Demonstration of Epstein-Barr Virus by In Situ Hybridization in Papillary Thyroid Carcinomas Developing on Background of Hashimoto's Thyroiditis.

AIM: This study aimed to demonstrate the role of Epstein-Barr Virus (EBV) in papillary thyroid carcinomas (PTC) developing on the background of Hashimoto's thyroiditis (HT). METHODS: The presence of EBV in tumoral tissue, lymphocytes, and peritumoral normal thyroid tissue was investigated using the in situ hybridization method in paraffin blocks. The subtypes of PTC, tumor diameter, TNM stage, multifocality, invasion of thyroid capsule, perineural invasion, and muscular tissue invasion were identified and compared according to EBV involvement. RESULTS: Eighty-one patients with HT diagnosis, with 93.8% (n=76) female and 6.2% (n=5) male, were included in the study. Papillary microcarcinoma was the pathological diagnosis in 24.2% (n=15) of the cases. EBV was identified in 58.06% (n=36) of the tumor cells nuclei, 58.06% (n=36) in the tumor cell cytoplasm, 16.12% (n=10) in tumor infiltrative lymphocytes, and 53.2% (n=33) in normal parenchymal follicle epithelial cells (NPFEC). In the T2 stage, the rate of EBV nuclear positivity in patients was significantly higher (p=0.034). The classic variant of papillary carcinoma was accompanied by a significantly higher rate of EBV-negative NPFEC (67.6%, p=0.049). In multifocal tumors, EBV positivity was found to be significantly higher in lymphocytes in the surrounding tissues (58.3%, p=0.034). CONCLUSION: A significant increase in EBV positivity in the surrounding tissue lymphocytes was observed in multifocal PTC developing on a background of HT. This suggests a possible association between HT and EBV.

Comparison of Monopolar and Bipolar Stimulator Probes for Intraoperative Nerve Mapping During Thyroidectomy: A Prospective Study.

OBJECTIVES/HYPOTHESIS: During intraoperative neuromonitoring in thyroid surgery, two different kinds of stimulator probes, monopolar and bipolar, are commonly used to stimulate the laryngeal nerves. We explore the unique characteristics of both of these probes as they relate to intraoperative laryngeal nerve mapping. METHODS: Twenty-one patients undergoing neuromonitored thyroidectomy by a single surgeon were enrolled. Electromyography (EMG) amplitude and latency measurements were prospectively recorded concurrently from 1 mA stimulation of vagus nerve (VN) and inferior/superior recurrent laryngeal nerve before (with and without fascia) and after thyroid resection using bipolar and monopolar stimulator probes. RESULTS: Significantly higher amplitudes were obtained with monopolar stimulator probes as compared to bipolar probes, in several stimulation scenarios such as at right VN pre-resection (carotid sheath intact), right VN pre-resection (carotid sheath dissected), right VN post-resection and left VN (carotid sheath dissected). No significant differences were found between amplitudes and latency values in all other stimulation scenarios. CONCLUSIONS: According to this study, both probes are reliable and safe for neural mapping. The kind of probe used during neural monitoring is based on surgical situations and surgeon preference. LEVEL OF EVIDENCE: 3 (According to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence) Laryngoscope, 131:E2718-E2726, 2021.

Influence of rocuronium on achieving optimal vagal stimulation during intraoperative nerve monitoring in thyroid surgery.

