The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Evaluating the Diagnostic Potential of Connected Speech for Benign Laryngeal Disease Using Deep Learning Analysis.

OBJECTIVES: This study aimed to evaluate the performance of artificial intelligence (AI) models using connected speech and vowel sounds in detecting benign laryngeal diseases. STUDY DESIGN: Retrospective. METHODS: Voice samples from 772 patients, including 502 with normal voices and 270 with vocal cord polyps, cysts, or nodules, were analyzed. We employed deep learning architectures, including convolutional neural networks (CNNs) and time series models, to process the speech data. The primary endpoint was the area under the receiver's operating characteristic curve for binary classification. RESULTS: CNN models analyzing speech segments significantly outperformed those using vowel sounds in distinguishing patients with and without benign laryngeal diseases. The best-performing CNN model achieved areas under the receiver operating characteristic curve of 0.895 and 0.845 for speech and vowel sounds, respectively. Correlations between AI-generated disease probabilities and perceptual assessments were more pronounced in the connected-speech analyses. However, the time series models performed worse than the CNNs. CONCLUSION: Connected speech analysis is more effective than traditional vowel sound analysis for the diagnosis of laryngeal voice disorders. This study highlights the potential of AI technologies in enhancing the diagnostic capabilities of speech, advocating further exploration, and validation in this field.

Detection of Cancer Recurrence Using Systemic Inflammatory Markers and Machine Learning after Concurrent Chemoradiotherapy for Head and Neck Cancers.

Pretreatment values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers, including head and neck cancers. However, there are no studies on whether temporal changes in the NLR and PLR values after treatment are related to the development of recurrence. Therefore, in this study, we aimed to develop a deep neural network (DNN) model to discern cancer recurrence from temporal NLR and PLR values during follow-up after concurrent chemoradiotherapy (CCRT) and to evaluate the model's performance compared with conventional machine learning (ML) models. Along with conventional ML models such as logistic regression (LR), random forest (RF), and gradient boosting (GB), the DNN model to discern recurrences was trained using a dataset of 778 consecutive patients with primary head and neck cancers who received CCRT. There were 16 input features used, including 12 laboratory values related to the NLR and the PLR. Along with the original training dataset (N = 778), data were augmented to split the training dataset (N = 900). The model performance was measured using ROC-AUC and PR-AUC values. External validation was performed using a dataset of 173 patients from an unrelated external institution. The ROC-AUC and PR-AUC values of the DNN model were 0.828 ± 0.032 and 0.663 ± 0.069, respectively, in the original training dataset, which were higher than the ROC-AUC and PR-AUC values of the LR, RF, and GB models in the original training dataset. With the recursive feature elimination (RFE) algorithm, five input features were selected. The ROC-AUC and PR-AUC values of the DNN-RFE model were higher than those of the original DNN model (0.883 ± 0.027 and 0.778 ± 0.042, respectively). The ROC-AUC and PR-AUC values of the DNN-RFE model trained with a split dataset were 0.889 ± 0.032 and 0.771 ± 0.044, respectively. In the external validation, the ROC-AUC values of the DNN-RFE model trained with the original dataset and the same model trained with the split dataset were 0.710 and 0.784, respectively. The DNN model with feature selection using the RFE algorithm showed the best performance among the ML models to discern a recurrence after CCRT in patients with head and neck cancers. Data augmentation by splitting training data was helpful for model performance. The performance of the DNN-RFE model was also validated with an external dataset.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Novel thrombospondin-1 transcript exhibits distinctive expression and activity in thyroid tumorigenesis.

Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1-splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed that TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type, as identified in vivo and in vitro. These activities of TSP1V are caused by inhibiting phospho-Smad and phospho-focal adhesion kinase. Reverse transcription polymerase chain reaction and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs enhanced IR. We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment. Additionally, sulindac sulfide reduced phospho-RBM5 levels in a time-dependent manner. Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression.

Deep learning model for tongue cancer diagnosis using endoscopic images.

