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Objective To analyze all the most recent guidelines/consensus as well as papers regarding the relationship between size of tumor, type of surgery, and prognosis, and to try to produce a critical synthesis for real practice. Background Differentiated thyroid cancer (DTC) is characterized by a wide range of biological behavior. The type of intervention can range from lobectomy (LT) to total thyroidectomy (TT), with tumor size being a point of discussion in choosing the treatment. Methods We carried out a search on PubMed, EMBASE, and Cochrane Library, looking at all the guidelines and consensus regarding DTC, as well as examining original articles, inserting as our research keys "total thyroidectomy vs. lobectomy in differentiated thyroid cancer" and "hemithyroidectomy in thyroid cancer". The guidelines and consensus published over the last 5 years were 6 in total: ATA Guidelines, Italian Consensus of Six Italian Societies, United Kingdom National Multidisciplinary Guidelines, ESMO Clinical Practice Guidelines, a Practical Guidance of a Multidisciplinary Panel of Experts, and The Revised Clinical Practise Guidelines on the Management of Thyroid Tumours by the Japanese Association of Endocrine Surgeons. There were 13 papers cited in the guidelines, and we found another 5 original articles, all of which were retrospective studies. Conclusions The type of initial surgical intervention must of course consider tumor size, but must also take into account all the risk factors, which is paramount in deciding the type of treatment. LT can have some advantages, and can represent an option that can be offered to patients. However, even in the absence of any special risk factors, a review of the literature suggests to us that patients should be informed that LT for tumors of a size between 2 and 4 cm can be associated with an increased risk of LR as well as with a possible reduced OS.

Background The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history. Methods We analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma—FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma—SNMTC group). Results In our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (p = 0,022), persistence of disease (p = 0,054) and necessity of radioiodine sessions (p = 0,005). Conclusions These findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.

Currently, laparoscopic adrenalectomy is worldwide considered the gold standard technique. Both transperitoneal and retroperitoneal approaches have proved their efficacy with excellent outcomes. Since the introduction of da Vinci System (Intuitive Surgical, Sunnyvale, CA), robotic surgery has made many steps forward gaining progressively more diffusion in the field of general and endocrine surgery. The robotic technique offers advantages to overcome some laparoscopic shortcomings (rigid instruments, loss of 3D vision, unstable camera). Indeed, the robotic system is provided of stereoscopic 3D-magnified vision, additional degree of freedom, tremor-filtering technology and a stable camera. Recently, several case series have demonstrated the feasibility and the safety of robot-assisted adrenalectomy in high-volume centers with outcomes comparable to laparoscopic adrenalectomy. Notwithstanding, the technical advantages of the robotic system have not yet demonstrated significant improvements in terms of outcomes to undermine laparoscopic adrenalectomy. Moreover, robotic adrenalectomy harbor inherits drawbacks, such as longer operative time and elevated costs, that limit its use. In particular, the high cost associated with the use of the robotic system is primarily related to the purchase and the maintenance of the unit, the high instruments cost and the longer operative time. Notably, these aspects make robotic adrenalectomy up to 2.3 times more costly than laparoscopic adrenalectomy. This literature review summarizes the current available studies and provides an overview about the robotic scenario including applicability, technical details and surgical outcomes.

Context Patients with amiodarone-induced thyrotoxicosis (AIT) and severely reduced left ventricular ejection fraction (LVEF) have a high mortality rate that may be reduced by total thyroidectomy. Whether in this subset of patients thyroidectomy should be performed early during thyrotoxicosis or later after restoration of euthyroidism has not yet been settled. Objectives Mortality rates, including peritreatment mortality and 5-year cardiovascular mortality, and predictors of death, evaluated by Cox regression analysis. Methods Retrospective cohort study of 64 consecutive patients with AIT selected for total thyroidectomy from 1997 to 2019. Four groups of patients were identified according to serum thyroid hormone concentrations and LVEF: Group 1 (thyrotoxic, LVEF Results Among patients with low LVEF (Groups 1 and 3), mortality was higher in patients undergoing thyroidectomy after restoration of euthyroidism (Group 3) than in those submitted to surgery when still thyrotoxic (Group 1): peritreatment mortality rates were 40% versus 0%, respectively (P = .048), whereas 5-year cardiovascular mortality rates were 53.3% versus 12.3%, respectively (P = .081). Exposure to thyrotoxicosis was longer in Group 3 than in Group 1 (112 days, interquartile range [IQR] 82.5-140, vs 76 days, IQR 24.8-88.5, P = .021). Survival did not differ in patients with LVEF ≥40% submitted to thyroidectomy irrespective of being thyrotoxic (Group 2) or euthyroid (Group 4): in this setting, peritreatment mortality rates were 6.3% versus 4% (P = .741) and 5-year cardiovascular mortality rates were 12.5% and 20% (P = .685), respectively. Age (hazard ratio [HR] 1.104, P = .029) and duration of exposure to thyrotoxicosis (HR 1.004, P = .039), but not presurgical serum thyroid hormone concentrations (P = .577 for free thyroxine, P = .217 for free triiodothyronine), were independent predictors of death. Conclusions A prolonged exposure to thyrotoxicosis resulted in increased mortality in patients with reduced LVEF, which may be reduced by early thyroidectomy.

To assess the reliability of a simple, accessible, cost-effective rule-out tool, for use in triaging patients with Bethesda IV nodules to appropriate surgery. The diagnostic tool was assembled by combining the negativity for suspicious ultrasound features (irregular margins, microcalcification, and a taller-than-wide orientation), and mutational marker negativity (BRAF and NRAS). The tool, (US−/mutation−), was tested on 167 patients with solitary Bethesda IV nodules. The primary outcome was its negative predictive value (NPV) for lesions requiring total thyroidectomy (TT). The impact of mutational marker negativity, as part of the tool, was evaluated by comparing the NPV of (US−/mutation−) to that of (US−/mutation+). 10 out of 167 lesions were positive for a mutational marker. These underwent TT, and only 2/10 (20%) were benign, on final histology. In 6/8 malignant lesions, TT was concordant with current clinical guidelines. 157 patients comprised the negative study cohort, for both mutational markers and suspicious US features. These underwent thyroid lobectomy, and 17 cases resulted in malignancy, only 8 of which required completion thyroidectomy. Accordingly, the NPV of (US−/mutation−) for malignancy was 89% (140/157), and 95% (149/157) for malignancy requiring TT. However, the NPV of (US−/mutation+) was 20% for malignancy, and 40% for malignancy requiring TT. These differences were statistically significant (89% vs. 20%; p