BACKGROUND: In the present study we determine the feasibility of intraoperative neuromonitoring following the administration of a nondepolarizing neuromuscular blocking agent during thyroid operations, as well as the influence of rocuronium on the achievement of optimal vagal stimulation during intraoperative neuromonitoring in thyroid surgery. We further investigate whether accelerometry is a reliable approach to obtaining an ipsilateral vagus signal prior to recurrent laryngeal nerve dissection. METHODS: Included in the study were 61 thyroidectomized patients whose demographic data, indications, type of surgery, vagus, and recurrent nerve values before and after resection were obtained. We created five groups of patients based on the twitch values recorded during ipsilateral vagus stimulation prior to the recurrent laryngeal nerve dissection: (1) <10%, (2) 11-25%, (3) 26-50%, (4) 51-75% and (5) >75%. RESULTS: The average electromyography amplitudes of the vagus nerve prior to the determination of the recurrent laryngeal nerve for each group were 552 µV, 463 µV, 543 µV, 513 µV and 551 µV, respectively. No difference between the groups was observed in this regard (p > 0.05). CONCLUSION: It can be expected that as soon as the effects of neuromuscular blockers on the peripheral muscles begin to abate, it will be possible to obtain the ipsilateral vagus signal prior to recurrent laryngeal nerve dissection at the desired levels. It can be concluded from this study that accelerometry using the pollicis muscle is an unreliable tool for the interpretation of the proper electromyography signals of the vagus nerve prior to the determination of the recurrent laryngeal nerve.

Objective analysis of swallowing and functional voice outcomes after thyroidectomy: A prospective cohort study.

BACKGROUND: Impairment in voice and swallowing functions are common after thyroidectomy. We aimed to evaluate the objective functional voice and swallowing outcomes in a series of patients undergoing thyroidectomy. METHODS: A total of 43 consenting patients who underwent thyroidectomy were prospectively recruited. Subjective evaluation of swallowing was assessed with 'Swallowing Impairment Score' and 'MD Anderson Dysphagia Inventory'. Fiberoptic endoscopic evaluation of swallowing (FEES) was applied for objective evaluation. Also, functional oral intake scale (FOIS) and functional outcome swallowing scale (FOSS) were used for swallowing assessment. Voice evaluation was assessed with videostrobolaryngoscopy (VSL) and 'The Multi-Dimensional Voice Program (MDVP)' was used for capturing and analyzing the voice samples. All evaluations were performed preoperatively and on 1st day, 2nd week and 6th months postoperatively. This study is registered with ClinicalTrials.gov, number NCT03436186. RESULTS: According to the objective analyses there was no difference between pre- and post-operative scores for the intake of fluid and thickened liquid food. There was a significant difference regarding light and moderate residual accumulation in solid food intake (p = 0.013). FOSS showed no difference, but FOIS revealed specific functional limitation (p = 0.034). Subjective data showed no correlation with objective findings (p > 0.05). Regarding voice evaluation, a significant increase was observed in standard deviation of average fundamental frequency and degree of subharmonics (p < 0.01). CONCLUSION: Even in the absence of recurrent laryngeal nerve injury, subjective and objective swallowing and voice alterations do occur after thyroidectomy.

Clinical behavior and outcome of papillary T1 thyroid cancers: South Korea vs. Turkey vs. Colombia in a cohort study analyzing oncological outcomes.

BACKGROUND/PURPOSE: There has not been an international multicentric study to examine the relationship between thyroid cancer clinical outcomes and geographic location for South Korea, Colombia, and Turkey, whereas thyroid cancer is amongst the highest three cancer types seen in South Korea and Turkey. The aim of the study was to assess regional differences of T1 papillary thyroid cancer outcomes in Korea, Turkey and Colombia. METHODS: This is an observational non-randomized study. A total of 2720 patients who have been operated for T1 papillary thyroid cancer between 2011 and 2014 and are on routine follow-up have been recruited. The mean follow-up was 46.4 ± 10.7 months. Data were collected in a commonly used database and analyses were conducted. RESULTS: Patients participated in South Korea (88.2%), Turkey (9.1%) and Colombia (2.6%). Eighty percent were female. Female dominance tended to be higher in Colombia (p = 0.01). Mean age at diagnosis was 45.2 years. There was no mortality. Recurrence tended to be higher in Colombia (p < 0.001). Moreover, statistical analysis revealed differences among patients regarding symptoms (p < 0.001), family history (p < 0.001), euthyroidism (p < 0.001), anti-Tg and/or anti-TPO positivity (p < 0.001), FNAB results (p < 0.001), type of resection (p < 0.001), prophylactic central node dissection (p < 0.001), tumor size (p < 0.001), multifocality (p < 0.001), bilaterality (p < 0.001), tumor subtype (p < 0.001) and radioactive iodine treatment (p < 0.01). CONCLUSION: Thyroid cancer is becoming more commonly diagnosed worldwide. This international multicentric study has identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.

