© Springer International Publishing AG 2018Ralph P. Tufano and Phillip K. Pellitteri (eds.)Reoperative Parathyroid Surgery doi.org/10.1007/978-3-319-60723-8_4
4. Reoperative Surgical Planning and Adjunct Localization Studies
Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins School of Medicine, 601 N. Caroline St., Baltimore, MD 21287, USA
Radiology and Radiological Science-Neuroradiology, Department of Radiology, Johns Hopkins Medical Institutions, 601 N. Caroline St., Baltimore, MD 21287, USA
Ralph P. Tufano
KeywordsParathyroid glandsThymusPharyngeal pouchesRecurrent laryngeal nerveThyroid gland
Pathology of the parathyroid glands is fairly prevalent in the United States. Each year, approximately ten cases of primary hyperparathyroidism (HPT) per 100,000 people are diagnosed in those younger than 40 years. The incidence is estimated to be four times higher in patients older than 60 years of age . Surgery for primary HPT, performed by an experienced surgeon, is curative in more than 95% of cases . In contrast, the success rate for low-volume surgeons is only 70% . Consequently, the hyperparathyroid state may not be cured for a number of patients following surgery. Those not cured either remain hypercalcemic in the immediate postoperative period or redevelop hypercalcemia after a period of normocalcemia. Hypercalcemia persisting or recurring within 6 months after initial parathyroidectomy is referred to as persistent HPT. Hypercalcemia recurring more than 6 months after an apparently curative initial parathyroidectomy is referred to as recurrent HPT. Regardless of terminology, in both cases, the patient is at continued risk of metabolic complications from hypercalcemia and may continue to have discomfort from the associated symptoms. Despite advances in preoperative imaging and adjunctive intraoperative tools, the incidence of persistent or recurrent HPT has been reported to be as high as 30% [4–6].
The indications for surgical intervention in reoperative cases must be clear, because the morbidity and technical difficulty are increased. Reoperations are unfortunately associated with a lower success rate than initial operations. Nonetheless, in experienced hands, the success rate of reoperative parathyroidectomy for persistent and recurrent HPT is reported to be more than 80–90% . However, the ideal period to cure the patient is during the initial operation, when the risks of surgical complications are least likely and the likelihood of cure is greatest. This chapter aims to outline a perioperative scheme for approaching persistent and recurrent primary HPT .
It has been estimated that 2–10% of surgical failures may be attributed to an incorrect preoperative diagnosis of primary HPT [8, 9]. Accordingly, one of the key requirements for success in reoperative parathyroidectomy is a proper diagnosis. The initial step is to perform a thorough personal and family history for endocrine diseases and a physical examination. The history should be focused on ruling out differential diagnoses. By definition, HPT (primary or secondary) must be confirmed with an elevated serum calcium concentration and an elevated or inappropriately high serum parathyroid hormone (PTH) level. Patients may also present with elevated serum PTH and serum calcium levels at the upper limit of normal (the so-called normocalcemic hyperparathyroidism). Checking an ionized calcium level can help confirm the diagnosis of HPT in most of these patients. Elevated serum chloride and decreased serum phosphate levels are frequently noted. In addition, if not previously performed, benign familial hypocalciuric hypercalcemia should be ruled out with an appropriately elevated 24 h urinary calcium measurement and subsequent genetic testing if indicated. If all these parameters are not present, other causes of hypercalcemia must be considered (i.e., patients with normocalcemic HPT caused by hypoalbuminemia, hyperphosphatemia, vitamin D deficiency, or hypomagnesemia), because a repeat parathyroidectomy is almost guaranteed to be unrewarding in these circumstances. The diagnosis of HPT has been facilitated by the development of immunometric assays [10, 11]. Clinical analysis with immunometric PTH assays typically distinguishes hypercalcemic patients with HPT from patients with other causes of hypercalcemia. Diagnostic errors of hyperparathyroidism can result from medications (i.e., calcium, vitamin D, furosemide, thiazide diuretics, calcitonin, or lithium), malignancy (i.e., bone metastases or humoral hypercalcemia), granulomatous disease (i.e. sarcoidosis), acute renal failure, bone disease (i.e., Paget’s disease or immobilization), hyperthyroidism, or adrenal insufficiency. Given the complexity of alternative explanations, a close relationship with medical specialists including endocrinologists can be invaluable to ensure that consensus is reached before the decision for further intervention is made. Such a relationship is likewise imperative in situations of more virulent forms of HPT, such as MEN, where multigland removal may be necessary.
