Angelo Nicolosi

Role of SPECT/CT in the preoperative assessment of hyperparathyroid patients

Purpose.Our purpose was to assess the clinical value and additional benefit of fusion single-photon computed tomography (SPECT) and computed tomography (CT) images in locating the parathyroids in a selected group of patients affected by primary (PHP) and secondary hyperparathyroidism (SHP).Materials and methods.Sixteen patients (11 women and five men; age range 35–80 years) with severe hyperparathyroidism (HP) (ten PHP, six SHP) were studied by ultrasound (US), and, after i.v. injection of 370 MBq of 99mTc-sestamibi, by planar parathyroid scintigraphy, SPECT and SPECT/CT using a dualdetector scintillation camera GE Infinia Hawkeye. All patients underwent parathyroidectomy.Results.US findings were inconclusive in 12/16 patients affected by multinodular goitre, and two probable eutopic parathyroid glands were identified. “Double phase” parathyroid scintigraphy identified 14 probable parathyroid glands, SPECT 23 (14 ectopic and nine eutopic) and SPECT/CT confirmed all 23 probable parathyroid lesions, offering more precise localisation and an evident improvement in diagnostic accuracy. Sixteen of these foci of increased uptake were hyperplastic parathyroid glands, six were adenomas, one was a parathyroid carcinoma and one was a thyroid follicular carcinoma. Surgical detection of the 23 sestamibi-positive lesions was correctly matched with 100% of SPECT/CT images and 61% of SPECT data alone. Hybrid imaging thus provided additional data in 39% of lesions, and in three patients with retrotracheal glands, it modified the surgical approach.Conclusions.We believe 99mTc-sestambi SPECT/CT to be a more reliable presurgical method to study a patient subgroup affected by PHP or SHP in whom conventional US and other scintigraphic methods have failed for intrinsic reasons due to the concomitant presence of multinodular goitre or ectopic parathyroid gland. The additional practical benefit derived from this methodology was evident. In fact, anatomical information provided by CT enables precise localisation of the functional abnormalities highlighted by SPECT, and both are essential to a correct surgical approach.

Thyroid diseases cause mismatch between MIBI scan and neck ultrasound in the diagnosis of hyperfunctioning parathyroids: usefulness of FNA–PTH assay

DESIGN To evaluate the efficacy of the main tools in the diagnostic localization of hyperfunctioning parathyroids (HP) in primary hyperparathyroidism (pHPT) with concomitant thyroid diseases. METHODS Forty-three patients with pHPT associated with nodular goiter (NG, n=32) and/or autoimmune thyroid diseases (AITDs, n=11) for a total of 63 neck lesions were considered. Sixteen patients displaying HP (16 lesions), unequivocally localized by sestaMIBI scintigraphy (MIBI) and neck ultrasound (US) (group I), were compared with 27 patients (47 neck lesions) displaying equivocal parathyroid localization (group II). In all cases, neck US, MIBI scan, cytology, and parathyroid hormone assay in fine-needle aspiration washout fluid (FNA-PTH) were performed. All patients finally underwent surgery. RESULTS According to histological examination, high FNA-PTH values (>103 pg/ml) correctly identified all HP in both groups of patients (100% of sensitivity and specificity). Both MIBI and US correctly identified all HP only in group I patients; in contrast, four patterns of mismatch between these techniques were observed in group II patients, leading to low diagnostic performances of neck US (71.4% sensitivity and 78.9% specificity) and of MIBI scan (35.7% sensitivity and 42.1% specificity). The latter was due to both false-negative (mainly in AITD) and false-positive (mainly in NG) scan images. CONCLUSIONS Coexistent thyroid diseases are responsible for mismatch between MIBI and US images resulting in equivocal HP localization. In these cases, FNA-PTH resulted in the most accurate tool to identify HP. However, although safe, it should be advised only to patients with uncertain HP localization.

Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it really useful?

