Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

A comprehensive review of interventional ablation techniques for the management of thyroid nodules and metastatic lymph nodes.

Thyroidectomy remains the gold standard treatment for benign, symptomatic, or enlarging thyroid nodules, malignant nodules, and metastatic lymph node disease. However, in the past 2 decades, image-guided interventional techniques have emerged as promising alternative treatments for these conditions. Percutaneous ethanol ablation is now an accepted first-line treatment for recurring cystic thyroid nodules. Thermal ablation techniques such as high-intensity focused ultrasound, laser ablation, radiofrequency ablation, and microwave ablation have shown efficacy in producing a nodular volume reduction of greater than 50% that is maintained for several years with resolution of local compressive symptoms. There is also increasing evidence that these techniques can effectively treat papillary thyroid microcarcinomas and recurrent metastatic lymph node disease. Because these interventional ablation techniques are performed safely in an outpatient setting, are well tolerated, and the risk for needing thyroid hormone supplementation is negligible, they are becoming a popular alternative treatment to surgical resection. In this comprehensive review, we discuss each of these percutaneous interventions: the devices and techniques, the advantages and disadvantages of each energy, and summarize the outcomes published in the literature.

Evaluation of LMR, NLR and PLR as predictors of malignancy in indeterminate thyroid nodules.

OBJECTIVE: Thyroid nodules with indeterminate cytology represent 20% of all thyroid nodules. Inflammation plays an important role in cancer. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent prognostic scores in numerous cancers, although no study has documented their role in cytology indeterminate nodules. The aim of this study is to evaluate the role of LMR, NLR and PLR values as predictors of malignancy in patients with cytology indeterminate nodules. METHODS: This retrospective study analysed data from 298 patients with indeterminate thyroid nodule. Anatomopathological and haematological data were analysed, dividing the population into two groups. LMR, NLR and PLR values were determined using ROC curve and data were analysed using independent samples t-test, test of proportions, Fisher's exact test and univariate and multivariate logistic regression. RESULTS: We found that a baseline LMR value ≥ 4.09 was indicative of benignity of indeterminate nodule. The probability of malignancy in patients with LMR < 4.09 was 26 times higher than patients with a LMR value ≥ 4.09. CONCLUSIONS: This study showed that only LMR has shown a concrete probability to find a thyroid cancer in patients with indeterminate nodules. Further studies are necessary to implement tailored treatment.

Laser Ablation Treatment of Recurrent Lymph Node Metastases from Papillary Thyroid Carcinoma.

(1) Background: The incidence of papillary thyroid cancers is increasing. Papillary neoplasm metastasizes to the central and lateral lymph nodes of the neck. The recurrence rate is less than 30%. The gold standard of treatment for lymph node recurrences is surgery, but surgery is burdened by a high rate of complications. Therefore, laser ablation of recurrent lymph nodes has been recognized as an alternative treatment with minimal invasiveness, a low complication rate and a curative effect. (2) Methods: We analyzed 10 patients who underwent a total thyroidectomy and metabolic radiotherapy and who developed a lymph node recurrence in the laterocervical compartment in the following 12-18 months. (3) Results: Patients developed lymph node recurrence at IV and Vb levels in 70% and 30% of cases, respectively. All patients were treated with a single laser ablative session. Hydrodissection was performed in all patients. The energy delivered was 1120 ± 159.3 Joules and 3-4 Watts in 362 ± 45.7 s. No complications were reported. All patients underwent a 6-month follow-up. A volumetric reduction of 40.12 ± 2.2%, 49.1 ± 2.13% and 59.8 ± 3.05%, respectively at 1-, 3- and 6-months of follow-up was reported. (4) Conclusions: At 6 months, a fine needle aspiration was performed, which was negative for malignant cells and negative for a dosage of Thyroglobulin in eluate. The laser ablation is an effective alternative to surgical treatment.

Clinical significance of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio and prognostic nutritional index in low-risk differentiated thyroid carcinoma.

