Tumor-targeted and stimulus-responsive polymeric prodrug nanoparticles to enhance the anticancer therapeutic efficacy of doxorubicin.

Polymeric prodrug nanoparticles have gained increasing attention in the field of anticancer drug delivery because of their dual functions as a drug carrier and a therapeutic agent. Doxorubicin (DOX) is a highly effective chemotherapeutic agent for various cancers but causes cardiotoxicity. In this work, we developed polymeric prodrug (pHU) nanoparticles that serve as both a drug carrier of DOX and a therapeutic agent. The composition of pHU includes antiangiogenic hydroxybenzyl alcohol (HBA) and ursodeoxycholic acid (UDCA), covalently incorporated through hydrogen peroxide (H2O2)-responsive peroxalate. To enhance cancer cell specificity, pHU nanoparticles were surface decorated with taurodeoxycholic acid (TUDCA) to facilitate p-selectin-mediated cancer targeting. TUDCA-coated and DOX-loaded pHU nanoparticles (t-pHUDs) exhibited controlled release of DOX triggered by H2O2, characteristic of the tumor microenvironment. t-pHUDs also effectively suppressed cancer cell migration and vascular endothelial growth factor (VEGF) expression in response to H2O2. In animal studies, t-pHUDs exhibited highly potent anticancer activity. Notably, t-pHUDs, with their ability to accumulate preferentially in tumors due to the p-selectin targeting, surpassed the therapeutic efficacy of equivalent DOX and pHU nanoparticles alone. What is more, t-pHUDs significantly suppressed VEGF expression in tumors and mitigated hepato- and cardiotoxicity of DOX. Given their cancer targeting ability, enhanced therapeutic efficacy and minimized off-target toxicity, t-pHUDs present an innovative and targeted approach with great translational potential as an anticancer therapeutic agent.

Acid-sensitive stable polymeric micelle-based oxidative stress nanoamplifier as immunostimulating anticancer nanomedicine.

Oxidative stress amplifying compounds could elicit selective killing of cancer cells with minimal toxicity to normal cells and also induce immunogenic cell death (ICD). However, compared to conventional anticancer drugs, oxidative stress amplifying compounds have inferior therapeutic efficacy. It can be postulated that the anticancer therapeutic efficacy and immunostimulating activity of oxidative stress amplifying hybrid prodrug (OSamp) could be fully maximized by employing ultrastable polymeric micelles as drug carriers. In this work, we developed tumour-targeted oxidative stress nanoamplifiers, composed of OSamp, amphiphilic poly(ethylene glycol) methyl ether-block-poly(cyclohexyloxy ethyl glycidyl ether)s (mPEG-PCHGE) and a lipopeptide containing Arg-Gly-Asp (RGD). Tumour targeted OSamp-loaded mPEG-PCHGE (T-POS) micelles exhibited excellent colloidal stability and significant cytotoxicity to cancer cells with the expression of DAMPs (damage-associated molecular patterns). In the syngeneic mouse tumour model, T-POS micelles induced significant apoptotic cell death to inhibit tumour growth without noticeable body weight changes. T-POS micelles also induced ICD and activated adaptive immune responses by increasing the populations of cytotoxic CD4+ and CD8+ T cells. Therefore, these results suggest that T-POS micelles hold great translational potential as immunostimulating anticancer nanomedicine.

Tumor-targeted redox-regulating and antiangiogenic phototherapeutics nanoassemblies for self-boosting phototherapy.

