Ann Thorac Surg 2005;80:1262-1265
© 2005 The Society of Thoracic Surgeons
Original article: General thoracic
Radioguided Thoracoscopic Mediastinal Parathyroidectomy With Intraoperative Parathyroid Hormone Testing
Tracey L. Weigel, MD
a
,
*
,
Jennifer Murphy, MD
a
,
Loay Kabbani, MD
a
,
Anna Ibele, MD
b
,
Herbert Chen, MD
a
a Section of Thoracic, Department of Surgery, University of Wisconsin, Madison, Wisconsin
b Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, Madison, Wisconsin
Accepted for publication April 14, 2005.
* Address reprint requests to Dr Weigel, Thoracic Surgery, CSC H4/346, 600 Highland Ave, Madison, WI 53792-3236 (Email: weigel{at}surgery.wisc.edu).
Presented at the Poster Session of the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.
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Abstract
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BACKGROUND: Primary hyperparathyroidism is the leading cause of hypercalcemia in the United States. The goal of this study was to evaluate the feasibility of radioguided thoracoscopic mediastinal parathyroidectomy and intraoperative immunoreactive parathyroid hormone (iPTH) level testing to guide completeness of resection.
METHODS: Mediastinal parathyroidectomy was performed thoracoscopically with intraoperative radioguidance using a hand-held gamma probe after injection of 10 mci of TC-99m sestamibi. Parathyroid excision was confirmed by ex vivo measurement of specimen radioactivity greater than 20% of background. Complete resection was confirmed by a greater than 50% decrease in serum iPTH level at 5 minutes postresection.
RESULTS: Four patients had mediastinal parathyroid glands successfully localized and resected thoracoscopically. Mean weight of the excised parathyroid adenoma was 1,714 mg (range, 425 to 4,400 mg). Baseline iPTH levels decreased from a mean of 202 to 39 pg/dL 5 minutes postresection. One patient underwent radioguided resection of a second enlarged cervical parathyroid adenoma at the same setting when his intraoperative iPTH levels failed to fall below 50% of baseline, despite resection of a 440 mg mediastinal parathyroid gland. Median hospital stay was one day. All mediastinal parathyroid glands resected were confirmed adenomas on final histologic examination. All patients were normocalcemic at follow-up (mean, 25 months), indicating cure.
CONCLUSIONS: Thoracoscopic mediastinal parathyroidectomy with intraoperative iPTH level monitoring is safe and effective. Radioguidance facilitates parathyroid localization. Ex vivo specimen radioactivity of greater than 20% of background confirms parathyroid resection and obviates the need for costly, time-consuming frozen section analysis. A 50% decrease in baseline iPTH level 5 minutes postresection confirms complete resection of parathyroid adenomas.
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Introduction
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Primary hyperparathyroidism is the leading cause of hypercalcemia in the United States. It is estimated that about 0.1% to 0.5% of the population have this disease, and up to 1% of people greater than 70 years of age are affected [1]. Approximately 85% of all cases are secondary to single adenomas. However, nearly 25% of parathyroid glands are ectopic, and 2% are not accessible to standard cervical surgical approaches because of locations deep in the mediastinum or high in the neck [2].
For these ectopic mediastinal parathyroid glands, resection was traditionally approached by median sternotomy. Although effective, sternotomy for parathyroid resection is associated with significant morbidity and a minimum 2 to 3 day hospitalization. Minimally invasive techniques such as video-assisted thoracoscopic surgery (VATS) avoids the morbidity associated with sternotomy and may result in shorter hospital stay and overall cost.
Preoperative and intraoperative localization and monitoring can be used to guide VATS resection so that a comparable success rate to sternotomy is achieved. Preoperative localization studies include scintigraphy, computed tomography (CT), magnetic resonance imaging, and ultrasound. Accurate localization is necessary to direct resection by minimally invasive techniques such as VATS especially when ectopic glands are located within, for example, fatty or thymic tissue, where they cannot be directly visualized.
At our institution we use preoperative localization with Tc-99m sestamibi-single photon emission computed tomography (SPECT) scanning to define the anatomy and direct dissection if the ectopic gland is located in the mediastinum. Using VATS guided by a hand held gamma probe (Neoprobe 2000; Neoprobe Corp, Dublin, OH), the ectopic gland is located and excised. Complete excision is confirmed with an intraoperative immunoreactive parathyroid hormone (iPTH) assay. In this paper we report our experience with four patients who underwent a radioguided VATS parathyroid resection at our institution.
