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Original article

Video assisted thoracoscopic resection of mediastinal ectopic parathyroid glands: a single-center experience

Aleksandar Ristanović1,2, Nebojša Marić1,2, Aleksandar Nikolić1, Stevan Čičić1
  • Military Medical Academy, Clinic for Cardiothoracic Surgery, Belgrade, Serbia
  • University of Defense, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia

ABSTRACT

Introduction: The majority of mediastinal ectopic parathyroid glands (MEPTG) can be successfully removed through the cervical approach, including parathyroid glands (PTG) located in the upper mediastinum. However, 1% – 3% of patients with hyperparathyroidism (HPT) require the thoracic surgical approach. The success of surgical treatment depends on the precise preoperative localization of MEPTGs and on the choice of the appropriate approach. In this group of patients, video assisted thoracoscopic excision of MEPTGs can be used as a reliable method, in order to avoid open surgery, but also because of its other advantages. We present the first 11 patients with MEPTGs who were successfully surgically treated at the Clinic for Cardiothoracic Surgery of the Military Medical Academy (MMA). Previous video assisted thoracoscopic resections in Serbia have not been reported.

Materials and methods: Between March 2014 and October 2022, 11 patients with biochemically proven hyperparathyroidism were surgically treated at the Clinic for Cardiothoracic Surgery of the MMA. MEPTGs were identified preoperatively with a Tc-99m sestamibi scan, a CT scan of the chest, and single photon emission computed tomography (SPECT).

Results: All MEPTGs were successfully excised using video assisted thoracoscopic surgery (VATS). There was no need for an open thoracic surgical approach (sternotomy or thoracotomy). The average length of the surgery was 80 minutes (between 34 and 150 minutes). The average length of hospitalization was 7 days. Postoperative wound infection occurred in one patient.

Conclusion: MEPTGs can be safely and successfully excised using VATS, thus avoiding classical chest opening. VATS provides good visualization of the tumor, low tissue trauma, short duration of surgery and hospitalization, a low rate of complications, and a good cosmetic/aesthetic effect.


INTRODUCTION

The first successful parathyroidectomy was performed in 1925 by Felix Mandel, as a bilateral neck exploration [1]. Indications for parathyroidectomy are primary and secondary hyperparathyroidism (HPT). Parathyroid glands (PTG) are located in the neck and, most often, there are four of them. Approximately 15% – 20% of patients in whom parathyroidectomy is indicated have ectopically localized PTGs [2],[3]. Ectopic localization of glands is a consequence of their embryonic development. The upper PTGs arise from the fourth pharyngeal pouch, while the lower PTGs arise from the third pharyngeal pouch. Therefore, during embryonic development, the lower PTGs travel a greater distance to reach their usual anatomical position. This is why, their ectopic localization is twice as likely. Since the thymus also develops from the third pharyngeal pouch, an ectopically localized lower PTG can commonly be found in the thymus itself or around the thymus. When an upper PTG is ectopically localized, it is usually located next to the esophagus, trachea, thyroid gland and large blood vessels [4],[5],[6],[7],[8],[9],[10],[11]. Most ectopically localized PTGs can be removed through the cervical approach, including PTGs located in the upper mediastinum. However, 1% – 3% of patients with mediastinal ectopic parathyroid glands (MEPTG) will require a thoracic surgical approach [4],[5],[6],[7],[12]. Nowadays, minimally invasive techniques are used more often, in order to minimize tissue trauma and reduce the complications of operative treatment. The success of surgical treatment primarily depends on the precise preoperative localization of MEPTGs and the choice of an appropriate approach. In this group of patients, video assisted thoracoscopic excision of MEPTGs can be used as a reliable and safe method, in order to avoid open surgery (sternotomy and thoracotomy), but also because of its other advantages.

MATERIALS AND METHODS

Between March 2014 and October 2022, 11 patients with biochemically proven hyperparathyroidism were surgically treated at the Clinic for Cardiothoracic Surgery of the Military Medical Academy (MMA).

Four patients had primary hyperparathyroidism, six patients had secondary hyperparathyroidism, and one patient had tertiary hyperparathyroidism. In 7 patients, a subtotal parathyroidectomy had previously been performed through the cervical approach (6 patients with secondary and one patient with tertiary hyperparathyroidism). Preoperatively, all of the patients had elevated levels of the parathyroid hormone (PTH), while two patients had elevated levels of serum calcium. One patient had a decreased level of serum phosphorus.

