Clinical Significance of the Preoperative Thyroidectomy-Related Voice Questionnaire Score in Thyroid Surgery.

BACKGROUND: The thyroidectomy-related voice questionnaire (TVQ) is an efficient screening tool for detecting postoperative vocal dysfunction. The aim of this study was to confirm the significance of the preoperative TVQ score in thyroid surgery. METHODS: We examined 180 women who underwent total thyroidectomy with central lymph node dissection from March 2014 to May 2016. Based on the preoperative TVQ score, participants were categorized under "normal" (TVQ score <5) and "abnormal" (TVQ score ≥5) groups. The laryngoscopic examination and acoustic analysis were performed and the TVQ score assessed before and after surgery (2 weeks, 2 months, and 8 months). RESULTS: In the normal group, the TVQ score increased up to 2 months postoperatively and had decreased at 8 months postoperatively but was significantly higher than the preoperative TVQ score. In the abnormal group, the TVQ score increased up to 2 months postoperatively but had recovered similar to the preoperative TVQ score 8 months postoperatively. The preoperative TVQ score in the abnormal group moderately correlated with the final TVQ score; however, the preoperative TVQ score in the normal group did not correlate with the TVQ score 8 months postoperatively. CONCLUSION: During preoperative patient counseling, it is important to explain that voice changes without vocal cord palsy may occur postoperatively and that it may take a long time to resolve, particularly in patients with a normal preoperative TVQ score.

Investigation of attachment location of adhesive skin electrodes for intraoperative neuromonitoring in thyroid surgery: Preclinical and clinical studies.

BACKGROUND: Recently, adhesive skin electrodes have been reported to be useful for recording electromyographic signals from intrinsic laryngeal muscles for intraoperative neuromonitoring in thyroid surgery and have shown good results compared to existing recording methods. In this study, we investigated the optimal attachment location of adhesive skin electrodes for intraoperative neuromonitoring in both porcine models and human cases. METHODS: Attachment locations were divided vertically into upper, middle, and lower locations and horizontally into medial and lateral locations to determine the optimal location of placing adhesive skin electrodes preclinically in four porcine models. This study included a total of 78 patients who underwent thyroidectomy under intraoperative neuromonitoring with adhesive skin electrodes. Sixteen patients were monitored using both adhesive skin electrodes and an electromyographic endotracheal tube. Two pairs of skin electrodes were attached to the level of the thyroid cartilage lamina. Evoked electromyographic data, including data on mean amplitude and latency, obtained by stimulating the recurrent laryngeal nerve and vagus nerve, were collected. RESULTS: Lateral attachment of adhesive skin electrodes showed significantly higher evoked amplitudes than medial attachment in both animal models and human patients. In cases where skin electrodes and an electromyographic endotracheal tube were used together, the electromyographic endotracheal tube showed a significantly higher amplitude than skin electrodes, and laterally attached skin electrodes showed a significantly higher amplitude than medially attached skin electrodes. CONCLUSION: Intraoperative neuromonitoring using adhesive skin electrodes was feasible in both animal models and human patients. We suggest that it would be better to attach adhesive skin electrodes to the lateral side of the thyroid cartilage lamina. Lateral attachment closer to the cricoarytenoid joint may be better for measuring muscle movement around the cricoarytenoid joint.

Clinical outcomes of T4a papillary thyroid cancer with recurrent laryngeal nerve involvement: a retrospective analysis.

Preoperative vocal cord palsy (VCP) may indicate locally invasive papillary thyroid cancer (PTC); using this relationship, we evaluated the clinical outcomes and risk factors for recurrence in post-thyroidectomy T4a PTC patients with recurrent laryngeal nerve (RLN) involvement. We retrospectively investigated thyroidectomy patients, recorded their clinical factors, recurrence rate, and pathological findings, and analysed the relationship between recurrence rate and clinical factors. Of 72 patients, 37 (51%) had preoperative VCP and 35 (49%) had normal preoperative vocal cord movement with confirmed intraoperative RLN invasion. Tracheal and esophageal invasion was observed in 13 (18%) and 15 (21%) patients, respectively. Thyroid cancer recurred in 18 (25%) patients over 58 months, resulting in 2 (3%) deaths. Recurrence was not associated with surgical extent, organ invasion, enlarged tumour size, or lymph node infiltration (p > 0.05). The recurrence rate was significantly higher in patients with positive resection margins (p < 0.05). T4a PTC patients with RLN involvement showed a poor prognosis. The recurrence rate was not affected by preoperative VCP, intraoperative detection of RLN invasion, nerve resection, nerve preservation by shaving, lymph node metastasis, or tracheal or esophageal invasion. The most important prognostic factor for recurrence was a positive resection margin.

