Massimo Monacelli

Genotyping of an Italian papillary thyroid carcinoma cohort revealed high prevalence of BRAF mutations, absence of RAS mutations and allowed the detection of a new mutation of BRAF oncoprotein (BRAFV599Ins)

Objectives  The genes RET and RAS, and more recently BRAF, have been shown to be frequently mutated in human papillary thyroid carcinomas (PTC). The aim of this study was to genotype for these mutations a cohort of thyroid tumours collected at our institutions.

Large-artery stiffness: A reversible marker of cardiovascular risk in primary hyperparathyroidism

OBJECTIVE Patients with primary hyperparathyroidism (pHPT) are at increased risk of cardiovascular mortality. We investigated whether aortic stiffness, an early marker of arteriosclerosis and a strong predictor of cardiovascular risk, is increased in pHPT, and whether it improves after parathyroidectomy. METHODS Twenty-four patients with mild pHPT (age 56 ± 10 years, blood pressure 136/85 mmHg, serum calcium 2.55-3.00 mmol/L) and 48 control subjects individually matched with cases by age, sex and blood pressure underwent aortic (carotid-femoral) and upper-limb (carotid-radial) pulse wave velocity (PWV) determination by applanation tonometry in a case-control study. Subjects with renal disease, diabetes, treated hypertension or overt cardiovascular disease were excluded from the study. Seventeen of the patients with pHPT were re-examined 4 weeks after surgical parathyroidectomy. RESULTS Aortic PWV was significantly higher among pHTP patients (11.4 ± 2 vs 9.6 ± 2 m/s, p<0.001). In a conditional logistic regression analysis, pHPT was independently associated with an increased risk of having an aortic PWV >12 m/s (odds ratio 3.28, 95% confidence interval 1.21-8.93). As expected, surgery was accompanied by a reduction in serum calcium (from 2.77 ± 0.2 to 2.25 ± 0.1 mmol/L, p<0.001) and parathyroid hormone (from 29.6 ± 10 to 3.3 ± 2 pmol/L, p<0.001). Aortic PWV decreased after surgery (from 10.9 ± 2 to 9.8 ± 2 m/s, p=0.003). The change in aortic PWV remained significant also after adjustment for changes in blood pressure (p<0.01). Changes in upper-limb PWV generally paralleled those in aortic PWV. CONCLUSION pHPT is associated with increased aortic stiffness, which improves after parathyroidectomy. Our data demonstrate that aortic stiffness may improve upon removal of hyperparathyroid stimuli.

Ultrasound-guided interstitial laser ablation for thyroid nodules is effective only at high total amounts of energy: results from a three-year pilot study.

Objective. According to cross-sectional surveys, the prevalence of nontoxic nodular goiter appears to be higher in the adult population. Surgical intervention is indicated for the following: (a) progressive goiter growth, (b) compression of organs such as the trachea and esophagus, and (c) significant aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules is a viable alternative to traditional surgery. However, studies that have appeared in literature since the introduction of ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules report contradictory data concerning the energy required for nodule ablation. The aim of the present trial was to evaluate retrospectively the efficacy of percutaneous laser thermal ablation in 2 groups of patients, one treated with low, and the other with high, total amount of energy. Design. Forty euthyroid patients were treated with 1 session of percutaneous laser photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured by the same investigator, blinded for treatment, using the ellipsoid formula before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years thereafter. Results. Thyroid nodule ablation is effective over time only if a sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated) is given, although it incurs proportionate side effects. Conclusions. Percutaneous laser thermal ablation is a viable alternative to traditional surgery for the treatment of benign nodular thyroid disease only if a sufficient amount of energy is delivered.

Surgical morbidity of cervical lymphadenectomy for thyroid cancer: A retrospective cohort study over 25 years.