The localization of MEPTGs was established preoperatively using the Tc-99m sestamibi scan and computed tomography (CT) of the chest, while one patient underwent single photon emission computed tomography (SPECT) (Figure 1).

video asistirana 01

Figure 1. CT and SPECT of an intrathymic mediastinal ectopic parathyroid gland (MEPTG)

Resection of the MEPTGs was performed using the VATS technique. Depending on the preoperative localization of the glands, resection using the VATS technique was performed 6 times on the left side and 5 times on the right. In two cases the operations were performed by placing three ports, in one case two ports were placed, while in 8 cases one port was placed, as the result of our growing experience. The ports were always placed in typical places. All surgical interventions were performed under general anesthesia, using a double-lumen endotracheal tube and single-lung ventilation. The patients were placed in a semirecumbent position with the ipsilateral arm in abduction and a towel placed under the patient’s ipsilateral thorax, in order to create a thirty-degree angle between the operating table and the thorax. All operations were performed using a standard 10-mm rigid thoracoscope. Ectopically localized parathyroid glands were resected using standard thoracoscopic instruments. After the operation, a thoracic drain was placed through a caudal incision. The criterion we used for intraoperative confirmation of an extirpated PTG was frozen section analysis of removed tissue.

RESULTS

Among the 11 patients who underwent parathyroidectomy, 8 (72.7%) were male. The mean age of the patients was 52 years. The average length of the surgery was 80 minutes (between 34 and 150 minutes). All patients were extubated in the operating room. No patient required a stay in the surgical intensive care unit. The thoracic drain was usually removed after one postoperative day (range: 0 days – 2 days). The average 24-hour drainage was 65 ml (range: 0 ml – 110 ml). The mean length of hospitalization was 7 days (between three and 15 days). One patient had a wound infection. Six patients developed postoperative hypocalcemia that required substitution therapy to prevent hungry bone syndrome. Wound infection and postoperative hypocalcemia were the main causes of prolonged hospitalization. There was no need for an open approach in the resection of the MEPTGs. Histological analysis indicated parathyroid adenoma in three patients, hyperplasia of the parathyroid gland in 7 patients, and chronic granulomatous inflammation of the lymph glands was found in one patient with sarcoidosis. The mean diameter of the excised glands was 20 mm, and they were all larger than 2 mm in diameter (range: 2 mm – 35 mm). After surgery, serum calcium levels returned to normal on the first postoperative day. After six-month follow-up, all patients, except one, had normal serum calcium values. The PTH level returned to normal levels in 10 patients. In one patient, the PTH level remained elevated, and the definitive pathohistological finding did not confirm parathyroid tissue, nor was the cause of the elevated calcium and parathyroid hormone levels determined by further investigations.

DISCUSSION

The success of surgical treatment depends on the precise localization of the ectopic parathyroid gland in the mediastinum and the choice of the most appropriate approach. Imaging methods used for preoperative visualization of MEPTGs are the following: US, CT, the Tc-99m sestamibi scan, MRI, SPECT and Dual phase Tc99m sestamibi scan with SPECT. The diagnostic sensitivity of these procedures is presented in Table 1 [13].

Table 1. Factors associated with risk of perinatal HIV transmission [25].

video asistirana 02

In patients with negative scintigraphy, a 4D-CT scan can be used to visualize MEPTGs. According to one study, the sensitivity of 4D-CT is 89% in PTG visualization [14]. In patients with multiple neck dissections and permanently elevated PTH values, in whom imaging methods did not visualize MEPTGs, selective venous catheterization can be applied in order to measure PTH levels [15]. PET/CT with 11C-methionine can also be used as another supplementary visualization method [16],[17]. We used the CT, the Tc-99m sestamibi scan, and SPECT for preoperative visualization of PTGs, although 18F-fluorocholine PET/CT imaging has higher sensitivity [37]. Some medical centers, in order to visualize intraoperative ectopic PTGs, use intravenous application of methylene blue [18],[19]. Parathyroid tissue has the ability to bind methylene blue and thus the tissue is easier to identify. A characteristic of the parathyroid gland is the ability to fluoresce when exposed to the infrared light spectrum, and specific wavelengths were used to visualize this. There are several methods used for intraoperative fluorescence visualization (near-infrared autofluorescence – NIRAF; contrast-enhanced fluorescence imaging) [38].

