Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Transoral thyroidectomy: a viable surgical option with unprecedented complications-a case series.

PURPOSE: To report the clinical implications of an initial experience with transoral endoscopic thyroidectomy vestibular approach (TOETVA). METHODS: From March to November 2017, five cases of TOETVA were performed. Data reported include patient demographics, indication for surgery, extent of surgery, operative time, the need to convert to cervicotomy, the length of hospital stay and post-operative pain and morbidity. Unconventional complications regarded as specific for TOETVA were reported. The burden of surgery on the patient's quality of life was evaluated using the 36-item short form (SF-36) health survey 1 month after surgery. RESULTS: All patients were females with a mean age of 36 years. They all underwent a right-sided hemithyroidectomy for a solitary thyroid nodule measuring on average 3.5 cm in size. The nodule was reported as Bethesda category II (n = 3), III (n = 1), and IV (n = 1) on fine needle aspiration cytology. The mean operative time was 122 min. Conversion to a transverse cervicotomy was required in one case. None of the patients developed post-operative bleeding, and none experienced vocal fold or mental nerve palsy. Surgical site infection did not occur. All patients developed subcutaneous emphysema that resolved within 12-48 h. All patients reported a long-standing bothersome pulling sensation along the surgical track that resulted in a poor outcome in some scales of the SF-36 survey. Flap perforation occurred in one case. The median VAS score was 3. CONCLUSION: Patients strongly motivated to undergo a novel surgical procedure tailored to their needs and desires should be properly counselled particularly regarding unconventional procedure-related complications.

Less is more: time to expand the indications for minimally invasive video-assisted parathyroidectomy.

PURPOSE: Minimally invasive video-assisted parathyroidectomy (MIVAP) is one of the most widespread targeted parathyroid surgeries for primary hyperparathyroidism (PHP). The aim of this study was to assess its limits and propose an expansion of its indications in the management of parathyroid pathology. METHODS: A retrospective analysis of 77 consecutive patients who underwent MIVAP for PHP between Jan and Oct 2016 was conducted. The adequacy of the procedure and/or the need to convert to a standard cervicotomy was the main outcome of interest. Secondary outcomes of interest included: operative time, postoperative morbidity, postoperative pain assessed by the visual analogue scale (VAS) score, and the length of the surgical incision. RESULTS: There were 64 females and 13 males with a mean age of 51 years. In one patient a concomitant en bloc thyroid lobectomy was required due to features suspicious of parathyroid carcinoma while exploration was required in two other patients. None of these three cases required conversion to standard cervicotomy. The mean operative time, length of incision and VAS score was 31 min, 17 mm and 1.6, respectively. Biochemical cure was achieved in all patients, and no postoperative morbidities were reported. CONCLUSION: MIVAP offers the ability to perform a neck exploration and/or an en bloc thyroid lobectomy without the need to convert to a standard cervicotomy. Therefore, it not only serves as a targeted parathyroid procedure but also a potential alternative to full neck exploration.

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Minimally invasive video-assisted thyroidectomy: reflections after more than 2400 cases performed.

BACKGROUND: The minimally invasive video-assisted approach was developed for primary hyperparathyroidism in 1997 and the year after for thyroid disease. Since then, the technique has been adopted worldwide, and indications moved from the initial benign disease to low-risk and intermediate-risk carcinoma, demonstrating a level of oncologic radicality comparable to the conventional open approach when inclusion criteria are strictly respected. METHODS: Between 1998 and 2014, 2412 minimally invasive video-assisted thyroidectomies (MIVAT) were performed in our department. The indication for surgery in 825 patients (34.3 %) was a malignant tumor, in particular, a papillary carcinoma in 800 patients. Among them, 528 patients operated on between 2000 and 2009 had a mean complete follow-up of 7.5 (standard deviation, 2.3) years. RESULTS: A total thyroidectomy was performed in 1788 patients (74.1 %) and a hemithyroidectomy in 564 (23.4 %). Also performed was central compartment lymphadenectomy in 31 patients (1.3 %) and parathyroidectomy for the presence of a solitary parathyroid adenoma in 29 (1.2 %). Mean duration of the procedure was 41 (standard deviation, 14) minutes. After a mean follow-up of 7. 5 years, 528 patients who underwent MIVAT for low-risk or intermediate-risk papillary carcinoma presented a cure rate of 85 % (undetectable thyroglobulin), comparable with the 80 % rate reported in patients who had undergone open thyroidectomy during the same period. CONCLUSIONS: After a long experience and a considerable number of procedures performed in a single center, MIVAT is confirmed as a safe operation, with a complication rate comparable with open thyroidectomy. MIVAT offers a cure rate for the treatment of low-risk and intermediate-risk malignancies that is comparable with an open procedure when inclusion criteria are strictly respected.