In this study, we developed a deep learning model to identify patients with tongue cancer based on a validated dataset comprising oral endoscopic images. We retrospectively constructed a dataset of 12,400 verified endoscopic images from five university hospitals in South Korea, collected between 2010 and 2020 with the participation of otolaryngologists. To calculate the probability of malignancy using various convolutional neural network (CNN) architectures, several deep learning models were developed. Of the 12,400 total images, 5576 images related to the tongue were extracted. The CNN models showed a mean area under the receiver operating characteristic curve (AUROC) of 0.845 and a mean area under the precision-recall curve (AUPRC) of 0.892. The results indicate that the best model was DenseNet169 (AUROC 0.895 and AUPRC 0.918). The deep learning model, general physicians, and oncology specialists had sensitivities of 81.1%, 77.3%, and 91.7%; specificities of 86.8%, 75.0%, and 90.9%; and accuracies of 84.7%, 75.9%, and 91.2%, respectively. Meanwhile, fair agreement between the oncologist and the developed model was shown for cancer diagnosis (kappa value = 0.685). The deep learning model developed based on the verified endoscopic image dataset showed acceptable performance in tongue cancer diagnosis.

A Personalized 3D-Printed Model for Obtaining Informed Consent Process for Thyroid Surgery: A Randomized Clinical Study Using a Deep Learning Approach with Mesh-Type 3D Modeling.

The aim of this study was to evaluate the usefulness of a personalized 3D-printed thyroid model that characterizes a patient's individual thyroid lesion. The randomized controlled prospective clinical trial (KCT0005069) was designed. Fifty-three of these patients undergoing thyroid surgery were randomly assigned to two groups: with or without a 3D-printed model of their thyroid lesion when obtaining informed consent. We used a U-Net-based deep learning architecture and a mesh-type 3D modeling technique to fabricate the personalized 3D model. The mean 3D printing time was 258.9 min, and the mean price for production was USD 4.23 for each patient. The size, location, and anatomical relationship of the tumor and thyroid gland could be effectively presented using the mesh-type 3D modeling technique. The group provided with personalized 3D-printed models showed significant improvement in all four categories (general knowledge, benefits and risks of surgery, and satisfaction; all p < 0.05). All patients received a personalized 3D model after surgery and found it helpful to understand the disease, operation, and possible complications and their overall satisfaction (all p < 0.05). In conclusion, the personalized 3D-printed thyroid model may be an effective tool for improving a patient's understanding and satisfaction during the informed consent process.

Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells.

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.

Wireless parathyroid detection device using autofluorescence and smart glasses: A preliminary study.

BACKGROUND: Autofluorescence imaging technology has been utilized for preserving or identifying parathyroid glands (PTGs) during thyroid surgery. We developed a wireless PTGs detection device linked with smart glasses that allows for real-time video recording and screen switching according to the light source. OBJECTIVE: This study aimed to confirm the feasibility of the device and whether it would help preserve the PTG during the surgery. METHODS: This prospective study was conducted in 30 patients with 66 PTGs. The device's agreement with the physician's judgment was evaluated, and we determined how many PTGs were preserved from thyroidectomy. RESULTS: The positive agreement rate for PTGs detection between the surgeon and device was 70.9%. Inadvertent parathyroidectomy was identified in surgical specimens of 6 patients (20%). No PTG was removed when it was confirmed by the device (0/39). Of the 27 glands not detected by the device, there was inadvertent removal of 6 PTGs. CONCLUSIONS: PTGs can be preserved successfully when the detection of them by the device is consistent with the surgeon's discretion. A large-scale controlled study is necessary to demonstrate the practical effect of this device on hypoparathyroidism after thyroidectomy.

The emergence of oral cavity cancer and the stabilization of oropharyngeal cancer: Recent contrasting epidemics in the South Korean population.

BACKGROUND: By analyzing the recent epidemiologic trajectory of head and neck squamous cell carcinoma (HNSCC) in South Korea, we tracked 2 findings that have been reported recently in other countries: the stabilization of human papillomavirus (HPV)-related HNSCC incidence and the acceleration of oral cavity cancer incidence. METHODS: We analyzed data from the comprehensive population-based Korean Central Cancer Registry for the period 1999 to 2017. The age-standardized incidence rate (ASR), annual percent change (APC), and relative survival were calculated. RESULTS: The ASR of total HNSCC decreased from 1999 to 2017 (APC, -0.2 [95% CI, -0.3 to -0.0]), as did the ASR of HPV-unrelated HNSCC (APC, -0.6 [95% CI, -0.8 to -0.5]); however, the ASR of HPV-related HNSCC increased (APC, 2.9 [95% CI, 2.5 to 3.2]). The rapidly increasing incidence of tonsil squamous cell carcinoma, which was the main subsite of HPV-related HNSCC, stabilized after 2011 (APC pre-2011, 6.8 [95% CI, 5.0 to 8.3]; APC post-2011, 1.6 [95% CI, -2.1 to 5.5]), and the difference was significant (P = .017). In contrast, oral cavity cancer incidence demonstrated the only increase among HPV-unrelated subsites, with the increase occurring after 2006 (APC pre-2006, 1.6 [95% CI, 0.3 to 2.8]; APC post-2006, 2.8 [95% CI, 2.2 to 3.5]); the main cause of this change was an increase in the ASR of tongue cancer. CONCLUSION: This study demonstrates the recent stabilization of tonsil cancer incidence and the contrasting increase in oral cavity cancer incidence, unlike other HPV-unrelated cancers. These trends require further surveillance and understanding in terms of tumor biology and prevention.

Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer.

OBJECTIVE: Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs). STUDY DESIGN: Retrospective cohort study. SETTING: A comprehensive cancer center. METHODS: Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection. RESULTS: Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all P < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients (P < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients. CONCLUSION: Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence. LEVEL OF EVIDENCE: 4.

Endoscopically Applied Biodegradable Stent in a Rabbit Model of Pediatric Tracheomalacia.

OBJECTIVES: A polydioxanone (PDO) stent was developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia-model rabbits. METHODS: In total, 29 New Zealand white rabbits were used: 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. The tracheomalacia model was successfully established in 12 rabbits, and PDO stents were placed in eight of those rabbits. RESULTS: The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and the mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia-model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0±6.8 and 1.0±0.8 days, respectively. Thus, the PDO stent yielded a significant survival gain (P=0.001). In the tracheomalacia rabbits, stent degradation and granulation tissue were observed 7 weeks after placement, leading to airway collapse and death. CONCLUSION: We successfully developed a PDO stent and an endoscopic guide placement system. The degradation time of the stent was around 10 weeks in normal rabbits, and its degradation was accelerated in the tracheomalacia model. The mucosal changes associated with PDO stent placement were reversible. Placement of the PDO stent prolonged survival in tracheomalacia-model rabbits.

Singing voice range profile: New objective evaluation methods for voice change after thyroidectomy.

BACKGROUND: After surgery in the thyroid region, patients may present with phonation or singing difficulty, even within their vocal range. We designed a novel voice evaluation method that reflects subjective and objective voice complications of the surgery. METHODS: This tool recorded patients' voice ranges while singing, which was named the singing voice range profile (singing VRP). Patients were asked to sing "Happy Birthday," which has a one-octave scale, at a comfortable tone and intensity. The singing VRP, standard VRP and voice handicap index-10 (VHI-10) results were recorded before thyroidectomy and 1 and 3 months after thyroidectomy for 128 patients. For subgroup analysis, a group where the maximum F0 of standard VRP in 1 month postoperatively was lower than the highest singing F0 of the preoperative singing VRP was defined as "Collapsed group" and the other group was "Preserved group." RESULTS: The changes in the highest, lowest and range of singing fundamental frequency (F0 ) had decreased at 1 month postoperatively. Subsequently, they had improved significantly at 3 months postoperatively but were lower than those preoperatively (all P < .05, except for the change in the lowest singing F0 between 1 and 3 months postoperatively, P = .274). In the subgroup analysis, the singing range of the collapsed group (n = 65) showed significantly lower VHI-10 scores, range of vocal F0 and singing F0 than those of the preserved group (n = 63) at 1 and 3 months postoperatively (all P < .001). At 3 months postoperatively, the singing F0 range in the preserved group had recovered to the range before surgery (13.0 ± 1.3 vs. 13.1 ± 1.4, P = .746 for the preserved group, and 13.0 ± 1.3 vs 11.5 ± 2.4, P < .001 for the collapsed group). CONCLUSIONS: Parameters measured by singing VRP showed a trend similar to the change in VHI-10 and the maximum F0 of standard VRP. In addition, singing VRP allowed a qualitative classification of the postoperative voice function when combined with standard VRP. Therefore, it can be used as a supplementary voice evaluation tool to reflect the physiologic and functional aspects of voice.

Prognostic Implication of SOX2 Expression Associated with p16 in Oropharyngeal Cancer: A Study of Consecutive Tissue Microarrays and TCGA.

