The Diagnostic Value of Contrast Enhanced Ultrasound for Localization of Parathyroid Lesions in Primary Hyperparathyroidism: Comparison With Color Doppler Ultrasound: Comparison With Color Doppler Ultrasound.

OBJECTIVES: Preoperative localization of pathological parathyroid glands with imaging is essential for focused unilateral neck exploration and minimally invasive techniques. Recently published studies suggested that contrast-enhanced ultrasonography (CEUS) had high accuracy in the localization of hyperfunctioning parathyroid glands, with a general increase in the sensitivity as compared to conventional sonography. The purpose of this study was to determine the usefulness of CEUS in the localization of parathyroid lesions relating to surgical and histopathological data, in comparison to color Doppler ultrasound (CDUS), in the same series of patients. METHODS: Records of 142 patients who underwent parathyroidectomy were retrospectively examined comparing imaging and intraoperative/histopathologic findings. RESULTS: The overall sensitivity of CEUS was 77.6% compared with 74.6% for CDUS, although no significative differences were found (P = .516). Conversely, CDUS has shown higher sensitivity than CEUS in the group of patients with associated thyroid pathology but there was no statistical difference (P = .529). The sensitivity for detection of multiple adenomas was the same for both procedures. CONCLUSIONS: We found no significative superior sensitivity of CEUS also in case of concomitant thyroid pathology and multiple glands disease.

Pre-operative imaging workup for surgical intervention in primary hyperparathyroidism: A tertiary referral center experience.

PURPOSE: Preoperative imaging in patients with primary hyperparathyroidism provides important localization information, allowing the surgeon to perform a focused surgery. However there are no evidence-based guidelines suggesting which preoperative imaging should be used, resulting in a risk of excessive prescription of exams and waste of economic resources. The main purpose of this study was to describe our experience on the performance of various imaging techniques for the preoperative localization of abnormal parathyroid gland/s, with a focus on the sensitivity and specificity of each technique. Secondly, we carried out an analysis of the cost utility of each technique in order to determine the most clinical and cost-effective combination of localization studies. MATERIALS AND METHODS: Records of 336 patients who underwent parathyroidectomy were retrospectively examined comparing imaging and intraoperative/histopathologic findings to evaluate the accuracy in parathyroid detection of each imaging technique. Costs were determined by regional health system reimbursement. RESULTS: We found that the sensitivity of color Doppler US was significantly higher than SPECT (p 0,023), while the sensitivity of 4D-CT was significantly better than US (p 0,029) and SPECT (p 0,0002). CONCLUSIONS: In experienced hands color Doppler US is a highly sensitive technique especially in patients with no thyroid diseases. In patients with concomitant thyroid pathology, the combination of US and 4D-CT represents a reliable localization technique.

Early experience in tracheostomy and tracheostomy tube management in Covid-19 patients.

In Italy, we have experienced Europe's first and largest coronavirus outbreak. Based on our preliminary experience, we discuss the challenges in performing tracheotomy and tracheostoma care in the setting of a new pathogen.

Unexpected Widespread Bone Metastases from a BRAF K601N Mutated Follicular Thyroid Carcinoma within a Previously Resected Multinodular Goiter.

Follicular thyroid carcinoma (FTC) represents the second most common malignant thyroid neoplasm after papillary carcinoma (PTC). FTC is characterized by the tendency to metastasize to distant sites such as bone and lung. In the last 20 years, the understanding of the molecular pathology of thyroid tumors has greatly improved. Uncommon BRAF non-V600E mutations have been identified and are generally believed to associate with follicular patterned tumors of low malignant potential, particularly non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (i.e., non-invasive encapsulated follicular variant PTC). We here report for the first time widespread bone metastases from a BRAF K601N mutated follicular tumor.

A roadmap to parathyroidectomy for kidney transplant candidates.