One of the biochemical ways to increase the efficiency of surgical treatment is intraoperative monitoring of PTH. It is considered that an MEPTG has been successfully extirpated if the PTH level measured 8 – 20 minutes after the removal of the tissue has fallen by more than 50%, as compared to the level before excision [20],[21]. If the PTH level does not drop to the desired values, surgical exploration should be continued [22]. There is no consensus on the percentage and speed of PTH decrease which could undoubtedly assert that an MEPTG has been removed. However, there is a number of defined criteria [23],[24],[25],[26],[27]. In our case, as intraoperative confirmation of parathyroid tissue, we used frozen section analysis of extirpated tissue. In only one case, the frozen section analysis did not confirm a PTG, rather a chronic granulomatous infection of the lymphatic glands. Previously, the most commonly used approach for extirpation of PTGs was cervical bilateral exploration of the neck without prior visualization of the PTGs [1]. Today, preoperative visualization of PTGs is an indispensable part of treatment planning. In the case of MEPTGs, the most common approaches used were sternotomy and thoracotomy [10],[12],[29]. Nowadays, minimally invasive techniques are increasingly used. Current opinion is that, in the case of mediastinal localization of PTGs, the method of choice is VATS.

In a large study by Wang et al. [33], of 30 parathyroid mediastinal glands, 24 were intrathymic while 6 were parathymic. Edis et al. [32] and Clark [33] presented a study involving 92 mediastinal parathyroid glands and found that 85% were adjacent to the thymus. Our results support this study – 8 glands were intrathymic, two glands were perithymic, and one gland was located in the aortopulmonary window.

Angiographic ablation is an option in the treatment of an MEPTG. This technique prevents blood flow to the gland. The disadvantage of this technique is reflected in the fact that, in 40% of cases, it was impossible to localize the gland, as well as in the early failure rate of 40%. With this technique, neurological complications rarely occur. However, it does not provide us with parathyroid tissue, if there is a need for autotransplantation [36],[37],[38].

The duration of surgery in our series averaged 80 minutes. All patients with primary hyperparathyroidism were discharged four days after surgery and patients with secondary hyperparathyroidism were discharged within 7 days of surgery. The reason for the longer hospital stays of patients with secondary HPT was postoperative hypocalcemia, which required substitution therapy. We had one postoperative complication in the form of a wound infection. This is different from the results of Russell et al. [4] for sternotomy, which showed an incidence of 21% of pulmonary complications, 8% of wound complications, atrial fibrillation, and deep vein thrombosis. Kohn et al. [12] reported a complication rate of 19% (four out of 21 patients) after sternotomy for resection of an ectopic parathyroid gland. Considering their small dimensions and mediastinal localization, VATS seems to be an ideal approach in the management of rare mediastinal ectopic parathyroid glands. The advantages of the VATS approach, as compared to open surgery (sternotomy or thoracotomy), are well known and described.

VATS is the least invasive and least painful technique, it provides the best visualization of the tumor, a shorter duration of surgery, a lower frequency of complications, shorter time of hospital treatment, and a good cosmetic/aesthetic effect.

CONCLUSION

We present our experience regarding the first eleven cases of ectopically localized parathyroid glands resected using the VATS technique. The advantages of the VATS approach, as compared to open surgery (sternotomy or thoracotomy), are well known and described, and can be applied in the surgical treatment of MEPTGs. It is recommended that the localization of the PTGs is obtained as precisely as possible preoperatively, and that the diagnosis of hyperparathyroidism is unequivocal. The VATS approach should be considered as the first and least invasive approach in the resection of ectopically localized parathyroid glands.

  • Conflict of interest:
    None declared.

Informations

September 2023

Pages 238-245
  • Keywords:
    video-assisted thoracoscopic surgery, hyperparathyroidism, excision of parathyroid glands, ectopic parathyroid glands
  • Received:
    19 May 2023
  • Revised:
    05 July 2023
  • Accepted:
    14 July 2023
  • Online first:
    25 September 2023
  • DOI:
  • Cite this article:
    Ristanović A, Marić N, Nikolić A, Čičić S. Video assisted thoracoscopic resection of mediastinal ectopic parathyroid glands: A single-center experience. Serbian Journal of the Medical Chamber. 2023;4(3):238-45. doi: 10.5937/smclk4-45101
Corresponding author