Risk factors of suprasternal lymph node metastasis in papillary thyroid carcinoma with clinical lateral cervical lymph node metastasis.

BACKGROUND: Metastatic lymph nodes are occasionally found in suprasternal lymph nodes in patients with papillary thyroid cancer (PTC). However, limited studies have examined these lymph nodes thus far. Therefore, we investigated the frequency and risk factors of suprasternal lymph node metastasis in patients with PTC and lateral cervical lymph node metastasis. METHODS: A total of 85 patients with cN1b PTC underwent total thyroidectomy, central neck dissection, and ipsilateral selective neck dissection including suprasternal lymph node dissection. We analyzed the correlation between suprasternal lymph node metastasis and sex, age, tumor characteristics, and cervical lymph node metastasis status. RESULTS: Eleven (12.9%) patients had pathological suprasternal lymph node metastasis. Suprasternal lymph node metastasis was associated with tumors located in the inferior pole of the thyroid gland and level IV lymph node metastasis (P=0.005 and 0.014, respectively). Receiver operating characteristic curve analysis indicated that two or more level IV metastatic lymph nodes had the best predictive value for suprasternal lymph node metastasis (P<0.001). CONCLUSIONS: In patients with cN1b PTC, especially those with tumors in the inferior pole of the thyroid gland or level IV lymph node metastasis, greater attention should be paid to the suprasternal lymph nodes and suprasternal lymph node dissection should be routinely included as part of selective neck dissection.

The incidence of myocardial infarction and stroke in head and neck cancer patients.

Various treatment modalities are used for head and neck cancer (HNC). This study analyzed the incidence and risks of myocardial infarction (MI) and stroke by cancer site and treatment modality in 22,737 patients newly diagnosed with HNC registered in the Korean National Health Insurance Service database in 2007-2013. An additional 68,211 patients without HNC, stroke, or MI were identified as the control group. The risks for MI (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.24-1.53), stroke (HR = 1.48, 95% CI 1.37-1.60), and mortality (HR = 5.30, 95% CI 5.14-5.47) were significantly higher in the HNC group. Analysis by cancer site showed the risk of MI and mortality was highest in hypopharynx cancer, while the risk of stroke was highest in nasopharynx and paranasal sinus cancer. Analysis by treatment modality showed the highest risks for MI (HR = 1.88, 95% CI 1.31-2.69) and mortality (HR = 2.95, 95% CI 2.75-3.17) in HNC patients receiving chemotherapy (CT) alone, while HNC patients receiving CT with surgery had the highest risk for stroke (HR = 1.81, 95% CI 1.14-2.88). Careful attention to MI and stroke risks in HNC patients is suggested, especially those who received both CT and radiotherapy.

Application of an Intraoperative Neuromonitoring System Using a Surface Pressure Sensor in Parotid Surgery: A Rabbit Model Study.

OBJECTIVES: Facial nerve monitoring (FNM) can be used to identify the facial nerve, to obtain information regarding its course, and to evaluate its status during parotidectomy. However, there has been disagreement regarding the efficacy of FNM in reducing the incidence of facial nerve palsy during parotid surgery. Therefore, instead of using electromyography (EMG) to identify the location and state of the facial nerve, we applied an intraoperative neuromonitoring (IONM) system using a surface pressure sensor to detect facial muscle twitching. The objective of this study was to investigate the feasibility of using the IONM system with a surface pressure sensor to detect facial muscle twitching during parotidectomy. METHODS: We evaluated the stimulus thresholds for the detection of muscle twitching in the orbicularis oris and orbicularis oculi, as well as the amplitude and latency of EMG and the surface pressure sensor in 13 facial nerves of seven rabbits, using the same stimulus intensity. RESULTS: The surface pressure sensor detected muscle twitching in the orbicularis oris and orbicularis oculi in response to a stimulation of 0.1 mA in all 13 facial nerves. The stimulus threshold did not differ between the surface pressure sensor and EMG. CONCLUSION: The application of IONM using a surface pressure sensor during parotidectomy is noninvasive, reliable, and feasible. Therefore, the IONM system with a surface pressure sensor to measure facial muscle twitching may be an alternative to EMG for verifying the status of the facial nerve.

Simple technique to preserve the external branch of the superior laryngeal nerve during thyroidectomy: Clinical practicability of an attachable nerve stimulator.