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Material and Methods
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Four patients had mediastinal parathyroid adenomas identified by preoperative Technetium 99m (Tc-99m)-sestamibi-SPECT scanning (Fig 1), and an abnormal mass in the mediastinum on preoperative CT scan. (One of these four had previous unsuccessful neck exploration.) Ten milliCuries of Tc-99m-sestamibi was administered an average of 157 minutes (50 to 240 minutes) preoperatively. This dosage of Tc-99m-sestamibi is half the dose utilized for Tc-99m-sestamibi-SPECT scanning and is given to allow intraoperative localization with the gamma probe (Fig 2). After anesthesia induction, single lung ventilation was achieved using a double lumen endotracheal tube. Left VATS was preformed using two 5 mm ports in the fourth and seventh intercostal spaces in the posterior axillary line and one 11.5 mm port in the fourth intercostal space in the midclavicular line; the latter was used to introduce a sterile gamma probe. In these patients, we utilized the Neoprobe 2000 (Neoprobe). The "background counts" were measured on the distal lung while compressed. When the gamma probe is utilized for neck explorations for primary hyperparathyroidism, the background counts are normally measured on the thyroid gland. During VATS, the lung is used rather than the thyroid, and provides the background counts reflecting uptake in normal tissues. Abnormal parathyroid tissue uptakes Tc-99m-sestamibi more intensely. The mediastinal tissues are then scanned with the gamma probe looking for counts above the background counts to determine the exact location of the parathyroid adenoma in the chest. After localization with the gamma probe, the adenoma was resected with a Harmonic scalpel (Ethicon Endo-Surgery, Inc, Cincinnati, OH). Excision of parathyroid tissue was confirmed by an ex vivo specimen radioactivity measurement greater than 20% of the background counts. We, and others [3, 4], have previously shown that abnormal, hyperplastic parathyroid tissue always has ex vivo counts greater than 20% of the background while fat, lymph nodes, and thyroid tissue all have counts less than 20% of background. While ex vivo gamma counts can determine whether or not abnormal parathyroid tissue has been resected, it cannot predict whether or not other abnormal parathyroids are present (second adenomas). Thus, we utilized intraoperative iPTH monitoring as previously describe by our group [5, 6]. A PTH level is drawn from a peripheral vein prior to surgical incision and serves as the "baseline" level. After resection of the target lesion by VATS, PTH levels are drawn after 5, 10, and 15 minutes. Our criterion for a curative resection is a greater than 50% drop in intraoperative PTH levels compared with baseline at 5, 10, or 15 minutes. If a greater than 50% drop occurs, the operation is terminated. If the PTH level fails to fall, the surgeon then explores the neck for a second adenoma or additional hyperplasic glands. Following resection of the second adenoma and/or other enlarged parathyroids, the PTH level is checked again after an additional 5 and 10 minutes. A 24F chest tube is placed prior to closure.
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Results
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All patients had elevated serum calcium and PTH levels preoperatively (Table 1). Four patients had mediastinal parathyroid glands successfully localized with the gamma probe and resected by VATS. Mean weight of the excised parathyroid adenoma was 1,714 mg (range, 425 to 4,400 mg). In three patients, the intraoperative PTH level drawn 5 minutes after resection of the mediastinal parathyroid adenoma fell greater than 50%. In patient No. 1, the preincision PTH level was 195 pg/mL. Five minutes after resection of the parathyroid adenoma, the PTH fell by 87% to 25 pg/mL. Similarly, patients No. 2 and No. 3 had drops in their PTH levels 5 minutes after resection of the target mediastinal parathyroid (52% and 82%, respectively). All 3 of these patients had normal calcium and PTH levels postoperatively indicating cure of their primary hyperparathyroidism. However, patient No. 4 did not have an appropriate 50% drop in intraoperative PTH levels after resection of the 440 mg mediastinal parathyroid. The PTH levels in this patient started at 168 pg/mL and fell to only 129 pg/mL (a 23% drop). Therefore, under the same anesthesia, the patient underwent a neck exploration for a second parathyroid adenoma. After resection of the second adenoma in the neck, the intraoperative PTH then fell to 53 pg/mL (68% drop). This patient was also normocalcemic postoperatively. All mediastinal parathyroid glands resected were adenomas on final histologic examination. All 4 patients were normocalcemic at follow-up times 13, 22, 26, and 37 months postoperatively. There were no perioperative complications and mean hospital stay was 1.0 day.