OBJECTIVE: Inflammation and nutritional status play an important role in the prognosis of cancer. Lymphocyte-to monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are independent prognostic scores in numerous cancers. However, any study showed their prognostic role in low-risk differentiated thyroid carcinoma (DTC). We aimed to clarify and identify the prognostic value of inflammation indices in low-risk DTC patients. METHODS: We analysed data from 116 patients, dividing the population into two groups, according to AJCC staging system (8th edition). The LMR, NLR, PLR and PNI cut-off value were determined using receiver operating characteristic (ROC) curve. Disease-free survival (DFS) was calculated with Kaplan-Meyer and Log-Rank tests and the risk of recurrence was calculated with univariate and multivariate Cox regression. Statistical significance was p < 0.05. RESULTS: We found a baseline NLR value ≥ 1.750 (75% sensitivity, 40.2% specificity) and a baseline LMR value of 3.83 (66.7% sensitivity, 48.9% specificity). Overall DFS was 74.995 ± 3.236 with a p value of 0.678. NLR showed a hazard ratio for recurrence with almost twice the risk of recurrence (Adjusted Hazard Ratio /HRA): 1.828, p-value = 0.019). CONCLUSIONS: NLR can be considered a prognostic score with twice the risk of recurrence in low-risk DTC patients with NLR < 1.750.

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases.

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto's thyroiditis and Graves' disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.

Transcutaneous laryngeal ultrasonography: a reliable, non-invasive and inexpensive preoperative method in the evaluation of vocal cords motility-a prospective multicentric analysis on a large series and a literature review.

Thyroidectomy is a largely performed intervention and its rate has sharply increased. The most feared postoperative complication is the recurrent laryngeal nerve paralysis, which is the most frequent cause of medicolegal litigations. Therefore, surgeons have introduced the preoperative evaluation of vocal cords function through laryngoscopy. Transcutaneous laryngeal ultrasonography has been proposed as a non-invasive indirect examination of vocal cords function. The aim of this study is to assess transcutaneous laryngeal ultrasonography reliability as an alternative painless and inexpensive method in the evaluation vocal folds function in patients amenable of thyroid surgery. We conducted a prospective multicentric study on patients affected by thyroid disease referred to the thyroid surgery divisions of two tertiary hospitals. All patients preoperatively underwent transcutaneous laryngeal ultrasonography and subsequently were evaluated via laryngoscopy by a blinded otolaryngologist. The ultrasonographical and laryngoscopical findings were then compared by an external blinded investigator. Our analysis on 396 patients showed an assessability rate of 96.46%, a sensitivity of 96.8%, a specificity of 95.6%, a positive predictive value of 65.2% and a negative predictive value of 99.7% in the identification of vocal cords alterations. A concordance between transcutaneous laryngeal ultrasonography and laryngoscopy of 95.7% was reported. In 14 patients (3.54%), the investigator reported a hard visualization of vocal cords through ultrasonography. Transcutaneous laryngeal ultrasonography is a valid non-invasive and painless alternative method in the assessment of vocal cords in a selected population; moreover, it could be useful in identifying patients addressable to second-level examination.

The Ablation of Thyroid Nodule's Afferent Arteries Before Radiofrequency Ablation: Preliminary Data.