Cancer cells are equipped with abundant antioxidants such as glutathione (GSH) that eliminate reactive oxygen species (ROS) to deteriorate the therapeutic efficacy of photodynamic therapy (PDT). Another challenge in PDT is circumventing PDT-induced hypoxic condition that provokes upregulation of pro-angiogenic factor such as vascular endothelial growth factor (VEGF). It is therefore reasonable to expect that therapeutic outcomes of PDT could be maximized by concurrent delivery of photosensitizers with GSH depleting agents and VEGF suppressors. To achieve cooperative therapeutic actions of PDT with in situ GSH depletion and VEGF suppression, we developed tumor targeted redox-regulating and antiangiogenic phototherapeutic nanoassemblies (tRAPs) composed of self-assembling disulfide-bridged borylbenzyl carbonate (ssBR), photosensitizer (IR780) and tumor targeting gelatin. As a framework of tRAPs, ssBR was rationally designed to form nanoconstructs that serve as photosensitizer carriers with intrinsic GSH depleting- and VEGF suppressing ability. tRAPs effectively depleted intracellular GSH to render cancer cells more vulnerable to ROS and also provoked immunogenic cell death (ICD) of cancer cells upon near infrared (NIR) laser irradiation. In mouse xenograft models, tRAPs preferentially accumulated in tumors and dramatically eradicated tumors with laser irradiation. The design rationale of tRAPs provides a simple and versatile strategy to develop self-boosting phototherapeutic agents with great potential in targeted cancer therapy.

A new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy.

Background: Unintended parathyroidectomy occasionally happens despite meticulous capsular dissection and the histopathological location of removed parathyroid glands were traditionally classified as extracapsular, subcapsular, and intrathyroidal location. This study aimed to investigate the new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy that was difficult to be found with naked eye despite capsular dissection. Methods: This study investigated unintended parathyroidectomy that occurred in 743 patients who received thyroid surgery by reviewing pathology reports and slides. The histopathological location of unintentionally removed parathyroid glands was classified as intracapsule and extracapsule, and the intracapsular glands were further classified as completely buried in the thyroid parenchyme, partially buried, and subcapsular locations. Results: The incidence of unintended parathyroidectomy was 12.8%. Among the 103 unintentionally removed parathyroid glands, 74 (71.8%) were found intracapsular and 29 were extracapsular. Among the intracapsular glands, 57 (55.4%) parathyroid glands were found in difficult locations such as completely buried (40.8%) and partially buried (14.6%). Conclusions: The partially buried parathyroid gland can act as a risk factor for unintended parathyroidectomy comparable to intrathyroidal parathyroid gland despite the surgeon's best effort with meticulous capsular dissection. However, continued advances in visualizing technique such as autofluorescence imaging may lower the chance of incidentally removed partially buried parathyroid glands in the future.

H2O2-activatable hybrid prodrug nanoassemblies as a pure nanodrug for hepatic ischemia/reperfusion injury.

Self-assembling prodrugs are able to form stable nanoparticles without additional excipients and therefore have gained increasing interest in the field of drug delivery. As a natural derivative of vitamin A, all-trans retinoic acid (atRA) exerts antioxidant, anti-inflammatory, and immunostimulatory effects. However, the clinical translation of atRA has been hampered by its insufficient therapeutic efficacy. In this work, to fully maximize the therapeutic potential of atRA, we developed delicately designed self-assembling RABA (atRA-based hybrid prodrug) as a hybrid prodrug of atRA and hydroxybenzyl alcohol (HBA). RABA could form nanoassemblies and decompose to release atRA and HBA simultaneously in response to hydrogen peroxide (H2O2). In a mouse model of hepatic ischemia/reperfusion (IR) injury, RABA nanoassemblies accumulated in liver preferentially and exerted highly potent antioxidant, anti-inflammatory, and antiapoptotic effects, leading to effective protection of liver from IR injury. RABA nanoassemblies exhibited significantly higher therapeutic efficacy than the combination of equivalent atRA and HBA. Given its H2O2-responsiveness, self-assembling and self-immolating behaviors, and cooperative therapeutic actions, RABA nanoassemblies have great potential as a pure nanodrug for hepatic IR injury. This study also provides a new valuable addition in the development of prodrug self-assemblies that will emerge as next generation of drugs.

Generation of induced pluripotent stem cell line (KRIBBi004-A) from adult bone marrow CD34+ cells from a patient carrying 46,XX,t(1;5)(p31.1;35.1) karyotype.