Molecular genetic features and risk assessment in a series of 30 patients who underwent an operation for gastrointestinal stormal tumours.

BACKGROUND: The objective of the study was to investigate the relationship between molecular genetic features and the standard criteria of risk assessment in patients affected by gastrointestinal stromal tumours (GISTs). METHOD: A review was conducted of a series of 30 patients, with a mean age of 67 years, who underwent surgery for primary GISTs. R0 resection was accomplished in 27 patients. CD117, CD34 desmin, vimentin, S-100 and smooth muscle actin were immunohistochemically tested to achieve a diagnosis of GIST. The loss of wild-type KIT or platelet-derived growth factor receptor alpha (PDGFRα) genes was investigated by sequencing the tumour DNA. RESULTS: Tumour genes mutations were reported in 23 patients (77%), and wild-type in seven. Mutations on the KIT gene occurred in 18 patients, and mutations on the PDGFRα gene in five. The average sizes of the GIST were 8.7 cm, 5.4 cm and 5.9 cm for KIT gene-mutated, PDGFRα gene-mutated and wild-type tumours, respectively. KIT gene mutations were detected in 50% of gastric and in 70% of extragastric GISTs. Moreover, 70% of tumours with a mitotic rate ≥ 5 x 50 highpower fi elds (HPFs) underwent KIT gene mutations. Conversely, PDGFRα mutations were observed only in gastric GISTs with a mitotic rate ≤ 5 x 50 HPFs. By stratifying GISTs according to classes of risk, KIT mutation was shown in most of the high-risk tumours. PDGFRα mutations occurred exclusively in lower classes of risk. CONCLUSION: Molecular analysis data might have a role as a prognostic variable in models of risk assessment for patients with GISTs.

Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study.

BACKGROUND: The benefits of prophylactic central compartment lymph node dissection (pCCND) in papillary thyroid cancer (PTC) are still under investigation. This treatment seems to reduce PTC recurrence/mortality rates but has a higher risk of surgical complications. The lack of prospective randomized trials does not allow definitive recommendations. The aim of this prospective randomized controlled study was to evaluate the clinical advantages and disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of followup, no difference was observed in the outcome of the two groups. However, a higher percentage of Group A were treated with a higher number of (131)I courses (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was observed in Group B (P = .02). No preoperative predictors of central compartment lymph node metastases (N1a) were identified. Only three patients were upstaged, and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost 50% of patients with PTC had micrometastatic lymph nodes in the central compartment, but none of the presurgical features analyzed, including BRAF mutation, was able to predict their presence; moreover, to be aware of their presence does not seem to have any effect on the outcome.

Surgery for recurrent goiter: complication rate and role of the thyroid-stimulating hormone-suppressive therapy after the first operation.

PURPOSE: This report examines outcomes in our series of patients who underwent surgery for recurrent goiter to assess the efficacy of thyroid-stimulating hormone (TSH)-suppressive therapy after the first less than total thyroidectomy. A further outcome was to understand whether redo surgery was burdened with a higher rate of complications. METHODS: We evaluated 214 patients undergoing a completion thyroidectomy for recurrent goiter who had received, as their first surgery, a bilateral subtotal thyroidectomy. After the first operation, 84 patients were given TSH-suppressive therapy with levothyroxine, 32 were treated with antithyroid drugs, and 92 did not receive any suppressive treatment but only a substitutive therapy. The 84 patients who received levothyroxine at a suppressive dosage (group A) were compared with 92 patients who did not receive levothyroxine or received it only at substitutive dosage (group B). We further compared the complication rate of a similar group of 175 patients who had undergone a primary thyroidectomy. RESULTS: The average age at intervention for relapse in group A patients was significantly lower than that of group B patients: 54.18 vs 60.8 years (p < 0.001). The average interval between the first intervention and the intervention for relapse was significantly shorter in group A than in group B: 24 vs 27 years (p = 0.03). After the operation, temporary hypoparathyroidism occurred in 37.7 % of patients and definitive hypoparathyroidism in 7.2 %. CONCLUSIONS: Our results clearly show that the interval between the two surgical interventions was significantly reduced in patients undergoing TSH-suppressive therapy with levothyroxine. The incidence of hypoparathyroidism dramatically increased.

Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery: II Consensus Conference of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

AIM: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008. METHODS: In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. CONCLUSIONS: The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.

BRAF mutation status in papillary thyroid carcinoma: significance for surgical strategy.

