Transoral Parathyroidectomy

Parathyroid surgery was initially described in 1925 when Felix Mandl, a young surgeon in Vienna, was able to successfully remove a parathyroid tumor from a patient with osteitis fibrosa cystica.[1]  In the decades that followed, few significant technical changes occurred in parathyroid surgery; however, the procedure is now most commonly performed to treat primary hyperparathyroidism.

Traditionally, the standard technique was four-gland exploration with removal of any abnormal or enlarged gland(s). As parathyroid imaging techniques advanced, minimally invasive parathyroidectomy became more commonplace and provided an equally high cure rate, a lower complication rate, a shorter hospital stay, and a large reduction in hospital costs.[2]  This approach uses a small anterior neck incision and targets a single parathyroid gland on the basis of imaging, as well as perioperative adjuncts (eg, gamma probe and intraoperative parathyroid hormone assay).  

The traditional surgical approach drastically changed in 1996 when Gagner[3]  described an endoscopic approach to subtotal parathyroidectomy with dissection in a subplatysmal plane, using four 5-mm trocars placed strategically in the neck. Despite a procedure duration of 5 hours and resultant subcutaneous emphysema, the door had been opened to investigate new approaches to an old surgical procedure.

In the following years, multiple minimally invasive procedures were developed—primarily for thyroidectomy—in an effort to avoid an anterior neck skin incision. Many procedures were described, including robotic[4, 5, 6, 7] and endoscopic[8, 9, 10, 11] approaches from the breast, axilla, or both breast and axilla; however, all necessitated varying degrees of tissue damage to obtain adequate access, as well as skin incisions elsewhere on the body.

In an effort to avoid skin incisions entirely, Witzel et al first proposed the idea of a transoral thyroidectomy in 2008[12]  after successfully performing the procedure via a sublingual approach in living pigs and human cadavers.

In 2010, Karakas et al[13] performed both hemithyroidectomies and parathyroidectomies in pigs and human cadavers. The following year, they published the first description of a transoral parathyroidectomy in two patients.[14]  Although the procedure was successful, one of the two patients suffered from perioperative dysphagia, tongue paresthesia, and hypoglossal nerve palsy, all of which resolved by the 6-week follow-up appointment.

Subsequently, in 2014, the same group published a case series describing their experience with five transoral endoscopic parathyroidectomies.[15]  Two of the five patients required conversion to an open technique, three developed hematomas and dysphagia, one had persistent dysgeusia and transient hypoglossal nerve palsy, and one developed transient recurrent laryngeal nerve palsy. The procedure was therefore deemed a feasible option but not a safe or viable one.[15]

The idea of endoscopic transoral parathyroidectomy was revisited in a 2016 article that described a transoral vestibular approach, which avoided the floor of the mouth and the associated complications.[16]  Sasanakietkul et al performed 12 parathyroidectomies via three incisions in the oral vestibule with promising results. In this series, there was one transient recurrent laryngeal nerve injury (symptom resolution within 1 month), no need for conversion to open surgery, and no other complications (eg, infection or neurovascular injury).

The conclusion that transoral parathyroidectomy is both a safe and a feasible surgical option was further supported by a subsequent series from Russell et al.[17]  Using a similar transoral vestibular approach, the authors performed 12 thyroidectomies and two parathyroidectomies using either an endoscopic or a robotic technique, with no surgical complications in either parathyroidectomy patient and no permanent complications in the thyroidectomy group.

The endoscopic versions of these procedures are sometimes referred to collectively as TOET/PVA (transoral endoscopic thyroidectomy/parathyroidectomy via the vestibular approach) or separately as TOETVA (transoral endoscopic thyroidectomy via the vestibular approach) and TOEPVA (transoral endoscopic parathyroidectomy via the vestibular approach).[18]  By 2020, more than 2000 TOET/PVA procedures had been performed, including more than 400 in North America.

