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Abstract Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P

Objectives. Facial nerve sacrifice during radical parotidectomy can impair quality of life. This study assessed the effectiveness of single-stage facial reanimation surgery performed concurrently with radical parotidectomy in restoring facial function. Methods. A retrospective analysis was conducted on patients who underwent single-stage facial reanimation combined with radical parotidectomy. The techniques employed included selective reinnervation and orthodromic temporalis tendon transfer. Outcomes were evaluated using the modified House-Brackmann and Terzis grading systems, Emotrics facial assessment, and the Facial Disability Index (FDI). Results. Among the 13 patients studied (median age, 54 years; 69% male), 10 underwent selective reinnervation. Of these, nine patients demonstrated improvement, achieving House-Brackmann grade III and Terzis grade 4 or 5. The other three patients underwent tendon transfer and achieved moderate functional outcomes. Emotrics analysis revealed balanced facial symmetry in the selective reinnervation group. Furthermore, FDI scores indicated satisfactory physical and social/well-being functions. Conclusion. Single-stage facial reanimation effectively restores facial function in patients undergoing radical parotidectomy. This approach offers meaningful benefits in the early recovery of facial function.

Abstract Obstructive sleep apnea (OSA) is closely associated with the development and chronicity of temporomandibular disorder (TMD). Given the intricate pathophysiology of both OSA and TMD, comprehensive diagnostic approaches are crucial. This study aimed to develop an automatic prediction model utilizing multimodal data to diagnose OSA among TMD patients. We collected a range of multimodal data, including clinical characteristics, portable polysomnography, X-ray, and MRI data, from 55 TMD patients who reported sleep problems. This data was then analyzed using advanced machine learning techniques. Three-dimensional VGG16 and logistic regression models were used to identify significant predictors. Approximately 53% (29 out of 55) of TMD patients had OSA. Performance accuracy was evaluated using logistic regression, multilayer perceptron, and area under the curve (AUC) scores. OSA prediction accuracy in TMD patients was 80.00–91.43%. When MRI data were added to the algorithm, the AUC score increased to 1.00, indicating excellent capability. Only the obstructive apnea index was statistically significant in predicting OSA in TMD patients, with a threshold of 4.25 events/h. The learned features of the convolutional neural network were visualized as a heatmap using a gradient-weighted class activation mapping algorithm, revealing that it focuses on differential anatomical parameters depending on the absence or presence of OSA. In OSA-positive cases, the nasopharynx, oropharynx, uvula, larynx, epiglottis, and brain region were recognized, whereas in OSA-negative cases, the tongue, nose, nasal turbinate, and hyoid bone were recognized. Prediction accuracy and heat map analyses support the plausibility and usefulness of this artificial intelligence-based OSA diagnosis and prediction model in TMD patients, providing a deeper understanding of regions distinguishing between OSA and non-OSA.

Abstract The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

The relationship between tumor microenvironments (TMEs) of regional lymph node metastases (LNMs) and primary tumors in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study compared tumor-infiltrating lymphocytes (TILs) and the immune phenotype (IP), characterized by spatial TIL distribution, between primary tumors and LNMs. Twenty-one HNSCC patients with regional LNM who received immune checkpoint inhibitors (ICIs) were included. A paired comparative analysis of TIL densities and IP between primary tumors and LNMs revealed no significant difference or correlation between TIL densities in primary tumors and LNMs. Their IPs were discordant in 12 patients (57.1%). Patients with high intratumoral TIL exhibited longer progression-free survival (PFS) than those with low intratumoral TIL in both primary tumors (median, 5.2 vs. 1.3 months, p = 0.003) and LNMs (median, 30.2 vs. 1.3 months, p = 0.012). Patients with inflamed IP exhibited longer PFS than those with non-inflamed IP in both primary tumors (median, 4.5 vs. 1.3 months, p = 0.043) and LNMs (median, 4.1 vs. 1.3 months, p = 0.037). Given the lack of correlation in TIL densities, the discrepancies in IP, and the predictive value of both TMEs, evaluating the TMEs of both primary tumors and LNMs may be beneficial for the precise use of ICIs in HNSCC. There was a significant discordance between the TME of primary tumors and LNMs, with implications in survival outcomes. Therefore, evaluating the TME of both the primary tumor and LNM could be beneficial for the precise use of ICIs in HNSCC.

