulating the rendered scan as it pertains to the operation. The authors describe a 77.2% and 64.9% accuracy of the CT scan with regard to the correct identification of laterality and location, respectively.^[8]

Four-dimensional computed tomography (4D-CT) is another option for preoperative localization of hyperactive and ectopic parathyroid glands.^[9] The most commonly utilized method involves a protocol consisting of pre-contrast, early-delayed, and late-delayed phases.^[10] This technique utilizes standard multiplanar CT scanning but measures changes in contrast attenuation over time. The reported sensitivity as an initial imaging modality in localizing an adenoma to a quadrant is 60–80%.^[11] Furthermore, Brown et al indicated that this technology might also be helpful when an abnormal gland is not identified by sestamibi scanning (in up to 80% of cases) and may be more sensitive than sestamibi scanning in patients undergoing reoperation.^[12]

Regardless of the localization imaging technique used, the parathyroid surgeon should be skilled at reading, interpreting, and understanding these films.

Outcomes

The reported outcomes from parathyroidectomy for primary hyperparathyroidism are excellent, with success rates nearing 100%. Adil et al reported that 100% of patients who underwent MIP had hyper-functional parathyroid identified and excised, with appropriate reductions in intraoperative PTH levels.^[2] Beyer et al reported 100% rates of eucalcemia (cure) at 3 months following bilateral neck exploration and 99% rates of eucalcemia following MIP (due to 1 failure). Additionally, Adil et al found MIP was associated with lower costs, operating time, and length of stay in the hospital.^[13] A review by Schneider et al found no difference in outcomes between minimally invasive and open approaches, with the exception of increased transient hypocalcemia in the open approach group (1.9% vs 0.1%).^[14] Leder et al reviewed the laryngeal physiology and acoustics of patients before and after MIP and found no differences amongst physiologic or voice acoustic measures.^[15] A meta-analysis by Ospina et al concluded that while both MIP and bilateral neck exploration are associated with high cure rates and low rates of complications, MIP displayed lower rates of hypocalcemia and recurrent laryngeal nerve injury compared to bilateral neck exploration.^[16] MIP also displayed shorter average operative times than bilateral neck exploration.^[17]Overall, while cure rates for primary hyperparathyroidism following parathyroidectomy via bilateral neck exploration and MIP are excellent, MIP offers the potential added benefit of fewer complications, shorter operation time and hospital stay, and subsequent decreased health care cost.

Neurocognitive benefits of parathyroidectomy

Although some patients with primary hyperparathyroidism may be classified asymptomatic, if asked, many report chronic fatigue, malaise, memory impairment, depression, lack of focus, and poor sleep.^[18] The prevalence of hyperparathyroidism increases with age and is particularly high in postmenopausal women. Geriatric patients with age-related decline in cognitive function may be at particular risk for further losses in cognitive ability.^[19] Overall, it has been demonstrated that operative intervention can successfully correct these neurocognitive disturbances with studies indicating improvements in neurocognition and quality of life following parathyroidectomies.^[20]Neurocognitive function and sleep have been shown to be restored to the level of the general population.^[21] Specifically, parathyroidectomy in geriatric patients has been shown to improve neurocognitive deficits significantly.^[22] These improvements have also been shown to occur extremely rapidly with improvements in memory, attention, anxiety, sleep, and other objective measurements seen as early as 1 week following surgery.^[23]

Patient education/Informed consent

Patient instructions

Patients are asked to stop anticoagulating agents 3–5 days before surgery if not medically contraindicated.

Postoperatively, patients are usually discharged the same day. Patients are asked to perform routine skin care for their incision, including hydrogen peroxide and an antibiotic ointment. Sutures are usually removed at the first postoperative visit within the first week. Outpatient management for patients following MIP is supported by Shin et al, who found no differences in complications following outpatient MIP between elderly (70 years and older) and younger patients despite higher preoperative creatinine and PTH levels in the elderly patients.^[24]

Elements of informed consent

A key component of the consent process includes discussing the risk of recurrent laryngeal nerve (RLN) injury. Additionally, the authors obtain patient consent for a possible parathyroid gland exploration if there is a failure to localize the parathyroid adenoma or if there is intraoperative evidence to suggest multiglandular disease. Other risks include persistent hyperparathyroidism, bleeding, infection, hypocalcemia, scarring, and the general risks of anesthesia.