For oropharyngeal squamous cell carcinoma (OPSCC), there are not enough additional robust biomarkers for subgrouping after the distinct classification using p16. As SOX2 is an emerging biomarker for cancer treatment, its clinical implication in OPSCC was evaluated using a consecutive tissue microarray (TMA) cohort consisting of 111 patients who underwent surgery as an initial treatment from May 2002 to December 2016 and 79 patients in The Cancer Genome Atlas (TCGA) dataset. In both datasets, p16+/SOX2High (HPV+/SOX2High in TCGA) showed the best prognosis among the four groups classified by SOX2 and p16 for 5-year overall survival (OS) and recurrence (all p < 0.05), but SOX2 did not make a significant difference in the prognosis of the p16- group. In the TMA cohort, SOX2High was significantly correlated with response to radiotherapy and lower pathologic T classification in the p16+ group (p = 0.001). In TCGA, correlations between SOX2 and tumor stage classification or radiotherapy were not observed; however, HPV+/SOX2High had a significantly low tumor mutation burden among the four groups (all p < 0.05). In summary, SOX2 was proven to be a potential marker to predict overall survival and recurrence in p16+ OPSCC. However, the role of SOX2 has not yet been confirmed in p16- OPSCC patients.

Novel robot-assisted thyroidectomy by a transaxillary gas-insufflation approach (TAGA): a preliminary report.

BACKGROUND: Robot-assisted transaxillary approaches to thyroidectomy have been well described. They have an advantage over the breast approach in that a circumareolar incision is avoided. However, they require a single long axillary incision to accommodate all 3 robotic arms and provide adequate visualization of the area around the thyroid. The purpose of this study was to test the feasibility of the robot-assisted transaxillary gas-insufflation approach (TAGA) and to attempt reducing the size of the scar. METHODS: We evaluated 47 patients who underwent robot-assisted thyroid lobectomy via TAGA from July 2015 to Aug 2017. The following variables were studied: patients' demographics, operative time according to each operation step, volume of drainage, duration of hospitalization, and perioperative complications. RESULTS: The mean age of all patients was 42.4±9.1 years. The mean total volume of drainage was 195.4±70.9 mL, and the duration of postoperative stay was 3.0±1.1 days. Two cases (4.3%) of transient vocal cord palsy and 2 cases (4.3%) of seroma were identified postoperatively. There was no post-operative cosmetic problem at the skin incisions made in the axilla. CONCLUSIONS: Robot-assisted thyroid lobectomy via TAGA is technically feasible while achieving good cosmetic results. TAGA can be an alternative robot-assisted method for thyroidectomy.

Feasibility of Brachial Plexus Schwannoma Enucleation With Intraoperative Neuromonitoring.

OBJECTIVES: To evaluate the feasibility of brachial plexus schwannoma enucleation under intraoperative neuromonitoring. METHODS: Five patients who were treated for brachial plexus schwannoma under intraoperative neuromonitoring from 2008 to 2018 were included in this retrospective review. Neuromonitoring was performed with a 100-µV event threshold of the neuromonitoring system (NIM-2 or 3) at the deltoid, biceps brachii, triceps brachii, and brachioradialis muscles. Patient characteristics, tumor size and location, intraoperative neuromonitoring findings, and postoperative function were evaluated. RESULTS: The intraoperative neuromonitoring findings were in accordance with the preoperative assessment of the included nerve root. Three patients had no postoperative morbidity, one patient had temporary paresthesia of the forearm for 2 months, and one patient mild loss of grip strength for 1 month. CONCLUSION: Intraoperative neuromonitoring of the arm and forearm muscles during enucleation of brachial plexus schwannoma promoted confident and successful surgery with minimal postoperative morbidity.

Significant Mendelian genetic contribution to pediatric mild-to-moderate hearing loss and its comprehensive diagnostic approach.

PURPOSE: Timely diagnosis and identification of etiology of pediatric mild-to-moderate sensorineural hearing loss (SNHL) are both medically and socioeconomically important. However, the exact etiologic spectrum remains uncertain. We aimed to establish a genetic etiological spectrum, including copy-number variations (CNVs) and efficient genetic testing pipeline, of this defect. METHODS: A cohort of prospectively recruited pediatric patients with mild-to-moderate nonsyndromic SNHL from 2014 through 2018 (n = 110) was established. Exome sequencing, multiplex ligation-dependent probe amplification (MLPA), and nested customized polymerase chain reaction (PCR) for exclusion of a pseudogene, STRCP, from a subset (n = 83) of the cohort, were performed. Semen analysis was also performed to determine infertility (n = 2). RESULTS: Genetic etiology was confirmed in nearly two-thirds (52/83 = 62.7%) of subjects, with STRC-related deafness (n = 29, 34.9%) being the most prevalent, followed by MPZL2-related deafness (n = 9, 10.8%). This strikingly high proportion of Mendelian genetic contribution was due particularly to the frequent detection of CNVs involving STRC in one-third (27/83) of our subjects. We also questioned the association of homozygous continuous gene deletion of STRC and CATSPER2 with deafness-infertility syndrome (MIM61102). CONCLUSION: Approximately two-thirds of sporadic pediatric mild-to-moderate SNHL have a clear Mendelian genetic etiology, and one-third is associated with CNVs involving STRC. Based on this, we propose a new guideline for molecular diagnosis of these children.