Chronic kidney disease mineral and bone disorder may persist after successful kidney transplantation. Persistent hyperparathyroidism has been identified in up to 80% of patients throughout the first year after kidney transplantation. International guidelines lack strict recommendations about the management of persistent hyperparathyroidism. However, it is associated with adverse graft and patient outcomes, including higher fracture risk and an increased risk of all-cause mortality and allograft loss. Secondary hyperparathyroidism may be treated medically (vitamin D, phosphate binders and calcimimetics) or surgically (parathyroidectomy). Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. There are no clear guidelines or long-term studies about the impact of hyperparathyroidism therapy. Parathyroidectomy is more effective than medical treatment, although it is associated with increased short-term risks. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes. We now propose a roadmap for the management of secondary hyperparathyroidism in patients eligible for kidney transplantation that includes the indications and timing (pre- or post-kidney transplantation) of parathyroidectomy, the evaluation of parathyroid gland size and the integration of parathyroid gland size in the decision-making process by a multidisciplinary team of nephrologists, radiologists and surgeons.

Erratum to: A roadmap to parathyroidectomy for kidney transplant candidates.

[This corrects the article DOI: 10.1093/ckj/sfac050.].

Impact of 18F-FDG PET/CT on Clinical Management of Suspected Radio-Iodine Refractory Differentiated Thyroid Cancer (RAI-R-DTC).

BACKGROUND: As reported in the literature, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) provides useful qualitative and semi-quantitative data for the prognosis of advanced differentiated thyroid cancer. Instead, there is a lack of data about the real clinical impact of 18F-FDG PET/CT on the choice of the more effective therapeutic approach for advanced differentiated thyroid cancer (DTC) that starts to lose iodine avidity. The primary aim of this retrospective study was to assess how 18F-FDG PET/CT can guide the choice of the best therapeutic approach to RAI-refractory DTC (RAI-R-DTC) in patients with a doubtful iodine uptake/negative 18F-FDG PET/CT I whole-body scan after several radioactive iodine therapies (RAIT). The secondary aim was to assess the prognostic role of clinical and semi-quantitative metabolic 18F-FDG PET/CT parameters in comparison to published data. MATERIALS AND METHODS: A monocentric retrospective observational study was performed, reviewing the medical records of 53 patients recruited from a database of 208 patients treated at our Institution between 2011 and 2019, with advanced DTC that underwent FDG PET/CT scan for a suspected RAI-R-DTC. Selected patients had to perform a 18F-FDG PET/CT scan after the second RAIT based on a doubtful iodine uptake/negative 131 I whole-body scan and/or persistent elevated thyroglobulin levels. Metabolic response was defined according to positron emission tomography response criteria in solid tumors (PERCIST) guidelines. Standardized uptake value (SUV)max, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The association between metabolic features, clinical parameters and progression free survival (PFS) was assessed applying Kruskal-Wallis, chi-square-Pearson correlation tests, and Cox regression analyses when appropriate. RESULTS: Among our sample of 53 patients (mean age 52.0 ± 19.9 years; 31 women and 22 men), 27 (51.0%) presented a positive 18F-FDG PET/CT scan: 16 (59.0%) underwent watchful waiting, 4 (15.0%) received external-beam radiation therapy (EBRT), 4 (15.0%) underwent surgery, 2 (7.4%) received another course of RAI therapy, and 1 underwent surgery + EBRT. PERCIST response was evaluated in 14/27 patients. Median follow-up was 5.8 ± 3.9 years and median PFS was 38.0 ± 21.8 months. At the last follow-up assessment, 14/53 (26.4%) demonstrated disease progression, 13/53 (24.5) persistence of structural disease, 25/53 (47%) persistence of biochemical disease, and 15/53 (28%) had an excellent response. A significant association was found between therapeutic approach, metabolic response, and final disease response evaluation, as well as a linear correlation between MTV and TLG with thyroglobulin level. CONCLUSIONS: Our Institutional experience confirmed the role of 18F-FDG PET/CT as a useful guide in the clinical management of RAI-R-DTC and obviated further unnecessary RAIT.