Induced pluripotent stem cell (iPS) technology may be advantageous for the study of genetic aberrations in terms of recapitulating the full manifestation of pathological features in vitro, identifying underlying pathways, and developing personalized therapeutics rather than procuring somatic cells from patients. Here, we derived an iPSC line from a patient with reciprocal chromosome translocation, t(1;5)(p31.1;35.1), as a novel alternative model to identify clinical phenotypes induced by genetic instability. The resulting iPSC line generated from somatic cells with an existing instability showed representative characteristics of PSCs, and might serve as an unparalleled cellular resource for the development of a custom remedy.

Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery.

Clinical Analysis of Pediatric Thyroid Cancer: A Single Medical Institution Experience of 18 Years.

OBJECTIVE: The incidence of pediatric thyroid cancer is relatively low compared to the disease in adults. This study aims to present the data in our institution on pediatric thyroid cancer patients, with particular emphasis on the risk factors of recurrence together with treatment outcomes. SUBJECTS AND METHODS: Between January 2000 and July 2018, patients <20 years who were diagnosed with thyroid carcinoma and primarily treated with surgery at a major large-volume tertiary medical center specializing in thyroid cancer were enrolled. A total of 83 patients were eligible for this study. RESULTS: The majority of the studied patients were girls and adolescents (age ≥13 years). Papillary thyroid carcinoma (PTC) was the most common pathology (n = 74). PTC tumors >1 cm showed higher rate of lymph node metastasis and extrathyroidal extension than tumors ≤1 cm. All patients survived with nine PTC patients who displayed treatment failure. Age, tumor size, multifocality, lateral lymph node metastasis, and postoperative thyroglobulin levels were significant prognosticators for disease recurrence. CONCLUSION: Pediatric thyroid cancer is relatively rare and should be considered a specific disease entity with respect to the thyroid cancer in adults, since there are several distinctive characteristics.

Comparison of functional outcomes after total thyroidectomy and completion thyroidectomy: Hypoparathyroidism and postoperative complications.

OBJECTIVE: This study aimed to investigate differences in functional outcomes of postoperative complications and hypoparathyroidism between patients who underwent completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT) as an initial treatment. MATERIALS AND METHODS: We retrospectively analyzed the differences of functional outcomes after completion thyroidectomy and total thyroidectomy without lymph node dissection. We reviewed the medical records of 396 patients who underwent CT or TT for thyroid disease at Korea University Guro Hospital from March 2002 to August 2016. RESULTS: Of the 396 patients, 32 underwent CT and 364 underwent TT. There were 72 male patients and 324 female patients. Transient hypoparathyroidism was observed in 4 (9.4%) of the CT patients and 97 (26.6%) of the TT patients, with a statistically significant difference (p=0.031). Permanent hypoparathyroidism was observed in 1 patient (3.1%) in the CT group and in 13 patients (3.6%) in the TT group, which was not significantly different. There were no significant differences in the postoperative complication of temporary recurrent laryngeal nerve injury, wound infection, and hematoma between two patients group. CONCLUSION: The incidence of transient hypoparathyroidism in CT patients was significantly lower than in TT patients. These safety and functional superiority of CT should be considered when determining the scope and extent of operation in patients requiring surgery for thyroid disease.

Extranodal involvement of diffuse large B-cell lymphoma in the head and neck: An indicator of good prognosis.

OBJECTIVE: In this study, we analyzed clinicopathological characteristics and survival outcomes according to extranodal involvement of diffuse large B-cell lymphoma (DLBCL) in the head and neck. METHODS: A retrospective analysis was conducted on 110 patients from 2004 to 2014 with CD20-positive DLBCL involving the head and neck area. Patients were categorized into two groups, extranodal and nodal, according to involvement of extranodal sites in the head and neck. Outcome measurements for the groups included clinical response to treatment and recurrence rates. RESULTS: Palatine tonsils were the most frequently involved extranodal site in the head and neck (29.1%). Among clinicopathological parameters, proportion of patients with lactate dehydrogenase over 350 IU/L (p=0.033), cell of origin (p<0.001), and treatment outcomes (p=0.007) were significantly different between the two groups. Among cell origin markers CD10, Bcl6, and MUM1, MUM1 was significantly correlated with extranodal involvement (p=0.029). Recurrence rates were similar between groups, while disease-specific survival was significantly higher in the extranodal group (p=0.011). Disease-specific survival of the extranodal group was also higher than the nodal group with extranodal involvement of other body sites (p=0.010). Among patients with negative expression of CD10 (p=0.015), Bcl6 (p=0.018), and MUM1 (p=0.005), survival was longer in the extranodal than the nodal group. CONCLUSIONS: DLBCL patients with extranodal involvement of the head and neck may have longer survival outcomes than patients with solely nodal involvement. Increased survival may be more prominent in patients with negative expression of CD10, Bcl6, and MUM1.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

