Costantino Pagetta

Identification of the Nonrecurrent Laryngeal Nerve during Thyroid Surgery: 20-Year Experience

The nonrecurrent laryngeal nerve, which is rarely observed during thyroidectomy, is at high risk for damage. During a 20-year period 6000 thyroidectomies were performed at our institution, and during these operations inferior laryngeal nerves were routinely identified in all the patients with a standard procedure based on the usual anatomic landmarks. A nonrecurrent laryngeal nerve was observed on the right side in 31 cases (0.51%), with no anatomic anomalies found on the left side. The nerve anomaly was diagnosed preoperatively in five patients. A vocal cord deficit, caused by a nerve lesion, was observed in four cases (12.9%). Our results suggest that the best way to avoid morbidity is routine identification of the nerve. This can be done by carefully identifying all the thyroid structures and being suspicious of the presence of the abnormality when the inferior laryngeal nerve is not found in a classic position.

Papillary thyroid carcinoma: 35-year outcome and prognostic factors in 1858 patients.

Background and Aim: Papillary thyroid carcinoma (PTC) is universally regarded as a curable malignancy with a favorable prognosis. However, a minority of patients may present, or subsequently develop, locoregional and distant metastases that may adversely affect survival. The value of the various staging methods is complicated by different approaches to diagnostic, therapeutic and follow-up strategies. We aimed at assessing the prognostic factors and survival rate in a large cohort of patients treated and followed up in the same center. Materials and Methods: A total of 1858 patients with PTC operated on by the same surgeon, and followed in the same center over a period of 35 years, were included. Total thyroidectomy was performed in the majority of patients after I-131 diagnostic scans and thyroglobulin assays. When the latter 2 were positive, therapy with I-131 was given. Follow-up was performed periodically and further therapy doses were administered when necessary. All patients were maintained on life-long thyroxine. Results: Ninety-three patients (5%) developed evidence of locoregional or distant metastases after an average follow-up period of 7.9 years (range 1.53–30.5 years). Univariate analysis showed all variables (except for gender) to be significantly correlated with disease recurrence and survival. Multivariate analysis showed 4 variables to be significant and independent prognostic factors: patient age at first treatment, extent of disease, extent of surgery, and the presence of I-131 positive metastases. Discussion and Conclusion: Our data agree with other scoring systems in that patient age at first treatment and the extent of disease are significant and independent prognostic factors. However, and at variance with other methods, we found that the extent of primary surgery and the presence of I-131 positive or negative metastases have similar prognostic significance. In high risk patients, total thyroidectomy and lymphadenectomy followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.

BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves preoperative identification of papillary thyroid carcinoma and represents a prognostic factor. A mono-institutional experience.

Abstract Background: The current preoperative diagnosis of a thyroid mass relies on microscopic evaluation of thyroid cells obtained by fine needle aspiration biopsy (FNAB). More recently, FNAB has been combined with molecular analysis to increase the accuracy of the cytological evaluation. In this mono-institutional prospective study, we evaluated whether the routine introduction of BRAF testing in thyroid FNAB could help ameliorate the preoperative recognition of papillary thyroid carcinoma (PTC) in “suspended” or malignant cytological categories. Moreover, we investigated the prognostic role of the BRAFV600E mutation in PTC. Methods: BRAFV600E analysis was performed in thyroid FNAB from 270 patients classified into one of five cytological categories THY1, THY2, THY3, THY4, THY5. All subsequently underwent thyroidectomy±node dissection, from October 2008 to September 2009 in our Department. For each cytological category, we considered the definitive histological diagnosis of PTC and the presence of the BRAFV600E mutation. In 141 patients with a final tissue diagnosis of PTC, we correlated the presence of BRAFV600E with gender, age, histotype, TNM, size of the lesion, extracapsular extension, node metastases and multifocality. Results: The prevalence of the BRAFV600E mutation, among PTCs at final tissue diagnosis, was 69%. It improved the FNAB diagnostic accuracy from 88% to 91%. The BRAFV600E mutation was correlated with older age, classical variant of PTC, advanced stages in patients >45 years. Conclusions: BRAFV600E testing could play a role in improving the diagnostic accuracy of FNAB for PTC, representing a useful adjuvant tool in presurgical characterization of thyroid nodes in particular cases. There is an association between the BRAFV600E mutation and some clinico-pathological characteristics of PTC.