Robot-assisted endoscopic mediastinal parathyroidectomy.

Ectopic parathyroid glands can be located at any anatomical location from the base of the tongue to the mediastinum. One-third of these glands migrate deep into the mediastinum, which are not accessible with a low cervical incision. In this article, we described the robotic approach to an ectopic mediastinal parathyroid gland. This management method of mediastinal adenomas has significant advantages when compared to conventional surgery.

What adds Valsalva maneuver to hemostasis after Trendelenburg's positioning during thyroid surgery?

BACKGROUND: Bleeding after thyroidectomy is life-threatening. The aim of the study was to evaluate whether controlling of further bleeding with Valsalva maneuver following Trendelenburg's positioning has an impact on hemostasis. METHODS: This prospective study included 68 consecutive patients undergoing thyroidectomy. Study protocol consisted of performing manual intra-abdominal pressure increase and Valsalva maneuver to check hemostasis and treating any bleeding point identified, after Trendelenburg's positioning. All identified bleeding points and treatments were recorded. RESULTS: Total number of bleeding points identified in Trendelenburg's tilt was 49, while it was 41 when using Valsalva maneuver. Abdominal pressure increase, carried out before Valsalva maneuver, identified 14 bleeding points, which was less than bleeding after Trendelenburg's positioning and Valsalva maneuver (P<0.05). All bleeding points, except 1 for Trendelenburg's positioning and 1 for Valsalva maneuver, were minor (<2 mm). Only 4.4% bleeding vessels required ties or stitching. CONCLUSIONS: Valsalva maneuver helps to detect any further bleeding following Trendelenburg's positioning.

Routine calcitonin measurement in nodular thyroid disease management: is it worthwhile?

PURPOSE: To evaluate the diagnostic accuracy of routine calcitonin measurement in patients with nodular thyroid disease. METHODS: Consecutive patients with nodular thyroid disease (n = 640) were studied. Serum calcitonin levels were measured under basal conditions, and when basal values were between 10-100 pg/mL, testing was repeated after pentagastrin (PG) stimulation. Patients with previously diagnosed or familial medullary thyroid cancer (MTC) were excluded. Patients were operated on when basal or stimulated calcitonin >100 pg/mL or when other surgical indications were present. RESULTS: Four cases of MTC were identified. MTC was diagnosed in 75% of patients with basal calcitonin >100 pg/mL. One out of 11 patients with basal calcitonin between 10-100 pg/mL was diagnosed with MTC. PG stimulation resulted in elevation in 4 cases, where 1 case was diagnosed with MTC. Positive predictive value for basal calcitonin levels in the preoperative diagnosis of MTC was 5% for values between 10-100 pg/mL and 100% for values >100 pg/mL. Possible reasons for false positivity were papillary thyroid cancer in 17%, renal insufficiency in 8.3%, Hashimoto thyroiditis in 17% and ß-blocker use in 33%. Positive predictive value for the PG test (>100 pg/mL) was 25% in the entire series. The cost of adding calcitonin measurement (±PG stimulation) to the preoperative work-up, resulted in €912.68 per MTC patient to detect the disease. CONCLUSION: Basal calcitonin measurement together with PG stimulation in cases of basal calcitonin >10 pg/mL detects MTC in 0.62% of patients with nodular thyroid disease.

Efficacy of simvastatin in reducing postoperative adhesions after thyroidectomy: an experimental study.