Objectives This study aimed to assess predictors of the response to varying durations of proton pump inhibitor (PPI) use and lifestyle modification treatment for laryngopharyngeal reflux disease (LPRD). Methods Between October 2014 and June 2016, a prospective, multicenter, open-label, single-cohort, intention-to-treat, observational study was conducted at eight referral hospitals across the Republic of Korea to examine predictors of early and late response to treatment in adult patients (age ≥19 years) with LPRD. Participants underwent standard treatment (PPI [Esomezol] and lifestyle modification) for 3 months. Response to treatment was defined as greater than 50% improvement in reflux symptom index score. The primary outcome was potential predictors of treatment response at 1 and 3 months. The secondary outcome was potential predictors distinguishing early from late responders. Results In total, 394 patients were enrolled. Improved sleep habits was a positive predictor (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.06–3.007; P=0.029), while initial alcohol consumption (OR, 0.587; 95% CI, 0.355–0.969; P=0.037) and past medication history (OR, 0.438; 95% CI, 0.215–0.891; P=0.005) were negative predictors of response after 1 month of treatment. High pre-reflux finding score was a positive predictor (OR, 1.187; 95% CI, 1.049– 1.344; P=0.007), while male sex (OR, 0.516; 95% CI, 0.269–0.987; P=0.046), higher depression score (OR, 0.867; 95% CI, 0.784–0.958; P=0.005), and past thyroid hormone medication history (OR, 0.161; 95% CI, 0.033–0.788; P=0.024) were negative predictors of response after 3 months of treatment. Past medication history (OR, 0.438; 95% CI, 0.215–0.891; P=0.023) was the only negative predictor for early responders compared to late responders. Conclusion Adult patients with LPRD and a history of prior medication use may require longer treatment durations to achieve a therapeutic response. Future research should explore the incorporation of diverse treatment approaches to improve treatment outcomes for patients exhibiting negative prognostic indicators.

Objectives Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. Results Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Abstract Background Control of 3D printing of highly tough hydrogel inks with adequate printability, scaffold fidelity and mechanical properties are highly desirable for biomedical and tissue engineering applications. However, developing a biocompatible tough ink with high-resolution printability, biodegradability, self-healing, adhesion, and integration with surrounding tissues is a big challenge in 3D printing. The aim of this study was to develop extrusion-based 3D printing of viscous hydrogel composing of maleic acid and propylene diepoxide by controlling continuous mechanisms of condensation and radical polymerization. Methods The molecular weight of highly adhesive propagating poly(malate-co-propylene oxide) copolymer was controlled by capping its growing chain with mono-functional lipoic acid with different compositions during condensation reaction to form lipoic acid capped gel (LP-capped gel). Poly(ethylene oxide)-diacrylate, PEGDA, is graft-polymerized to the LP-capped backbone polymer (MPLE gel) by UV irradiation during 3D printing process to control the properties of gel printability, mechanical properties, and cell adhesiveness and post-printing fidelity of the printed scaffolds with high resolution and mechanical properties (MPLE scaffold). The scaffolds in complex geometries have been printed out in diverse forms with addition of model drugs with different molecular weights and chemical structures. Both the highly adhesive LP-capped gel and printing-controlled MPLE gel/scaffolds are diversely characterized and compared with for their applications to the extrusion-based printability, including biocompatibility, self-healing, drug releasing, adhesiveness, multi-layered high-resolution printing. Further in vitro/in vivo tests were done to observe cytotoxicity, immune response and tissue formation by using different cells in mice model. Results LP-capped hydrogel from maleic acid and propylene diepoxide gel showed control of gel properties with lipoic acid with one function group of thiol during condensation reaction, and the ratio at 1:0.3 (w/v) between LP-capped gel and PEGDA was chosen for the optimal results during radical polymerization process for 3D printing at high resolution (90-140 μm in strut thickness) with various complex geometries (lattice, rhombus, and honeycomb). The hydrogel showed excellent properties of self-healing, mechanical strength, biocompatibility, etc. In addition, the long-term release profiles of bioactive molecules were well-controlled by incorporating drugs of high molecular bovine serum albumin (BSA, 21 days, 98.4 ± 0.69%), or small molecule ornidazole (ORN, 14 days, 97.1 ± 1.98%) into the MPLE gel scaffolds for the tests of potential therapeutic applications. More importantly, the MPLE gels represents excellent in vitro cyto-compatibility against osteoblast-like cells (MC3T3) with viability value at 96.43% ± 7.48% over 7 culturing days. For in-vivo studies, the flexible MPLE scaffolds showed significant improvement on angiogenesis with minor inflammatory response after 4-week implantation in mice. Conclusion The MPLE gel inks was well-controlled for the fabrication of flexible complex tissue engineering scaffold with high resolutions, shear-thinning, 3D printability and post-printing fidelity, by modulating the composition of the highly adhesive LP-capped gel and inert PEGDA as well as end capping of lipoic acid to the propagating poly(malate-co-propylene oxide) copolymer. The gel ink demonstrated its excellent printability, in vitro/in vivo biocompatibility and mechanical properties as well as sustained drug release from the gel. Graphical Abstract