AIM The aim of this study was to evaluate the ability of intraoperative recurrent laryngeal nerve monitoring to predict the postoperative functional outcome and the potential role of this technique in reducing the postoperative nerve palsy rate. MATERIALS AND METHODS Between June 2007 and December 2011, 1693 consecutive patients who underwent thyroidectomy by a single surgical team were evaluated. We compared patients who have had a neuromonitoring and patients who have undergone surgery with the only visualization. Patients in which NIM was not utilized (Group A) were 942 against the others 751 (group B). RESULTS In group A there were 28 recurrent laryngeal nerve injuries (2.97%) of which 21 were transients (2.22%) and 7 were permanents (0.74%). In group B there were 20 recurrent laryngeal nerve injuries (2.66%) of which 14 (1.86%) transients and 6 (0.8%) permanents. Differences between the two groups were not statistically significative. CONCLUSIONS The technique of intraoperative neuromonitoring in thyroid surgery is safe and reliable in excluding postoperative recurrent laryngeal nerve palsy; it has high accuracy, specificity, sensitivity and negative predictive value. Neuromonitoring is useful to identify the recurrent laryngeal nerve and it can be a useful adjunctive technique for reassuring surgeons of the functional integrity of the nerve but it does not decrease the incidence of injuries compared with visualization alone. Its application can be particularly recommended for high-risk thyroidectomies.

Identification alone versus intraoperative neuromonitoring of the recurrent laryngeal nerve during thyroid surgery: experience of 2034 consecutive patients

BackgroundThe aim of this study was to evaluate the ability of intraoperative neuromonitoring in reducing the postoperative recurrent laryngeal nerve palsy rate by a comparison between patients submitted to thyroidectomy with intraoperative neuromonitoring and with routine identification alone.MethodsBetween June 2007 and December 2012, 2034 consecutive patients underwent thyroidectomy by a single surgical team. We compared patients who have had neuromonitoring and patients who have undergone surgery with nerve visualization alone. Patients in which neuromonitoring was not utilized (Group A) were 993, patients in which was utilized (group B) were 1041.ResultsIn group A 28 recurrent laryngeal nerve injuries were observed (2.82%), 21 (2.11%) transient and 7 (0.7%) permanent. In group B 23 recurrent laryngeal nerve injuries were observed (2.21%), in 17 cases (1.63%) transient and in 6 (0.58%) permanent. Differences were not statistically significative.ConclusionsVisual nerve identification remains the gold standard of recurrent laryngeal nerve management in thyroid surgery. Neuromonitoring helps to identify the nerve, in particular in difficult cases, but it did not decrease nerve injuries compared with visualization alone. Future studies are warranted to evaluate the benefit of intraoperative neuromonitoring in thyroidectomy, especially in conditions in which the recurrent nerve is at high risk of injury.

Total thyroidectomy without prophylactic central neck dissection in clinically node-negative papillary thyroid cancer: is it an adequate treatment?

BackgroundCervical lymph node metastases in papillary thyroid cancer are common. Although central neck dissection is indicated in clinically nodal-positive disease, it remains controversial in patients with no clinical evidence of nodal metastasis. The aim of this retrospective study was to determine the outcomes of clinically lymph node-negative patients with papillary thyroid cancer who underwent total thyroidectomy without a central neck dissection, in order to determine the rates of recurrence and reoperation in these patients compared with a group of patients submitted to total thyroidectomy with central neck dissection.MethodsTwo-hundred and eighty-five patients undergoing total thyroidectomy with preoperative diagnosis of papillary thyroid cancer, in the absence of suspicious nodes, were divided in two groups: those who underwent a thyroidectomy only (group A; n = 220) and those who also received a central neck dissection (group B; n = 65).ResultsSix cases (2.1%) of nodal recurrence were observed: 4 in group A and 2 in group B. Tumor histology was associated with risk of recurrence: Hürthle cell-variant and tall cell-variant carcinomas were associated with a high risk of recurrence. Multifocality and extrathyroidal invasion also presented a higher risk, while smaller tumors were at lower risk.ConclusionsThe role of prophylactic central lymph node dissection in the management of papillary thyroid cancer remains controversial. Total thyroidectomy appears to be an adequate treatment for clinically node-negative papillary thyroid cancer. Prophylactic central neck dissection could be considered for the more appropriate selection of patients for radioiodine treatment and should be reserved for high-risk patients only. No clinical or pathological factors are able to predict with any certainty the presence of nodal metastasis. In our experience, tumor size, some histological types, multifocality, and locoregional infiltration are related to an increased risk of recurrence. The potential use of molecular markers will hopefully offer a further strategy to stratify the risk of recurrence in patients with papillary thyroid cancer and allow a more tailored approach to offer prophylactic central neck dissection to patients with the greatest benefit. Multi-institutional larger studies with longer follow-up periods are necessary to draw definitive conclusions.