PURPOSE: Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry. METHODS: The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs. RESULTS: Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC. CONCLUSION: This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

Low expression of CD40L in tumor-free lymph node of oral cavity cancer related with poor prognosis.

BACKGROUND: Recently, the genetic alterations associated with tumor progression and impaired host immunity against transformed cells draw increased attention. Here, we characterized the differential gene expression patterns and protein expression in tumor-free lymph node from recurrent and non-recurrent tumors to identify independent prognostic markers for oral squamous cell carcinoma (OSCC). METHODS: A cDNA microarray analysis was performed to identify the differentially expressed genes in regional tumor-free lymph nodes from OSCC patients with and without recurrence. Then, the protein expression of the selected genes was analyzed by immunohistochemistry in 60 OSCC patients to determine their association with survival. RESULTS: Widespread down-regulation of genes involved in antigen processing and recognition in lymph nodes was a distinctive feature. In univariate Kaplan-Meier analysis, lower expression of CD40L and CD80 in tumor-free lymph nodes was significantly correlated with poorer survival. In multivariate Cox regression analysis, CD40L was identified as an independent prognostic marker of disease-free survival. CONCLUSION: Our data indicate that impaired host immunity (decreased CD40L expression) along with the TNM staging might be an important factor determining the prognosis of OSCC.

Changes in Voice- and Swallowing-Related Symptoms After Thyroidectomy: One-Year Follow-Up Study.

OBJECTIVE: We analyzed the changes in voice- and swallowing-related symptoms that occurred over time in patients who underwent thyroidectomy and identified any associated risk factors. METHODS: One hundred and three patients who underwent thyroidectomy were enrolled. RESULTS: The mean thyroidectomy voice-related questionnaire (TVQ) score before surgery was 12.41 ± 12.19; it significantly increased to 28.24 ± 18.01 ( P < .001) 1 month postoperatively, decreased to 24.02 ± 17.30 ( P = .014) and 20.66 ± 15.29 ( P = .023) 3 and 6 months postoperatively, respectively. It was continuously decreased to 18.83 ± 14.63 twelve months postoperatively. The temporal changes in TVQ scores between patients who underwent total thyroidectomy or lobectomy were significantly different. There was a statistically significant difference in the temporal changes in TVQ according to whether neck dissection was performed. The temporal changes in TVQ in patients with and without extrathyroidal extension were significantly different. CONCLUSIONS: Voice- and swallowing-related discomfort in patients who received thyroidectomy showed dynamic changes over time. There was a significant difference in the degree of change according to clinicopathological factors. Patients with these risk factors may benefit from appropriate patient education and various rehabilitation programs for symptom relief.

Survival and recurrence of resectable tongue cancer: Resection margin cutoff value by T classification.

BACKGROUND: The purpose of this study was to determine an appropriate cutoff value for the resection margin according to the initial T classification. METHODS: The medical records of 151 patients treated by surgery for tongue cancer were retrospectively reviewed to identify the significant perioperative parameters and appropriate cutoff value associated with disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS: The posterior resection margin was significantly correlated with survival and local recurrence (P = .020 and .016, respectively), whereas the deep resection margin was correlated with overall recurrence (P = .047). The cutoff values of the posterior and deep resection margins for survival and recurrence were different and larger in the advanced-stage T classification group (0.45 cm vs 0.95 cm and 0.25 cm vs 0.80 cm, respectively). CONCLUSION: Posterior and deep resection margins are significant prognosticators in tongue cancer. A larger resection margin may be needed in advanced-stage T classification.

A prognostic scoring system using inflammatory response biomarkers in oral cavity squamous cell carcinoma patients who underwent surgery-based treatment.