Subjects with obesity may exhibit an increase in serum TSH concentrations. Several mechanisms have been proposed to explain this association, including the presence of a compensatory mechanism to counterbalance an accelerated turnover of thyroid hormones in subjects with obesity. This study aimed at evaluating whether the thyroids of subjects with obesity differs from those of normal-weight individuals regarding histology and gene expression profiling. Ninety-eight patients were selected among those scheduled for thyroidectomy. At histology, thyroid tissue samples were investigated for the presence of adipocytes and/or lymphocyte infiltration. In a subset of patients, the expression at mRNA level of several genes involved in metabolic pathways and immune cell-related mechanisms was quantified by NanoString Technology. The presence of adipose cells was documented in thyroid specimens from 40% normal weight, 52.9% overweight and 73.5% patients with obesity. The number of infiltrating adipocytes was greater in specimens of patients with overweight or obesity compared to normal weight. The lymphocytes common antigen (CD45) and mast cell (MC) scores, and the number of CD3+ and CD8+ lymphocytes were higher in patients with overweight and obesity than in normal-weight subjects. Several genes involved in metabolic pathways were differently expressed in patients with overweight or obesity compared to normal weight, with upregulation of Leptin receptor and downregulation of Fatty Acid-Binding Protein 5. Increased BMI is associated with adipocyte and lymphocyte infiltration of the thyroid, not related to an autoimmune process, which might affect thyroid function in subjects with obesity. A differential gene expression profiling of metabolic and immune pathways in thyroid tissues of patients with obesity was also observed.

Over the past decade, the incidence of thyroid cancer has rapidly increased worldwide, and thyroid surgery has become one of the most common performed surgical procedure. Even though conventional open thyroidectomy remains the gold standard, this approach leaves a neck scar which could be worrying mainly for young women. The recent progress in surgical technology, as well as patient cosmetic requests, have led to the development of alternative access to the thyroid lodge. Thus, alternative techniques have been established in order to potentially provide a more appealing cosmetic result, both with a minimally-invasive cervical or remote-access approach. However, the introduction of these new techniques was initially approached with caution due to technical challenges, the introduction of new complications and, above all, skepticism about the oncologic effectiveness. Among several alternative approaches proposed, the minimally invasive video-assisted thyroidectomy and the robot-assisted transaxillary thyroidectomy became popular and obtained the favor of the scientific community. Moreover, the recent introduction of the trans-oral endoscopic thyroidectomy with vestibular approach, although the safety and the efficacy are still under discussion, deserves particular attention since it represents the only technique truly scarless and provides the best cometic result. The purpose of this article is to provide an overview of the current main alternative approaches for the treatment of thyroid cancer with particular focus on the oncological effectiveness of the procedures.

Introduction: Intraoperative neuromonitoring (IONM) has proven safe and effective for the evaluation of recurrent laryngeal nerve (RLN) integrity during conventional thyroid surgery. IONM ...

Introduction: Continuous intraoperative nerve monitoring (C-IONM) during thyroid surgery can be used to assess the recurrent laryngeal nerve (RLN) function and preventing unilateral and bi...

Papillary thyroid carcinoma (PTC) presents distinct clinico-pathological and molecular differences in children compared with adult patients. Whether the presence of rearrangements or point mutations is associated with aggressive PTC clinical presentation is still controversial. In this study, PTCs diagnosed in patients aged less than 18 years were retrospectively searched from the institutional archive and tumor tissue was tested for point mutations in BRAF and RAS genes and for rearrangements in RET, NTRK1, NTRK3, ALK, PPARG, BRAF and THADA. A total of 163 PTCs were analyzed. Point mutations were found in 83 (51%) and gene fusions in 48 cases (30%). The most frequent alteration was the BRAFV600E mutation (36.8%), followed by NTRK3 fusion (11%), NRAS mutation (10.4%) and RET fusion (10.4%). Fusion-driven PTCs showed more frequently infiltrative growth, larger tumors, extrathyroidal extension and N1b disease. PTCs showing solid growth pattern were significantly enriched in gene fusions. This is one of the largest cohorts of pediatric PTCs. Fusion-driven tumors most frequently show aggressive pathological features, the search for rearrangements, especially in tumors with solid areas, could improve the characterization of pediatric PTCs and offer possible therapeutic options.

Background: Postoperative hypocalcemia is a frequent complication after thyroid surgery. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. The present study analyzes rates and factors associated with the development of TtHP or PtHP following thyroid surgery in a pediatric population. Procedure: A retrospective multicenter study analyzing 363 patients was carried out. We recorded gender, age, tumor size, type of surgery, lymph node dissection, histology. Calcium levels were acquired daily for 72 hours after discharge. Subsequent sample collection was customized on the patient’s hypocalcemia severity. Results: We analyzed 363 patients aged ≤18 years (mean age 14.2 years) who underwent thyroid surgery clustered into age groups (≤15 or >15). Patients mean follow-up was 5.8 years (1-11yrs). At histology 310 (85%) were papillary carcinoma, 32 (9%) were follicular carcinoma, 6 (2%) presented diffuse sclerosing variant of papillary thyroid carcinoma whilst 15 (4%) had familial medullary carcinoma. TtHP developed in 36 (9,9%), PtHP in 20 (5.5%) cases. TtHP was more frequent in younger patients (p=0,009). Both PtHP and TtHP were increased in case of larger tumors (≥2 cm) (p=0,001). All TtHP and PtHP were in TT group. PtHP rate was increased if lymph node dissection was carried out (p

Medullary thyroid cancers (MTCs) are neuroendocrine tumors, which secrete calcitonin and carcinoembryonic antigen, both of which can serve as tumor markers. Extensive and accurate surgical resection is the primary treatment for MTC, whereas the use of external beam radiotherapy is limited. Moreover, since MTC is derived from thyroid parafollicular cells or C cells, it is not responsive to either radioiodine or thyroid-stimulating hormone suppression, and therefore, they cannot be considered as treatment strategies. Traditional therapies for advanced or metastatic progressive medullary thyroid cancer (pMTC) are poorly effective. Among the new approaches tested in clinical trials, targeted chemotherapies with tyrosine kinase inhibitors (TKIs) are now available and they represent effective interventions for progressive disease, with additional investigational options emerging. This paper reviews the efficacy and safety of vandetanib in patients with a pMTC, as it has been shown to improve progression-free survival (30.5 vs 19.3 months in controls). Vandetanib is approved by the FDA and EMA for symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease in adults, adolescents, and children older than 5 years. The most common adverse events in vandetanib-treated patients are diarrhea, rash, folliculitis, nausea, QTc prolongation, hypertension, and fatigue. More data are required to deepen our knowledge on molecular biology of tumor and host defense, with the aim to achieve better prognosis and higher quality of life for affected patients.