With a confirmed diagnosis of persistent or recurrent HPT, further information obtained by clinical evaluation, review of preoperative localization studies, operative reports, and pathology reports is critical to help determine the location of potentially normal and abnormal glands. The operative report should document the extent of the initial parathyroidectomy; which parathyroid glands were identified; whether these glands were excised, biopsied, and/or clipped to mark for future identification; where scar tissue can be expected to be encountered; the relationship of the glands to the recurrent laryngeal nerve; intraoperative PTH results if evaluated; and the number and the position of normal and abnormal glands. Unfortunately, it often doesn’t contain most of these components which are all critical to operative planning. The pathology report confirms how many parathyroid glands were indeed excised, whether biopsied glands were definitely parathyroid tissue, and whether parathyroid glands examined were normal or hypercellular. Review of old pathology slides may be required. It may be useful to correlate previous localization studies with intraoperative findings. Direct laryngoscopy is necessary before reoperation to assess vocal fold function.
A battery of localization studies prior to reoperation are usually employed, due to the associated risks of surgical complications and the lower likelihood of surgical cure. Approximately 90% of missed parathyroid tumors can be removed through the initial cervical incision. Successful localization permits a focused approach in most cases. This limits the amount of dissection required, preferably to a unilateral approach, as one prefers not to perform bilateral re-exploration when possible, avoiding the increased risk of hypoparathyroidism and RLN injury [12, 13]. Localization studies, in combination with previous information from operative and histologic findings, usually direct the surgeon to the abnormal parathyroid gland, thus minimizing complications and shortening the operative time. Knowledge of anatomy and expected locations of both normal and ectopic locations for parathyroid glands is paramount in reoperative parathyroidectomy, and the reader is referred to previous chapters. A variety of invasive and noninvasive techniques are available to image or localize abnormal parathyroid glands. Intraoperative PTH monitoring is a helpful adjunct for confirming when all abnormal parathyroid tissue has been removed [14–17].
As in the initial work up of primary HPT, a number of imaging studies are available for the evaluation of recurrent or persistent HPT. Unfortunately, all available imaging modalities are far from perfect, and it is common practice to obtain multiple studies in this setting as the accuracy of two concordant exams is higher than a single localizing exam . Despite all efforts, there can be a high rate of nonlocalization which requires further workup with invasive tests. The abnormal parathyroid glands are mostly found in eutopic locations although there are higher rates of mediastinal, intrathyroid , and intrathymic glands as well as multigland disease in the reoperative setting. Local expertise and availability of imaging technology are the most important factors in determining which imaging algorithm is followed [19, 20].
Ultrasound’s sensitivity is quite low given the potentially increased incidence of mediastinal glands in a reoperative scenario, and the inability to visualize with US. However, the majority of abnormal glands are in eutopic locations, and US remains the most cost-effective and least harmful imaging study to start with, as it does not involve radiation exposure or contrast administration.
Most centers perform an unenhanced CT followed by one, two, or three additional acquisitions after intravenous contrast administration. CT takes advantage of the fact that parathyroid glands are more vascular compared to the surrounding tissue and show a greater degree of enhancement in the arterial phase of the acquisition followed by a sharp decrease in attenuation in the venous phase due to rapid washout. In addition, state-of-the-art CT exams provide exquisite anatomic detail. When an abnormal gland is confidently identified with multiphase CT, surgical eligibility can be confirmed even if US and sestamibi scans are nonlocalizing [21, 22]. It has been demonstrated that two phases may be sufficient, thus sparing the patient additional ionizing radiation . Intrathyroid adenomas are relatively difficult to localize with CT as arterial enhancement and venous washout features of adenomas and the thyroid gland nodules are often similar.