Induced radiofrequency thermal ablation is the cytoreductive treatment of symptomatic benign thyroid nodules, metastatic and recurrent thyroid tumors and papillary thyroid microcarcinomas. It is a safe and effective alternative to surgery and it allows to obtain satisfactory results in terms of volumetric reduction of the nodule with significant improvement in the quality of life. The trans-isthmic approach and the moving shot technique are the two basic techniques; however, an advanced technique, artery-first feeding radiofrequency ablation, has been developed and validated. We have prospectively included 29 consecutive patients who have undergone radiofrequency ablation (Group A) or artery- first vRFA (Group B). All included patients had a diagnosis of benign nodular goiter and they underwent a single session of radiofrequency ablation. All patients followed a follow-up program at 1 month, 3 months, and 6 months. Continuous variables (age, TSH value, basal volume of nodule, used Joule, time in second of the procedure, nodules' volume at 1-, 3-, and 6- months of follow-up and percentage of volume reduction at 1-, 3-, and 6- months of follow-up) were described as mean, standard deviation and range, while categorical variables (gender, nodule structure and nodule vascularization) were described as number of cases and percentage. Independent samples t-test were performed to compare the continuous variables. A Test of Proportions was applied to the categorical variables. The Fisher's exact test was used to analyze the gender. Statistical significance was considered in case of p-value <0.05. Solid structure and spongiform structure showed statistic differences with p-values of 0.022 and 0.023 respectively between two groups. The percentage of reduction at 1 month did not show a significant difference between two groups; instead, the percentage of volume reduction was decreased mostly in the Group B at 3 months and 6 months of follow-up with a p-value of 0.003 and 0.013, respectively. The Joules/energy used showed a statistically significant difference (p-value=0.05), more energy must be used in vascular radiofrequency ablation. These data allow us to hypothesize that vRFA may improve the effectiveness of the procedure, allowing for a reduction in volume more quickly. They were preliminary but promising results, clearly a larger series of cases and prolonged follow-up are needed to clarify and confirm our observations.

Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review.

BACKGROUND: Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. CASE PRESENTATION: We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. CONCLUSION: A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

Advanced hemostasis in axillary lymph node dissection for locally advanced breast cancer: new technology devices compared in the prevention of seroma formation.

BACKGROUND: Breast cancer is the most frequent neoplasm in women. Axillary lymph nodes dissection represents the treatment of choice in locally advanced breast cancer for prognostic and curative purposes. Seroma formation, an abnormal collection of fluid in the dead space of the axilla, is described in Literature with a wide range of incidence (3-85%). It is a source of significant morbidity and discomfort. The aim of the study is to compare the different haemostasis devices used in breast surgery, investigating the eventual superiority of an instrument among the others in terms of intraoperative and postoperative outcome, especially of seroma formation. METHODS: Clinical cases of female patients undergone axillary lymph nodes dissection for local advanced breast cancer between January 2013 and July 2017 at the Surgery Unit of University of Campania "Luigi Vanvitelli" were retrospectively reviewed. Patients were divided into four groups, according to device utilized during surgery: Electrocautery, Harmonic Scalpel, LigaSure and Thunderbeat. All patients underwent II level axillary lymph nodes dissection associated to radical mastectomy or quadrantectomy. RESULTS: One hundred consecutives patients were enrolled in the study. Intra-operative blood loss resulted statistically significant different (P < 0,01) between the Electrocautery group (94,7 ml) and the Thunderbeat group (57,2 ml), while the Harmonic Scalpel group and the Ligasure group, despite presented a lower amount of blood loss, did not differ significantly. Drainage volume resulted significantly lower (P = 0,002) in the comparison between the Electrocautery group and the Thunderbeat group; the Ligasure group and Harmonic Scapel group showed no difference between them and Electrocautery group. About the seroma formation, the Electrocautery group resulted affected by the highest seroma formation rate (64%). Seroma incidence in Harmonic Scalpel group was 24%, in Ligasure group was 44%, while Thunderbeat group showed the lowest presentation of seroma with 16%. CONCLUSIONS: In patients affected by breast cancer requiring axillary lymphnodes dissection, the use of advanced hemostasis devices is highly desirable. Among the non-traditional tools, Thunderbeat resulted to be superior in terms of reduction of intra-operative blood loss and post-operative drainage output, moreover associated to a substantial reduction of postoperative seroma incidence.

The role of prophylactic central compartment lymph node dissection in elderly patients with differentiated thyroid cancer: a multicentric study.