Stevan Čičić
Military Medical Academy, Clinic for Cardiothoracic Surgery
17 Crnotravska Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


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REFERENCES

1. Prescott JD, Udelsman R. Remedial operation for primary hyperparathyroidism. World J Surg. 2009 Nov;33(11):2324-34. doi: 10.1007/s00268-009-9962- 0. [CROSSREF]

2. Gomes EM, Nunes RC, Lacativa PG, Almeida MH, Franco FM, Leal CT, et al. Ectopic and extranumerary parathyroid glands location in patients with hyperparathyroidism secondary to end stage renal disease. Acta Cir Bras. 2007 Mar-Apr;22(2):105-9. doi: 10.1590/s0102-86502007000200005. [CROSSREF]

3. Phitayakorn R, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006 Mar;191(3):418-23. doi: 10.1016/j.amjsurg.2005.10.049. [CROSSREF]

4. Russell CF, Edis AJ, Scholz DA, Sheedy PF, van Heerden JA. Mediastinal parathyroid tumors: experience with 38 tumors requiring mediastinotomy for removal. Ann Surg. 1981 Jun;193(6):805-9. doi: 10.1097/00000658- 198106000-00016. [CROSSREF]

5. Alesina PF, Moka D, Mahlstedt J, Walz MK. Thoracoscopic removal of mediastinal hyperfunctioning parathyroid glands: personal experience and review of the literature. World J Surg. 2008 Feb;32(2):224-31. doi: 10.1007/s00268- 007-9303-0. [CROSSREF]

6. Cupisti K, Dotzenrath C, Simon D, Röher HD, Goretzki PE. Therapy of suspected intrathoracic parathyroid adenomas. Experiences using open transthoracic approach and video-assisted thoracoscopic surgery. Langenbecks Arch Surg. 2002 Jan;386(7):488-93. doi: 10.1007/s00423-001-0254-x. [CROSSREF]

7. Randone B, Costi R, Scatton O, Fulla Y, Bertagna X, Soubrane O, et al. Thoracoscopic removal of mediastinal parathyroid glands: a critical appraisal of an emerging technique. Ann Surg. 2010 Apr;251(4):717-21. doi: 10.1097/ SLA.0b013e3181c1cfb0. [CROSSREF]

8. Cope O. Surgery of hyperparathyroidism: the occurrence of parathyroids in the anterior mediastinum and the division of the operation into two stages. Ann Surg 1941;114(4):706–733. [CROSSREF]

9. Iihara M, Suzuki R, Kawamata A, Horiuchi K, Okamoto T. Thoracoscopic removal of mediastinal parathyroid lesions: selection of surgical approach and pitfalls of preoperative and intraoperative localization. World J Surg 2012;36(6):1327–1334. [CROSSREF]

10. Said SM, Cassivi SD, Allen MS, Deschamps C, Nichols FC 3rd, Shen KR, et al. Minimally invasive resection for mediastinal ectopic parathyroid glands. Ann Thorac Surg. 2013 Oct;96(4):1229-1233. doi: 10.1016/j.athoracsur.2013.05.084. [CROSSREF]

11. Arnault V, Beaulieu A, Lifante JC, Sitges Serra A, Sebag F, Mathonnet M, et al. Multicenter study of 19 aortopulmonary window parathyroid tumors: the challenge of embryologic origin. World J Surg. 2010 Sep;34(9):2211-6. doi: 10.1007/s00268-010-0622-1. [CROSSREF]

12. Conn JM, Goncalves MA, Mansour KA, McGarity WC. The mediastinal parathyroid. Am Surg. 1991 Jan;57(1):62-6.

13. Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes. 2012 Nov;120(10):604-10. doi: 10.1055/s-0032-1327628. [CROSSREF]

14. Day KM, Elsayed M, Beland MD, Monchik JM. The utility of 4-dimensional computed tomography for preoperative localization of primary hyperparathyroidism in patients not localized by sestamibi or ultrasonography. Surgery. 2015 Mar;157(3):534-9. doi: 10.1016/j.surg.2014.11.010. [CROSSREF]

15. Lebastchi AH, Aruny JE, Donovan PI, Quinn CE, Callender GG, Carling T, et al. Real-Time Super Selective Venous Sampling in Remedial Parathyroid Surgery. J Am Coll Surg. 2015 Jun;220(6):994-1000. doi: 10.1016/j.jamcollsurg.2015.01.004. [CROSSREF]

16. Traub-Weidinger T, Mayerhoefer ME, Koperek O, Mitterhauser M, Duan H, Karanikas G, et al. 11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/ CT-negative patients with primary hyperparathyroidism and previous neck surgery. J Clin Endocrinol Metab. 2014 Nov;99(11):4199-205. doi: 10.1210/ jc.2014-1267. [CROSSREF]

17. Hellman P, Ahlström H, Bergström M, Sundin A, Långström B, Westerberg G, et al. Positron emission tomography with 11C-methionine in hyperparathyroidism. Surgery. 1994 Dec;116(6):974-81.