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Comment
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The parathyroid glands are derived from the third and fourth branchial pouches and descend with the thyroid and thymus into the neck to their final position posterior to the thyroid gland. In approximately 25% of cases of hyperparathyroidism, the hyperfunctioning gland is found to be in an ectopic location. Approximately 2% of ectopic parathyroid adenomas are located deep within the mediastinum and are inaccessible by standard cervical approaches [7].
Historically the surgical approach for these descended mediastinal parathyroid adenomas has been sternotomy and mediastinal exploration. Sternotomy, however, is associated with significant morbidity including bleeding and infection. Furthermore, patients undergoing sternotomy, whether partial or complete, have an increased length of hospitalization, pain, and a prolonged period of recovery [7, 8].
As the use of Tc-99m-sestamibi scanning has become the standard of care for the preoperative localization of parathyroid adenomas, so has the practice of minimally invasive cervical parathyroid adenoma resection (MIP) [5, 9, 10]. In MIP, radioguidance can be used to direct anatomic dissection (Fig 3), and more importantly to confirm excision of parathyroid tissue [11]. Adenoma resection is achieved through a small cervical incision with minimal risk to the recurrent laryngeal nerve, as excessive dissection is not required. More significantly, confirmation of adenoma excision is immediate, and the need for costly and time-consuming frozen sections is avoided.
The use of intraoperative parathyroid hormone testing has added to the minimally invasive approach by accurately confirming the removal of the causative parathyroid adenoma [3, 5, 10, 12, 13]. Furthermore, intraoperative PTH testing allows for the exclusion of the diagnoses of parathyroid hyperplasia and multiple parathyroid adenoma.
The application of these technologies to the problem of the mediastinal adenoma appears to have yielded similar results. Patients with mediastinal parathyroid adenomas confirmed by Tc-99m-sestamibi scanning were injected with Tc-99m-sestamibi and subsequently underwent VATS. The gamma probe allows for rapid localization of the suspect adenoma, thus minimizing dissection in the mediastinum. The VATS also allows for excellent visualization of the recurrent laryngeal and phrenic nerves, thereby minimizing risk of injury to these structures. Ex vivo gamma probe measurement of tracer uptake in the resected adenoma of greater than 20% confirms the removal of the involved gland and obviates immediate frozen section pathologic review [11]. Intraoperative PTH testing, as in cervical minimally invasive parathyroidectomy, verifies complete resection.
Patients do require double lumen endotracheal ventilation or the use of a bronchial blocker for the purpose of single lung ventilation. In addition, patients are taken from the operating room with a small chest tube, which is placed through the 11 mm port. This was removed immediately postoperatively or on postoperative day number one in all of our patients. Furthermore, the patients in our series had all returned to their activities of daily living, and without the need for narcotic analgesia, prior to their first postoperative visit, which was one week from the day of surgery.
Resection of a mediastinal parathyroid adenoma using the radioguided probe and thoracoscopic techniques requires the endocrine and thoracic surgeon to work closely together. At our center, the endocrine surgeons have utilized the gamma probe for over 400 radioguided parathyroidectomies, and, therefore, have a lot of experience localizing parathyroids with the probe. Likewise, our thoracic surgeons have performed many complex thoracoscopic surgeries. Thus, utilizing the expertise of both endocrine and thoracic surgeons is critical to the success of these operations.
Radioguided thoracoscopic resection of mediastinal parathyroid adenomas is safe, is effective, and supplants the need for sternotomy. Immediate ex vivo specimen radioactivity measurement obviates the need for costly, time-consuming frozen section analysis. Intraoperative iPTH level monitoring rapidly confirms complete resection of the parathyroid adenoma limiting the extent of dissection and possibly shortening operative time. In our experience, patients experience minimal morbidity, pain, length of hospitalization, and recovery time.
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References
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Abstract
Introduction