The value of neurostimulation and intraoperative nerve monitoring of inferior laryngeal nerve in thyroid surgery.

OBJECTIVE: To determine the accuracy of neurostimulation with laryngeal palpation (NSLP) and intraoperative neuromonitoring (IONM) to predict the postoperative function of recurrent laryngeal nerve (RLN) in thyroid surgery. STUDY DESIGN: Historical cohort study. SUBJECTS AND METHODS: A retrospective case control study with 993 patients. The control group (799 patients with 1450 nerves at risk) included patients who underwent NSLP and the case group (194 patients with 354 nerves at risk) consisted of those who underwent NSLP in association with IONM. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy were calculated for NSLP and IONM, with nerve palsy as the target outcome. RESULTS: A significant difference in nerve injury between the case and the control group (P = 0.31) was not observed. The presence or absence of laryngeal twitch (LT) (P < 0.0001) and the acoustic response to electrical stimulation (P = 0.003) were significantly associated with nerve function at the end of the surgery. CONCLUSION: Our results indicate that NSLP is a safe and reliable intraoperative method of RLN monitoring. Moreover our data confirm that IONM is not a helpful tool to reduce the rate of palsy in thyroid surgery.

Parathyroid Tissue Cryopreservation: Does the Storage Time Affect Viability and Functionality?

Parathyroidectomy is a standard practice to treat recurrent or persistent hyperparathyroidism. However, this can lead to the onset of hypoparathyroidism, treatable with the autotransplantation of parathyroid tissue (PT). Tissue can be transplanted immediately after parathyroidectomy or cryopreserved and transplanted only in case of necessity. Since 2011, the Cord Blood Bank and Cardiovascular Tissue Bank of Emilia-Romagna has been storing PT for potential autologous transplantation. To date, there are highly variable data about the viability and function of PT after thawing. However, it is not clear if the PT quality is affected by different cryopreservation protocols and/or by the storage time. The aim of this study was to assess the ex vivo function and viability of the PTs of ten patients stored in the Bank. Tissue morphology was evaluated before and after cryopreservation through histological investigations. PT function was analyzed by assessing the ability of cryopreserved PT to synthesize and secrete parathyroid hormone (PTH) in response to different calcium concentrations. Moreover, viability and function were also investigated on tissue-isolated cells in culture. These data show that tested tissues appear to be viable and able to produce PTH even after 5 years of storage, and the histological architecture is well preserved.

BRAF V600E Status and Stimulated Thyroglobulin at Ablation Time Increase Prognostic Value of American Thyroid Association Classification Systems for Persistent Disease in Differentiated Thyroid Carcinoma.

BACKGROUND: Stimulated thyroglobulin levels measured at the time of remnant ablation (A-hTg) and BRAFV600E mutation had shown prognostic value in predicting persistent disease in differentiated thyroid cancer (DTC). The aim of this study was to evaluate the prognostic role of A-hTg combined with the BRAFV600E status in association with the revised American Thyroid Association (ATA) risk stratification. MATERIAL AND METHODS: 620 patients treated for a DTC were included in this study with a median follow-up duration of 6.1 years. All patients underwent total thyroidectomy followed by radioiodine ablation. Patients with positive anti-thyroglobulin antibodies were excluded. The predictive value of A-hTg was calculated by receiver operating characteristic curve (ROC curve) analysis. The Cox proportional hazard regression model, including the BRAF status, A-hTg, and ATA classification system, was assessed to evaluate the existing persistent disease risk. RESULTS: Taken together, the BRAF status and A-hTg levels improve the ATA risk classification in all categories. In particular, in the low-risk ATA classification, only the combination of BRAFV600E+A-hTg > 8.9ng/ml was associated with persistent disease (P = 0.001, HR 60.2, CI 95% 5.28-687). In the intermediate-risk ATA classification, BRAFWT+A-hTg > 8.9ng/ml was associated with persistent disease (P = 0.029, HR 2.71, CI 95% 1.106-6.670) and BRAFV600E+A-hTg > 8.9ng/ml was also associated with persistent disease (P < 0.001, HR 5.001, CI 95% 2.318-10.790). In the high-risk ATA classification, both BRAFV600E+A-hTg < 8.9ng/ml and BRAFV600E+A-hTg > 8.9 ng/ml were associated with persistent disease (P = 0.042, HR 5.963, CI 95% 1.069-33.255 and P = 0.002, HR 11.564, CI 95% 2.543-52.576, respectively). CONCLUSIONS: The BRAF status and stimulated thyroglobulin levels at ablation time improve the ATA risk stratification of differentiated thyroid cancer; therefore, even A-hTg could be included in risk classification factors.