BACKGROUND: The aim of this study was to evaluate the effectiveness of a scoring system based on the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting disease-specific survival of oral cancer patients treated by surgery. METHODS: From January 2007 to December 2016, we retrospectively analyzed data from 69 oral cancer patients who received surgery. RESULTS: Lymphocyte-to-monocyte ratio was significantly associated with T classification, N classification, and pathologic stage. Neutrophil-to-lymphocyte ratio was significantly associated with T classification and pathologic stage. Platelet-to-lymphocyte ratio was significantly associated with N classification and pathologic stage. In multivariate analysis, only a higher score on this scoring system was significantly associated with poorer disease-specific survival. CONCLUSIONS: We found that the prognostic score system based on these three values was significantly associated with disease-specific survival of oral cancer patients who received surgery, indicating that the prognostic scoring system was effective in indirectly predicting systemic inflammatory response.

Clinical implications of pathologic factors after thyroid lobectomy in patients with papillary thyroid carcinoma.

OBJECTIVE: We evaluated the clinical and prognostic significance of pathologic factors by analyzing the treatment results of patients who underwent thyroid lobectomy. MATERIALS AND METHODS: We retrospectively analyzed data from 734 patients diagnosed with papillary thyroid cancer who underwent thyroid lobectomy at Korea University Hospital from January 2004 to December 2016. RESULTS: A total of 734 patients were included in the study and their mean age was 44.5 years (range, 15-83). On univariate analysis, tumor size and recurrence-free survival were significantly related. The 10-year recurrence-free survival was 98.3% for tumors ≤1cm, 77.8% for >1cm and ≤2cm, and 66.7% for >2cm (p = 0.014). Recurrence-free survival was significantly different between patients with and without microscopic extrathyroidal extension (p=0.002). The 10-year recurrence-free survival rate was 99.2% for patients without extrathyroidal extension and 92.2% for patients with microscopic extrathyroidal extension. Multivariate analysis showed only microscopic extrathyroidal extension was significantly correlated with recurrence-free survival (p=0.029). CONCLUSION: In patients undergoing thyroid lobectomy for low-risk papillary thyroid cancer, microscopic extrathyroidal extension was an important prognostic factor associated with recurrence-free survival. However, in cases with microscopic extrathyroidal extension findings on postoperative pathologic examination, appropriate ultrasonographic follow-up of the contralateral thyroid lobe and cervical lymph node to facilitate early detection and prompt treatment of recurrence can control the disease without a deterioration of survival rate.

In vivo assessment of hair cell damage and developmental toxicity caused by gestational caffeine exposure using zebrafish (Danio rerio) models.

The aim of the present study was to evaluate hair cell damage and associated developmental toxicity caused by gestational caffeine exposure. We exposed embryos to various caffeine concentrations (25µM, 125µM, 250µM, and 500µM) and evaluated developmental toxicity of the embryos at 72 and 120h and hair cell damage at 120h after fertilization. The average number of total hair cells within four neuromasts exposed to various concentrations of caffeine was compared with that of the control group. To seek the underlying mechanisms, TUNEL and DASPEI assay were carried out to evaluate hair cell apoptosis and mitochondrial damage, respectively. Morphologic abnormality, mortality, hatching rate, and heart rate were also evaluated. Caffeine induced significant hair cell damage compared with control group (p<0.01, control; 35.64±10.48 cells, 500µM caffeine; 23.32±12.14 cells, n=25-30). Significant increase in the hair cell apoptosis was confirmed in a dose-dependent manner (p<0.01, TUNEL assay) and the mitochondrial damage in high caffeine concentrations (250, 500µM) (p<0.01, DASPEI assay).Morphologic abnormalities were significantly increased in high caffeine concentrations (250 or 500µM) for body shape, notochord, and heart at both 3-, and 5-dpf. The control group exhibited 3.3% mortality which increased up to 11.6% at 500µM caffeine. Rapid hatching was present at 48h (control; 46.6%, 500µM caffeine; 100%). In conclusion, gestational caffeine exposure caused significant hair cell damage and developmental toxicities in zebrafish at early developmental stages.

Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/ß-Catenin and ERK Pathways.

In this study, we investigated the effect and mechanism of Undariopsis peterseniana, an edible brown alga, on hair growth. The treatment of vibrissa follicles with U. peterseniana extract ex vivo for 21 days significantly increased the hair-fiber lengths. The U. peterseniana extract also significantly accelerated anagen initiation in vivo. Moreover, we found that U. peterseniana extract was able to open the KATP channel, which may contribute to increased hair growth. The U. peterseniana extract decreased 5α-reductase activity and markedly increased the proliferation of dermal papilla cells, a central regulator of the hair cycle. The U. peterseniana extract increased the levels of cell cycle proteins, such as Cyclin D1, phospho(ser780)-pRB, Cyclin E, phospho-CDK2, and CDK2. The U. peterseniana extract also increased the phosphorylation of ERK and the levels of Wnt/ß-catenin signaling proteins such as glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin. These results suggested that the U. peterseniana extract had the potential to influence hair growth by dermal papilla cells proliferation through the activation of the Wnt/ß-catenin and ERK pathways. We isolated a principal of the U. peterseniana extract, which was subsequently identified as apo-9'-fucoxanthinone, a trichogenic compound. The results suggested that U. peterseniana extract may have a pivotal role in the treatment of alopecia.

Efficiency of intraoperative neuromonitoring on voice outcomes after thyroid surgery.

OBJECTIVE: Voice disturbance is an important problem after thyroidectomy. The aim of this study was to evaluate the efficiency of intraoperative neuromonitoring (IONM) in reducing early phonation change by comparing postoperative voice outcomes. METHODS: The study retrospectively enrolled 68 consecutive female patients who had undergone IONM thyroidectomy for papillary thyroid carcinoma occurring between January 2014 and November 2014. A historical group of 117 similar female patients not receiving IONM thyroidectomy was used as an external control. Voice analyses were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Voice outcomes between the IONM group and no IONM group were compared in patients who underwent hemithyroidectomy and total thyroidectomy. RESULTS: In patients who underwent IONM, there were significantly smaller changes in the fundamental frequency at postoperative 1 month and in the maximum voice pitch of the voice range profile at postoperative 1 week irrespective of the extent of thyroid surgery. CONCLUSION: IONM during thyroid surgery resulted in better outcomes regarding fundamental frequency and high-pitch voice in the early postoperative period. IONM appears to be an effective method to reduce temporary phonation alteration after thyroid surgery.

Analysis of Temporal Change in Voice Quality After Thyroidectomy: Single-institution Prospective Study.

OBJECTIVES: This study analyzed the temporal changes of voice quality after thyroidectomy and assessed the predictive perioperative parameters of postthyroidectomy voice disorder (PTVD). STUDY DESIGN: This is a prospective cohort study. METHODS: From March 2011 to July 2014, 559 patients who underwent thyroidectomy with or without central neck dissection were prospectively enrolled. All patients underwent prospective voice evaluation using the subjective and objective comprehensive battery of assessments, preoperatively and postoperatively at 1 week, 1 month, 3 months, 6 months, and 12 months. RESULTS: Fundamental frequency (F0) was not significantly decreased during the postoperative follow-up. Maximal vocal pitch (MVP) and maximal intensity were not recovered, even at 1 year postoperatively, whereas the Grade, Roughness, Breathiness, Asthenia, Strain scale reached preoperative value at postoperative 3-6 months and voice handicap index at 1 year. Postoperative 1-month MVP was the best predictor for PTVD, and the cut-off value was 80% of preoperative value. Wide surgical extent and high preoperative F0 were the parameters that significantly correlated with PTVD (P = 0.021 and P < 0.001, respectively), and large tumor, higher preoperative MVP, and lower postoperative 1-month F0 were significantly associated with permanent PTVD (P = 0.028, P < 0.001, and P = 0.003, respectively). CONCLUSIONS: Different recovery patterns of voice parameters should be considered in preoperative counseling. Intensive voice therapy may be needed for patients with the ability to produce higher pitch than normal preoperatively and wide surgical extent.