Papillary Thyroid Cancers of the Thyroid Isthmus: The Pattern of Nodal Metastasis and the Significance of Extrathyroidal Extension.

BACKGROUND: Cancers of the thyroid isthmus are less frequent compared with the lobar cancers yet have their own unique clinicopathological characteristics. Herein, we sought to examine the isthmic papillary thyroid carcinomas (PTCs) for the pattern of and risk factors for nodal metastasis and the significance of extrathyroidal extension (ETE). METHODS: The medical records of 3138 patients diagnosed with solitary PTC who had undergone surgery were retrospectively reviewed. Of these, 122 isthmic PTCs were matched to common lobar PTCs at a ratio of 1:3 for age, sex, and nodule size. Patient demographics, surgical findings, and pathology reports were analyzed. RESULTS: Isthmic PTCs comprised 4.6% of all PTCs and had more lymphatic invasion (22.1% vs. 13.4%, p = 0.021), ETE (73.0% vs. 57.1%, p = 0.002), and perithyroidal and prelaryngeal node metastasis (18.0% vs. 9.0%, p = 0.006) compared with lobar PTCs. However, there were no significant differences in the rate of central and lateral node metastasis between the two groups. ETE was identified not to be a risk factor for isthmic PTCs for central and lateral node metastasis, in contrast to lobar PTCs in which ETE was a significant risk factor (odds ratio 3.18, 95% confidence interval [CI] 1.89-5.34; and 4.72, 95% CI 1.04-21.41). CONCLUSION: The rates of central and lateral node metastasis of isthmic PTCs are comparable with that of lobar PTCs despite a higher rate of ETE in the isthmic counterpart. Although the extent of surgery for isthmic PTCs remains to be investigated, careful dissection of perithyroidal and prelaryngeal nodes may be necessary for isthmic PTCs.

Natural Course of Unilateral Vocal Fold Paralysis and Optimal Timing of Permanent Treatment.

Importance: Permanent surgical treatment for unilateral vocal fold paralysis (UVFP) should be performed when further neural recovery is improbable. Conservative delay of the surgical procedure may cause unnecessary deterioration of the patient's quality of life. Knowledge of the natural course of UVFP is important for better management and counseling. Objective: To evaluate the natural course of UVFP, focusing on the recovery time according to the injury level to assess the optimal timing for permanent surgical intervention. Design, Setting, and Participants: This retrospective case series enrolled 1264 patients with UVFP who visited the voice clinic of Seoul National University Hospital, Seoul, Korea, from November 1, 2005, through December 31, 2016. Medical records and stroboscopic video images were reviewed to obtain data on demographic characteristics, vocal fold movement, onset and recovery time, follow-up duration, and cause. Cases of UVFP were classified into 5 groups based on the location of injury: distal to the thyroid level, thyroid level, esophagus and mediastinum level, heart and lung level, and proximal to the thorax level. Data analysis was performed from January 23, 2018, to May 21, 2018. Main Outcomes and Measures: Recovery of vocal fold movement defined as more than vocal fold twitching confirmed by stroboscopy video images, estimated injury level, and start time of recovery. The recovery time was analyzed according to age, sex, paralytic side, and 5 injury levels. Results: Of 1264 eligible patients with UVFP (655 [51.8%] male; median age, 56 years [range, 1-90 years]), 208 had evidence of recovery with the recovery time relatively accurate. The maximum recovery time for the group with distal to the thyroid-level injury was 120 days; the group with thyroid-level injury, 157 days; the group with esophagus and mediastinum-level injury, 244 days; the group with heart and lung-level injury, 328 days; and the group with proximal to the thorax-level injury, 333 days with the exception of 1 outlier value (482 days). Recovery time did not differ according to age, sex, or paralytic side. As distance between the vocal fold and injury level increased, the maximum recovery time increased, plateauing at 1 year. Among the patients who showed recovery of the vocal fold movement, most patients with injuries distal to or at the level of the thyroid recovered within 6 months, whereas those with injury more distant from the vocal fold recovered within approximately 1 year. Conclusions and Relevance: A linear association between injury level and maximum recovery time was observed. The findings suggest that the decision to proceed with permanent phonosurgical treatment should be based on the level of injury associated with UVFP.