Equipment

The authors use the following tools during surgery:

Basic head-and-neck set - No. 3 knife handle, No. 15 blade, Adson tissue forceps with and without teeth, DeBakey Forceps, Halsted mosquito forceps, Rienhoff swan neck clamp (or burlisher clamp), Allis tissue forceps, Richardson retractor, peanut/Kittner sponges, double-pronged skin hooks
Mini Weitlaner retractor (alternatively, other self-retaining retractors may be used)
Bovie electrocautery, harmonic scalpel, and/or Shaw scalpel
Bipolar electrocautery forceps
Nerve monitoring leads and surface electrode–primed endotracheal tube; nerve stimulator

Patient Preparation

Anesthesia

Unless contraindicated, the authors perform MIPs with the patient under general endotracheal anesthesia.

Shindo et al reviewed MIPs performed using local anesthesia and intravenous sedation at their institution. The study found MIP could be performed safely using this method of anesthesia. In addition, they noted low complication rates and shorter operating times compared to when MIP is performed using general anesthesia.

The literature has also described the use of regional anesthesia via a cervical block. Miccoli et al compared bilateral deep cervical blocks with intravenous sedation to general anesthesia. This study found no significant difference in complications but found shorter operating times and decreased postoperative pain using regional anesthesia.^[25]

Carling et al studied those cases requiring conversion to general anesthesia and found the conversions occurred secondary to concurrent thyroid lesions, evidence of multiglandular disease, or patient discomfort. In all cases (47 of 441), the conversion was performed in a safe, controlled manner.^[26]

A previous report by Inabnet et al. describes the use of local anesthesia without routine sedation during parathyroidectomy. The technique used local anesthetic injection to the skin, strap muscles, and thyroid capsule.^[27]

Positioning

The authors position the patient supine with a gel roll under the shoulders to allow for neck extension.

Monitoring and follow-up

PTH monitoring

If intraoperative PTH values are being used during surgery, vials of blood for PTH levels should be sent 5 minutes following removal. As described in the literature, a drop in the PTH level of 50% is consistent with the removal of the parathyroid adenoma.^{[28, 29, 30]}Leiker et al reviewed PTH half-life data and determined the median half-life to be approximately 4 minutes. Although the half-life was affected by body mass index and age, this was not clinically significant.^[31]

RLN monitoring

Intraoperative nerve monitoring (IONM) of the RLN can serve as an aid and adjunct to MIP. While the RLN is always identified during MIP, using IONM may help prevent a transient injury to the RLN.^[32]

Harrison and Triponez reviewed common intraoperative techniques for primary hyperparathyroidism, including the use of intraoperative parathyroidectomy, gamma probe, frozen section, methylene blue, and IONM. The review notes level II evidence supporting intraoperative PTH monitoring for MIP and level IV evidence supporting the gamma probe or IONM.^[33]

Approach considerations

Depending on the surgical technique, the length of the incision varies from 15 to 40 mm. Additionally, some authors describe placing the incision 20–40 mm above the sternal notch within a skin crease, while others describe placing the incision in a skin crease overlying the suspected adenoma.^{[25, 26, 34, 35]}The authors use a 15- to 25-mm incision placed midline at a level two finger breaths above the clavicles.

Two approaches to the parathyroid are described: the more common anterior approach and a lateral or "backdoor" approach. Depending on the location of the parathyroid adenoma, as well as a history of prior parathyroid or thyroid operation, one approach may be preferred over the other. Shindo et al described using a lateral approach when the parathyroid adenoma is either located posterior to the thyroid lobe, inferior to the thyroid in a plane posterior to the thyroid lobe, or deep to the carotid.^[35]

Anterior approach

The anterior approach involves approaching the thyroid and parathyroids from the midline. After the incision is made, subplatysmal planes should be elevated circumferentially from the thyroid cartilage to the sternal notch. Self-retaining retractors can be used to maximize exposure, and then the sternothyroid muscles should be separated at the midline (electrocautery or the harmonic scalpel can be used). This allows for adequate exposure of the thyroid gland and its overlying fascia. If necessary, the thyroid gland is grasped at two points and medialized. This may be more commonly necessary with an upper rather than lower parathyroid adenoma.

Once the suspicious parathyroid tissue has been identified, careful dissection with blunt instruments is used to free the gland from the surrounding fascia. A harmonic scalpel can be used to simultaneously ligate the vascular supply to the gland and remove the specimen.

It is imperative to obtain hemostasis after parathyroidectomy. This is best performed with selective, careful bipolar cautery. A thin layer of thrombin mesh may be applied if deemed necessary. The neck is then closed in a layered fashion with special attention to meticulous skin closure.