Accuracy of PTH assay and corrected calcium in early prediction of hypoparathyroidism after thyroid surgery.

OBJECTIVE: To evaluate the accuracy of the intraoperative parathyroid hormone (ioPTH) and 6-hour PTH (6hPTH) assay in predicting transient hypoparathyroidism after thyroidectomy. STUDY DESIGN: A nonrandomized prospective study was conducted on patients undergoing thyroid surgery. SUBJECTS AND METHODS: Of 138 patients undergoing thyroid surgery, intraoperative PTH was measured 10 minutes after gland removal. Serum calcium, magnesium, inorganic phosphorus, albumin, and PTH levels were assayed 6 and 16 hours after surgery and daily until patient discharge. RESULTS: The development of postoperative hypocalcemia was associated with low ioPTH (P < 0.0001) and 6hPTH (P < 0.0001) values, and the decline of PTH from baseline (P < 0.0001). The cutoff for percentage decline of ioPTH and 6hPTH (55.7% and 379%, respectively) was more accurate than an absolute value. Accuracy, and positive and negative predictive values were 88 percent, 63 percent, and 100 percent for ioPTH and 75 percent, 46 percent, and 100 percent for 6hPTH, respectively. CONCLUSION: With the use of ioPTH decline in association with 16-hour corrected calcium, it is possible to distinguish early normocalcemic patients from hypocalcemic ones in most cases.

Intraoperative intermittent neuromonitoring of inferior laryngeal nerve and staged thyroidectomy: our experience.

PURPOSE: To evaluate the reliability of intermittent intraoperative neuromonitoring (I-IONM) through recurrent laryngeal nerve (RLN) stimulation and laryngeal palpation in predicting postoperative vocal cord palsy and to examine the reliability of this technique in providing useful information in the decision to perform a staged surgery in initially planned total thyroidectomy. METHODS: This was a retrospective cohort study of patients who underwent thyroid surgery at the ENT Department of the University of Bologna from January 2014 to June 2017. In all cases, preoperative and postoperative laryngoscopy was performed. All surgeries were conducted with I-IONM and RLN simultaneous laryngeal palpation (NSLP) to detect contraction (laryngeal twitch) of the posterior crico-arytenoid muscle. The incidence of vocal cord palsy was calculated for nerves at risk. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated with a confidence interval determined at 95% level. RESULTS: Seven hundred and sixteen patients were enrolled in the study. The incidence of vocal cord palsy was 3.16%. Specificity of I-IONM in predicting vocal cord paralysis was 99.1% and sensitivity was 90%. The NPV was 99.7% and PPV 78.3%. Two-stage thyroidectomy (ST) was performed in 22 cases (22/570: 3.85%). Six patients (27.3%) were false positive and 16 true positive (72.7%) at I-IONM. CONCLUSION: High sensitivity and specificity values confirm the validity of I-IONM with NSLP in predicting postoperative normal vocal cord function. Our results confirm that I-IONM may safely guide an ST overall in benign thyroid diseases and in low-grade malignancies.

