Unilateral radiotherapy for tonsillar cancer with multiple ipsilateral neck lymph nodes.

PURPOSE: For tonsillar cancer with multiple ipsilateral neck lymph nodes, the safety and efficacy of unilateral radiotherapy (RT) have long been a topic of debate. We performed retrospective analyses of patients having ipsilateral neck lymph nodes treated with unilateral RT in two tertiary referral hospitals. MATERIALS AND METHODS: This study accrued 29 patients who were diagnosed as well-lateralized tonsillar cancer with multiple ipsilateral neck lymph nodes and underwent unilateral RT from March 2000 to March 2020. Patients underwent treatment with one of the following options or a combination of them: induction chemotherapy, surgery, RT, and concurrent chemoradiotherapy. We analyzed the recurrence pattern and survival with special attention to contralateral neck failure. Also, treatment-related toxicities were compared with a 1:1 matched cohort of those who received bilateral RT, using propensity score matching analysis. RESULTS: At a median follow-up of 68 months, no contralateral neck failure was observed. Five-year actuarial locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 85.6%, 91.8%, and 92.7%, respectively. Both the acute and chronic grade 2 xerostomia occurred in 10.3% of the patients. When the toxicity for unilateral RT was compared to that of bilateral RT using a propensity score-matched cohort, a significantly lower rate of acute xerostomia was observed in unilateral RT group (55.1% vs. 82.7%, p=0.002), primarily at grade 2 level (10.3% vs. 51.7%, respectively). CONCLUSION: The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph nodes.

Early injection laryngoplasty for acute unilateral vocal fold paralysis after thoracic aortic surgery.

OBJECTIVE: Unilateral vocal fold paralysis (UVFP) following open thoracic aortic surgery increases pulmonary complications and hospital stays. An intervention protocol with early injection laryngoplasty (IL) and swallowing maneuvers was developed for acute UVFP following thoracic aortic surgery. This study aimed to compare the incidence of complications and length of medical care between the non-VFP and the IL-UVFP group managed under this protocol. METHODS: Patients who underwent open thoracic aortic surgery from March 2020 to February 2023 were included, excluding those with preoperative VFP or postoperative bilateral VFP. Under the protocol, patients with UVFP and incomplete glottic closure received IL and swallowing maneuvers within one week after diagnosis, while those without a glottic gap started a soft diet along with swallowing maneuvers. Postoperative complications, including reintubation, ICU re-transfer, pneumonia, stroke, delirium, wound infection, and bleeding, as well as hospital and ICU stay, were assessed. RESULTS: Of the 355 patients included in the study, 51 (14.4%) developed postoperative UVFP, while 304 (85.6%) had normal VF function. In the UVFP group, 42 patients underwent IL, while 9 patients without a glottic gap did not undergo IL. The incidence of complications and length of medical care were analyzed in the non-VFP and the IL-UVFP groups. The IL-UVFP group had a longer median hospital stay compared to the non-VFP group (20.5 vs. 16.0 days), though this difference was not statistically significant (P = .0681). ICU stay (P = .5396) and ICU re-transfer rates (P = 1.00) were also comparable between the groups. There was no significant difference in the incidence of pneumonia between the IL-UVFP group (4.8%) and the non-VFP group (9.5%) (P = .4003). Additionally, no significant differences were observed in the incidence of stroke, delirium, wound infection, or bleeding between the groups. No IL-related complications were reported. CONCLUSIONS: The protocol with early IL appears to help reduce complication rates in acute UVFP patients following thoracic aortic surgery to levels comparable to those in patients without VFP. This protocol could serve as a guideline for otolaryngologists in managing UVFP patients. LEVEL OF EVIDENCE: 2b/Individual cohort study.

The Impact of a Twice-daily Versus Once-daily Proton Pump Inhibitor Dosing Regimen on Laryngopharyngeal Reflux Symptoms: A Prospective Randomized Controlled Trial.

Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16- week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups. Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions: Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.

Prediction of the efficacy of proton-pump inhibitors in patients with contact granuloma using 24-hour combined dual channel pH/impedance monitoring.

OBJECTIVES: We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. METHODS: We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. RESULTS: Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. CONCLUSION: Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG.

Injectable alginate-based in situ self-healable transparent hydrogel as a vitreous substitute with a tamponading function.

Retinal detachment and other vision-threatening disorders often necessitate vitreous body removal and tamponade injection for retina stabilization. Current clinical tamponades such as silicone oil and expansile gases have drawbacks, including patient discomfort and the need for secondary surgery. We introduce a transparent alginate-phenylboronic acid/polyvinyl alcohol composite hydrogel (TALPPH) as a novel vitreous substitute with tamponading capabilities. In vitro physicochemical, rheological, and optical characterization of in situ self-healable TALPPH was performed, and long-term biocompatibility was assessed in a rabbit model of vitrectomy retinal detachment. In vivo evaluations confirmed TALPPH's ability to inhibit retinal detachment recurrence and preserve rabbit vision without adverse effects. TALPPH's close resemblance to the natural vitreous body suggests potential as a vitreous tamponade substitute for future ophthalmological applications.

Self-Assembled Skin-Penetrating Peptides with Controlled Supramolecular Properties for Enhanced Transdermal Delivery.

The use of nanocarriers decorated with penetration-enhancing agents (PEAs) is considered to be a promising approach for efficient transdermal delivery. In this study, we developed short amphiphilic skin-penetrating peptides (17 amino acids) that functioned not only as PEAs but also as building blocks of nanocarriers without the incorporation of additional macromolecules for self-assembly and guest molecule encapsulation. Interestingly, varying only two amino acids in the hydrophobic moiety of the peptides resulted in significantly different self-assembly behavior, thermal stability, protease resistance, and skin-penetration efficiency in a human skin model. The analysis of the peptide secondary structure revealed that such characteristic changes arose due to the sequence variation-mediated conformational change in the hydrophobic block. These findings hold significant promise for the development of simple and effective delivery systems exhibiting controllable supramolecular properties.

Self-assembling biomolecules for biosensor applications.

Molecular self-assembly has received considerable attention in biomedical fields as a simple and effective method for developing biomolecular nanostructures. Self-assembled nanostructures can exhibit high binding affinity and selectivity by displaying multiple ligands/receptors on their surface. In addition, the use of supramolecular structure change upon binding is an intriguing approach to generate binding signal. Therefore, many self-assembled nanostructure-based biosensors have been developed over the past decades, using various biomolecules (e.g., peptides, DNA, RNA, lipids) and their combinations with non-biological substances. In this review, we provide an overview of recent developments in the design and fabrication of self-assembling biomolecules for biosensing. Furthermore, we discuss representative electrochemical biosensing platforms which convert the biochemical reactions of those biomolecules into electrical signals (e.g., voltage, ampere, potential difference, impedance) to contribute to detect targets. This paper also highlights the successful outcomes of self-assembling biomolecules in biosensor applications and discusses the challenges that this promising technology needs to overcome for more widespread use.

Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

PSMD1 as a prognostic marker and potential target in oropharyngeal cancer.

BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 µm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. RESULTS: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction.

Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.

Revisiting Loré's retrograde thyroidectomy from the perspective of preserving the external branch of the superior laryngeal nerve.