Objectives. We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. Methods. In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. Results. No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. Conclusions. Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Abstract Objective The aim of this study was to report the incidence and clinical course of a series of patients who were misdiagnosed with Bell’s palsy and were eventually proven to have occult neoplasms. Methods Two hundred forty patients with unilateral facial paralysis who were assessed at the facial nerve reanimation clinic, Victoria Hospital, London Health Science Centre, from 2008 through 2017 were reviewed. Persistent paralysis without recovery was the presenting complaint. Results Nine patients (3.8%) who were proven to have occult neoplasms initially presented with a diagnosis of Bell’s palsy. The mean diagnostic delay was 43.5 months. Four patients were proven to have skin cancers, 3 patients had parotid cancers, and 2 patients had facial nerve schwannomas as a final diagnosis. Initial magnetic resonance imaging (MRI) was performed in all 9 patients and 8 underwent a follow-up MRI. An occult tumor was identified upon review of the original MRI in one patient and at follow-up MRI in 8 patients. The mean time interval between the initial and follow-up imaging was 30.8 months. The disease status at most recent follow-up were no evidence of disease in 2 patients (22%) and alive with disease in 7 patients (78%). An irreversible, progressive pattern of facial paralysis combined with pain, multiple cranial neuropathies or history of skin cancer were predictable risk factors for occult tumors. Seven out of the 9 patients (77.8%) underwent at least one type of facial reanimation surgery, and the final subjective results by the surgeon were available for 5 patients. Three out of the 5 (60%) patients who were available for final subjective analysis were reported as Grade III according to the modified House-Brackmann scale. Conclusion Occult facial nerve neoplasm should be suspected in patients with progressive and irreversible facial paralysis but the diagnosis may only become evident with follow-up imaging. Facial reanimation surgery is a satisfactory option for these patients. Graphical abstract

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.

Purpose Hypoparathyroidism (hypoPTH) is the most common complication following thyroidectomy. We investigated the frequency and risk factors of hypoPTH after total thyroidectomy (TT) in pediatric patients with thyroid cancer. Methods This retrospective study included 98 patients younger than 20 years who were diagnosed with thyroid cancer after T T during 1990–2018 and followed for more than 2 years at Seoul National University Hospital. HypoPTH was defined as receiving active vitamin D (1-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol) after surgery. Results The study included 27 boys (27.6%) and 71 girls (72.4%). The mean age at diagnosis was 14.9±3.7 years. HypoPTH occurred in 43 patients (43.9%). Twenty-one patients (21.4%) discontinued active vitamin D less than 6 months after surgery, while 14 (14.3%) continued active vitamin D for more than 2 years. Tumor multifocality (odds ratio [OR], 3.7 vs. single tumor; P=0.013) and preoperative calcium level (OR, 0.2; P=0.028) were independent predictors of hypoPTH immediately after TT. In addition, age (OR, 0.8; P=0.011) and preoperative calcium level (OR, 0.04; P=0.014) significantly decreased the risk for persistent hypoPTH requiring active vitamin D for more than 2 years. Conclusions HypoPTH occurred in 43.9% of pediatric thyroid cancer patients after TT in this study. Among them, one-third of patients continued active vitamin D medication for more than 2 years, which was predicted by young age and low preoperative calcium level.