18. Amer K, Khan AZ, Rew D, Lagattolla N, Singh N. Video assisted thoracoscopic excision of mediastinal ectopic parathyroid adenomas: a UK regional experience. Ann Cardiothorac Surg. 2015 Nov;4(6):527-34. doi: 10.3978/j. issn.2225-319X.2015.09.04. [CROSSREF]

19. Dudley NE. Methylene blue for rapid identification of the parathyroids. Br Med J. 1971 Sep 18;3(5776):680-1. doi: 10.1136/bmj.3.5776.680. [CROSSREF]

20. Phitayakorn R, McHenry CR. Parathyroidectomy: overview of the anatomic basis and surgical strategies for parathyroid operations. Clin Rev Bone Miner Metab 2007;5:89-102. [CROSSREF]

21. Sagan D, Goździuk K. Surgical treatment of mediastinal parathyroid adenoma: rationale for intraoperative parathyroid hormone monitoring. Ann Thorac Surg. 2010 Jun;89(6):1750-5. doi: 10.1016/j.athoracsur.2010.02.076. [CROSSREF]

22. Neves MC, Ohe MN, Rosano M, Abrahão M, Cervantes O, Lazaretti-Castro M, et al. A 10-year experience in intraoperative parathyroid hormone measurements for primary hyperparathyroidism: a prospective study of 91 previous unexplored patients. J Osteoporos. 2012;2012:914214. doi: 10.1155/2012/914214. [CROSSREF]

23. Udelsman R, Åkerström G, Biagini C, Duh QY, Miccoli P, Niederle B, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3595-606. doi: 10.1210/jc.2014-2000. [CROSSREF]

24.  Di Stasio E, Carrozza C, Pio Lombardi C, Raffaelli M, Traini E, Bellantone R, et al. Parathyroidectomy monitored by intra-operative PTH: the relevance of the 20 min end-point. Clin Biochem. 2007 Jun;40(9-10):595-603. doi: 10.1016/j.clinbiochem.2006.12.007. [CROSSREF]

25. Richards ML, Thompson GB, Farley DR, Grant CS. An optimal algorithm for intraoperative parathyroid hormone monitoring. Arch Surg. 2011 Mar;146(3):280-5. doi: 10.1001/archsurg.2011.5. [CROSSREF]

26. Barczynski M, Konturek A, Hubalewska-Dydejczyk A, Cichon S, Nowak W. Evaluation of Halle, Miami, Rome, and Vienna intraoperative iPTH assay criteria in guiding minimally invasive parathyroidectomy. Langenbecks Arch Surg. 2009 Sep;394(5):843-9. doi: 10.1007/s00423-009-0510-z. [CROSSREF]

27. Carneiro DM, Irvin GL 3rd, Inabnet WB. Limited versus radical parathyroidectomy in familial isolated primary hyperparathyroidism. Surgery. 2002 Dec;132(6):1050-4; discussion 1055. doi: 10.1067/msy.2002.128695. [CROSSREF]

28. Downey NJ, McGuigan JA, Dolan SJ, Russell CF. Median sternotomy for parathyroid adenoma. Ir J Med Sci. 1999 Jan-Mar;168(1):13-6. doi: 10.1007/ BF02939573. [CROSSREF]

29. Obara T, Fujimoto Y, Tanaka R, Ito Y, Kodama T, Yashiro T, et al. Mid-mediastinal parathyroid lesions: preoperative localization and surgical approach in two cases. Jpn J Surg. 1990 Jul;20(4):481-6. doi: 10.1007/BF02470837. [CROSSREF]

30. Sukumar MS, Komanapalli CB, Cohen JI. Minimally invasive management of the mediastinal parathyroid adenoma. Laryngoscope. 2006 Mar;116(3):482- 7. doi: 10.1097/01.mlg.0000200582.65418.37.  [CROSSREF]

31. Wang C, Gaz RD, Moncure AC. Mediastinal parathyroid exploration: a clinical and pathologic study of 47 cases. World J Surg. 1986 Aug;10(4):687-95. doi: 10.1007/BF01655558. [CROSSREF]

32. Edis AJ, Sheedy PF, Beahrs OH, van Heerden JA. Results of reoperation for hyperparathyroidism, with evaluation of preoperative localization studies. Surgery. 1978 Sep;84(3):384-93.