Context Recent diagnostic criteria updates of the tall cell variant of papillary thyroid carcinoma (TCPTC) by the World Health Organization (WHO) have determined the inclusion of tumors with 30% to 49% of tall cells. However, the impact of tall cell percentage on papillary thyroid carcinoma (PTC) patients’ prognosis is still debated. Objective We aimed to evaluate whether tall cell percentage affects patient outcome in the absence of aggressive features. Methods Rates of aggressive features, recurrence-free survival (RFS), and distant RFS (5-year median follow-up) were compared among tumors with less than 30%, 30% to 49% and at least 50% tall cells. We also evaluated the impact of the new tall cell cutoff on patient management. Results Overall, 3092 tumors (15.7% of all PTCs) were collected: A total of 792 PTCs had less than 30%, 503 had 30% to 49%, and 1797 had 50% or more tall cell areas. With the new WHO definition, the number of TCPTCs increased by 28%. There were no differences in recurrence rates according to tall cell percentage. The coexistence of BRAF and TERT promoter mutations predicted a worse RFS. Considering the new definition of TCPTC, the level of risk according to the American Thyroid Association increased from low to intermediate in 4.2% of cases. However, the recurrence rate within this subgroup was comparable to low risk. Conclusion TCPTC and PTC with tall cell areas can be considered as a unique group with similar recurrence risk. However, whenever aggressive features are absent, tumors have a low risk of recurrence independently of tall cell percentage.

Contains fulltext : 238976.pdf (Publisher’s version ) (Open Access) On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

Sporadic medullary thyroid carcinoma (MTC) is a rare malignancy with a heterogeneous clinical course. Several potential prognostic factors have been investigated, but the impact of some of these is controversial, such as age at diagnosis. We evaluated the data of 432 sporadic MTC patients followed-up for a median of 7.4 years. Patients were divided and compared according to their age at diagnosis in group A (&lt, 65 years&mdash, n = 338, 78.2%) and group B (&ge, n = 94, 21.8%). No differences were detected between the two groups. Median follow-up time was significantly longer in patients &lt, 65 than &ge, 65 years. We observed 41 (9.5%) cancer-related death events. The death rate was similar between the two age groups. However, the Kaplan Meier curve showed a longer survival time for younger patients compared to older patients [HR 2.5 (CI 95%: 1.27&ndash, 4.94), p &lt, 0.01]. Nevertheless, no differences in the aggressiveness of the disease at presentation and in the number and type of treatments performed were found in the two subgroups of dead patients. In patients with sporadic MTC, age at diagnosis did not correlate with any clinical and pathological features. Cancer-related death events are similar in older and younger patients, but survival time is longer in the younger.

Purpose. Recent clinical practice guidelines consider thyroid lobectomy a viable alternative for low-risk papillary thyroid carcinoma PTC measuring 1–4 cm in size. We aimed to assess the likelihood of finding postoperatively determined high-risk histopathologic features that would lead to the recommendation of completion thyroidectomy. Methods. A retrospective review of patients who underwent total thyroidectomy for PTC measuring 1–4 cm in size between Jan 2012-Jan 2018 was conducted. Patients with pre-operative high-risk characteristics were excluded; history of radiation exposure, positive family history, clinically suspicious cervical lymphadenopathy, and gross extrathyroidal extension (ETE). A hypothetical group of 245 patients remained eligible for lobectomy. The pathology specimens from the cancer-containing lobes were evaluated for high-risk features: aggressive histology, capsular and/or vascular invasion, microscopic ETE, and multifocality. A subgroup analysis was performed with 2 cm being the cut-off size. Results. The average age was 39 years with 73% being females. Mean cancer size was 16 mm. Evaluation of the cancer-containing lobe for high-risk features revealed: aggressive histology (33%), ETE (12%), capsular invasion (33%), vascular invasion (17%), and ipsilateral multifocality (30%). The cumulative risk of having ≥ 1 high-risk feature mandating completion thyroidectomy was 59%. The risk was considerably higher for lesions ≤ 2 cm compared to larger lesions (64% vs.48%; p = 0.049; RR = 1.3). Conclusion. A considerable proportion of patients initially eligible for lobectomy have high-risk features that only become evident at pathology. Therefore, a comprehensive approach is advocated to determine the extent of surgery for PTC incorporating patient preferences regarding risks and benefits.

Context Tumor capsule integrity is becoming a relevant issue to predict the biological behavior of human tumors, including thyroid cancer. Objective This work aims to verify whether a whole tumor capsule in the classical variant of papillary thyroid carcinoma (CVPTC) could have as a predictive role of a good outcome as for follicular variant (FVPTC). Methods FVPTC (n = 600) and CVPTC (n = 554) cases were analyzed. We distinguished between encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and noninvasive (En-FVPTC and En-CVPTC) tumors, according to the invasion or integrity of the tumor capsule, respectively. Cases without a tumor capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). The subgroup of each variant was evaluated for BRAF mutations. Results E-FVPTC was more frequent than E-CVPTC (P Conclusion En-CVPTC is less prevalent than En-FVPTC. However, it has good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumor capsule in CVPTC as well. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (ie, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NIFTP) could be envisaged.

Background In thyroid surgery, wrong-site surgery (WSS) is considered a rare event and seldom reported in the literature. Case presentation This report presents 5 WSS cases following thyroid surgery in a 20-year period. We stratified the subtypes of WSS in wrong target, wrong side, wrong procedure and wrong patient. Only planned and elective thyroid surgeries present WSS cases. The interventions were performed in low-volume hospitals, and subsequently, the patients were referred to our centres. Four cases of wrong-target procedures (thymectomies [n = 3] and lymph node excision [n = 1] performed instead of thyroidectomies) and one case of wrong-side procedure were observed in this study. Two wrong target cases resulting additionally in wrong procedure were noted. Wrong patient cases were not detected in the review. Patients experienced benign, malignant, or suspicious pathology and underwent traditional surgery (no endoscopic or robotic surgery). 40% of WSS led to legal action against the surgeon or a monetary settlement. Conclusion WSS is also observed in thyroid surgery. Considering that reports regarding the serious complications of WSS are not yet available, these complications should be discussed with the surgical community. Etiologic causes, outcomes, preventive strategies of WSS and expert opinion are presented.

ContextAtypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.ObjectiveThis work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations.MethodsThis monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included.ResultsFifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P = .048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30 ± 17 years vs 55 ± 13 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60 ± 56.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery.ConclusionThe large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation–positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.

Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis, either one associated with a number of symptoms/complications. Most literature regarding the LT4 dosage deals with the treatment of primary hypothyroidism, whereas a limited number of studies handle the issue of thyroxin replacement after total thyroidectomy. A literature review was performed focusing on all papers dealing with this topic within the last 15 years. Papers that reported a scheme to calculate the proper LT4 dose were collected and compared to set up a review exploring limits and drawbacks of LT4 replacement therapy in the wide population of patients who had undergone thyroidectomy. Most of the methods for monitoring and adjusting thyroid hormone replacement after thyroidectomy for benign disease use LT4 at an empirical dose of approximately 1.6 μg/kg, with subsequent changes according to thyroid function test results and assessments of the patient’s symptoms. Approximately 75% of patients require a dose adjustment, suggesting that factors other than body weight play a role in the determination of the proper LT4 dose. Hence, several schemes are reported in the literature for the proper initial dose of LT4. An inadequate level of thyroid hormone levels in these patients can be due to several factors. The most common ones that lead to the necessity of LT4 dose adjustments include lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits. Moreover, concomitant ingestion of calcium supplements, ferrous sulfate, proton-pump inhibitors, bile acid sequestrants, and sucralfate might influence LT4 absorption and/or metabolism. Furthermore, some gastrointestinal conditions and their treatments can contribute to suboptimal LT4 performance by altering gastric acidity and thereby reducing its bioavailability, particularly in the solid form. Beyond the classic tablet form, new formulations of LT4, such as a soft gel capsule and an oral solution, recently became available. The liquid formulation is supposed to overcome the food and beverages interference with absorption of LT4 tablets.

Background. Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by RET proto-oncogene mutation. Two different clinical variants of MEN2 are known (MEN2A and MEN2B): medullary thyroid carcinoma (MTC) almost always present and associated with pheochromocytoma (Pheo), and primary hyperparathyroidism (HPTH) in MEN2A and with Pheo and other nonendocrine diseases in MEN2B. Case Report. A 7-year-old girl, previously treated for a pelvic plexiform neurofibroma, arrived at our observation with a peculiar MEN2B syndrome and with HPTH. The neck ultrasound showed bilateral thyroid nodules, local lymph node lesions, and a suspicious left hyperplastic parathyroid. The CT scan showed a megacolon and described the persistence of the pelvic tumor. A new RET germline deletion in exon 11 (c.1892_1899delCGAGCT; p.Glu632_Leu633del) was found. She underwent total thyroidectomy, central compartment and latero-cervical lymph node dissection, and neck exploration for primary HPTH. The histology confirmed bilateral MTC, multiple lymph node metastases, a hyperplastic parathyroid, and a parathyroid adenoma. Conclusions. This is the first case of a complex syndrome characterized by peculiar features of MEN2B, without Pheo but with a pelvic plexiform neurofibroma and with HPTH, which is typical of MEN2A. A “de novo” new germline RET deletion located in exon 11 was found.

Background: Our previous retrospective study demonstrated that the absence of tumor capsule or, if present, its invasion were independent risk factors for the persistence of the disease (OR 6.75, CI 1.97-23.08 and OR 7.89, CI 1.78-34.94, respectively) in papillary thyroid cancer (PTC). This data was confirmed also analyzing separately the most frequent PTC variants [follicular variant (FVPTC) and classical variant (CVPTC)]. Moreover, we demonstrated that the absence of tumor capsule was significantly more frequent in FVPTC BRAF V600E mutated than FVPTC wild-type for BRAF gene or with rare-BRAF mutations (e.g., BRAF K601E, BRAF V600_K601delinsE). These data confirmed the importance of the integrity of the tumor capsule in FVPTC which led in 2016 to the definition of a new thyroid neoplasm entity named NIFTP. According to these retrospective data, we have assumed that the integrity of the tumor capsule in CVPTC could have a prognostic role similar to that confirmed in the NIFTP group. Methods: we have prospectively collected data of patients (pts) underwent total thyroidectomy or lobectomy for encapsulated-CVPTC (E-CVPTC) or NIFTP. In both cases the tumor was accurately analyzed by the pathologists according to the criteria used for the NIFTP (in particular with one capsule sample every 1 mm). All pts performed at least one clinical control and neck US within 6 months from surgery. Results: From January 2018 to June 2019, 144 E-CVPTC and 177 NIFTP were prospectively collected. 83/144 (57.6%) E-CVPTC and 106/177 (59.8%) NIFTP cases were included. The others were excluded due to the presence of other thyroid tumors associated in the same gland. No differences in epidemiological and pathological features were found between E-CVPTC and NIFTP except for the tumor size, significantly bigger in NIFTP than E-CVPTC [22±16mm (2-68) vs 8±11mm (1-80), p Conclusions: These prospective data demonstrated that NIFTP and E-CVPTC have a similar clinical behavior in a short-term follow-up, thus suggesting that the presence of an intact tumor capsule is predictive of a good outcome. A longer follow up is needed to confirm these initial interesting findings.

Background: Minimally-invasive video-assisted parathyroidectomy (MIVAP) can be considered as the primary treatment of choice for single parathyroid adenoma. Often, this technique is performed in a day surgery setting and is associated with regional anaesthesia (RA). Many studies have already reported the feasibility and safety of MIVAP in day surgery. Here our focus has been on the patient’s personal experience with these procedures through an assessment of their recovery at home. Methods: We conducted a prospective observational study in the University Hospital of Pisa Day Surgery Unit. Forty-eight patients were enrolled and divided by personal choice of anaesthesia technique: a regional anaesthesia group (RAg) and general anaesthesia group (GAg). Data were extracted from the medical records and three questionnaires: the first was self-compiled at discharge (Q1), while the second (Q2) and the third (Q3) were administered as telephone surveys. Results: None of the patients in RAg reported pain longer than 1 day after discharge, whereas 15% of patients in GAg reported pain relief the third day after discharge (P=0.0065). Discharge in RAg was within 3 hours in 12.5% of patients, within 4 hours in 78.1%, and within 5 hours in 9.4%. Discharge in GAg was within 5 hours in 53.8% and in more than 5 hours in 46.1% (P=0.0027). Conclusions: Patients highly appreciated day-case parathyroidectomy. Furthermore, the association of RA with MIVAP leads to better results than those of general anaesthesia (GA) and MIVAP. Finally, we point out that it is fundamental that the physicians pay attention to what the patients consider important for them; that is, the personal meaning of the hospitalization.