Objectives Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Abstract 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.

Abstract Background Unilateral vocal cord paralysis may result from nerve compression by tumors or direct nerve injuries during tumor resections, which can cause dysphonia or dysphagia, and reduced quality of life. Objectives This prospective, single‐group study aimed to investigate the effect of percutaneous injection laryngoplasty on voice and swallowing function in patients with cancer‐related unilateral vocal cord paralysis. Methods Patients underwent percutaneous injection laryngoplasty with hyaluronic acid under local anesthesia. Stroboscopy and videofluoroscopic swallowing study were conducted to evaluate the voice‐ and swallowing‐related outcome measures, respectively. The participants were evaluated before injection laryngoplasty, as well as after two weeks and three months. Results Injection laryngoplasty significantly improved the glottal gap, vocal fold position, Maximum Phonation Time, and Voice Handicap Index‐10. Post‐hoc analysis using Bonferroni correction showed that the improvements occurred within two post‐treatment weeks and remained at three post‐treatment months. In the subgroup analysis, the patients who underwent injection laryngoplasty within 8 weeks from onset showed significantly higher improvements in the videofluoroscopic dysphagia scale and swallowing function than the patients who received the procedure after 8 weeks or more. Conclusion Percutaneous injection laryngoplasty improves glottal closure and voice in patients with cancer‐related unilateral vocal cord paralysis. Early injection laryngoplasty may lead to greater benefits on swallowing function. Level of Evidence 4.

Abstract Objective This study aimed to analyze the usefulness of an additional axillary port in robotic retroauricular thyroidectomy by comparing the perioperative data and postoperative function between the operations with and without an additional axillary port. Materials and methods A retrospective review of the medical records of 11 patients who underwent robotic thyroid operations using a unilateral retroauricular approach with or without an additional axillary port between 2016 and 2021 was conducted. Patient demographics, operation time, drainage amount, hospital stay, complication, postoperative cosmetic satisfaction, and postoperative neck and shoulder pain were analyzed. Results Among the 11 patients who underwent robotic retroauricular thyroidectomy, an additional axillary port was used in 6 patients and not used in 5 patients. The total operation time was significantly shorter in the axillary port group (174.5 ± 23 minutes) compared to the without the axillary port group (207.6 ± 20.1 minutes) (P = .033). The intraoperative estimated blood loss (P = .525), total amount of drainage (P = .172), and postoperative hospital stays (P = .092) were not different between the 2 groups. There was no postoperative recurrent laryngeal nerve palsy, hypoparathyroidism, hematoma, seroma in the two groups. There was no significant difference for either group in the pain score and cosmetic satisfaction at 2 weeks (P = .378, P = .650) and 6 weeks (P = .242, P = .546) postoperatively. Conclusion Robotic retroauricular thyroidectomy using an additional axillary port was a novel, safe, and feasible procedure. Dissection was easy due to the availability of the fourth robotic arm to retract the thyroid gland. Level of Evidence: 4.