BACKGROUND: BRAF mutation is probably the only molecular marker acting as a risk factor that is available before surgery: for this reason, soon after it became quite widespread, it seemed an important tool as a guide towards an individualized surgical therapy in papillary thyroid carcinoma. PURPOSE: Capsule invasion, multifocality, and lymph node involvement are the most important parameters influencing the choice of surgical strategy in front of small papillary cancers and, in more detail, of micro papillary carcinomas. The relationship between these parameters and the BRAF mutation are closely examined through the more recent literature. Capsular invasion seems to show the strongest correlation with the mutation and this has important correlations, thus suggesting that a more aggressive local surgery might be advisable, whereas the correlation between the mutation and lymph node involvement would be weaker, at least according to the most recent studies. CONCLUSIONS: The personalization of surgical therapy, today, seems easier to achieve thanks to molecular testing. In particular, an important result could be in the short term reduction in the number of completion thyroidectomies following simple lobectomies. Also, post operative radioactivated iodine therapies should be more carefully evaluated and tailored according to BRAF status. A possible flow chart for the decision of the therapeutic approach is proposed in accordance to the results of the literature.

Follicular-derived neoplasms: morphometric and genetic differences.

BACKGROUND: The distinction between follicular adenomas (FAs) and well differentiated follicular and papillary carcinomas is often a demanding task and sometimes only intuitive. AIM: We report an histomorphological evaluation of follicular neoplasms [FAs, follicular carcinomas (FCs), and follicular variant of papillary carcinomas (FVPTCs)], supported by a qualitative and quantitative image analysis and by a molecular characterization. MATERIAL AND METHODS: Tumor fibrosis and haemorrhage, neoplastic capsule thickness, follicle diameter, number of neoplastic cells, nuclear diameter of neoplastic cells, vessels density, vessels area and intratumoral distribution were evaluated. Ras and BRAF mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements were analyzed. Correlations with clinico-pathological features have been studied. RESULTS: We found that FAs had a more extensive intratumoral haemorrhage, while malignant neoplasms were characterized by an evident fibrosis, higher cellularity and larger size. FVPTCs had higher nuclear diameter; cells count was higher in the minimally invasive follicular thyroid carcinomas, as well as a thickener neoplastic capsule. The CD34 stain showed a higher microvessel density in the FVPTCs group. A higher peripheral vessels distribution was observed only in malignant neoplasms. We observed overall Ras mutations in 2.4% of adenomas, in 41.5% of FVPTCs, and in 44.8% of FCs. It is outstanding that there is a marked difference in the Ras mutation distribution between the benign and malignant tumors in our series. CONCLUSIONS: We found that genotyping of Ras gene family together with an accurate analysis of selected morphological features could help in the differential diagnosis of follicular-derived thyroid neoplasms.

Antiproliferative effects of 5-fluorouracil and oxaliplatin in colon cancer cell lines: comparison of three different cytotoxicity assays.

Adjuvant therapy in colorectal cancer has evolved to become the standard of care, whereas the tumor capability of activating effective mechanisms of defence against both chemical and physical cytotoxic agents represents a serious obstacle to the successful therapy of human tumors. Therefore, the possibility to have an assay useful to measure the drug sensitivity of tumor cells has a great importance. A number of cytotoxicity assays are currently available, each of them using a specific approach to detect different aspects of cell viability, such as cell integrity, proliferation and metabolic functions. The purpose of this study is to compare, under identical experimental conditions, three common cytotoxicity assays (ATP-lite, MTT and CCK-8 assays) in the assessment of the anti-proliferative effects of 5-fluorouracil (5-FU) and oxaliplatin (OHP) on three colon cancer cell lines (WiDr, SW620 and HT-29). Regarding 5-FU, the three assays were found to be significantly correlated with a moderate or high correlation coefficient, whereas in the case of OHP we found different outcomes among the assays. Our study demonstrates that the CCK-8 is the most sensitive assay for detecting changes of cell viability, suggesting that the viability measured in cells after drug exposure depends on several parameters like the drug used, the biological characteristics of the target cell and the specific approach employed by the method to detect distinct cell growth and metabolic functions.

Minimally invasive video assisted thyroidectomy versus endoscopic thyroidectomy via the areola approach: a retrospective analysis of safety, postoperative recovery, and patient satisfaction.