33. Clark OH. Mediastinal parathyroid tumors. Arch Surg. 1988 Sep;123(9):1096- 100. doi: 10.1001/archsurg.1988.01400330072011. [CROSSREF]

34. Heller HJ, Miller GL, Erdman WA, Snyder WH 3rd, Breslau NA. Angiographic ablation of mediastinal parathyroid adenomas: local experience and review of the literature. Am J Med. 1994 Dec;97(6):529-34. doi: 10.1016/0002- 9343(94)90348-4. [CROSSREF]

35. Doppman JL, Brown EM, Brennan MF, Spiegel A, Marx SJ, Aurbach GD. Angiographic ablation of parathyroid adenomas. Radiology. 1979 Mar;130(3):577- 82. doi: 10.1148/130.3.577. [CROSSREF]

36. Doherty GM, Doppman JL, Miller DL, Gee MS, Marx SJ, Spiegel AM, et al. Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism. Ann Surg. 1992 Feb;215(2):101-6. doi: 10.1097/00000658-199202000-00002. [CROSSREF]

37. Huber GF, Hüllner M, Schmid C, Brunner A, Sah B, Vetter D, et al. Benefit of 18F-fluorocholine PET imaging in parathyroid surgery. Eur Radiol. 2018 Jun;28(6):2700-2707. doi: 10.1007/s00330-017-5190-4. [CROSSREF]

38. Wong A, Wong JCY, Pandey PU, Wiseman SM. Novel techniques for intraoperative parathyroid gland identification: a comprehensive review. Expert Rev Endocrinol Metab. 2020 Nov;15(6):439-457. doi: 10.1080/17446651.2020.1831913. [CROSSREF]

1. Prescott JD, Udelsman R. Remedial operation for primary hyperparathyroidism. World J Surg. 2009 Nov;33(11):2324-34. doi: 10.1007/s00268-009-9962- 0. [CROSSREF]

2. Gomes EM, Nunes RC, Lacativa PG, Almeida MH, Franco FM, Leal CT, et al. Ectopic and extranumerary parathyroid glands location in patients with hyperparathyroidism secondary to end stage renal disease. Acta Cir Bras. 2007 Mar-Apr;22(2):105-9. doi: 10.1590/s0102-86502007000200005. [CROSSREF]

3. Phitayakorn R, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006 Mar;191(3):418-23. doi: 10.1016/j.amjsurg.2005.10.049. [CROSSREF]

4. Russell CF, Edis AJ, Scholz DA, Sheedy PF, van Heerden JA. Mediastinal parathyroid tumors: experience with 38 tumors requiring mediastinotomy for removal. Ann Surg. 1981 Jun;193(6):805-9. doi: 10.1097/00000658- 198106000-00016. [CROSSREF]

5. Alesina PF, Moka D, Mahlstedt J, Walz MK. Thoracoscopic removal of mediastinal hyperfunctioning parathyroid glands: personal experience and review of the literature. World J Surg. 2008 Feb;32(2):224-31. doi: 10.1007/s00268- 007-9303-0. [CROSSREF]

6. Cupisti K, Dotzenrath C, Simon D, Röher HD, Goretzki PE. Therapy of suspected intrathoracic parathyroid adenomas. Experiences using open transthoracic approach and video-assisted thoracoscopic surgery. Langenbecks Arch Surg. 2002 Jan;386(7):488-93. doi: 10.1007/s00423-001-0254-x. [CROSSREF]

7. Randone B, Costi R, Scatton O, Fulla Y, Bertagna X, Soubrane O, et al. Thoracoscopic removal of mediastinal parathyroid glands: a critical appraisal of an emerging technique. Ann Surg. 2010 Apr;251(4):717-21. doi: 10.1097/ SLA.0b013e3181c1cfb0. [CROSSREF]