BACKGROUND: We aimed to investigate whether simvastatin had any impact on the prevention of adhesion formation after thyroidectomy in a rat model. METHODS: This study was performed in 66 Wistar albino rats randomized into three experimental groups. A right hemithyroidectomy was carried out in all the rats. Simvastatin was administered locally at a dose of 0.5 mg/kg and 0.8 mg/kg. Control rats received a saline solution only. Changes during the 1st week, 1st month and 3rd month were evaluated. Efficacy of the treatment was assessed by using a scoring system. RESULTS: The severity of adhesions in low-dose simvastatin group was significantly less than the control and high-dose groups during the 1st and 3rd month (p < .05). In addition, adhesions were less in the high dose group during the 3rd month, when compared to the control group (p < .05). Moreover, fibrosis and fibroblast scores, which represent adhesions, were significantly lower in low-dose and high-dose groups at 3rd month, compared to controls (p < .05). CONCLUSIONS: We investigated the influence of simvastatin application on post-thyroidectomy adhesion formation in rats. Whether adhesions, causing technical difficulties during neck redo surgery, can be reduced by the use of simvastatin in human, needs to be studied.

The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors.

OBJECTIVES: Parathyroid carcinoma (PC) is a rare parathyroid tumor compared to parathyroid adenoma (PA) and atypical parathyroid adenoma (APA). Recent studies have suggested parafibromin has a role in the differential diagnosis of parathyroid tumors. We sought to determine the role of parafibromin as well as galectin-3, Ki-67, and HBME-1 as diagnostic markers in the differential diagnosis of parathyroid tumors. METHODS: A total of 92 cases diagnosed with PA, APA, or PC at Sifa University and Private Ege Pathology Laboratory between 2006-2012 were included in the study. Parafibromin (microarray), galectin-3, Ki-67, and HBME-1 were evaluated using immunohistochemistry in all parathyroid tumors. RESULTS: Eighty-four cases were diagnosed with PA, six with APA, and two with PC. The study group consisted of 82 females and 10 males. Their mean age was 50.9 years, and the mean tumor diameter was 1.97 cm. Parafibromin was negative in the two PC cases but positive in all APA and PA cases. Positivity was observed with galectin-3 in 17 adenoma cases, three atypical adenomas, and two carcinoma cases. Positivity with HBME-1 was found in 26 PA cases and one PC case. Parafibromin and galectin-3 expression was significant between the three tumor groups but not for HBME-1 expression. Parafibromin expression increased in PA whereas galectin-3 expression decreased. A statistical significance was found between the three tumor groups according to the Ki-67 score (p=0.010). Additionally, the Ki-67 proliferation index was under 1% in PAs. CONCLUSION: The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki-67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors.

Medullary carcinoma of the thyroid with axillary metastasis: a case report.

We report a case of axillary lymph node metastasis as a consequence of medullary thyroid carcinoma (MTC) in a 42-year-old man. On January 2009, the patient was referred to us for the management of right cervical lymph node enlargement. Total thyroidectomy was performed with right-sided functional neck dissection. Postoperative histopathology revealed MTC in the right lobe of the thyroid, with extrathyroidal extension and right-sided neck metastases. Multiple left cervical, mediastinal, and right axillary lymphadenopathies were detected at the third year follow-up exam. Left-sided functional neck dissection, axillary lymph node dissection, and mediastinal lymph node dissection were performed, and the pathologic outcomes revealed as the metastatic dissemination of MTC. After a disease-free term for 1 year, multiple metastatic lesions were detected in the patient.

Should subtotal thyroidectomy be abandoned in multinodular goiter patients from endemic regions requiring surgery?

The most convenient surgical procedure for benign thyroid diseases is still controversial. The aim of this study is to determine the recurrence rate and risk factors for recurrence after different thyroidectomy procedures in multinodular goiter patients. Patients were separated into two groups according to the detection of a recurrent nodule or not after thyroidectomy. Of the 748 patients, 216 (29%) had recurrence, while 532 had no recurrent nodule. The difference between surgical procedures described as subtotal (ST), near total (NT) and total thyroidectomy (TT) was statistically significant. Transient hypoparathyroidism was significantly higher in NT and TT, when compared to ST patients (P < 0.05). Young age, bilateral multinodular goiter and insufficient surgery are risk factors affecting recurrence for benign nodular thyroid disease. Currently, subtotal procedures should be discontinued and total or near total procedures should be preferred. Meanwhile, the probability of a higher risk of hypoparathyroidism should be kept in mind.