To compare the epidemiological, clinical, and pathological features of follicular (FVPTC) and classical (CVPTC) variants of papillary thyroid cancer and to correlate their outcomes according to different features. Retrospective analysis of FVPTC and CVPTC patients selected at the moment of surgical treatment from 1999 to 2004, with a median follow-up of 15 years. Several significant differences were found between FVPTC and CVPTC such as the mean age at diagnosis, the presence of tumor capsule, the presence of thyroid capsule invasion, the presence of perithyroid soft tissue invasion, the lymph node metastases, the multifocality and bilaterality. At the end of follow-up only 9% (77/879) patients were not cured. However, a statistically significant lower percentage of persistent disease was found in the FVPTC than in the CVPTC group (3% vs. 14.5%, respectively, p

L’identificazione routinaria e la visualizzazione diretta del nervo laringeo ricorrente (NLR) sono riconosciute in tutto il mondo come i gold standard nella tecnica di dissezione della tiroide. Il neuromonitoraggio intraoperatorio (IONM) puo completare l’informazione offerta dall’identificazione diretta attraverso un’analisi funzionale. L’esperienza oramai decennale in Italia con il neuromonitoraggio ha notevolmente contribuito a una piu estesa comprensione della fisiopatologia della paralisi del NLR. Il vantaggio principale dello IONM, tuttavia, e la possibilita di riconoscere una paralisi del NLR visivamente non rilevabile, identificando i potenziali meccanismi di danno e, talvolta, riducendo il rischio di un danno nervoso bilaterale. Poiche la perdita del segnale intraoperatorio puo richiedere una modifica della strategia chirurgica preoperatoriamente pianificata, le presenti raccomandazioni forniscono informazioni sulle possibilita e sui limiti dello IONM nel momento decisionale di una perdita del segnale intraoperatoria. Ci si augura, comunque, che ulteriori studi, il progressivo affinamento della tecnologia e la corretta applicazione dello IONM nella chirurgia tiroidea si evolvano in modo significativo nei prossimi anni.

Context It is not known whether total thyroidectomy is more favorable than medical therapy for patients with amiodarone-induced thyrotoxicosis (AIT). Objective To compare total thyroidectomy with medical therapy on survival and cardiac function in AIT patients. Methods Observational longitudinal cohort study involving 207 AIT patients that had received total thyroidectomy (surgery group, n = 51) or medical therapy (medical therapy group, n = 156) over a 20-year period. AIT types and left ventricular ejection fraction (LVEF) classes were determined at diagnosis of AIT. Cardiac and thyroid function were reevaluated during the study period. Survival was estimated using the Kaplan-Meier method. Results Overall mortality and cardiac-specific mortality at 10 and 5 years, respectively, were lower in the surgery group than in the medical therapy group (P = 0.04 and P = 0.01, respectively). The lower mortality rate of the surgery group was due to patients with moderate to severely compromised LVEF (P = 0.005 vs medical therapy group). In contrast, mortality of patients with normal or mildly reduced LVEF did not differ between the 2 groups (P = 0.281 and P = 0.135, respectively). Death of patients with moderate to severe LV systolic dysfunction in the medical therapy group occurred after 82 days (interquartile range, 56–99), a period longer than that necessary to restore euthyroidism in the surgery group (26 days; interquartile range, 15–95; P = 0.038). Risk factors for mortality were age (hazard ratio [HR] = 1.036) and LVEF (HR = 0.964), whereas total thyroidectomy was shown to be a protective factor (HR = 0.210). LVEF increased in both groups after restoration of euthyroidism, above all in the most compromised patients in the surgery group. Conclusions Total thyroidectomy could be considered the therapeutic choice for AIT patients with severe systolic dysfunction, whereas it is not superior to medical therapy in those with normal or mildly reduced LVEF.

La tecnica del monitoraggio intraoperatorio continuo (CIONM) del nervo laringeo ricorrente (NLR) e riconosciuta come uno strumento utile per riconoscere le lesioni nervose imminenti e interrompere la relativa manovra chirurgica per prevenire le lesioni permanenti durante la tiroidectomia. Il CIONM fornisce costantemente preziose informazioni in tempo reale, il che e molto utile durante interventi chirurgici complessi della tiroide, specialmente in contesti di anatomia insolita. Il CIONM supera la limitazione metodologica inerente al neuromonitoraggio intermittente (IINOM). L’evento elettromiografico (EMG) combinato clinicamente importante (riduzione ampiezza e aumento latenza del segnale EMG), indicativo di imminente lesione del NLR, previene la maggior parte delle lesioni legate alla trazione del NLR anatomicamente intatto consentendo la modifica della manovra chirurgica che ne e causa nell’80% dei casi. Come ulteriore estensione, il CIONM aiuta anche a identificare il recupero del nervo funzionale intraoperatorio, qualora avvenga una ripresa del valore di ampiezza ≥50% rispetto ai valori della baseline iniziale; cio consente di continuare la resezione del lato controlaterale. Il CIONM facilita un’azione correttiva precoce prima che sia stato fatto un danno permanente al NLR. Il CIONM e una tecnica recente ma in rapida evoluzione, in via di perfezionamento da vari studi incentrati sul miglioramento della sua attuazione e interpretazione, nonche sull’eliminazione degli ostacoli tecnici.

Although robot-assisted transaxillary thyroidectomy (RATT) has become a widely used treatment modality for thyroid disease in the Far East, the procedure remains under discussion in Western World (1,2). Different body mass index, anthropometric characteristics, size of tumours, goitre and ethical considerations, combined with elevated cost of the procedure and the need of training, hinder the diffusion of this approach in US and Europe (1,3). To date, RATT, although excellent results in terms of feasibility, oncological safety and patient’s compliance are described, plays a niche role in selected patients with appropriate pathology in high-volume centers (1,4).

Cosmetic satisfaction is not only based on the patient’s perception of the scar itself but is also related to body image self-evaluation. Cosmetic superiority of Robot-assisted transaxillary thyroidectomy (RATT) over conventional thyroidectomy (CT) has not yet been clearly demonstrated. Aim of our study was to compare body image in patients undergoing CT versus RATT. The study included 160 (80 CT and 80 RATT) patients undergoing thyroidectomy between August 2014 and March 2018 at the Endocrine Surgery Department. The inclusion criteria were age 18 to

Background: Minimally invasive video-assisted thyroidectomy (MIVAT) was first described in 1999 and it has become a widespread technique performed worldwide. Although initially limited to benign thyroid nodules, MIVAT was progressively adopted for all types of thyroid diseases, while remaining within the selection criteria. It is reported that, in selected cases, MIVAT is comparable to standard open thyroidectomy (SOT) in terms of oncologic radicality, time, costs and complications rate, with the advantage of a better cosmetic result and a lower post-operative pain. Methods: The authors conducted a retrospective analysis about patients who underwent MIVAT between 1998 and 2019 in the Endocrine Surgery Unit of the University Hospital in Pisa. Indications and contraindications are mentioned and strictly followed. Results: Total thyroidectomy was performed in 1,862 cases (69%) and hemithyroidectomy was performed in 763 cases (28.3%). Conversion occurred in 43 cases (1.6%). In 188 cases (7%) a postoperative transient hypoparathyroidism was reported, whereas definitive hypoparathyroidism was reported in 12 cases (0.4%). Thirty-eight patients (1.4%) suffered from a definitive postoperative recurrent laryngeal nerve palsy. No definitive bilateral recurrent laryngeal nerve palsy occurred. Conclusions: From our multi-years’ experience which spreads over 20 years, we can reaffirm the concept that MIVAT is a safe procedure which is not burdened by an increase complications rate or additional costs. Furthermore, this technique offers advantages in terms of cosmetic results and post-operative pain.