Background: Injury to the external branches of the superior laryngeal nerve (EBSLN) is the main reported cause of inexplicable post-thyroidectomy dysphonia (PTD) without recurrent laryngeal nerve (RLN) injury. Loré proposed a retrograde thyroidectomy (RT) technique in which the superior pole is dissected as a final step after the Berry ligament division, making this approach advantageous for protecting the EBSLN. However, evidence of this protective effect remains insufficient. We aimed to evaluate EBSLN function following RT and conventional thyroidectomy (CT) using postoperative electromyography (EMG). Methods: This is a retrospective cohort study conducted at a single tertiary center. Consecutive patients who had undergone CT or RT were included. Bilateral EMG of the cricothyroid muscle was performed 2-3 months postoperatively in all patients. Patient characteristics, postoperative findings of bleeding events, drain amount, hypocalcemia, calcium replacement, RLN function, and EBSLN function were thoroughly reviewed and compared between the two surgical approaches. Abnormalities in the EMG findings were reported based on the wave configuration, and the results were graded into four categories. Results: Seven hundred and thirty-one consecutive patients who underwent CT (n=341), or RT (n=390) were included, and a total of 1,179 RLNs and EBSLNs were at risk in CT (n=601) and RT (n=578). The CT and RT groups had similar clinical characteristics and surgical data. Two groups presented similar postoperative results for bleeding incidence, drain amount, and hypocalcemia. All RLNs were identified in both groups and their permanent function was preserved. EBSLN was significantly less frequently identified in the surgical field during RT than it was during CT (0.3% vs. 4.2%, respectively; P<0.001). Abnormal rates of postoperative EMG on the EBSLN were significantly lower in the RT group than in the CT group (1.7% vs. 7.8%, respectively; P<0.001), while the CT group presented with a higher grade of abnormal EMG (P<0.001). Conclusions: The RT technique may be beneficial for preserving EBSLN function. Meticulous capsular dissection and appropriate traction of the upper pole facilitated by RT are crucial for decreasing the risk of EBSLN injury, which can be achieved without directly identifying the nerve.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a ß-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded ß-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the ß-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Single, Double and ETL-Sandwiched PVPy Interlayer Effect on Charge Injection Balance and Performance of Inverted Quantum Dot Light-Emitting Diodes.

A desire to achieve optimal electron transport from the electron transport layer (ETL) towards the emissive layer (EML) is an important research factor for the realization of high performance quantum dot light-emitting diodes (QD-LEDs). In this paper, we study the effect of a single, double, and electron transport layer sandwiched Poly(4-vinylpyridine) (PVPy here on) on the charge injection balance and on the overall device performance of InP-based red quantum dot light emitting diodes (red QD-LEDs). The results showed general improvement of device characteristic performance metrics such as operational life with incorporation of a PVPy interlayer. The best performance was observed at a lower concentration of PVPy (@ 0.1 mg/mL) in interlayer with continual worsening in performance as PVPy concentration in the interlayer increased in other fabricated devices. The AFM images obtained for the different materials reported improved surface morphology and overall improved surface properties, but decreased overall device performance as PVPy concentration in interlayer was increased. Furthermore, we fabricated two special devices: in the first special device, a single 0.1 mg/mL PVPy sandwiched between two ZnO ETL layers, and in the second special device, two 0.1 mg/mL PVPy interlayers were inter-sandwiched between two ZnO ETL layers. Particular emphasis was placed on monitoring the maximum obtained EQE and the maximum obtained luminance of all the devices. The first special device showed better all-round improved performance than the second special device compared to the reference device (without PVPy) and the device with a single 0.1 mg/mL PVPy interlayer stacked between ZnO ETL and the emissive layer.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

Predictors of treatment outcomes following treat-and-extend regimen with aflibercept for branch retinal vein occlusion: post-hoc analysis of the PLATON trial.