Ectopic parathyroid adenomas located at the carotid bifurcation: the role of preoperative Tc-99m MIBI scintigraphy and the intraoperative gamma probe procedure in surgical treatment planning.

Purpose The prevalence of ectopic parathyroid adenoma (PA) is relatively low, despite some studies in which it has been reported to be as high as 20%. Ectopic PA is a frequent cause of surgical failure, and therefore some authors recommend preoperative imaging to localize the condition in patients with primary hyperparathyroid (HPT) disease before initial surgery. Methods Two unusual cases of primary HPT caused by an ectopic PA located at the carotid bifurcation are reported. The patients were examined before operation using Tc-99m MIBI scintigraphy and then underwent radioguided surgery using the intraoperative gamma probe technique with injection of a low dose (37 MBq; 1 mCi) of Tc-99m MIBI. Results The first patient had a history of primary HPT and coexisting multinodular goiter. She had undergone total thyroidectomy in another center, but no enlarged parathyroid gland was found at bilateral neck exploration and serum calcium and parathyroid hormone levels remained elevated after intervention. The patient was referred to our center. A Tc-99m MIBI scan showed a focus of abnormal tracer uptake in the superior left laterocervical region that was thought to be a PA. The next day she underwent radioguided surgery and an 18-mm PA located at the left carotid bifurcation was easily removed through a 2.5-cm skin incision. The second patient was examined in our center before surgery. A neck ultrasound showed a multinodular goiter but no enlarged parathyroid glands. A pertechnectate–MIBI subtraction scan revealed a focus of abnormal Tc-99m MIBI uptake in the right superior laterocervical region that was thought to be a PA. One week later, at radioguided surgery, a 25-mm PA was identified at the right carotid bifurcation and removed successfully. Conclusions These data strongly support the utility of preoperative imaging with Tc-99m MIBI in patients with primary HPT before initial neck exploration with the aim of avoiding surgical failure. Furthermore, the intraoperative gamma probe technique seems to be useful to reduce surgical trauma and, possibly, complications in patients with ectopic PA.

99mTc-MIBI radio-guided surgery in primary hyperparathyroidism: A prospective study of 128 patients

Aims and study design We investigated the role of an intraoperative gamma probe (IGP) technique in 128 patients with primary hyperparathyroidism (HPT). The patients were evaluated before surgery by 99mTcO4/MIBI scintigraphy and neck ultrasound and then operated on by the same surgical team. The IGP technique consisted of the injection of a low dose (37 MBq) of 99mTc-MIBI in the operating room shortly before the start of surgery. Quick parathyroid hormone (QPTH) was routinely measured during the operation. Results In 94/97 patients (96.9%) with a preoperative diagnosis of solitary parathyroid adenoma (PA) minimally invasive radioguided surgery (MIRS) was successfully performed; in the other 3/97 patients (3.1%) conversion to bilateral neck exploration (BNE) was required because of the intraoperative diagnosis of parathyroid carcinoma in two cases and multiglandular disease (MGD) in one. MIRS was successfully performed also in 23 patients who had undergone previous thyroid or parathyroid surgery. In 31 patients with a preoperative diagnosis of MGD (n = 5) or concomitant nodular goiter (n = 26) the IGP technique was used during a bilateral neck exploration. Among these patients IGP was useful in localizing an ectopic parathyroid gland in the thymus in one case of MGD and a PA located deep in the neck (n = 2) or ectopic at the carotid bifurcation (n = 1) in three cases with nodular goiter. However, in several other patients with nodular goiter it was difficult for the probe to distinguish intraoperatively between thyroid nodules and PA located close to the thyroid gland. Conclusions It can be concluded that a) in primary HPT patients with a high likelihood (according to scintigraphic and ultrasound findings) of being affected by a single PA and with a normal thyroid gland, the IGP technique appears useful in MIRS; b) a 99mTc-MIBI dose as low as 37 MBq appears to be adequate to perform MIRS; c) the measurement of QPTH is strongly recommended in HPT patients selected for MIRS to confirm the radicality of parathyroidectomy; d) MIRS can be useful also in HPT patients who underwent previous parathyroid or thyroid surgery to limit the surgical trauma of reoperation and minimize complications; e) with the exception of PAs located at ectopic sites or deep in the neck, the IGP technique does not seem to be recommendable in HPT patients with concomitant nodular goiter.