8. Cope O. Surgery of hyperparathyroidism: the occurrence of parathyroids in the anterior mediastinum and the division of the operation into two stages. Ann Surg 1941;114(4):706–733. [CROSSREF]

9. Iihara M, Suzuki R, Kawamata A, Horiuchi K, Okamoto T. Thoracoscopic removal of mediastinal parathyroid lesions: selection of surgical approach and pitfalls of preoperative and intraoperative localization. World J Surg 2012;36(6):1327–1334. [CROSSREF]

10. Said SM, Cassivi SD, Allen MS, Deschamps C, Nichols FC 3rd, Shen KR, et al. Minimally invasive resection for mediastinal ectopic parathyroid glands. Ann Thorac Surg. 2013 Oct;96(4):1229-1233. doi: 10.1016/j.athoracsur.2013.05.084. [CROSSREF]

11. Arnault V, Beaulieu A, Lifante JC, Sitges Serra A, Sebag F, Mathonnet M, et al. Multicenter study of 19 aortopulmonary window parathyroid tumors: the challenge of embryologic origin. World J Surg. 2010 Sep;34(9):2211-6. doi: 10.1007/s00268-010-0622-1. [CROSSREF]

12. Conn JM, Goncalves MA, Mansour KA, McGarity WC. The mediastinal parathyroid. Am Surg. 1991 Jan;57(1):62-6.

13. Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes. 2012 Nov;120(10):604-10. doi: 10.1055/s-0032-1327628. [CROSSREF]

14. Day KM, Elsayed M, Beland MD, Monchik JM. The utility of 4-dimensional computed tomography for preoperative localization of primary hyperparathyroidism in patients not localized by sestamibi or ultrasonography. Surgery. 2015 Mar;157(3):534-9. doi: 10.1016/j.surg.2014.11.010. [CROSSREF]

15. Lebastchi AH, Aruny JE, Donovan PI, Quinn CE, Callender GG, Carling T, et al. Real-Time Super Selective Venous Sampling in Remedial Parathyroid Surgery. J Am Coll Surg. 2015 Jun;220(6):994-1000. doi: 10.1016/j.jamcollsurg.2015.01.004. [CROSSREF]

16. Traub-Weidinger T, Mayerhoefer ME, Koperek O, Mitterhauser M, Duan H, Karanikas G, et al. 11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/ CT-negative patients with primary hyperparathyroidism and previous neck surgery. J Clin Endocrinol Metab. 2014 Nov;99(11):4199-205. doi: 10.1210/ jc.2014-1267. [CROSSREF]

17. Hellman P, Ahlström H, Bergström M, Sundin A, Långström B, Westerberg G, et al. Positron emission tomography with 11C-methionine in hyperparathyroidism. Surgery. 1994 Dec;116(6):974-81.

18. Amer K, Khan AZ, Rew D, Lagattolla N, Singh N. Video assisted thoracoscopic excision of mediastinal ectopic parathyroid adenomas: a UK regional experience. Ann Cardiothorac Surg. 2015 Nov;4(6):527-34. doi: 10.3978/j. issn.2225-319X.2015.09.04. [CROSSREF]

19. Dudley NE. Methylene blue for rapid identification of the parathyroids. Br Med J. 1971 Sep 18;3(5776):680-1. doi: 10.1136/bmj.3.5776.680. [CROSSREF]

20. Phitayakorn R, McHenry CR. Parathyroidectomy: overview of the anatomic basis and surgical strategies for parathyroid operations. Clin Rev Bone Miner Metab 2007;5:89-102. [CROSSREF]

21. Sagan D, Goździuk K. Surgical treatment of mediastinal parathyroid adenoma: rationale for intraoperative parathyroid hormone monitoring. Ann Thorac Surg. 2010 Jun;89(6):1750-5. doi: 10.1016/j.athoracsur.2010.02.076. [CROSSREF]

22. Neves MC, Ohe MN, Rosano M, Abrahão M, Cervantes O, Lazaretti-Castro M, et al. A 10-year experience in intraoperative parathyroid hormone measurements for primary hyperparathyroidism: a prospective study of 91 previous unexplored patients. J Osteoporos. 2012;2012:914214. doi: 10.1155/2012/914214. [CROSSREF]

23. Udelsman R, Åkerström G, Biagini C, Duh QY, Miccoli P, Niederle B, et al. The surgical management of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3595-606. doi: 10.1210/jc.2014-2000. [CROSSREF]