To delineate the clinicopathologic features and biologic behavior of the diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and to report its outcome. The clinical records of 25 patients who had surgery for DSV-PTC from 2004 to 2017 were retrospectively analyzed. Comparisons were made to similar studies in the literature reporting ≥8 cases and a cohort of classical PTC. There were 20 females and 5 males with an average age of 23 years (range 10–39 years). Bilateral disease occurred in 80% of cases. The mean size of the dominant mass was 4.2 ± 1.92 cm. In 92% of cases, therapeutic neck dissection was performed. Male sex significantly correlated with a higher yield of positive lymphadenopathy (p = 0.045). 62% of patients had recurrent disease. Recurrence significantly correlated with male sex, the number of metastatic lymph nodes (cutoff: 22 lymph nodes), and multifocality (p = 0.044, p ˂ 0.008, p ˂ 0.003, respectively). However, it did not correlate with the age at presentation. No disease-specific mortality occurred after an average follow-up of 77 months (range 12–168 months). The two comparisons made demonstrated a statistically significant greater tendency of the current series of DSV-PTC toward more aggressive clinicopathologic features and biologic behavior. No differences in overall survival were observed. The DSV-PTC should be considered a high-risk PTC that mandates an aggressive therapeutic strategy with the intent of optimizing disease-free survival.

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and it is less than 2% of thyroid carcinomas (TCs). The standard treatment of ATC includes surgical debulking, accelerated hyperfractionated external beam radiation therapy (EBRT), and chemotherapy, in particular with cisplatin or doxorubicin, achieving about 10 months of median survival. Since ATC is a rare and aggressive tumor, it is still challenging to predict the patient clinical therapy responsiveness. Several genetic mutations have been described in ATC, involved in different molecular pathways linked to tumor progression, and novel therapies acting on these molecular pathways have been investigated, to improve the quality of life in these patients. Here we review the new targeted therapy of ATC. We report interesting results obtained with molecules targeting different pathways: angiogenesis (vandetanib, combretastatin, sorafenib, lenvatinib, sunitinib, CLM94, CLM3, etc.); EGFR (gefitinib, docetaxel); BRAF (dabrafenib/trametinib, vemurafenib); PPARγ agonists (rosiglitazone, pioglitazone, efatutazone); PD-1 and PD-L1 (pembrolizumab); TERT. To escape resistance to monotherapies, the evaluation of combination strategies with radiotherapy, chemotherapy, or targeted drugs is ongoing. The results of clinical trials with dabrafenib and trametinib led to the approval from FDA of this combination for patients with BRAF V600E mutated ATC with locally advanced, unresectable, or metastatic ATC. The anti-PD-L1 antibody immunotherapy, alone or combined with a BRAF inhibitor, has been shown also promising in the treatment of ATC. Furthermore, to increase the therapeutic success and not to use ineffective or even harmful treatments, a real tailored therapy should be pursued, and this can be achieved thanks to the new available genomic analysis methods and to the possibility to test in vitro novel treatments directly in primary cells from each ATC patient. Exploring new treatment strategies is mandatory to improve the survival of these patients, guaranteeing a good quality of life.

Objective: In intermediate risk (IR) differentiated thyroid cancer (DTC) patients, selective use of radioiodine (131-I) for remnant ablation and/or as adjuvant therapy (RRA) is advocated. The recently suggested postoperative evaluation could delay the use of RRA. The aim of this study was to evaluate if a delayed RRA can worsen the clinical outcome of IR-DTC patients. Methods: Four hundred and fourteen consecutive IR-DTC patients were divided according to the time elapsed from surgery to RRA

Prophylactic central compartment lymph node dissection (pCCND) results in a higher percentage of surgical-related complications. To date, no evidence of the impact of pCCND on the clinical outcome of papillary thyroid carcinoma (PTC) patients with synchronous ipsilateral cervical lymph node metastases has been reported.We evaluated all consecutive patients affected by PTC and synchronous ipsilateral cervical, but without evidence of central compartment, lymph node metastases. We selected 54 consecutive patients (group A) treated by total thyroidectomy, ipsilateral cervical lymph node dissection, and pCCND and 115 patients (group B) matched for sex, age at diagnosis, number and dimension of the metastatic lateral cervical lymph nodes, without pCCND. Clinical outcome after a median of 5 years and surgical-related complications were assessed.The two groups were completely similar in terms of clinical features. Clinical outcomes showed a higher percentage of biochemical and indeterminate but not structural response in group B. Group B required significantly more radioiodine treatments, but no difference was shown in the need to repeat surgery for recurrences. Conversely, the prevalence of permanent hypoparathyroidism was significantly higher in group A (14.8%) than in group B (4.3%).In PTC patients with synchronous ipsilateral cervical lymph node metastases, in absence of clinically evident lymph node metastases of the central compartment, performing pCCND does not improve the 5-year outcome in terms of structural disease, despite a greater number ofIQR = interquartile range; pCCND = prophylactic central compartment lymph node dissection; PTC = papillary thyroid carcinoma; Tg = thyroglobulin; US = ultrasound.

Objective No consistent data are present in literature about the effectiveness of Levothyroxine (L‐T4) liquid formulation in patients without malabsorption after thyroidectomy. The aim of this study is to compare the effectiveness of L‐T4 liquid formulation, with L‐T4 tablets, in thyroid cancer patients after thyroidectomy (without malabsorption or drug interference). Methods One hundred five patients were recruited; 52 patients were treated with liquid L‐T4 formulation, while 53 with L‐T4 tablets, at the same dosage (1.5 mcg/kg/day). Patients started to assume the drug the day after surgery, 30 min before breakfast. In both groups circulating levels of thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were dosed at week 6 (first control), and then at week 12 (second control). Results We obtained significantly lower TSH values in the liquid L‐T4 group patients, compared to the tablet L‐T4 group, at the first control (P 3.6 mcU/mL) was significantly more prevalent in the patients treated with L‐T4 tablet. Conclusions A better control of TSH was observed in thyroidectomized patients (without malabsorption, gastric disorders, or drug interference) with liquid L‐T4 regimen. Level of Evidence 2c–Outcomes Research