Transient hypoparathyroidism following thyroidectomy: a prospective study and multivariate analysis of 604 consecutive patients.

OBJECTIVE: The purpose of this study was to identify the risk factors for postoperative transient hypoparathyroidism in a group of patients undergoing thyroid surgery. STUDY DESIGN: A prospective study was conducted on 604 patients undergoing thyroid surgery. SUBJECTS AND METHODS: Gender, final diagnosis, extent of resection, biology of pathology, intrathoracic involvement, surgery for recurrent multinodular goiter, and presence and number of parathyroid glands in a surgical specimen were analyzed as risk factors for postoperative transient hypoparathyroidism. The chi-square test and a logistic regression analysis were applied. RESULTS: On logistic regression analysis, only the extent of surgery constituted an independent variable for transient hypoparathyroidism (P = 0.001). CONCLUSION: The extent of surgery to central and/or lateral neck lymph nodes is responsible for a high rate of transient hypoparathyroidism owing to a high probability of unplanned parathyroidectomy or parathyroid gland devascularization.

Minimally invasive nonendoscopic thyroidectomy.

OBJECTIVES: Minimal-access thyroid surgery, using various techniques, is increasingly being reported. The present study reviews our experience with thyroid surgery using a minimally invasive approach (MIT). STUDY DESIGN: Between October 2002 and December 2004, a prospective nonrandomized study of patients undergoing thyroid surgery was performed to evaluate the variables that might condition the indications to minimally invasive nonendoscopic approach. RESULTS: 296 patients underwent thyroid surgery; 46 of these were eligible for MIT through a 2.5- to 3-cm incision. There was one case of transient inferior laryngeal nerve palsy and no postoperative definitive hypoparathyroidism. MIT was converted to conventional thyroidectomy only in two cases. Cosmetic results were considered excellent by all patients. CONCLUSIONS: Minimal-access thyroid surgery is a safe and feasible alternative to conventional thyroid surgery in selected cases. The advantage that this technique offers, in addition to low morbidity, is an improved cosmetic result.

Intraoperative neuromonitoring in thyroid surgery: a point prevalence survey on utilization, management, and documentation in Italy.

The frequency of neuromonitoring during thyroid surgery is underreported in Italy. The present survey depicts and describes the patterns of use, management, documentation for IONM devices of IONM during thyroid surgery by surgeons in Italy. A point prevalence survey was undertaken. Source data were mixed from Italian surgeons attending the 2014 International Neuromonitoring Study Group (INMSG) meeting, four IONM manufacturers available in Italy and surgical units were identified from Company sales data. Qualitative and quantitative data were used to analyze. Questions probed IONM prevalence, surgeon background, hospital geographic practice locations, type of hospital, rationale for IONM use, sources of initial capital investment for IONM acquisition, type of equipment, use of continuous IONM, monitoring management, use of distinctive standards, and IONM documentation. IONM is currently delivered through 48 units in Italy. In 2013, the distribution of IONM by specialties included: general (50 %), ENT (46 %), and thoracic surgery (4 %). Overall, 12.853 IONM procedures were performed in the period from 2006 to 2013: 253 were performed in 2007 and about 5,100 in 2013. Distribution according to the type of hospital is: public 48 %, academic setting 37 %, and private maintenance 15 %. The use category of high volume thyroid hospitals represented 33 %. Initial capital investment for the acquisition of the monitoring equipment was 67 % public and 33 % with charitable/private funding. Audio plus graphic and EMG electrodes surface endotracheal tube-based monitoring systems accounted for the majority. Continuous IONM was introduced in 5 Academic Centers. Overall motivations expressed are legal (30 %), RLN confirmation (20 %), RLN identification (20 %), prognosis (10 %), helpful in difficult cases (10 %), decrease surgical time (5 %), and educational (5 %). The survey revealed that participants had few experience with the standardized approach of IONM technique (28 %). General IONM information to patients and/or subsequent specific IONM informed consent was initiated in 8 % of centers. EMG determinations were included in medical chart in 20 %. There were no significant associations found between all parameters considered. The present study describes an increased utilization of IONM in Italy. We highlighted areas for improvement in the management and documentation of IONM.