Differentiated Thyroid Cancer: Indications and Extent of Central Neck Dissection—Our Experience

The aim of this retrospective study was to determine the rate of metastases in the central neck compartment and examine the morbidity and rate of recurrence in patients with differentiated thyroid cancer treated with or without a central neck dissection. Two hundred and fifteen patients undergoing total thyroidectomy with preoperative diagnosis of differentiated thyroid cancer, in the absence of suspicious nodes, were divided in two groups: those who underwent a thyroidectomy only (group A; n = 169) and those who also received a central neck dissection (group B; n = 46). Five cases (2.32%) of nodal recurrence were observed: 3 in group A and 2 in group B. Tumor histology was associated with a risk of recurrence: Hürthle cell-variant and tall cell-variant carcinomas were associated with a high risk of recurrence. Multifocality and extrathyroidal invasion also presented a higher risk, while smaller tumors were at lower risk. The results of this study suggest that prophylactic central neck dissection should be reserved for high-risk patients only. A wider use of immunocytochemical and genetic markers to improve preoperative diagnosis and the development of methods for the intraoperative identification of metastatic lymph nodes will be useful in the future for the improved selection of patients for central neck dissections.

Renal cell carcinoma metastasis to thyroid tumor: a case report and review of the literature

IntroductionMetastatic neoplasms to the thyroid gland are rare in clinical practice. Clear cell renal carcinoma is the most frequent site of origin of thyroid metastases and represents 12 to 34% of all secondary thyroid tumors. Tumor-to-tumor metastases, in which a thyroid neoplasm is the recipient of a metastasis, are exceedingly rare. We report a case of clear cell renal carcinoma metastatic to a follicular adenoma. This is the tenth case of renal cell carcinoma metastasis to thyroid tumor reported in the literature.Case presentationA 62-year-old Caucasian woman with a history of clear cell renal carcinoma was admitted to our institution for multinodular goiter. A histological examination after total thyroidectomy revealed clear cell renal carcinoma metastasis to a thyroid follicular adenoma.ConclusionsPreoperative diagnosis of secondary thyroid neoplasm is difficult to achieve. The diagnosis of metastatic disease should be taken into account if patients have a history of clear cell renal carcinoma or if there is a multifocal growth pattern and clear cell appearance of the cytoplasm.

Intraoperative parathyroid hormone assay during focused parathyroidectomy: the importance of 20 minutes measurement

BackgroundParathyroid hormone (PTH) monitoring during the surgical procedure can confirm the removal of all hyperfunctioning parathyroid tissue, as the half-life of PTH is approximately 5 min. The commonly applied Irvin criterion is reported to correctly predict post-operative calcium levels in 96-98% of patients. However, the PTH baseline reference concentration is markedly influenced by surgical manipulations during preparation of the affected glands, interindividual variability of the PTH half-life and modifications in the physiological state of the patient during surgery. The aim of this study was to evaluate the possible impact of the measurement of intraoperative PTH 20 minutes after surgery.MethodsBetween 2003 and 2012, 188 patients underwent a focused parathyroidectomy associated to rapid intraoperative PTH assay monitoring. Blood samples were collected: 1) at pre-incision time, 2) at 10 min after gland excision and 3) at 20 min after excision, if a sufficient reduction of PTH value was not observed. On the bases of the Irvin criterion, an intra-operative PTH drop>50% from the highest either pre-incision or pre-excision level after parathyroid excision was considered a surgical success.ResultsA >50% decrease of PTH after gland excision compared to the highest pre-excision value occurred in 156/188 patients (83%) within 10 min and in further 12/188 after 20 minutes (6.4%). In the remaining 20 patients (10.6%) values of PTH remained substantially unchanged or decreased less than 50% and for this reason bilateral neck exploration was performed. An additional pathologic parathyroid was removed in 9 cases, a third in one. In the other 10 cases further neck exploration by a standard cervical approach was negative and in four of these persistent postoperative hypercalcemia was demonstrated. The overall operative success was 97.3%. Intraoperative PTH monitoring was accurate in predicting operative success or failure in 96.3% of patients.ConclusionsThe 20 minutes PTH measurement appears very useful, avoiding unnecessary bilateral exploration and the related risk of complications with only a slight increase of the duration of surgery and of the costs. PTH values decreasing appeared to be influenced by surgical manipulations during minimally invasive parathyroidectomy.