AIM: Minimally invasive video-assisted thyroidectomy (MIVAT) and endoscopic thyroidectomy through areola (ETA) access are among the endoscopic approaches for thyroidectomy that have been perfected, but reports comparing the two are lacking. This study evaluated the safety, postoperative recovery, and patient satisfaction of MIVAT compared with ETA. METHODS: This study included 119 patients undergoing MIVAT and 42 patients undergoing ETA from January 2006 to October 2009. Operative time, complications, postoperative recovery, cosmetic result, and patient satisfaction were analyzed. RESULTS: The ETA group had a higher percentage of women (100% vs. 78.2%, P<0.05) and was younger (33.5 vs. 39 years, P<0.05). Thyroid volume (24.5 vs. 14.5 mL, P<0.001) and nodular diameter (26 vs. 22 mm, P<0.05) were larger in ETA group. The MIVAT group had a shorter operative time (28.2 vs. 112.8 minutes) and a lower rate of intraoperative (7.2 vs. 21.2 mL) and postoperative (0 vs. 80 mL, P<0.0001) blood loss. Rates of conversion and complications were similar. Postoperative pain at 12 hours was 1.9 in MIVAT vs. 3.1 in ETA (P<0.0001). Hospitalization was 1 day in the MIVAT group vs. 3.5 days in ETA (P<0.0001). Patient satisfaction was similar. CONCLUSION: MIVAT and ETA showed similar results for safety, although ETA might be considered more invasive than MIVAT. Patients of both groups were equally satisfied with the cosmetic result. Differently from ETA, MIVAT allows total thyroidectomy to be performed also for malignant diseases. Although different, the two approaches were safe and reliable and both are valid options. Choice might depend on the surgeon's preference, thyroid size, type of disease, and the patient's expectation about cosmesis.

Bupivacaine 0.5% versus ropivacaine 0.75% wound infiltration to decrease postoperative pain in total thyroidectomy, a prospective controlled study.

AIM: Control of postoperative pain is one of the most important concerns for both the patients and the surgical team. In this regard the efficacy of wound infiltration with local analgesia and the most proper drugs to be used are not settled. We conducted our study trying to investigate this point in a prospective randomized double blinded manner. METHODS: With inclusion criteria of: age (18-65 y), volume <90 mL, first time, no lymph node enlargement and exclusion criteria of: duration >90 min, incision length >10 cm, neck dissection decided during surgery and a postoperative complication within the first 24 hours. Sixty patients planned for total thyroidectomy under general anesthesia were enrolled in the study in three groups with twenty patients assigned randomly to each one: group (A) a control group in which no wound infiltration was done, group (B) in which preoperative wound infiltration with 10 mL bupivacaine 0.5% was done, and group (C) in which preoperative wound infiltration with 10 mL ropivacaine 0.75% was done. Postoperative pain was evaluated by Visual Analogue Score (VAS) with a scale of (0-10) at 1 hour, 4 hours, 8 hours and 16 hours. RESULTS: The postoperative pain experienced by all the patients reached a maximum point at 1 hour postoperatively then started to decrease to be minimal at 8 hours and almost negligible at 16 hours. Ropivacaine group showed a statistically significant decrease in pain perception at 1 hour postoperatively (P=0.028), bupivacaine group showed also a decrease in pain perception at 1 hour but it was not statistically significant. At 4 hours of operation and after; neither ropivacaine nor bupivacaine showed an effect on pain perception. CONCLUSION: The benefit of local wound infiltration with local analgesia in decreasing postoperative pain is limited to a short period after surgery in which the use of ropivacaine 0.75% is recommended over pubivaccaine 0.5%.

Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment.

BACKGROUND: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.

Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency.

BACKGROUND: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. AIM: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. SUBJECTS AND METHODS: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. RESULTS: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. CONCLUSIONS: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.

High-intensity focused ultrasound as an alternative to the surgical approach in primary hyperparathyroidism: a preliminary experience.

BACKGROUND: Surgery is the therapy of choice in primary hyperparathyroidism (PHPT), although other less invasive techniques have been used in the attempt to cure the disease. Recently, high-intensity focused ultrasound (HIFU), a totally non-invasive technique, has become available to cure solid tumors. AIM: The aim of this pilot study has been to assess the safety and efficacy of HIFU in symptomatic patients with PHPT. MATERIAL AND METHODS: Four out of 31 patients with surgical indications within a cohort of 47-screened patients with PHPT were considered eligible for the study. All patients accepted to participate and were submitted to HIFU treatment in a single session. One patient was submitted to surgery after HIFU treatment. Patients were followed-up for 12 months after the procedure. RESULTS: A persistent or a partial remission of the disease, respectively, were obtained in 2 patients (50%), including the one who underwent surgery after HIFU treatment. Safety was assessed performing laryngoscopy in all patients after HIFU procedure. A transient vocal cord paralysis was observed in all patients treated by HIFU only. No permanent side effects were observed in the long term. CONCLUSIONS: HIFU might be a promising technique in treating PHPT, provided that further development of the software decreases the rate of side effects and improves the short- and long-term efficacy.