Clinical significance of BRAF mutation in thyroid papillary cancer.

OBJECTIVE: To correlate the presence of BRAF V600E mutation with clinicopathological parameters. STUDY DESIGN: Case-control study. SETTING: BRAF mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency and its relationship with clinicopathological parameters of poor outcome. We analyzed BRAF mutation in a cohort of patients affected by PTCs to identify its association with clinical variables. SUBJECTS AND METHODS: We analyzed retrospectively a series of 304 patients, treated for PTC from 1999 to 2011 at Bologna University Hospital. We searched BRAF mutation by reverse transcription polymerase chain reaction (PCR) followed by PCR and direct sequencing. RESULTS: BRAF mutation was found in 77.4% of classical PTCs, 31.9% of the follicular variant, and 72.2% of high tall cell PTCs, being significantly associated, at univariate analysis, with recurrence, stage, multicentricity, histologic subtype, extrathyroidal extension, nodule dimension, body mass index, and American Thyroid Association (ATA) risk stratification. Furthermore, higher T, but not N or M, stage was associated with BRAF mutation. In the multivariate analysis, the BRAF mutation was significantly associated only with the ATA risk stratification, in turn showing a significant negative association with recurrence-free survival time with Cox multivariate analysis. CONCLUSION: Our results indicate that BRAF mutation identifies a subset of PTC with increased risk of recurrence. The presence of BRAF mutation might be a valuable diagnostic and prognostic marker of the disease. To confirm the diagnostic usefulness of this marker, further studies should be carried out.

Laryngeal neuromonitoring and neurostimulation versus neurostimulation alone in thyroid surgery: a randomized clinical trial.

BACKGROUND: The aim of this study was to assess a prospective, randomized clinical trial (RCT) comparing neurostimulation with laryngeal palpation (NSLP) of recurrent laringeal nerve (RLN) alone with NSLP associated with laryngeal neuromonitoring (LNM) to evaluate the ability of LNM in reducing the rates of RLN palsy. METHODS: In all, 250 consecutive patients scheduled to have thyroidectomy were randomized to NSLP alone (NSLP group) or NSLP with LNM (LNM group). The primary endpoint was to assess the rate of RLN palsy. RESULTS: The incidence of palsy was 2.7% in the LMN group and 2.6% in the NSLP group. No significant statistical difference between the groups was observed either for permanent or for transient paralysis (respectively, Fisher's Exact test: p = 1.0 and p = 1.0). CONCLUSIONS: This RCT shows that the use of LNM during thyroidectomy does not reduce the rates of recurrent laryngeal injuries compared with NSLP alone.

Anterolateral thigh free flap for tracheal reconstruction after parastomal recurrence.

BACKGROUND: Stomal recurrence after total laryngectomy is 1 of the most serious issues in head and neck surgery, both because of the complexity of its management and because of its morbidity. Prior to the introduction of free-tissue transfer, mediastinal tracheostomy has been the standard reconstructive procedure with high rate of complications. The ideal reconstructive solution to these problems must provide well-vascularized soft tissues that can cover the defect after resection and also allow suturing of the tracheal remnant to skin edges without tension. METHODS AND RESULTS: We describe a case of a 56-year-old man with stomal recurrence after total laryngectomy treated by the use of a tubed anterolateral thigh (ALT) flap to elongate the shortened trachea and simultaneously cover the cervical skin defect. CONCLUSIONS: The ALT can be accepted as an ideal free-flap choice for stomal recurrence, because it has maximal reconstructive capacity and produces minimal donor-site morbidity.