Background/Aims Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor characterized by indolence, with a high rate of local recurrence and distant metastasis. This study aimed to investigate the effect of concurrent chemoradiation (CCRT) on locally advanced unresectable ACC. Methods We retrospectively analyzed clinical data from 10 patients with pathologically confirmed ACC of the head and neck who received CCRT with cisplatin in Seoul National University Hospital between 2013 and 2018. Results Ten patients with unresectable disease at the time of diagnosis or with positive margins after surgical resection received CCRT with weekly cisplatin. Eight patients (80%) achieved complete remission, of which three later developed distant metastases without local relapse; one patient developed distant metastasis and local relapse. Two patient achieved partial remission without progression. Patients experienced several toxicities, including dry mouth, radiation dermatitis, nausea, and salivary gland inflammation of mostly grade 1 to 2. Only one patient showed grade 3 oral mucositis. Median relapse-free survival was 34.5 months (95% confidence interval, 22.8 months to not reached). Conclusions CCRT with cisplatin is effective for local control of ACC with manageable toxicity and may be an effective treatment option for locally advanced unresectable ACC.

Background/Aims Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. Methods Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. Results A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3–4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). Conclusions Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) come with a dismal prognosis. Here, Yoo and colleagues reveal the genomic and transcriptomic landscape of ATC and DTC, highlighting potential therapeutic vulnerabilities.

Abstract Background Hybrid scaffolds combining biodegradable polymers and ceramic particles for control of cell adhesion and proliferation are interesting materials for tissue engineering applications. Combinations of biodegradable polymers and ceramics are to provide higher beneficial functionalities to tissue engineering scaffolds with addition of different cell specific bio-factors. Many such hybrid combinations have been reported by several researchers around the world by using various methods and solvents as well as bioactive matrix polymers to fabricate such biomaterials. However, thin hybrid scaffolds with high porosity, cell adhesion factors and biodegradability, as well as the ability to support stem cells often require tedious processes like electrospinning, freeze drying, etc. A simple method to develop porous biodegradable hybrid scaffolds with proper cell adhesion factors is still the need of the hour in tissue engineering and regenerative medicine. Method Thin biodegradable poly(ε-caprolactone) (PCL) based hybrid scaffolds were developed in combination with α-tricalcium phosphate (TCP) particles, gelatin and fibronectin separately and the fabricated scaffolds were evaluated systematically using human mesenchymal stem cells (hMSCs) for tissue engineering applications. A simple modified solvent casting method combined with gas foaming process was used to develop porous thin hybrid structures and compared their properties with those of corresponding non-porous hybrid scaffolds. The TCP particles distribution, morphology, biodegradability and functional groups of the different hybrid scaffolds were analyzed using energy-dispersive X-ray spectroscopy (EDX), light microscopy/scanning electron microscopy (SEM), buffer solutions and Fourier-transform infrared spectroscopy (FTIR), respectively The cellular and tissue regeneration behaviors such as in vitro cell attachment (live/dead assay), cell proliferation (CCK-8 assay) and histological studies were performed using hMSCs. Results Thin PCL-based hybrid scaffolds were fabricated using modified solvent casting method. Homogeneous distribution of TCP particles in the scaffolds were confirmed by EDX. Cellular interactions of the hybrid scaffolds demonstrated overall higher cell adhesion, proliferation and tissue regeneration on the non-porous thin films of PCL-TCP, PCL-TCP-gelatin and PCL-TCP-fibronectin. Coating of fibronectin was remarkable in induction of cell adhesion and proliferation. Conclusions The experimental results revealed that diversely designed PCL-TCP thin hybrid films showed high cell interaction and proliferation with hMSCs. From the results of the cell viability, attachment, proliferation and histological analyses as well as their biodegradation and coating effects, we conclude that these thin PCL-TCP hybrid films are suitable for tissue engineering applications.

The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration.