// Cristina Romei 1 , Raffaele Ciampi 1 , Francesca Casella 1 , Alessia Tacito 1 , Liborio Torregrossa 2 , Clara Ugolini 2 , Fulvio Basolo 2 , Gabriele Materazzi 2 , Paolo Vitti 1 and Rossella Elisei 1 1 Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy 2 Department of Surgical, Medical and Molecular Pathology, University Hospital of Pisa, Pisa, Italy Correspondence to: Rossella Elisei, email: rossella.elisei@med.unipi.it Keywords: medullary thyroid carcinoma; RET; genetic instability; tumor clonality Received: August 09, 2017 Accepted: November 16, 2017 Published: January 04, 2018 ABSTRACT Purpose : Medullary Thyroid Cancer (MTC) whose pathogenesis is strictly related to RET proto-oncogene alterations, has been shown to have a heterogenic RET mutation profile in subpopulations of MTC. The aim of our study was to investigate the RET somatic mutation profile in primary MTC and in the corresponding metastatic tissues in a series of advanced metastatic cases. Results : This study demonstrated that in about 20% of cases a different RET mutation profile can be found when comparing primary tumor and its corresponding metastases. Furthermore in 8% of tumors, RET intratumor heterogeneity was observed We also showed that in some cases an imbalance of RET copy number was present. We confirmed a high prevalence (90%) of RET somatic mutations in advanced tumors. Materials and Methods : Fifty-six MTC patients (50 somatic and 6 hereditary cases) have been included in the study and a total of 209 specimens have been analysed by direct sequencing. Multiplex ligation-dependent probe amplification (MLPA) has been used to investigate amplification/deletion of RET alleles. Conclusions : In conclusion, this study showed a genetic intra- and intertumor heterogeneity in MTC, But in only 20% of CASES These results could justify the relatively moderate level of aggressiveness of the disease with respect to more aggressive human tumors that are characterized by a high rate of mutation and heterogeneity.

Post-thyroidectomy neck hematoma represents a major concern for surgeons because it can result in severe and even life-threatening complications. In fact, postoperative hemorrhage may result in airway compression and respiratory distress, and therefore, effective hemostasis is an important goal in thyroid surgery. Postoperative hematoma occurs at a rate of approximately 0.1% to 1.1%. Almost all cases occur in the first 6 h after surgery and can be the result of several surgeon or patient factors. For many years the clamp-and-tie technique has been the most common way to divide the main vascular pedicles of the thyroid gland. Alternatively, bipolar electrocautery has been used for only very small vessels. Other hemostatic systems have been introduced and proved to be potentially very useful in neck surgery and, in particular, for thyroid surgery. This new class of instruments is generally known as “energy devices” because they use different forms of energy, such as advanced bipolar (LigaSureTM Small Jaw Medtronic, Covidien product, Mineapolis, MN, USA) and ultrasound (Harmonic Focus; Ethicon, Johnson and Johnson, Cincinnati, OH, USA), and hybrid devices that join these two technologies (Thunderbeat by Olympus, Japan). Although they all generate a significant elevation of temperature in the tissues, as in any form of energy, the temperatures reached by these instruments are never as high as the standard monopolar electrocautery. For small bleeding very close to critical structures, where energy devices are too dangerous to be used and clamp and tie is not possible, several studies have assessed the use of adjunctive hemostatic agents. In conclusion, all energy devices have been shown to significantly decrease operative times without increasing costs or complications. Adjunctive hemostatic agents have shown equivalent differences when added to standard methods from a clinically significant perspective.

Purpose To evaluate the efficacy and safety of radiofrequency (RF) ablation in the treatment of benign thyroid nodules (BTNs) by applying a modification of the moving-shot technique. Materials and Methods Fifty-one BTNs in 46 patients for whom surgery was contraindicated or who refused surgery were treated with RF ablation: 31 had lesion volumes 3 (group A) and 20 had volumes ≥ 20 cm 3 (group B). The solid component percentage of each lesion was assessed, and any present fluid component was aspirated. Symptomatic scores and cosmetic scores (CSs) were assessed. All RF ablations were performed under ultrasound (US) guidance with an 18-gauge electrode. Treatment response was evaluated by contrast-enhanced US at 6-month intervals for 18 months in group A. In group B, after the 6- and 12-month follow-up assessments, a second treatment was performed in selected cases, and the 6-month contrast-enhanced US follow-up was started again. Volume reduction rate (VRR) was evaluated at each follow-up examination. Results No permanent paralysis of the laryngeal nerve was observed; 2 patients experienced transient hoarseness. In all nodules treated with a single RF ablation session, the VRRs at 6, 12, and 18 months were 69.4%, 78.7%, and 84% in group A, respectively, and 66.6%, 79.4%, and 81.5% in group B, respectively. The VRRs of group B nodules treated with a second RF ablation procedure (n = 6) were 86.4% and 88.2% at 6 and 12 mo after the second treatment, respectively. All patients reported symptom relief and CS improvement. Conclusions RF ablation is a reliable alternative to surgery in patients affected by BTNs and can be safely repeated in selected cases.

Robot-assisted transaxillary thyroidectomy (RATT) is widely accepted in Asian countries. However, concerns regarding the balance between its real advantages and safety and cost have been raised by North American authorities. In Europe, assessments have been limited by small numbers since now. The purpose here is to report a large European experience with RATT. A retrospective analysis was conducted of 257 patients who underwent RATT for nodular disease between February 2012 and September 2016. Data collected included patient demographics, diagnosis, ultrasound-estimated mean thyroid volume and nodule size, type of resection, operative time, postoperative pain and morbidity, and the hospital length of stay. Pain was assessed by visual analog scale score 12 h postoperatively (on the first postoperative day, before discharge). Feasibility, effectiveness, and safety were the outcomes of interest. Follow-up of thyroid carcinoma patients was carried out measuring thyroglobulin levels and ultrasound examination (median follow-up 24 months (6–48 months)). First control after 12 months and successively once a year. There were 253 women and 4 men, with a mean age of 37.3 years. Indications included benign disease in 116, papillary carcinoma in 56, and indeterminate nodule in 85. Mean thyroid volume was 16.8 mL, and nodule size was 25.3 mm. A hemithyroidectomy was performed in 138 patients and total thyroidectomy in 118. The mean operative time was 77.5 min for the former and 99.7 min for the latter. One conversion was required. Complications included transient hypoparathyroidism in 7/118 (total thyroidectomy) patients (5.9%), transient vocal fold palsy in 3/257 (1.1%), 1 delayed tracheal injury (0.4%), and 3 postoperative hematoma (1.1%). Mean visual analog scale score was 1.79, and the mean length of stay was 1.6 days for hemithyroidectomy and 1.9 days for total thyroidectomy. RATT is safe and effective and could serve as a viable treatment modality in selected cases.