The current literature suggests that TOET/PVA is a safe and viable alternative for patients who are concerned about the aesthetics of an anterior neck incision.[19, 20, 21] Additional study (eg, of complications, expense, instrument limitations, and overall safety) is warranted.[22]

The indications for parathyroidectomy in general and the workup to determine whether surgical intervention is appropriate are discussed elsewhere (for more information, see Parathyroidectomy). The indications for the transoral approach to parathyroidectomy are exclusively cosmetic in nature. Candidates would include patients with a history of hypertrophic scarring or keloids, as well as those with a particular interest in avoiding a cervical skin incision.

Transoral parathyroidectomy is contraindicated in patients who have a history of significant thyroiditis, have undergone previous neck surgery or irradiation, or have a suspected malignancy. In a description of this approach for thyroidectomy, Anuwong also included the presence of dental braces as a contraindication.[23]

Other relative contraindications are the presence of large thyroid nodules or a significantly enlarged thyroid gland. In one study, patients were excluded if a thyroid nodule larger than 6 cm was found on preoperative imaging[17] or if the thyroid gland was larger than 10 cm in diameter.[23] Although not explicitly mentioned in current reports, additional relative contraindications to consider would include obesity and inability to achieve adequate neck extension (eg, from previous cervical spine injury or fixation).

Given that this surgical technique is still at a relatively early stage of development, it is possible that additional contraindications may become apparent in the future. The contraindications for traditional parathyroidectomy still apply (see Parathyroidectomy).

Anatomy

Although the anatomy of a traditional open parathyroidectomy remains relevant, additional factors must be considered during a transoral approach. The method that has proved to be best tolerated and to cause the fewest complications employs vestibular incisions only (see the image below).

The midline incision does not place any neurovascular structures at risk. On the other hand, the lateral incisions (used for placement of 5-mm trocars), if placed incorrectly, may approach the mental foramen and the facial vessels as they cross the mandibular body.

An anatomic study by Cai et al evaluated the position of these structures in five human cadavers.[24]  The mental foramen—the exit point for the mental nerve and vessels—is found in the midpoint of the mandibular body, typically below the second premolar tooth. The mean distance from the mental foramen to the median mandibular point is approximately 3.5 cm, and the mean distance to the location where the facial vessels cross the mandibular body is 6.0 cm.

These landmarks are critical for determining where to make the oral vestibule incisions, all of which should remain medial to the mental foramen. Of note, the marginal mandibular branch of the facial nerve is unlikely to be injured during this procedure, given its superficial location. After the initial incisions, the development of submental and subplatysmal planes will ensure that no critical structures are at risk for injury during the approach.

With any parathyroid surgery, an understanding of parathyroid gland anatomy and embryology is critically important for ensuring that the procedure is completed safely and effectively. (For a more detailed discussion, see Parathyroid Gland Anatomy.)

Two case series describing transoral vestibular parathyroidectomy showed good outcomes.[16, 17] In the 14 described parathyroidectomies, the cure rate was 100%, with no postoperative infections or permanent complications; however, the follow-up in one study[16] was only 30 days, which makes it harder to determine whether the operation was in fact curative. As noted, this remains a relatively novel surgical technique, and available data are therefore quite limited.

It should be noted that this technique may be less than ideal for four-gland exploration or for excision of intrathyroidal parathyroid glands, given the longer operating times.[16]

Bhargav et al prospectively evaluated the feasibility and safety of transoral lower-vestibular endoscopic parathyroidectomy in 12 patients with hyperparathyroidism.[25] The mean operating time was 112 ± 15 minutes (range, 95-160). Postoperatively, there was no major morbidity, hypocalcemia, or recurrent laryngeal nerve palsy. Cure and diagnosis were confirmed by a fall of more than 50% fall in intraoperative parathyroid hormone levels and histopathology (all were benign solitary adenomas).