24.  Di Stasio E, Carrozza C, Pio Lombardi C, Raffaelli M, Traini E, Bellantone R, et al. Parathyroidectomy monitored by intra-operative PTH: the relevance of the 20 min end-point. Clin Biochem. 2007 Jun;40(9-10):595-603. doi: 10.1016/j.clinbiochem.2006.12.007. [CROSSREF]

25. Richards ML, Thompson GB, Farley DR, Grant CS. An optimal algorithm for intraoperative parathyroid hormone monitoring. Arch Surg. 2011 Mar;146(3):280-5. doi: 10.1001/archsurg.2011.5. [CROSSREF]

26. Barczynski M, Konturek A, Hubalewska-Dydejczyk A, Cichon S, Nowak W. Evaluation of Halle, Miami, Rome, and Vienna intraoperative iPTH assay criteria in guiding minimally invasive parathyroidectomy. Langenbecks Arch Surg. 2009 Sep;394(5):843-9. doi: 10.1007/s00423-009-0510-z. [CROSSREF]

27. Carneiro DM, Irvin GL 3rd, Inabnet WB. Limited versus radical parathyroidectomy in familial isolated primary hyperparathyroidism. Surgery. 2002 Dec;132(6):1050-4; discussion 1055. doi: 10.1067/msy.2002.128695. [CROSSREF]

28. Downey NJ, McGuigan JA, Dolan SJ, Russell CF. Median sternotomy for parathyroid adenoma. Ir J Med Sci. 1999 Jan-Mar;168(1):13-6. doi: 10.1007/ BF02939573. [CROSSREF]

29. Obara T, Fujimoto Y, Tanaka R, Ito Y, Kodama T, Yashiro T, et al. Mid-mediastinal parathyroid lesions: preoperative localization and surgical approach in two cases. Jpn J Surg. 1990 Jul;20(4):481-6. doi: 10.1007/BF02470837. [CROSSREF]

30. Sukumar MS, Komanapalli CB, Cohen JI. Minimally invasive management of the mediastinal parathyroid adenoma. Laryngoscope. 2006 Mar;116(3):482- 7. doi: 10.1097/01.mlg.0000200582.65418.37.  [CROSSREF]

31. Wang C, Gaz RD, Moncure AC. Mediastinal parathyroid exploration: a clinical and pathologic study of 47 cases. World J Surg. 1986 Aug;10(4):687-95. doi: 10.1007/BF01655558. [CROSSREF]

32. Edis AJ, Sheedy PF, Beahrs OH, van Heerden JA. Results of reoperation for hyperparathyroidism, with evaluation of preoperative localization studies. Surgery. 1978 Sep;84(3):384-93.

33. Clark OH. Mediastinal parathyroid tumors. Arch Surg. 1988 Sep;123(9):1096- 100. doi: 10.1001/archsurg.1988.01400330072011. [CROSSREF]

34. Heller HJ, Miller GL, Erdman WA, Snyder WH 3rd, Breslau NA. Angiographic ablation of mediastinal parathyroid adenomas: local experience and review of the literature. Am J Med. 1994 Dec;97(6):529-34. doi: 10.1016/0002- 9343(94)90348-4. [CROSSREF]

35. Doppman JL, Brown EM, Brennan MF, Spiegel A, Marx SJ, Aurbach GD. Angiographic ablation of parathyroid adenomas. Radiology. 1979 Mar;130(3):577- 82. doi: 10.1148/130.3.577. [CROSSREF]

36. Doherty GM, Doppman JL, Miller DL, Gee MS, Marx SJ, Spiegel AM, et al. Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism. Ann Surg. 1992 Feb;215(2):101-6. doi: 10.1097/00000658-199202000-00002. [CROSSREF]

37. Huber GF, Hüllner M, Schmid C, Brunner A, Sah B, Vetter D, et al. Benefit of 18F-fluorocholine PET imaging in parathyroid surgery. Eur Radiol. 2018 Jun;28(6):2700-2707. doi: 10.1007/s00330-017-5190-4. [CROSSREF]

38. Wong A, Wong JCY, Pandey PU, Wiseman SM. Novel techniques for intraoperative parathyroid gland identification: a comprehensive review. Expert Rev Endocrinol Metab. 2020 Nov;15(6):439-457. doi: 10.1080/17446651.2020.1831913. [CROSSREF]


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