OBJECTIVE: This study aimed to demonstrate the usefulness of an attachable magnetic nerve stimulator for preservation of the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy. METHODS: We retrospectively analyzed 120 female patients, of which 60 underwent thyroidectomy with an attachable magnetic nerve stimulator (magnetic group) and the remaining 60 underwent thyroidectomy with a conventional method without EBSLN identification (control group). For both groups, objective and subjective voice parameters were investigated on the day before surgery and at 2 weeks and 2 months after surgery. RESULTS: In the magnetic group, a magnetic nerve stimulator was used to ligate only the site without cricothyroid muscle (CTM) twitching, and thyroid surgery was successfully performed without damage to the EBSLN. In the control group, objective voice parameters, including fundamental frequency, voice range profile (VRP), highest VRP (VRP-H), and maximal phonation time, and the subjective thyroidectomy-related voice questionnaire score were significantly decreased at 2 months after surgery compared to preoperative values. Compared to the control group, the magnetic group did not show a significant decrease in the objective VRP and VRP-H at 2 months after surgery. CONCLUSION: The use of metallic surgical instruments with an attachable magnetic nerve stimulator may provide surgeons with real-time feedback on CTM twitching feedback and EBSLN status. Compared to direct EBSLN identification during thyroidectomy, this is a simple, easy, and noninvasive method for EBSLN preservation that is useful, especially for less-experienced surgeons.

The mechanism of submandibular gland dysfunction after menopause may be associated with the ferroptosis.

Salivary gland dysfunction is a common symptom that occurs after menopause. This study was performed to investigate the mechanism of salivary gland dysfunction to confirm the relationship between ferroptosis and salivary gland dysfunction by ovariectomy. Forty-eight female rats were randomly divided into four groups (12 rats in each group). Histology, real time PCR, western blot, immunohistochemistry, electron microscopy, cytosolic iron assay, and salivary function were analyzed. Human salivary gland tissue analysis was also done. Lipogenesis and lipid deposition in the submandibular gland tissue occurred after ovariectomy. ROS generation, MDA+HAE was increased and GPX4 activity was decreased and in the OVX group compared to the CON group. Iron deposition in the submandibular gland tissue was increased in the OVX group. Submandibular gland fibrosis was increased and saliva secretion was decreased in the OVX group. In human submandibular gland analysis, lipid and iron deposition was also increased in the postmenopause group. This is the first in vivo study in which salivary gland dysfunction is associated with the ferroptosis in postmenopausal animal model. Increased lipid and iron deposition in normal submandibular gland tissues of postmenopausal women can suggest that the salivary gland dysfunction after menopause may be associated with the ferroptosis.

Application of Novel Intraoperative Neuromonitoring System Using an Endotracheal Tube With Pressure Sensor During Thyroid Surgery: A Porcine Model Study.

OBJECTIVES: The loss of signal during intraoperative neuromonitoring (IONM) using electromyography (EMG) in thyroidectomy is one of the biggest problems. We have developed a novel IONM system with an endotracheal tube (ETT) with an attached pressure sensor instead of EMG to detect laryngeal twitching. The aim of the present study was to investigate the feasibility and reliability of this novel IONM system using an ETT with pressure sensor during thyroidectomy in a porcine model. METHODS: We developed an ETT-attached pressure sensor that uses the piezoelectric effect to measure laryngeal muscle twitching. Stimulus thresholds, amplitude, and latency of laryngeal twitching evaluated using the pressure sensor were compared to those measured using transcartilage needle EMG. The measured amplitude changes by EMG and the pressure sensor during recurrent laryngeal nerve (RLN) traction injury were compared. RESULTS: No significant differences in stimulus threshold intensity between EMG and the pressure sensor were observed. The EMG amplitude detected at 0.3 mA, increased with increasing stimulus intensity. When the stimulus was more than 1.0 mA, the amplitude showed a plateau. In a RLN traction injury experiment, the EMG amplitude did not recover even 20 minutes after stopping RLN traction. However, the pressure sensor showed a mostly recovery. CONCLUSION: The change in amplitude due to stimulation of the pressure sensor showed a pattern similar to EMG. Pressure sensors can be feasibly and reliably used for RLN traction injury prediction, RLN identification, and preservation through the detection of laryngeal muscle twitching. Our novel IONM system that uses an ETT with an attached pressure sensor to measure the change of surface pressure can be an alternative to EMG in the future.

Human Tonsil-Derived Mesenchymal Stromal Cells Maintain Proliferating and ROS-Regulatory Properties via Stanniocalcin-1.

Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are not yet precisely elucidated. We investigated the role of stanniocalcin-1 (STC1), an anti-oxidative hormone, in the functions of TMSCs. We found that STC1 was highly expressed in TMSC compared with MSCs from bone marrow or adipose tissue. The proliferation, senescence and differentiation of TMSCs were assessed after the inhibition of STC1 expression. STC1 inhibition resulted in a significant decrease in the proliferation of TMSCs and did not affect the differentiation potential. To reveal the anti-oxidative ability of STC1 in TMSCs themselves or against other cell types, the generation of mitochondrial reactive oxygen species (ROS) in TMSC or ROS-mediated production of interleukin (IL)-1ß from macrophage-like cells were detected. Interestingly, the basal level of ROS generation in TMSCs was significantly elevated after STC1 inhibition. Moreover, down-regulation of STC1 impaired the inhibitory effect of TMSCs on IL-1ß production in macrophages. Taken together, these findings indicate that STC1 is highly expressed in TMSCs and plays a critical role in proliferating and ROS-regulatory abilities.

Increased calcium channel in the lamina propria of aging rat.

The alterations of the extracellular matrix (ECM) in lamina propria of the vocal folds are important changes that are associated with decreased vibrations and increased stiffness in aging vocal fold. The aim of this study was to investigate the differences in gene expression of lamina propria using next generation sequencing (NGS) in young and aging rats and to identify genes that affect aging-related ECM changes for developing novel therapeutic target molecule. Among the 40 genes suggested in the NGS analysis, voltage-gated calcium channels (VGCC) subunit alpha1 S (CACNA1S), VGCC auxiliary subunit beta 1 (CACNB1), and VGCC auxiliary subunit gamma 1 (CACNG1) were increased in the lamina propria of the old rats compared to the young rats. The synthesis of collagen I and III in hVFFs decreased after si-CACNA1S and verapamil treatment. The expression and activity of matrix metalloproteinases (MMP)-1 and -8 were increased in hVFFs after the treatment of verapamil. However, there was no change in the expression of MMP-2 and -9. These results suggest that some calcium channels may be related with the alteration of aging-related ECM in vocal folds. Calcium channel has promising potential as a novel therapeutic target for the remodeling ECM of aging lamina propria.

Right posterior paratracheal lymph nodes metastasis is one of the predictive factors in right-sided papillary thyroid carcinoma.

BACKGROUND: Lymph nodes in the right paratracheal region are separated as anterior and posterior on the basis with right recurrent laryngeal nerve. Dissection of the right posterior paratracheal lymph nodes is sometimes overlooked during a central neck dissection. Therefore, this study was designed to assess the clinicopathologic risk factors and prognostic implication for recurrence related to the presence of right posterior paratracheal lymph nodes metastasis in patient with right-sided papillary thyroid carcinoma. METHODS: Records from 763 patients with papillary thyroid carcinoma who underwent total thyroidectomy with central neck dissection, including the right posterior paratracheal lymph nodes, between January 2007 and March 2015 were reviewed retrospectively. RESULTS: Among 763 patients (120 men and 643 women; mean age 49.04 years) with right-sided papillary thyroid carcinoma, 127 exhibited right posterior paratracheal lymph nodes metastases. In multivariate analysis, central-compartment lymph nodes metastases (odds ratio 5.203; 95% confidence interval, 2.864-9.453) and lateral cervical lymph nodes metastases (odds ratio 3.668; 95% confidence interval, 2.375-5.667) were independently correlated with right posterior paratracheal lymph nodes metastases. Twenty-three patients (3.0%) showed loco-regional recurrence. The loco-regional recurrence rate was greater in the groups for males (P = .012), larger tumor size (>10 mm; P = .044), extrathyroidal extention (P = .002), and right posterior paratracheal lymph nodes metastasis (P < .001). CONCLUSION: Right posterior paratracheal lymph nodes metastases are predictive factors of loco-regional recurrence, and these lymph nodes should be removed completely during a right central neck dissection in patients with right-sided papillary thyroid carcinoma with central or lateral cervical lymph node metastasis.

Development of a Novel Intraoperative Neuromonitoring System Using an Accelerometer Sensor in Thyroid Surgery: A Porcine Model Study.