Papillary thyroid cancer, macrofollicular variant: the follow-up and analysis of prognosis of 5 patients.

Objective. The main aim of this study was to comparatively analyze the recurrence and prognosis of this rare variant with the literature by analyzing the follow-up data of 5 patients diagnosed with papillary cancer macrofollicular variant. Methods. The demographic data, radiological and pathological data, and prognostic data of 5 patients who underwent surgery for thyroid cancer and were diagnosed with papillary cancer macrofollicular variant pathologically were retrospectively analyzed. Results. The mean age of patients whose mean follow-up period was determined as 7.2 years was 41, and the male/female ratio was 4/1. All patients underwent total thyroidectomy. The pathology report of 2 patients (40%) revealed macrofollicular variant of papillary microcancer, and 3 patients papillary cancer macrofollicular variant. Central dissection was performed in one patient (20%) due to macroscopic pathologic lymph node and 4 metastatic lymph nodes were reported. Also, locoregional recurrence was present in 3 out of 5 patients (60%). Conclusions. Although an impression of earlier and increased risk of recurrence in papillary carcinoma with macrofollicular variant has been documented, more studies with extensive follow-up times and large populations are required.

How informed are endocrine surgery patients about the risks of surgery after approving an informed consent?

OBJECTIVE: The aim is to evaluate if patients reach the level of competence that enables them to make the best decision for themselves with oral and written informed consent process that is legally valid. MATERIAL AND METHODS: This study included 62 patients who applied to Ege University Hospital Department of General Surgery Endocrine Surgery Clinics and in whom oral and written informed consent was obtained by a surgeon. Patients who were willing to participate in the study were asked to fill in a questionnaire containing questions regarding the concept of consent. RESULTS: Seventy-one percent of patients were female and 29% were male, with a mean age of 50.4±17.9 years. Six percent of patients were illiterate, 51.6% had primary education and 16.1% were college graduates. One in every two patients stated that they have never heard of informed consent concept before, 16% stated that they signed the consent without reading it. Among these patients, 88% reported that they trusted the physician and did not bother reading because they have already been verbally informed. Verbal briefing by the doctor was detected as 92%. Similarly, 91% of the patients reported that the time allocated to read and fill-in the form was enough. CONCLUSION: Informing is not composed simply of conveying information, but also to elevate patients to a proficiency level where they could decide with their best interest. It is thought that the results obtained in this study might guide studies to improve the quality of information in patients undergoing surgery.

The importance of staging systems for the determination of prognosis of well-differentiated thyroid cancer.

OBJECTIVE: In this study, we aimed to determine the significance of the staging systems (EORTC, De Groot, MACIS, and TNM) on the prognosis of well-differentiated thyroid cancer patients who underwent surgery in our clinics. MATERIAL AND METHODS: This retrospective study included 181 patients who were operated between December 1995-December 2007, with a diagnosis of thyroid cancer. In order to obtain data related to cancer staging, a computer program for PDA was developed to facilitate parameter recording. Survival analysis was performed. The findings were compared to the predicted rates by the staging systems. RESULTS: According to the De Groot staging system, stage 1 and stage 2 patients' results were compatible, but stage 3 and 4 patients' results were different (stage 3; 87% versus 66.6%, stage 4; 35% versus 100%, p=0.04). In the MACIS staging system, 20-year survival rates are determined and comparison should not be made due to insufficient follow-up period in this study. When compared to the EORTC staging system, stage 3 and stage 4 patients' results were determined different (stage 3; 51% versus 100%, stage 4; 33% versus 50%, p=0.02). The most consistent results in terms of prognosis was determined in comparison with the TNM staging system (stage 1; 100% versus 97.8%, stage 4; 45.3% versus 50%). CONCLUSION: Many classification systems are proposed for well-differentiated thyroid cancer, to predict the behavior of the tumor. In this study, we concluded that for determination of prognosis in well-differentiated thyroid cancer, the TNM staging system could best predict prognosis consistent with clinical findings.