ObjectivesThe purpose of study was to report the current role of transnasal esophagoscopy (TNE) in Korea.MethodsOne hundred thirty-seven patients who underwent TNE at Soonchunhyang University Bucheon Hospital (n=69) and Korea University Anam Hospital (n=68) from July 2007 to February 2009 were prospectively analyzed. Laryngopharyngeal reflux disease (LPRD) patients without any response to proton-pump inhibitor (n=102), and patients with complaints that require esophagoscopy as part of their evaluation (n=35) were included in this study; investigation of metachronous lesions or routine follow-up screening of head and neck cancer patients, n=17; dysphagia, n=9; blood tinged saliva, n=4; to determine the cause of vocal fold paralysis as screening tool, n=4; suspicious esophageal foreign body, n=1.ResultsFifty-three patients (38.7%) had positive findings on TNE. Positive finding ratio was highest in group of dysphagia (7 among 9 patients, 78%). Forty-two patients (41.1%) were found to have pathology (esophagitis, n=41; esophageal diverticulum, n=1) during the screening examination for LPRD. There were no significant complications in any of the patients.ConclusionTNE is a high-yield diagnostic and therapeutic modality available to otolaryngologists for use on awake patients in the office setting.

ObjectivesThe purpose of study was to determine the clinical efficacy of primary tumor volume measurements of different primary sites in the oropharynx compared to the oral cavity.MethodsA retrospective analysis of 85 patients with oral cavity or oropharynx cancer. The tumor area was manually outlined from axial magnetic resonance (MR) series. The software calculated the tumor volumes, automatically. The values of the primary tumor volumes were then subdivided into separate groups (≤3,500 mm3, >3,500 mm3).ResultsThe prognostic indicators were the cT and cN (oral cavity); age, primary site, cT, cN, and primary tumor volume (oropharynx) on the univariate analysis. There was no significant prognostic factor for oral cavity cancer on the multivariate analysis. Primary site, cN, and primary tumor volume were independent prognostic indicators for oropharynx cancer by multivariate analysis.ConclusionPrimary tumor volume measurement is a reliable way to stratify outcome, and make up for the weak points in the American Joint Committee on Cancer staging system with oropharynx cancer.

Neuroendocrine neoplasm of the larynx is a morphologically heterogeneous group of tumors. This unusual neoplasm includes the four different type of tumors. Paraganglioma is the best-known neural origin tumor. The epithelial origin tumor is further divided based on the degree of differentiation into well, moderately, and poorly differentiated carcinoma. The diverse biological behavior of neuroendocrine neoplasm of larynx makes an accurate diagnosis of paramount importance, since treatment depends on diagnostic accuracy. The diagnosis is based primarily on light microscopy, and immunohistochemical and/or ultrastructural investigations are needed to diagnose correctly. The mainstay of treatment of moderately differentiated neuroendocrine carcinoma of the larynx is surgery. Elective neck treatment should be performed considering the high likelihood of cervical lymph node metastases. The 5-yr survival rate approximates 50%, and 10-yr survival rate is only 30%.

Purpose: Hypoparathyroidism (hypoPTH) is the most common complication following thyroidectomy. We investigated the frequency and risk factors of hypoPTH after total thyroidectomy (TT) in pediatric patients with thyroid cancer. Methods: This retrospective study included 98 patients younger than 20 years who were diagnosed with thyroid cancer after TT during 1990–2018 and followed for more than 2 years at Seoul National University Hospital. HypoPTH was defined as receiving active vitamin D (1-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol) after surgery. Results: The study included 27 boys (27.6%) and 71 girls (72.4%). The mean age at diagnosis was 14.9±3.7 years. HypoPTH occurred in 43 patients (43.9%). Twentyone patients (21.4%) discontinued active vitamin D less than 6 months after surgery, while 14 (14.3%) continued active vitamin D for more than 2 years. Tumor multifocality (odds ratio [OR], 3.7 vs. single tumor; P=0.013) and preoperative calcium level (OR, 0.2; P=0.028) were independent predictors of hypoPTH immediately after TT. In addition, age (OR, 0.8; P=0.011) and preoperative calcium level (OR, 0.04; P=0.014) significantly decreased the risk for persistent hypoPTH requiring active vitamin D for more than 2 years. Conclusion: HypoPTH occurred in 43.9% of pediatric thyroid cancer patients after TT in this study. Among them, one-third of patients continued active vitamin D medication for more than 2 years, which was predicted by young age and low preoperative calcium level. [ABSTRACT FROM AUTHOR]