We investigated predictors of visual outcomes and injection interval in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated with a treat-and-extend (TAE) regimen. All 48 patients in a multicenter study were followed for 52 weeks and received three monthly intravitreal aflibercept injections before the TAE regimen, with treatment intervals adjusted by 4 weeks, up to a maximum of 16 weeks. Various laboratory biomarkers and optical coherence tomography parameters were evaluated. Patients were classified into the extension failure group if they had ≥ 1 treatment interval decreased due to an increase in the central macular thickness compared to the previous visit and 18 patients were assigned to this group. In multivariate logistic analyses, presence of microaneurysms and prominent middle limiting membrane (p-MLM) sign, increased initial external limiting membrane (ELM) disruption, and higher total cholesterol were correlated with inhibiting a sustained extension in the injection interval (P = 0.015, P = 0.032, P = 0.037, P = 0.009, respectively). Therefore, in the patients with ME secondary to BRVO with these risk factors, early consideration of frequent injection may improve treatment outcome.

Superior Laryngeal Nerve Block in Transcutaneous Vocal Fold Injection: A Pilot Study.

OBJECTIVES: Topical lidocaine remains the mainstay for anesthesia in transcutaneous vocal fold injection (VFI). While using topical lidocaine, laryngologists sometimes encounter uncontrolled reflexes or poor compliance. Superior laryngeal nerve block (SLNB) provides deep and rapid anesthesia on the larynx above the vocal folds and abolishes the glottic closure reflex. Herein, we present a pilot study to evaluate the feasibility and safety of SLNB for transcutaneous VFI and explored its usefulness. METHODS: Fifty-nine patients were prospectively anesthetized with SLNB during transcutaneous VFI for unilateral vocal fold paralysis. In the SLNB group, 0.5 to 1 mL of 2% lidocaine was infiltrated on bilateral SLNs through the thyrohyoid membrane. As the control group, we included previous 47 patients who underwent VFI with topical lidocaine. In the control group, 10% lidocaine spray was applied to the laryngopharyngeal mucosa. Demographic data, laryngeal exposure, patient compliance, procedural interruption, and complications were investigated. Patient compliance was evaluated based on the frequency of cough and swallowing during VFI procedures. RESULTS: SLNB enabled endoscopic contact on the epiglottis and pharyngeal wall without gag reflex and provided good exposure of the procedure field on the vocal folds. In the SLNB group, the laryngeal exposure is significantly better than in the control (P = 0.005). The frequency of cough and swallowing was significantly lower in the SLNB group than in the control (P < 0.001). The number of procedural interruptions was lower in the SLNB group than in the control (P < 0.001). There was no acute or delayed complication related to SLNB such as bleeding, hematoma, delayed sensory/swallowing problems, or unscheduled hospital visits. CONCLUSIONS: SLNB might be safe and effective for anesthesia in transcutaneous VFI. SLNB could be a good anesthetic option for patients with poor compliance despite the sufficient application of topical lidocaine.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Cumulative sum analysis of the learning curve for robotic retroauricular thyroidectomy.

Background: Remote-access robotic thyroid surgery enables avoiding a visible scar on the neck and allows precise manipulation through a magnified surgical view. The retroauricular approach has many advantages. This study aimed to evaluate the learning curve for robotic retroauricular thyroidectomy using cumulative sum analysis. Methods: The medical records of 36 patients who underwent robotic retroauricular thyroidectomy between 2018 and 2021 were retrospectively reviewed. The clinical features and surgical outcomes were analyzed; the learning curve was evaluated using the cumulative sum analysis. Results: The learning curve using cumulative sum analysis was divided into two phases based on 15 cases: phase I (first 15 cases) and phase II (remaining 21 cases). The total operation time was significantly shorter in phase II than that in phase I (161.9±23.4 vs. 199±41.0 min, P=0.002). The flap dissection and docking time (77.1±14.3 vs. 90.0±21.5 min, P=0.037) and console time (36.5±16.2 vs. 50.3±17.8 min, P=0.020) were significantly shorter in phase II than that in phase I. There was no significant difference between the two phases in the total amount of drainage, duration of hospital stay, and complications after the surgery. Conclusions: The learning curve for robotic retroauricular thyroidectomy demonstrates that the operation time decreased rapidly after 15 cases. Proficiency in docking and manipulating the instruments accelerate the learning curve.