Minimally invasive radioguided parathyroidectomy: an attractive therapeutic option for elderly patients with primary hyperparathyroidism.

Background and aimSurgery for primary hyperparathyroidism (PHPT) due to a solitary parathyroid adenoma (PA) is moving from traditional bilateral neck exploration (BNE) towards the use of limited neck exploration. The aim of the present study was to define the efficacy of minimally invasive radioguided surgery (MIRS) in PHPT patients with a high probability of a solitary PA with particular regard to benefits achievable in elderly patients. Patients and methodsThe study population included a total of 266 consecutive PHPT patients who had undergone surgery at our centre between September 1999 and February 2003. Preoperative imaging consisted of [99mTc]pertechnetate/99mTc sestamibi (99mTcO4/sestamibi) scintigraphy and neck ultrasound obtained in the same session. One hundred and eighty-seven patients from the whole series (75 of whom were older than 65 years) with a high scan/ultrasound probability of a solitary PA, a high PA sestamibi uptake, and a normal thyroid gland were selected for MIRS. The other 79 patients were selected for traditional BNE. The intra-operative technique was based on the injection of a low dose (37 MBq) of sestamibi in the operating theatre a few minutes before the beginning of intervention and on the use of a 11 mm collimated gamma probe. ResultsMIRS was successfully performed in 97.8% of all PHPT patients selected for this type of surgery and, in particular, in 100% of the subgroup (n=75) of elderly patients. MIRS required a mean operating time of 35 min and a mean hospital stay of 1.2 days; that is, approximately half of that required for traditional BNE. Moreover, local anaesthesia was successfully performed in 27 patients, 19 of whom were >65 years with concomitant invalidating diseases contraindicating general anaesthesia. No major surgical complications were recorded. Transitory hypocalcaemia was observed in 9% of cases treated with MIRS compared with 27% of patients treated with BNE. ConclusionMIRS can be accurately planned in elderly PHPT patients with a solitary PA on the basis of a 99mTcO4/sestamibi scan and neck ultrasound. MIRS has been proven to be safe and effective in our experience, and allows a significant reduction of operating and recovery time, as well as the possibility of using local anaesthesia, especially in elderly patients with concomitant invalidating diseases.

Efficacy of sequential double tracer subtraction and SPECT parathyroid imaging in the precise localization of a low mediastinal parathyroid adenoma successfully removed surgically.

The case of a 58-year-old female patient with primary hyperparathyroidism (serum calcium levels = 12.3 mg/dL, serum PTH levels = 254 pg/mL) resulting from a rare case of solitary parathyroid adenoma located in the low mediastinum is described. The sequential acquisition of planar Tc-99m pertechnetate-MIBI subtraction scan and SPECT imaging precisely localized an intrathymic parathyroid adenoma located in the lower portion of the mediastinum anteriorly close to the body of the sternum. High-resolution 10-MHz neck ultrasonography and neck-mediastinum spiral computed tomography scan did not reveal parathyroid enlargement. A 14-mm sized intrathymic parathyroid adenoma was successfully removed through a 4-cm median cervicotomy by pulling up and excising the thymus. Thus, in this patient, the accurate preoperative scintigraphic localization of the parathyroid adenoma allowed the surgeon to avoid a sternotomy as is usually required in these cases. Intraoperative, rapid PTH levels fell to the normal range and serum calcium levels remained in the normal range in the subsequent 15-month follow up.

Central Node Neck Dissection for Papillary Thyroid Carcinoma: ClinicalImplications, Surgical Complications and Follow up. A Prospective vs aRestrospective Study