OBJECTIVES: The sensitivity and positive predictive value of widely used intraoperative neuromonitoring (IONM) using electromyography (EMG) of the vocalis muscle in thyroid surgery are controversial. Thus, we developed a novel IONM system with an accelerometer sensor that uses the piezoelectric effect instead of EMG to detect laryngeal twitching. The objective of this study was to evaluate the feasibility and safety of this novel IONM system during thyroid surgery in a porcine model. METHODS: We developed an accelerometer sensor that uses the piezoelectric effect to measure laryngeal twitching in three dimensions. This novel accelerometer sensor was placed in the anterior neck skin (transcutaneous) or postcricoid area. Stimulus thresholds, amplitude, and latency of laryngeal twitching measured using the accelerometer sensor were compared to those measured through EMG of the vocalis muscle. RESULTS: The amplitudes of the accelerometer sensor at the anterior neck and postcricoid area were significantly lower than those of EMG because of differences in the measurement method used to evaluate laryngeal movement. However, no significant differences in stimulus thresholds between the EMG endotracheal tube and transcutaneous or postcricoid accelerometer sensors were observed. CONCLUSION: Accelerometer sensors located at the anterior neck or postcricoid area were able to identify laryngeal twitching. The stimulus intensity measured with these sensors was equivalent to that from conventional vocalis EMG. Our novel IONM system with an accelerometer sensor that checks changes in surface acceleration can be an alternative to EMG of the vocalis muscle for IONM in the future.

Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGß1) expression, while total ITGß1 expression was not affected. Inhibition of ITGß1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGß1 expression.

Evaluation of decellularized xenogenic porcine auricular cartilage as a novel biocompatible filler.

Fillers are products that fill the space in soft tissues of the human body and actively used in the various medical fields. Unfortunately, most of the cost-effective commercially available fillers are synthetic and have limitations in terms of their biocompatibility. Here, we evaluated the possible application of decellularized xenogenic cartilage as a long-lasting material for soft tissue augmentation and compared it with two commercially available fillers Artesense (polymethylmethacrylate microspheres) and Radiesse (calcium hydroxyapatite [CaHa]). To do so, porcine auricular cartilage was harvested, followed by freezing and grinding of the tissue into flakes. Then, we used 1% Triton X-100 to decellularize the flakes. We then, respectively, injected 0.1 cc of each material (decellularized xenogenic cartilage, Radiesse, and Artesense) into the subcutaneous layer at three different sites per subject in 12 Sprague-Dawley rats, and evaluated the inflammatory cell infiltration and foreign body reactions of each. Our data indicate that the infiltration of giant cells in the injection area was significantly lower in the decellularized xenogenic cartilage injection group than that in the Radiesse and Artesense injection groups. Further, we observed some neutrophil infiltration in the xenogenic cartilage and Artesense injection groups at 1 month, but these levels were much lower at 3 months (comparable to the Radiesse injection group). Thus, decellularized xenogenic cartilage may have a distinct advantage in terms of biocompatibility compared with other commercial injectable long-lasting fillers, making it one of the most feasible, natural, and cost effective materials in the market. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2708-2715, 2018.

Simultaneous enhancement of upconversion and downshifting luminescence via plasmonic structure.

We describe a metal nanodisk-insulator-metal (MIM) structure that enhances lanthanide-based upconversion (UC) and downshifting (DS) simultaneously. The structure was fabricated using a nanotransfer printing method that facilitates large-area applications of nanostructures for optoelectronic devices. The proposed MIM structure is a promising way to harness the entire solar spectrum by converting both ultraviolet and near-infrared to visible light concurrently through resonant-mode excitation. The overall photoluminescence enhancements of the UC and DS were 174- and 29-fold, respectively.

Additive-free hollow-structured Co3O4 nanoparticle Li-ion battery: the origins of irreversible capacity loss.

Origins of the irreversible capacity loss were addressed through probing changes in the electronic and structural properties of hollow-structured Co3O4 nanoparticles (NPs) during lithiation and delithiation using electrochemical Co3O4 transistor devices that function as a Co3O4 Li-ion battery. Additive-free Co3O4 NPs were assembled into a Li-ion battery, allowing us to isolate and explore the effects of the Co and Li2O formation/decomposition conversion reactions on the electrical and structural degradation within Co3O4 NP films. NP films ranging between a single monolayer and multilayered film hundreds of nanometers thick prepared with blade-coating and electrophoretic deposition methods, respectively, were embedded in the transistor devices for in situ conduction measurements as a function of battery cycles. During battery operation, the electronic and structural properties of Co3O4 NP films in the bulk, Co3O4/electrolyte, and Co3O4/current collector interfaces were spatially mapped to address the origin of the initial irreversible capacity loss from the first lithiation process. Further, change in carrier injection/extraction between the current collector and the Co3O4 NPs was explored using a modified electrochemical transistor device with multiple voltage probes along the electrical channel.