Lateral approach

The lateral approach can still be used with a relatively midline incision,^[35]although it was initially described with an incision overlying the sternocleidomastoid (SCM) muscle.^[36]

Instead of separating the strap muscles at the cervical linea alba, the parathyroid gland is approached by dissecting between the anterior border of the sternocleidomastoid muscle and the lateral aspect of the strap muscles (sternohyoid muscle). Once the anterior border of the SCM is identified, the SCM is retracted laterally to expose the strap muscles. The fascia overlying the strap muscles is incised, and dissection is carried posteriorly to expose the thyroid lobe. Dissection is carried out medial to the carotid sheath and lateral to the thyroid lobule down to the groove. Dissection can then be carried medially (posterior to the thyroid lobule) to expose the region where the parathyroid adenoma can be found.

Once the parathyroid has been identified, a similar procedure described for the anterior approach can be carried out.

Nonlocalizing parathyroid

Despite preoperative localization studies, occasionally, individuals fail to have a single localizing gland. Initial scans may have shown ambiguous results or mildly positive localization or be misleading. Additionally, if multiple localization studies were performed (i.e., ultrasound and sestamibi), they may reveal conflicting results. In the event, intraoperative evidence of multiglandular disease is sought. In these cases, it may be necessary to evaluate the other 3 parathyroid glands.

Ultrasound-guided MIP

Surgeons have described the use of intraoperative ultrasound to confirm localization and removal.^[37]Davis et al and Livingston et al used ultrasound in those patients with sestamibi negative scans and described a 56% and 94% localization rate, respectively.^{[38, 39]}Prasannan et al used surgeon-performed ultrasonography in the preoperative evaluation and intraoperatively, determining it to have a sensitivity and positive predictive value of 82% and 96.3%, respectively, and an 85% correlation with the sestamibi scan.^[40]

Minimally invasive video-assisted parathyroidectomy (MIVAP)

Casserly and Timon describe the gasless MIVAP procedure in detail, initially described by Miccoli et al in 1998.^[41]The patient is positioned without a shoulder roll for extension before a 1.5- to 2-cm midline incision is made 3 cm above the sterna notch. Dissection is carried down to the thyroid gland. The strap muscles are dissected off the gland on the side with the parathyroid adenoma. The dissection is carried into the space between the thyroid capsule and the carotid sheath. After opening this space, a 30° endoscope is introduced, pointing towards the patient's head. Using the view from the endoscope, dissection and removal of the parathyroid gland is carried out.^{[42, 43]}

In 2010, a follow-up report by Casserly et al described the average incision length from MIVAP to be 1.7 cm, which significantly improved scar outcomes compared with a traditional open parathyroidectomy approach.^[34]Lombardi et al performed a thorough review of the literature regarding video-assisted approaches, including fully endoscopic approaches using carbon dioxide insufflation. The review found level II evidence supporting the use of MIVAP over the insufflation-based techniques, and they also found evidence indicating lower pain, shorter operating times, and better scar outcomes compared with "open minimally invasive parathyroidectomy" based on a prospective randomized trial from Poland.^{[44, 45]}

Overlay tissue imaging system

The FDA has approved two devices that prove real-time location of parathyroid tissue: the Fluobeam 800 Clinic Imaging Device from Fluoptics and the Parathyroid Detection PTeye System from AiBiomed. The method of visualizing parathyroid tissue is described by Thomas et al. Parathyroid tissue emits a much higher near-infrared autofluorescence (NIRAF) compared to surrounding neck tissue.^[46]By normalizing the sensor to the thyroid tissue, parathyroid tissue can become easily identifiable by placing a visible green light in real time over the parathyroid tissue. It can overlay a visible image indicating parathyroid tissue versus non-parathyroid tissue through focusing optics directly onto the operative field. The overlay tissue imaging system identified 97% of parathyroid gland compared to the 91% detection rate by surgeon visualization alone.^[47]Another study demonstrated a 100% identification rate with parathyroid tissue consistently showing 2.4 to 8.5 times higher emission intensity.^[46]

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Media Gallery

Location of incision for minimally invasive parathyroidectomy (MIP). The standard (larger) incision is also shown. All MIPs should be performed through a centrally located incision so that both sides of the neck can be examined. This incision allows all 4 parathyroid glands to be visualized.
Radioactivity levels seen with removed parathyroid glands. When using a probe designed for parathyroid surgery (not for sentinel node surgery), the probe can distinguish between fat, lymph nodes, normal parathyroid glands, hyperplastic parathyroid glands, and parathyroid adenomas. Only parathyroid adenomas show more than 20% of background activity. The proper probe must be used.