Introduction: The treatment and particularly the extension of surgical therapy of papillary thyroid carcinoma (PTC) remain still controversial in some issues, especially for the lack of preoperative information or variables that allow predicting the level of aggressiveness of the tumor. Aim of the study: The purpose of the study was to assess the impact of the central node neck dissection (CNND) on surgical outcome and disease free- follow up of PTC- patients operated on at our center by evaluation of postoperative complications (parathyroid and recurrent nerve damage, hemorrhage rates) and pts rates presenting detectable serum Thyroglobulin (TG) or TG-Antibodies (TG-AB) values, at the time of 131Iodine treatment and subsequently at 6-12 months, combined with neck high-resolution ultrasound (HRUS) The results of a prospective study on 149 pts preoperatively diagnosed and HR-US staged N0-PTC who underwent total thyroidectomy and CNND were compared with the results of a retrospective study on 114 similar postoperatively diagnosed PTC-pts who received total thyroidectomy, without nodes dissection. Materials and methods: 149 patients who underwent total thyroidectomy (TT)+CNND from March 2012 to August 2013 (group-A) and 114 patients who underwent TT from January to December 2011 (group-B) were compared on the following variables: gender, age, histological variant of PTC, tumor size, TNM stage, multifocality, vascular invasion, thyroiditis, expression of BRAF mutation, surgical complications (transient postoperative hypocalcemia and hypoparathyroidism, temporary or permanent dysphonia and hemorrhage), values of TG and anti- TG Ab in suspension or under TSH stimulus, in pre-ablation and on the last clinical and instrumental evaluation of the patient. Statistical analysis was performed using the Student t-test and Fisher. A p value less than 0.05 was considered statistically significant. Results: Comparing the patients of group-A with group-B the following variables present with statistically significant differences: transient postoperative hypocalcemia (group-A 50.3% vs group-B 21.9% , p<0.0001) , association with lymphocitary chronic thyroiditis (group-A 63.1% vs group-B 37.7%, p<0.0001), median postoperative serum TG value (group-A 1,05 ng/L vs group-B 2,4 ng/L , p=0.01), median postoperative anti-TG antibodies value (group-A 903 kU/L vs group-B 118.5 kU/L, p=0.006 ), median value of anti-TG antibodies at the last follow up after radioiodine therapy (group-A 481,5 kU/L vs group-B 35 kU/L, p=0.0001). The following variables do not present statistically significant differences: gender (females 83.2% group-A vs group-B 82.5%, p ns), mean age at diagnosis (>45 years group-A 59.7% vs group-B 53.1%, p ns) , the histological subtypes (p ns), microcarcinomas (group-A 29,5% vs group-B 35%, p ns) , pT (p ns) , presence of multifocal lesions (group A 45.6% vs group B 55.3%, p ns), temporary dysphonia ( 7,4% group-A vs. group B 2.6%, p ns), definitive dysphonia (group-A 1,3% vs group-B 0,9%, p ns), post-operative hemorrhage (group-A 2% vs group-B 1.8%, p ns), radioiodine therapy (group-A 80.6% vs group-B 80.7%, p ns), rhTSH (group-A 88.3% vs group-B 82.6%, p ns), median value of TG at the last follow up after radioiodine therapy (group-A 0,2 ng/ml vs group-B 0,3 ng/ml, p ns), median value of TG at the last follow-up in patients not receiving therapy (group-A 0.4 ng/ml vs group-B 0.3 ng/ml, p ns). Discussion and conclusion: In our study we observed that the CNND has allowed a more complete postoperative staging, the TG values after surgery were lower in patients in group A vs group B patients (p<0.0001). Moreover, in group-A any recurrence occurred whereas in group B it was observed a case of relapse at 8 months.

Mini-invasive videoassisted thyroid lobectomy for neonatal hyperfunctioning adenoma related to a somatic TSHr gene mutation

We report here a case of a paediatric hyperthyroidism due to a micro-macro-follicular thyroid adenoma in the presence of heterozygous point mutation of TSH receptor (TSHr). We describe the case from the initial diagnosis, through laboratoristic examinations and imaging techniques, until the radical surgical treatment made by a mini-cervicotomic videoassisted technique. We also explained the genetic work-up from peripheral blood and thyroid adenoma tissue.

Differentiated thyroid carcinoma in elderly patients (over 70 years)

Background Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy, and it usually has a favourable course, with a good prognosis, more than 90% at 10year follow-up. Nevertheless, a subset of patients develops local recurrence or distant metastasis and may die from DTC, indicating the possibility of more aggressive variants of this carcinoma. In this study we retrospectively analyzed the incidence, the treatment and the stage of DTC in a selected group of patients aged 70 or more years old compared with a group of patients less than 70 years old.