Elements of informed consent

The details of the procedure should be clearly explained, including the novel nature of the procedure and the consensus that open parathyroidectomy continues to be the gold standard. The risks of open parathyroidectomy should be reviewed, in that they are all relevant to transoral parathyroidectomy as well. These risks include, but are not limited to, the following:

• Scar formation and complications related to the incision
• Injury to the recurrent and superior laryngeal nerves
• Persistent or recurrent hyperparathyroidism
• Postoperative hypocalcemia
• Hematoma or seroma formation
• Damage to adjacent structures
• Need for further surgery

In addition to the risks associated with a standard approach to parathyroidectomy, the following risks that are specific to transoral parathyroidectomy should be discussed:

• Increased risk of infection as a consequence of the approach through the oral cavity
• Mental nerve injury with resultant lip or chin numbness
• Possible conversion to an open procedure with an anterior neck incision
• Injury to lips, gums, and teeth
• Subcutaneous emphysema
• Pneumomediastinum

Diagnosis of hyperparathyroidism and candidacy for surgery should be established and reviewed with the patient. As with any elective surgical procedure, medical conditions should be optimized, and anticoagulant medications should be withheld prior to surgery. Preoperative laboratory tests (especially parathyroid hormone [PTH] and serum calcium) should be ordered during the medical workup.

Preoperative parathyroid localization studies should be completed before the operation, with all imaging reviewed by and available to the surgeon.[26] Use of intraoperative localization may also be considered (eg, by means of rapid PTH or gamma probe).

See Parathyroidectomy for a review of the National Institutes of Health (NIH) guidelines for surgery in asymptomatic patients, as well as a detailed discussion of preoperative and intraoperative parathyroid location studies.

The surgical equipment used in the procedure will depend to a large extent on the surgeon’s preference and comfort level. A key determinant is whether the transoral parathyroidectomy is to be performed endoscopically or robotically.

If the endoscopic approach is followed, one 10-mm trocar is used in the midline incision, and two 5-mm trocars are used, one in each of the two lateral incisions. Dissection involves a combination of hydrodissection with a Veress needle and blunt dissection with a dilator. An L-hook with monopolar cautery should be available, along with 30° 10-mm endoscopes and other standard endoscopic instrumentation. Surgical drains may be placed at the conclusion of the procedure, and supplies for a pressure dressing will be needed.

If the robotic approach is followed, the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA) and associated instruments will have to be available, along with the aforementioned supplies and equipment.

Anesthesia

General anesthesia should be used, with a nerve-monitoring endotracheal tube (eg, NIM TriVantage EMG Endotracheal Tube; Medtronic, Minneapolis, MN) taped near the oral commissure.

Positioning

The patient should be placed supine on the operating room table, with a shoulder roll positioned to allow slight neck extension. The arms should be tucked to the side so that the surgeon can stand on either side of the patient in the event that the transoral parathyroidectomy is converted to an open procedure. If intraoperative PTH levels are drawn, access to an intravascular site must be considered.

Intraoperative nerve monitoring of the vocal cords should be available throughout the procedure. Specific follow-up times are based on the individual surgeon's preference. Whatever the timing of follow-up, however, vocal cord function should be assessed on the first postoperative visit, and repeat laboratory tests should be obtained to rule out recurrent or persistent hyperparathyroidism. 

The sublingual approach to transoral parathyroidectomy was the first to be described[12, 13, 14, 15] ; however, it was associated with a high rate of complications—including hematoma, dysphagia, hypoglossal and recurrent laryngeal nerve injury, and dysgeusia—and has since been largely abandoned in favor of the vestibular approach described by Anuwong.[16]  At present, the vestibular approach appears to be the safest and most appropriate surgical option when a transoral approach to parathyroidectomy is being considered.

The procedure is sometimes referred to as TOEPVA (transoral endoscopic parathyroidectomy via the vestibular approach). Robotic approaches have been described.[27, 28]

As noted previously, the open approach to parathyroidectomy remains the standard of care, and the risks and benefits of alternative surgical approaches should be discussed with the patient in detail.

As described in the literature,[16, 17]  this endoscopic approach to parathyroidectomy is done entirely via transoral incisions (see the image below).

After induction of general anesthesia and intubation with a nerve-monitoring endotracheal tube, a midline 10-mm incision is made inside the lower lip, approximately 1 cm above the gingivobuccal sulcus, to preserve a cuff of mucosa for closure. Electrocauterization and blunt dissection are employed to expose the mandibular periosteum. Hydrodissection is then accomplished by injecting 1:500,000 epinephrine from inside the incision toward the anterior neck through a Veress needle or a fat injection syringe.