INTRODUCTION Prognosis of thyroid cancer is strictly related to loco-regional metastases. Cervical lymphadenectomy has a specific oncologic role but may lead to significant increase of morbidity. Aim of the study is the analysis of surgical morbidity in cervical lymphadenectomy for thyroid cancer. METHODS We retrospectively analyzed 1.765 thyroid cancers operated over a period of 25 years at S. Maria University Hospital, Terni, University of Perugia, Italy. Type of lymphadenectomy, histology and complications were analysed. RESULTS A prevalence of differentiated and medullary cancers was observed (respectively 88% and 7.2%). Central lymphadenectomy was carried out in 425 patients, lateral modified and radical lymphadenectomy respectively in 651 and 17 cases. Following central neck dissection we observed: bilateral and unilateral temporary recurrent nerves palsy respectively of 0.7% and 3.5%, unilateral permanent palsy in 1.6% of cases, temporary and permanent hypoparathyroidism respectively in 17.6% and 4.4%. After lateral neck dissection we observed: intra and post-operative haemorrhage respectively in 2% and 0.29%, respiratory distress in 0.29%, lesions of facial nerve in 0.44%, of vagus in 0.14%, of phrenic nerve in 0.14%, of hypoglossal nerve in 0.29%, of the accessory nerve, transient in 1.34% and permanent in 0.29%, permanent lesion of cervical plexus in 0.29%, salivary fistula in 0.14% and chylous fistula in 1.04% of patients. Students t test was used to compare groups when appliable. CONCLUSION Central and lateral cervical lymph node dissection are associated to severe morbidity. Correct indication, surgical expertise, high volume of patients and early multidisciplinary management of complications is the key of an acceptable balance between oncologic benefits and surgical morbidity.

The Administration of Anesthetic in the Thyroid Pericapsular Region Increases the Possibility of Side Effects During Percutaneous Laser Photocoagulation of Thyroid Nodules

Nodular thyroid disease is very frequent in iodine‐deficient areas affecting at least 50% of the population. Percutaneous laser ablation (LA) represents an effective method and an alternative to conventional surgery. Since the first description of the LA methodology for thyroid nodules, various studies have suggested some modifications to increase the percentage of volume reduction of the nodules. One of these alternatives involves the injection of anesthetic in the pericapsular thyroid space with detachment of the capsule itself from the surrounding tissue. The aim of this study was to retrospectively evaluate whether using local anesthetic during LA is more effective in reducing volume size of treated nodules, and whether it causes fewer side effects than using no local anesthesia.

A Gelatin–Thrombin Matrix Topical Hemostatic Agent (Floseal) in Combination With Harmonic Scalpel Is Effective in Patients Undergoing Total Thyroidectomy A Prospective, Multicenter, Single-Blind, Randomized Controlled Trial

Background. Hemostasis during thyroidectomy is essential; however, the safest, most efficient, and most cost-effective way to achieve this is unclear. This randomized, multicenter, single-blind, prospective study evaluated the efficacy and safety of using different hemostatic approaches in patients undergoing total thyroidectomy. Methods. Patients aged ≥18 to 70 years were randomized to Floseal + a harmonic scalpel (HS), Floseal alone, HS alone, or standard total thyroidectomy. Primary endpoint was 24-hour drain output. Secondary endpoints included surgery duration and complications. Results. Two hundred and six patients were randomized to Floseal + HS (n = 52), Floseal alone (n = 54), HS alone (n = 50), and standard total thyroidectomy (n = 50). The 24-hour drain output was lower in the Floseal + HS group compared with standard thyroidectomy. Floseal + HS also had a shorter surgery time (P < .0001) versus the other 3 treatments. Conclusion. Floseal + HS can be effective at reducing postsurgical drain output and provides a complementary hemostatic approach in patients undergoing total thyroidectomy.

Thyroid cancer invading the airway: diagnosis and management.