Robot-assisted transaxillary thyroidectomy (RATT) is an emerging technique with excellent cosmetic results but is supposedly more invasive and painful than conventional thyroidectomy (CT). This prospective study compared pain after RATT and CT.Inclusion criteria were a nodule5 cm and volume30 mL. Patients received the same analgesia. Pain was evaluated by visual analog scale (VAS) in the recovery room (VASrr), on the first postoperative day at 8:00 a.m. (VAS 8 a.m.) and 8:00 p.m. (VAS 8 p.m.), at 8:00 a.m. on the second postoperative day (VAS 8*a.m.), and after 7 days (VAS 7). Operative time and complications were evaluated.From May 2015 to September 2015, 124 patients (all women) underwent thyroidectomy: 62 underwent RATT and 62 underwent CT. Mean age was 39.7 ± 10.2 years in the RATT group and 41.4 ± 12.5 years in the CT group. Groups were comparable for thyroid volume and nodule diameter. Operative time was longer in the RATT group than in the CT group (119.4 ± 25.5 versus 70.3 ± 11.0 minutes). Complications were three transient hypocalcemia in RATT and four in the CT group. No definitive complications occurred. VASrr was lower in the RATT group (1.79 ± 2.06 versus 2.5 ± 1.18; P .0001). There was no difference between groups for VAS 8 a.m., VAS 8 p.m., and VAS 8*a.m., but VAS 7 was higher in the RATT group (0.85 ± 1.77 versus 0.17 ± 0.52; P .010).RATT is as safe and effective as CT. Patients undergoing RATT, surprisingly, experienced less pain in the immediate postoperative period. However, the VAS 7 score was higher in the RATT group, probably because the intact neck is favorable in the early phase of recovery, but the large dissection takes longer for healing.

Background. The tyrosine kinase inhibitors (TKIs) are indicated for the treatment of locally advanced or metastatic progressive thyroid carcinoma (CDT), refractory to radioactive iodine. The following report describes the efficacy of lenvatinib administered through a nose-gastric tube (SNG) in a patient affected with a poorly differentiated thyroid carcinoma (PDTC) which determined a stenosis of the esophagus. Material and Methods. A patient was followed up for papillary thyroid carcinoma follicular variant (T3NxMx), subjected to total thyroidectomy and treated with iodine-131 radio metabolic therapy. Two years after surgery, following the onset of dysphonia and dysphagia, patient was submitted to a computed tomography (CT) scan of the neck that showed the presence of a lesion of 6 × 2.5 × 3.5 cm, which determined trachea deviation and cervical esophagus compression. The biopsy indicated the presence of PDTC, triggering tracheal lumen reduction and sub-stenosis of the cervical esophagus for an ab-extrinsic compression. A nose-gastric tube (SNG) was placed and lenvatinib was started at a dose of 20 mg/day, administered via this probe after opening the capsules and diluting the drug in 10 ml of saline solution. Results. One month later, CT showed a significant cervical lesion reduction. Bronchoscopy confirmed tracheal infiltration, but the residual caliber was improved from 50% to 75%. At the esophagogastroduodenoscopy (EGDS), the sub stenosis of the cervical esophagus was no longer appreciated; however, a double perforation of the esophagus was found, without fistula. Conclusion. Lenvatinib therapy is effective also when administered via SNG. Our result is of particular relevance in the management of thyroid cancer patients, especially in the presence of subjects unable to swallow. Further studies are needed to validate the administration of lenvatinib by SNG, in order to extend the indications to this alternative administration way, beside the oral one.

Since the effectiveness of levothyroxine (L-T4) in soft gel capsule formulation in patients recently subjected to total thyroidectomy is not yet well known, we investigated on its efficacy in comparison to L-T4 tablets in these type of patients, who not reported any issues of malabsorption or drug interference. In our study we have included 230 patients who were split in two groups: one of 115 in treatment with soft gel capsule L-T4 formulation, the other one of 115 in treatment with L-T4 tablets. All subjects received the same dosage of L-T4 (1.5 mcg/kg/day), administered 30 min before breakfast. The treatment started the day after surgery, then at week 6 (1st control), and at week 12 (2nd control) for both the groups of patients, thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated. We observed significantly lower TSH values in the soft gel capsule L-T4 group, in comparison to the tablet L-T4 group, in both the first (P < 0.05) and the second control (P < 0.01), meanwhile no significant differences were observed for FT4 and FT3 levels. In the L-T4 tablet group a higher prevalence of patients in the hypothyroid range (TSH>3.6 mcU/ml) was present with respect to that observed in the soft gel capsule L-T4 group. In conclusion, a better control of TSH levels in patients previously undergone to total thyroidectomy for thyroid cancer (not reporting issues of malabsorption, gastric disorders, or drug interference) has been obtained with soft gel capsule L-T4 respect to L-T4 tablets.

We aimed to evaluate the early detection of metastatic lateral neck lymph nodes (LNL) in patients with papillary or follicular differentiated thyroid cancer (DTC), and long-term follow-up after I131 and/or surgery. LNL evaluation has been made by thyroglobulin (Tg) measurement and neck ultrasonography (NU). We have enrolled 710 patients with DTC that previously underwent a near-total thyroidectomy and I131 ablation of residual tissue, and a follow-up by Tg, NU, diagnostic and post-therapy whole body scan (WBS), alone or in combination. LNL were detected by TSH-stimulated Tg alone with a sensitivity of 86%, and a negative predictive value (NPV) of 84%; whereas NU had a sensitivity of 70%, and NPV of 68%. TSH-stimulated Tg plus NU increased the sensitivity to 98%, and of NPV to 96%. In patients with LNL uptaking radioiodine and then treated with I131, the following outcomes were observed: 49% responded after a median of 4 cycles (median 354 mCi, cumulative dose; 7.4 years median follow-up) with “disappearence of uptake at post-therapy WBS and Tg

To assess the utility of mutational markers in determining the most appropriate initial surgery for patients with thyroglossal duct cyst carcinoma (TGDCCa) and a normal thyroid gland. Our sample comprised 15 patients with a diagnosis of TGDCCa and a thyroid gland histologically negative for any malignant involvement, who underwent surgery between the years 1994 and 2017. Clinical records were reviewed and tissue specimens were genetically tested for the presence of the most commonly encountered mutational markers in differentiated thyroid cancer: BRAF, N-RAS, and H-RAS. The primary outcome of interest was the correlation between mutational marker positivity and the T-stage of the primary tumor and its potential implication on therapeutic decision making. All 15 cases were papillary carcinomas with a mean tumor size of 17 mm (2–40 mm). According to the 7th edition of the American Joint Committee on Cancer TNM staging system, these represented: T1 (n = 3), T2 (n = 1), and T3 (n = 11). Cancerous invasion of the pericystic soft tissue and/or hyoid bone was considered T3. BRAFV600E was the only mutational marker identified (7 in 15 cases). All BRAFV600E-positive lesions were T3, necessitating radioactive iodine ablation (RIA) therapy, therefore, total thyroidectomy. The correlation between BRAFV600E positivity and extracystic cancerous extension was statistically significant [1.0 (7/7) vs. 0.5 (4/8); p value = 0.0035]. BRAFV600E positivity seems to be predictive of locally advanced disease mandating RIA therapy. Therefore, it could serve as a preoperative tool that predicts the need for total thyroidectomy, in addition to Sistrunk’s procedure.