The working space is created by means of blunt dissection with a dilator in a submental and subplatysmal plane. Next, two 5-mm lateral incisions are made on either side of the midline incision, approximately at the junction between the canines and the incisors. Endoscopic ports are then placed, with a 10-mm trocar inserted through the midline incision and two 5-mm trocars inserted in the two lateral incisions. Insufflation is begun at a pressure of 5-7 mm Hg. If a robotic procedure is being done, the robot is docked at this time.

Additional dissection is carried out to create an optimal working space with a subplatysmal pocket that should extend inferiorly to the level of the sternum and laterally to each sternocleidomastoid muscle. The midline raphe of the strap muscles is divided, and the strap muscles are dissected laterally to expose the thyroid gland. These muscles can be retracted laterally by using 2.0 silk as an external hanging suture.

The dissection continues in a capsular plane around the thyroid gland. The upper parathyroid glands are typically found in this capsular plane at the posterior aspect of the superior pole. If the parathyroid glands are prominent, they can be seen with retraction of the thyroid medially. If they are normal in size, dissection of the superior thyroid vessels with an ultrasonic scalpel may be required for better mobilization of the superior pole of the thyroid.

Removal of the lower parathyroid glands may necessitate identification and dissection of the recurrent laryngeal nerve; these glands are often located at the junction between this nerve and the inferior thyroid artery. The abnormal gland(s) can be removed with an ultrasonic scalpel and retrieved with an endoscopic bag through the midline vestibular incision.

Intraoperative frozen specimens can be sent to confirm removal of abnormal parathyroid tissue. Additionally, an intraoperative parathyroid hormone (PTH) level may be obtained 10-15 minutes after removal of the abnormal gland(s) to assist in confirming whether further exploration is needed (see Parathyroidectomy).

Hemostasis is confirmed and the surgical site irrigated. The strap muscles are reapproximated with 3-0 absorbable suture, and the oral vestibule incisions are closed with layered absorbable sutures. A compression dressing is then applied over the neck and chin, and the patient is transferred to the anesthesia team for extubation.

Postoperative management is largely based on individual surgeons' preferences. Typically, however, patients are monitored at least overnight with regular (eg, every 6 hr) serum calcium checks and are discharged home the next day if calcium levels remain stable. Serum calcium should continue to be followed on an outpatient basis, as should postoperative vocal cord function via flexible fiberoptic laryngoscopy or indirect mirror examination.

The pressure dressing placed in the operating room can be removed on postoperative day 1, before the patient is discharged home. Follow-up appointments should check for any fluid that may have collected in the submentum or anterior neck because of the large subplatysmal space created during the parathyroidectomy.

As with open thyroid and parathyroid surgical procedures, one of the most serious complications is injury to the recurrent and superior laryngeal nerves. Identification and careful dissection of these structures during the operation are therefore critical, particularly if there is any difficulty in identifying the abnormal gland(s). Additional complications include hematoma or seroma, postoperative hypocalcemia, failure to correct hyperparathyroidism and hypercalcemia, and the need for further procedures in the future.

As with any surgical procedure, bleeding and infection are potential complications. Because transoral parathyroidectomy is a clean-contaminated procedure, there is an increased risk of infection, though a number of case reports failed to document perioperative infection or abscess with this technique.[14, 15, 16, 17, 23]

Several other complications are specific to this surgical approach. The mental nerves are at risk for injury if the oral vestibule incisions are improperly placed. The creation of the subplatysmal pocket and the use of CO2 insufflation give rise to a potential for subcutaneous emphysema, pneumomediastinum, or both. This subplatysmal pocket may also increase the rate of postoperative hematoma or seroma, though, on the basis of the current literature, this appears to be a rare complication.[16, 17, 23]

A review of 32 Turkish patients who underwent successful TOEPVA at 11 centers cited a 19% rate of complications.[29] These included ecchymosis, subcutaneous emphysema, nasal bleeding, surgical-site infection, and seroma; however, there were no recurrent nerve palsies, nor were there any mental nerve root or branch injuries.