INTRODUCTION Aim of this study is to analyze outcome and the decision making process to approach airway invasion by thyroid tumors. METHODS Retrospective study of 30 years experience in thyroid surgery for cancer invading airway. Clinical records, surgical and pathology reports have been analyzed to assess which principles and procedural details are significant to facilitate efficient diagnosis, staging and treatment. Medical therapy was not evaluated. RESULTS Out of a consecutive series of 2165 thyroid cancer patients, T4a cancers are 303 (14%). Airway invasion was found in 141 (6.5%) cases. Well-differentiated pattern was determined in 110 (78%) while other histology was reported in 31 (22%). Airway-related symptoms have been recorded in 111 (78%) patients. Flexible bronchoscopy was performed in all patients. Rapidly evolving disease or non-resectable airway was found in 105 (74.5%) cases. Permanent tracheotomy was performed in 43 (30.5%) cases, airway lumen restoration with or without stenting in 39 (27.7%), laryngectomy in 8 (5.7%), segmental airway resection and reconstruction in 28 (19.9%). Perioperative mortality was recorded after palliative treatment only. In resected patients, completely radical surgery was not always achievable. All patients with positive margin after resection underwent adjuvant treatment and showed comparable survival to radical surgery patients after 5 years. Tumor relapse occurred in 8 (28.6%) cases (distant or locoregional). Patients with unresectable disease require treatment for symptoms relief but survival is poor. CONCLUSION Although some patients are currently referred with a severely advanced disease, the indication for tracheotomy, salvage procedures or supportive care has decreased over time. Resection is feasible for differentiated tumors with an overall good outcome.

The role of surgery in the treatment of thyroid anaplastic carcinoma in the elderly

INTRODUCTION Anaplastic thyroid carcinoma (ATC) is characterized by local invasiveness, risk of recurrence and very poor prognosis. METHODS We retrospectively analysed the multimodality treatment of ATC in 79 patients considering the impact of surgery on survival. RESULTS Patients were divided in two age groups A and B (cut-off 75 years) and in two size subgroups (cut-off 5 cm). Surgery was performed in 78.5% patients of group A and 32.4% of B (p < 0.05). Radiation respectively in 73.8% and 43.2% (p < 0.05). Tracheostomy and endoprosthesis were used in 45.2% and 16.6% in group A and in 43.2% and 35.1% in group B. The use of tracheostomy was significantly higher (p < 0.05) in larger tumours. In group B comparing operated and not operated patients significant difference in survival was observed for larger tumours (p = 0.043). In Kaplan Meir analysis significant difference in survival was observed comparing surgical and no surgical patients of all four subgroups. Surgery plus radiotherapy offered a significant better outcome in smaller tumours (p = 0.017). Considering the effect of the single treatment, compared to no treatment at all, survival is significantly improved by surgery for smaller and larger tumours respectively with 4.42 (p = 0.001) and with 3.5 months (p = 0.0001) and by radiotherapy respectively with 3.44 and with 3.28 months (p = 0.047 and p = 0.0001). CONCLUSION In elderly patients with ATC, although poor prognosis, surgery is still fundamental in the multimodality treatment with significant advantage in selected patients. Nevertheless most of elderly patients with large tumours are suitable only for palliative management.

Thyroid nodule morphology affects the efficacy of ultrasound-guided interstitial laser ablation: A nested case-control study

Abstract Purpose: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate. Materials and methods: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy. Results: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months. Conclusions: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature.

Breast cancer micrometastasis and axillary sentinel lymph nodes frozen section. Our experience and review of literature

BACKGROUND Sentinel lymph node (SLN) biopsy plays a major role in the surgical management of primary breast cancer. The aim of this study was to assess the diagnostic accuracy of the assessment of axillary frozen sections of SLNs for micrometastasis diagnosis. PATIENTS AND METHODS This study focused on 250 SLNs from 137 patients. Each lymph node was fully analyzed by frozen section. After fixation, serial sections were cut and stained by hematoxylin and eosin (HE) and for pan-cytokeratins by immunohistochemistry (IHC). RESULTS Tumor cells were detected in 57 SLNs, 37 on frozen sections and 20 on controls. Of these 57 positive SLNs, 38 contained metastases, 9 contained micrometastases and 10 contained isolated tumor cells. The specificity and positive predictive value of SLN frozen sections for micrometastasis was 100%. The sensitivity was 83.3% for metastasis, 40% for micrometastasis; the false-negative rate was 16.7% for metastasis and 60% for micrometastasis. CONCLUSION Analysis of frozen section of SLNs is an accurate method for metastasis detection, allowing concurrent axillary dissection when positive. The protocol for SLN analyses described herein shows good sensitivity for micrometastasis detection.