Assessing RET/PTC in thyroid nodule fine needle aspirates: the FISH point of view

RET/PTC rearrangement and BRAF(V600E) mutation are the two prevalent molecular alterations associated with papillary thyroid carcinoma (PTC), and their identification is increasingly being used as an adjunct to cytology in diagnosing PTC. However, there are caveats associated with the use of the molecular approach in fine-needle aspiration (FNA), particularly for RET/PTC, that should be taken into consideration. It has been claimed that a clonal or sporadic presence of this abnormality in follicular cells can distinguish between malignant and benign nodules. Nevertheless, the most commonly used PCR-based techniques lack the capacity to quantify the number of abnormal cells. Because fluorescence in situ hybridization (FISH) is the most sensitive method for detecting gene rearrangement in a single cell, we compared results from FISH and conventional RT-PCR obtained in FNA of a large cohort of consecutive patients with suspicious nodules and investigated the feasibility of setting a FISH-FNA threshold capable of distinguishing non-clonal from clonal molecular events. For this purpose, a home brew break-apart probe, able to recognize the physical breakage of RET, was designed. While a ≥3% FISH signal for broken RET was sufficient to distinguish nodules with abnormal follicular cells, only samples with a ≥6.8% break-apart FISH signal also exhibited positive RT-PCR results. On histological analysis, all nodules meeting the ≥6.8% threshold proved to be malignant. These data corroborate the power of FISH when compared with RT-PCR in quantifying the presence of RET/PTC in FNA and validate the RT-PCR efficiency in detecting clonal RET/PTC alterations.

Role of intraoperative neuromonitoring of recurrent laryngeal nerves in the outcomes of surgery for thyroid cancer.

INTRODUCTION The aim of this retrospective study was to evaluate the ability of intraoperative neuromonitoring to predict the postoperative functional outcome and its role in reducing the postoperative recurrent laryngeal nerve palsy rate during thyroidectomy for thyroid malignancy. METHODS Between June 2007 and March 2013, 656 consecutive patients with thyroid cancer underwent thyroidectomy by a single surgical team. We compared 357 patients who have had neuromonitoring (Group A) to 299 patients who have undergone surgery with nerve visualization alone (group B). RESULTS In group A 7 recurrent laryngeal nerve paralysis were observed (1.96%), 6 (1.68%) transient and 1 (0.28%) permanent; a bilateral recurrent laryngeal palsy was observed in 1 of the 7 cases (0.28%). In group B 6 recurrent laryngeal nerve paralysis were observed (2.01%), 5 (2.01%) transient and 1 permanent (0.33%); bilateral palsy was observed in 1 of the 6 cases (0.33%). Differences were not statistically significative. CONCLUSIONS Routine visual nerve identification remains the gold standard of recurrent laryngeal nerve management in surgery for thyroid cancer. Intraoperative neuromonitoring is safe, effective, reliable, and easy to perform in excluding postoperative recurrent laryngeal palsy. It helps to identify the nerve in thyroid cancer, but it did not decrease the injuries compared with visualization alone in this study; however, its use can change the operative strategy in order to prevent the risk of bilateral damage in case of signal loss. Future studies are needed to evaluate the benefit of intraoperative neuromonitoring in thyroidectomy for thyroid cancer.