What should be done in thyroid nodules less than two centimeters, ultrasonographically suspicious and cytologically benign?

OBJECTIVE: Although fine needle aspiration biopsy has a high sensitivity in thyroid nodule assessment, ultrasonography findings should not be underestimated. With this study, we aimed to evaluate cytologically benign nodules smaller than two centimeters, where ultrasonography findings were suspicious. MATERIAL AND METHODS: Thirty-one patients undergoing thyroidectomy between January 2009 and January 2013 were included in this retrospectively designed study. Thyroid ultrasonography and thyroid fine needle aspiration biopsy (FNAB) results were evaluated. Ultrasonographically, all patients had multinodular tissue formation and nodules had at least one of the suspicious features (nodules with hypoechogenicity, irregular margins, absence of halo, taller-than-wide, increased vascularity and microcalcifications). Maximum size of the nodules was 2 cm. Thyroidectomy was performed in this ultrasonographically suspicious, but cytologically benign group due to clinical suspicion, cosmetic reasons or patient preference. RESULTS: All patients underwent a total thyroidectomy. The group consisted of 27 female and 4 male patients, with a mean age of 49.5 years. According to the final pathology reports, there were 13 (41.9%) multinodular goiters, 2 (6.4%) follicular adenomas, 1 (3.2%) Hashimoto's thyroiditis and 15 (48.3%) thyroid cancers. Patients with cancer had at least two suspicious ultrasound findings. Except five patients with papillary microcarcinoma, cancer was diagnosed in ultrasonographically suspicious nodules in all patients. The percentage of patients with benign FNAB results, but with at least two suspicious ultrasound findings of malignancy in the biopsied nodules, was 32.2%. CONCLUSION: FNAB remains to be the gold standard in the management of ultrasonographically suspicious nodules smaller than 2 centimeters. Nevertheless, due to its high sensitivity, in case of presence of suspicious features on ultrasonography, we believe that thyroidectomy should be a treatment option if there is a clinical suspicion and the patient carries at least two suspicious ultrasonography findings.

A puzzling case of phospho-soda-induced hypocalcemia in a patient with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism.

Although rare, symptomatic hypocalcemia may develop after the administration of phospho-soda. We herein present the case of a patient with phospho-soda-induced hypocalcemia who was surprisingly diagnosed with multiple endocrine neoplasia type 1 (MEN1) caused by a heterozygous mutation in the MEN1 gene (c628_631delACAG), thus resulting in a frameshift mutation (210ThrfsX224). In addition to being the first report of phospho-soda-induced hypocalcemia in a patient with MEN1-associated primary hyperparathyroidism, our report highlights the complex nature of calcium balance in the human body and helps clinicians to appreciate how confounding factors might affect the presentation of endocrine disorders.

The interaction of oxidative stress response with cytokines in the thyrotoxic rat: is there a link?

Oxidative stress is regarded as a pathogenic factor in hyperthyroidism. Our purpose was to determine the relationship between the oxidative stress and the inflammatory cytokines and to investigate how melatonin affects oxidative damage and cytokine response in thyrotoxic rats. Twenty-one rats were divided into three groups. Group A served as negative controls. Group B had untreated thyrotoxicosis, and Group C received melatonin. Serum malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and nitric oxide derivates (NO*x), and plasma IL-6, IL-10, and TNF-alpha were measured. MDA, GSH, NO*x, IL-10, and TNF-alpha levels increased after L-thyroxine induction. An inhibition of triiodothyronine and thyroxine was detected, as a result of melatonin administration. MDA, GSH, and NO*x levels were also affected by melatonin. Lowest TNF-alpha levels were observed in Group C. This study demonstrates that oxidative stress is related to cytokine response in the thyrotoxic rat. Melatonin treatment suppresses the hyperthyroidism-induced oxidative damage as well as TNF-alpha response.