MRI is not commonly utilized outside a few centers in localizing abnormal parathyroid glands. Multiparametric imaging and high contrast resolution provides a greater ability to differentiate adenomas from the surrounding tissue. Dynamic contrast-enhanced sequences allow assessment of blood flow through parathyroid glands in a similar fashion with multiphase CT and increase MRI’s accuracy compared to standard protocols .
Because Tc sestamibi is accumulated and retained by the mitochondria-rich oxyphil cells in parathyroid glands more than thyroid tissue, it is more specific compared to other imaging modalities, although its sensitivity is limited due to lower spatial resolution. Thus, it often fails to localize small glands. SPECT is an acquisition technique that affords higher sensitivity and anatomic accuracy compared to planar Tc sestamibi scans. When SPECT is combined with other modalities in multiphase fusion techniques such as SPECT/CT, localization is further improved .
Fine needle aspiration biopsy may be applied using both computed tomographic and ultrasound guidance for correct needle placement in suspected abnormal parathyroid tissue during localization in preparation for reoperative surgery. Investigations have shown FNA to be a specific modality in distinguishing between parathyroid and nonparathyroid tissues [26, 27]. Cytologic evaluation of tissue samples obtained by fine needle aspiration biopsy is less sensitive than measuring washout PTH levels of the aspirate material, because follicular thyroid tumors may be misinterpreted as parathyroid tissue under cytologic review. The role of FNA in reoperative parathyroid surgery can be especially helpful in situations where a thyroid nodule is noted and imaging is suggestive of a possible intrathyroidal parathyroid adenoma, which is otherwise rare. It may also be particularly helpful in a multiply operated patient where there is intense scarring and a focused surgery would be most prudent.
Selective angiographic injection of the inferior thyroid arteries will demonstrate a vascular blush which may be present in up to 25–70% of parathyroid adenomas . Although rare, significant complications attributable to this technique have been reported and include central nervous system embolic infarction and potential quadriplegia . As a consequence of these potential risks and because of improvements in noninvasive imaging studies, selective parathyroid arteriography is rarely performed and should be reserved for patients who need surgery and in whom previous noninvasive testing has failed to identify the adenoma in a usual or ectopic location .
Selective Venous Sampling
Similar to super-selective digital subtraction angiography, selective venous sampling is reserved for selected patients. This modality is performed by catheterization of veins draining the neck and mediastinum . By obtaining blood samples and comparing PTH levels obtained from sampling of the iliac veins with those obtained from thyroid veins (superior, middle, and inferior), vertebral veins, and the thymic vein, the anticipated localization of the adenoma will be within the area where venous PTH levels are at least twice as high as the systemic levels. Selective venous sampling has been shown to be more accurate than large vein sampling, with accuracy of 83% as contrasted to 29%, respectively . This modality became significantly more accurate with the utilization of improved intact parathyroid hormone (iPTH) assays , which increased the sensitivity of venous sampling to 87–95% in some investigations . Selective venous sampling should be reserved for patients requiring reoperation and in whom noninvasive studies are negative, equivocal, or conflicting. This modality is technically challenging, and its success depends on an experienced interventional radiologist .
The availability of high-resolution US has led some surgeons to further utilize it in their operating room. Intraoperative US may be useful in a number of operative settings, primarily that of re-exploration in a neck that demonstrates significant surgical fibrosis. Using this adjunct will allow one to scan the neck and, where possible, correlate structures with preoperative images just prior to surgery. This achieves accurate visualization of the ultimate position of both the parathyroid lesion and other structures in the neck, in particular the relation to the internal jugular vein and carotid artery. This technique may also assist in precisely localizing the incision once the patient is in the neck extension position, for an ideal access for removal of parathyroid tissue. US can be combined with fine needle aspiration for PTH to interrogate hypoechoic structures identified in the thyroid or neck intraoperatively. Utilization of US once surgical exploration begins is compromised by disruption of tissue planes and is not often helpful.