BACKGROUND: Prophylactic central neck lymph-nodes dissection is still a topic of major debate in Literature. There is a lack of randomized controlled trials proving advantages in its application in terms of overall survival and local recurrence. Due to the recent rapid increase of elderly population, differentiated tumor carcinoma diagnosis increased in patients over 65 years old. The aim of this study was to compare recurrence rate, complications rate and histological features of tumors in elderly population. METHODS: A retrospective study was carried out collecting data from 371 patients with differentiated thyroid cancer without clinical evidence of lymph-nodes involvement in three Italian referral centers from 2005 to 2015. All patients were aged ≥ 65 years and were divided in two groups based on the performed surgery (total thyroidectomy alone or associated with central lymph-nodes dissection). Moreover, patients were stratified according to the age between 65 and 74 years old and over 75 years old. RESULTS: Total thyroidectomy alone was performed in 184 patients (group A) and total thyroidectomy with prophylactic central neck dissection was performed in 187 cases (group B). There was a statistically significant difference in complications between the groups in terms of neck hematoma (0.5% group A vs 3.7% group B), temporary hypoparathyroidism (11.4% group A vs 21.4% group B), and temporary unilateral recurrent nerve injury (1.5% group A vs 6.4% group B). Lymph nodes recurrence rate was 9.2% in group A and 8.5% in group B, with no statistically significant difference. There was a statistically significant difference in patients over 75 years old in terms of temporary hypoparathyroidism (24% group A vs 11% group B), permanent hypoparathyroidism (2,7% group A vs 0,3% group B) and recurrent nerve injury (9,5% group A vs 2% group B). CONCLUSIONS: The role of prophylactic central neck dissection is still controversial, especially in elderly patients, and an aggressive surgical approach should be carefully evaluated. The Authors reported a similar low recurrence rate between total thyroidectomy and total thyroidectomy associated with prophylactic central neck dissection, with increased postoperative complications in the lymphadenectomy group and in patients over 75 years old, advocating a tailored surgical approach in elderly population.

The impact of the ultrasonic, bipolar and integrated energy devices in the adrenal gland surgery: literature review and our experience.

BACKGROUND: The gold standard approach for surgical treatment of benign and malignant adrenal lesion is considered the laparoscopic one, due to a lot of advantages compared to open approach. The rapid propagation of this surgical technique is due to the diffusion of haemostatic devices in laparoscopic adrenal surgery. The principal aim of this study is to analyze the outcome of LA using each energy modality, evaluating the eventual superiority of an instrument over the others. METHODS: A retrospective study, involving 75 consecutive patients submitted to LA by transperitoneal lateral approach from January 2013 to June 2017, was performed. Age less than 70 years old, adrenal adenomas less than 8 cm in diameter, incidentalomas < 6 cm, myelolipomas < 13 cm, adrenal metastases < 7 cm and ASA score ≤ III were the main surgical inclusion criteria. All involved patients were divided into three group, one for each energy device: group 1 - Harmonic Scalpel, group 2 - Ligasure vessel sealing system and group 3 - Thunderbeat. In each group only one device was applied for dissection and haemostasis during the whole operation. Each group consisted of 25 patients, well matched for histology, tumor size and site, gender and age. The following parameters were collected: age, gender, size of the tumor, side of the affected gland, pathology, operating time, intraoperative blood losses, hospitalization time, complication and conversion rate. RESULTS: There was no significant statistical difference between groups regarding the relationship between male/female, right site/left site, the mean age, hospitalization time and the tumor size (p > 0.05). Significant statistical difference are detectable in operation time and intraoperative blood losses. Thunderbeat, compared respectively with Ligasure and Harmonic Scalpel, is the fastest device (p < 0,001). The second faster device resulted Harmonic Scalpel, which meanly reduced the operation time compared to Ligasure (p = 0.048). intraoperative blood losses are reduced using Thunderbeat (p < 0,001) and HS (p = 0.006) compared to Ligasure, but between Thunderbeat and Harmonic Scalpel there isn't significant statistical difference (p = 0.178). CONCLUSIONS: Analyzing the results, laparoscopic adrenalectomy carried out using Thunderbeat appeared to show a statistically significant decrease in operation time and intraoperative blood losses compared with laparoscopic adrenalectomy performed using Harmonic Scalpel and Ligasure, while hospitalization time was superimposable in all groups. According to our data, a responsible use of advanced energy devices can improve surgical outcomes guarantying a cost savings and patient's satisfaction.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BACKGROUND: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Single center experience with laparoscopic adrenalectomy on a large clinical series.

BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies. METHODS: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies. RESULTS: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes.