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Abstract Circular utilization of distillery byproducts is crucial, and pyrolysis has emerged as a viable technology for converting them into fuels and high-value chemicals. This review investigates the thermochemical reactions of byproducts generated during the grain fermentation process. We begin by discussing the physicochemical properties of these byproducts as they relate to their potential conversion into fuels. Subsequently, we explore various thermochemical processes for biomass-to-energy conversion, including the influence of reaction conditions and catalysts. The intricate interactions between cellulose, hemicellulose, lignin, and protein during pyrolysis are then examined. These interactions, particularly the Maillard reaction between proteins and carbohydrates and vapor–solid interactions, significantly impact the reaction pathways and ultimately the yield and quality of bio-oil, a key product of the pyrolysis process. Understanding these interactions, as evidenced by studies demonstrating the influence of levoglucosan, furfural, and hydroxyacetic acid on product yields, is essential for optimizing pyrolysis processes of distillery byproducts and maximizing the efficiency of biomass energy conversion. By elucidating the theoretical foundation and scientific basis for optimizing the energy conversion of distillery byproducts, this review aims to contribute to the development of sustainable and environmentally friendly practices within the brewing industry.

Abstract Reconstruction of severe osteochondral defects in articular cartilage and subchondral trabecular bone remains a challenging problem. The well-integrated bilayer osteochondral graft design expects to be guided the chondrogenic and osteogenic differentiation for stem cells and provides a promising solution for osteochondral tissue repair in this study. The subchondral bone scaffold approach is based on the developed finer and denser 3D β-tricalcium phosphate (β-TCP) bioceramic scaffold process, which is made using a digital light processing (DLP) technology and the novel photocurable negative thermo-responsive (NTR) bioceramic slurry. Then, the concave-top disc sintered 3D-printed bioceramic incorporates the human adipose-derived stem cells (hADSCs) laden photo-cured hybrid biohydrogel (HG + 0.5AFnSi) comprised of hyaluronic acid methacryloyl (HAMA), gelatin methacryloyl (GelMA), and 0.5% (w/v) acrylate-functionalized nano-silica (AFnSi) crosslinker. The 3D β-TCP bioceramic compartment is used to provide essential mechanical support for cartilage regeneration in the long term and slow biodegradation. However, the apparent density and compressive strength of the 3D β-TCP bioceramics can be obtained for ~ 94.8% theoretical density and 11.38 ± 1.72 MPa, respectively. In addition, the in vivo results demonstrated that the hADSC + HG + 0.5AFnSi/3D β-TCP of the bilayer osteochondral graft showed a much better osteochondral defect repair outcome in a rabbit model. The other word, the subchondral bone scaffold of 3D β-TCP bioceramic could accelerate the bone formation and integration with the adjacent host cancellous tissue at 12 weeks after surgery. And then, a thicker cartilage layer with a smooth surface and uniformly aligned chondrocytes were observed by providing enough steady mechanical support of the 3D β-TCP bioceramic scaffold.

ObjectivesThe feasibility and reliability of trans-thyroid cartilage EMG recording method (TCERM) during intraoperative monitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery have been established. This study compared two different recording electrode placements on the ipsi-lateral and contra-lateral lamina of the thyroid cartilage (TC).MethodsFifty consecutive patients undergoing total thyroidectomy with 100 RLNs at risk were enrolled. Two paired subdermal needle electrodes were inserted into the subperichondrium of the bilateral TC lamina to record electromyography (EMG) signals. The channel leads from the TC electrodes were connected to the patient interface with two different modes. In A-mode, the electrode leads were placed ipsi-laterally, and channel 1 monitored the left RLN and channel 2 monitored the right RLN respectively. In B-mode, the electrode leads were placed contra-laterally, and channels 1 and 2 simultaneously monitored the same side of the RLN. The amplitudes of four EMG signals (V1-R1-R2-V2) recorded by A-mode and B-mode were compared.ResultsAll EMG amplitudes of V1-R1-R2-V2 signals recorded with B-mode were all above 500μV and significantly higher than those with A-mode (p

Abstract Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p

Abstract This prospective, randomized controlled trial evaluated the effect of neostigmine for intraoperative neuromonitoring (IONM) during thyroid surgery. Forty subjects undergoing thyroidectomy with IONM, randomized into neostigmine administration after tracheal intubation (Group N, n = 20) or control treatment with normal saline (Group C, n = 20), completed the trial. Electromyography amplitudes of the vagus nerve (V1) were recorded before thyroid dissection. The time from the initial V1 signal check to successful V1 stimulation was recorded. In Group N, all the patients had a successful V1 signal at the first check, whereas ten (50%) patients in Group C had a time delay between the initial V1 check and successful V1 (p

Abstract Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery to reduce recurrent laryngeal nerve injury. The use of neuromuscular blockade agent to facilitate tracheal intubation, is a common cause of IONM failure. We performed a retrospective analysis to assess the efficacy of neostigmine‐glycopyrrolate as a neuromuscular blockade reversal agent for IONM during thyroid surgery. Rocuronium (0.6 mg/kg) was administered for muscle relaxation. Neostigmine (2 mg) and glycopyrrolate (0.4 mg) were administered immediately after intubation. Cricothyroid muscle‐twitch response upon external branch of superior laryngeal nerve stimulation and electromyography amplitudes of vagal and recurrent laryngeal nerves before (V1, R1) and after thyroid resection (V2, R2) were recorded. Fifty patients (23 males, 27 females) were included in the analysis. The diagnoses comprised 43 papillary thyroid carcinomas and seven benign diseases. The mean time between rocuronium injection and neostigmine‐glycopyrrolate injection was 5.1 ± 1.2 min, and the mean time from neostigmine‐glycopyrrolate injection to successful cricothyroid muscle twitching upon external branch of superior laryngeal nerve stimulation was 21.0 ± 4.5 min. All patients had V1 and R1 amplitudes of more than 500 μV each, with mean V1 and R1 amplitudes of 985.3 ± 471.6 μV and 1177.2 ± 572.7 μV, respectively. Neostigmine‐glycopyrrolate was effectively used as a neuromuscular blockade reversal agent for IONM in thyroid surgeries without a significant increase in bucking events. Administration of neostigmine‐glycopyrrolate immediately after intubation can be recommended for successful NMB reversal to facilitate IONM during thyroid surgery.

Introduction Titration of neuromuscular block (NMB) plays a key role in intraoperative recurrent laryngeal nerve monitoring during thyroid surgery. The combination of neuromuscular blocking agent and timely partial reversal of NMB was investigated in both animal experiments and clinical neuro-monitored thyroidectomy. Methods In animal experiments, 8 piglets received sugammadex to assess the laryngeal EMG recovery after rocuronium-induced NMB. In clinical monitored thyroidectomy, 40 patients each were allocated to conventional group and sugammadex group. Conventional group received rocuronium 0.3 mg/kg at anesthesia induction, while sugammadex group received partial NMB recovery protocol- 0.6 mg/kg of rocuronium at anesthesia induction and 0.5 mg/kg of sugammadex. Main outcome was assessed by first (V1) and final (V2) EMG signal induced by vagal stimulation. Results In the porcine model, 50% recovery of laryngeal EMG amplitude was achieved at 16.8 ± 1.9 and 6 ± 2.7 minutes respectively after 0.5 and 1 mg/kg of sugammadex (p

Abstract Objective Proper position of an electromyographic (EMG) endotracheal tube within the larynx plays a key role in functional electrophysiologic intraoperative neural monitoring (IONM) in thyroid surgery. The purpose of this study was to determine the feasibility of a portable video‐assisted intubation device (UEScope) to verify the optimal placement of an EMG tube. Methods A retrospective study enrolled 40 consecutive patients who underwent monitored thyroidectomies. After positioning the patient for surgery, an anesthesiologist performed tracheal intubation with UEScope and checked the position of the tube at the proper depth without rotation to the vocal cords. The main outcome measured was the proper EMG tube position, free from further adjustment. The secondary outcomes assessed were the percentage of available initial vagal stimulation (V1) signals. Results All tracheal intubations were successful at first attempt. Proper EMG tube placement without position adjustment was found in 97.5% of the patients. Tube withdrawal was required in a male patient. All patients obtained detectable V1 signals; the lowest and median V1 amplitude was 485 and 767 μV as a reference value, respectively. Conclusion The UEScope is a valuable and reliable tool for placing an EMG tube and confirming its position during monitored thyroidectomy. In addition, further tube adjustment might be waived in most cases when the anesthesiologist placed the EMG tube after patient positioning for surgery. Routine use of video‐assisted intubation devices is highly recommended. Level of Evidence 4.

Abstract Continuous intraoperative neural monitoring (C-IONM) during thyroid surgery is a useful tool for preventing recurrent laryngeal nerve (RLN) injury. The present study aims to analyze the tensile strength tolerance of C-IONM electrodes on the vagal nerve (VN). A C-IONM wire was enclosed in a hand-held tensile testing system. The probe displacement on the VN was continuously monitored by positioning a second probe far-up/proximally in a piglet model, and an automatic periodic stimulation (APS) accessory was used. The 3-mm and 2-mm APS accessory has a mean tensile strength of 20.6 ± 10 N (range, 14.6–24.4 N) and 11.25 ± 8 N (range, 8.4–15.6 N), respectively (P = 0.002). There was no difference between bilateral VNs. The mean amplitude before and during electrode displacement was 1.835 ± 102 μV and 1.795 ± 169 μV, respectively (P = 0.45). The mean percentage of amplitude decrease on the electromyography (EMG) was 6.9 ± 2.5%, and the mean percentage of latency increase was 1.9 ± 1.5%. No significant amplitude reduction or loss of signal (LOS) was observed after > 50 probe dislocations. C-IONM probe dislocation does not cause any LOS or significant EMG alterations on the VN.

BackgroundInducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium.MethodsTwelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value.ResultsNeostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P

ObjectivesTraction injury is the most common type of recurrent laryngeal nerve (RLN) injury in thyroid surgery. Intraoperative neuromonitoring (IONM) facilitates early detection of adverse electromyography (EMG) effect, and this corrective maneuver can reduce severe and repeated nerve injury. This study aimed to evaluate intraoperative patterns and outcomes of EMG decrease and recovery by traction injury.Methods644 patients received nerve monitored thyroidectomy with 1142 RLNs at risk were enrolled. Intermittent IONM with stimulating dissecting instrument (real-time during surgical procedure) and trans-thyroid cartilage EMG recording method (without electrode malpositioning issue) were used for nerve stimulation and signal recording. When an EMG amplitude showed a decrease of >50% during RLN dissection, the surgical maneuver was paused immediately. Nerve dissection was restarted when the EMG amplitude was stable.Results44/1142 (3.9%) RLNs exhibited a >50% EMG amplitude decrease during RLN dissection and all (100%) showed gradual progressive amplitude recovery within a few minutes after releasing thyroid traction (10 recovered from LOS; 34 recovered from a 51-90% amplitude decrease). Three EMG recovery patterns were noted, A-complete EMG recovery (n=14, 32%); B-incomplete EMG recovery with an injury point (n=16, 36%); C-incomplete EMG recovery without an injury point (n=14, 32%). Patients with postoperative weak or fixed vocal cord mobility in A, B, and C were 0(0%), 7(44%), and 2(14%), respectively. Complete EMG recovery was found in 14 nerves, and incomplete recovery was found in another 30 nerves. Temporary vocal cord palsy was found in 6 nerves due to unavoidable repeated traction.ConclusionEarly detection of traction-related RLN amplitude decrease allows monitoring of intraoperative EMG signal recovery during thyroid surgery. Different recovery patterns show different vocal cord function outcomes. To elucidate the recovery patterns can assist surgeons in the intraoperative decision making and postoperative management.

ObjectivesIntraoperative neuromonitoring (IONM) is a useful tool to evaluate the function of recurrent laryngeal nerve (RLN) in thyroid surgery. This study aimed to determine the necessity and value of routinely testing the proximal and distal ends of RLN.MethodsIn total, 796 patients undergoing monitored thyroidectomies with standardized procedures were enrolled. All 1346 RLNs with visual integrity of anatomical continuity were routinely stimulated at the most proximal (R2p signal) and distal (R2d signal) ends after complete RLN dissection. The EMG amplitudes between R2p and R2d signals were compared. If the amplitude of R2p/R2d ratio reduction (RPDR) was over 10% or loss of signal (LOS) occurred, the exposed RLN was mapped to identify the injured point. Pre- and post-operative vocal cord (VC) mobility was routinely examined with video-laryngofiberscope.ResultsNerve injuries were detected in 108 (8%) RLNs, including 94 nerves with incomplete LOS (RPDR between 13%-93%) and 14 nerves with complete LOS. The nerve injuries were caused by traction in 80 nerves, dissecting trauma in 23 nerves and lateral heat spread of energy-based devices in 5 nerves. Symmetric VC mobility was found in 72 nerves with RPDR ≤50%. The occurrence of abnormal VC mobility (weak or fixed) was 14%, 67%, 100%, and 100% among the different RPDR stratifications of 51%-60%, 61%-70%, 71%-80%, and 81-93%, respectively. Of the 14 nerves with complete LOS, all showed fixed VC mobility. Permanent VC palsy occurred in 2 nerves with thermal injury.ConclusionRoutinely testing the proximal and distal ends of exposed RLN helps detect unrecognized partial nerve injury, elucidate the injury mechanism and determine injury severity. The procedure provides accurate information for evaluating RLN function after nerve dissection and should be included in the standard IONM procedure.

ObjectivesQuantum molecular resonance (QMR) devices have been applied as energy-based devices in many head and neck surgeries; however, research on their use in thyroid surgery is lacking. This study aimed to investigate the safety parameters of QMR devices during thyroidectomy when dissection was adjacent to the recurrent laryngeal nerve (RLN).MethodsThis study included eight piglets with 16 RLNs, and real-time electromyography (EMG) signals were obtained from continuous intraoperative neuromonitoring (C-IONM). QMR bipolar scissor (BS) and monopolar unit (MU) were tested for safety parameters. In the activation study, QMR devices were activated at varying distances from the RLN. In the cooling study, QMR devices were cooled for varying time intervals, with or without muscle touch maneuver (MTM) before contacting with the RLN.ResultsIn the activation study, no adverse EMG change occurred when QMR BS and MU were activated at distances of 2 mm or longer from the RLNs. In the cooling study, no adverse EMG change occurred when QMR BS and MU were cooled in 2-second intervals or immediately after MTM.ConclusionQMR devices should be carefully used when performing RLN dissection during thyroid surgery. According to the activation and cooling safety parameters in this study, surgeons can avoid RLN injury by following standard procedures when using QMR devices.

Abstract Red wine compounds have been reported to reduce the rate of atherosclerosis by inducing nitric oxide (NO) production and antioxidant enzyme expression in vascular endothelial cells (VECs). The present study compared the effects of the three red wine compounds resveratrol and its dimers, ε‐viniferin and δ‐viniferin, on VECs function for the first time. Both 5 μM ε‐viniferin and δ‐viniferin, but not 5 μM resveratrol, significantly stimulated wound repair of VECs. Increased levels of wound repair induced by 10 and 20 μM ε‐viniferin were significantly higher than those stimulated by 10 and 20 μM resveratrol, respectively. These stimulatory effects of the three compounds were suppressed by the NO synthase inhibitor L‐NAME. When VECs were exposed to each compound, endothelial NO synthase was activated and the expression of sirtuin 1 (SIRT1) and HO‐1 was induced. Addition of the SIRT1 and HO‐1 inhibitors EX527 and ZnPPiX, respectively, suppressed wound repair stimulated by the three compounds, demonstrating that SIRT1 and HO‐1 are involved in these wound repair processes. Furthermore, each compound induced the suppression of H2O2‐dependent reduction of cell viability as well as the expression of the antioxidant enzyme catalase. These data suggest that not only resveratrol, but also its dimers, ε‐viniferin and δ‐viniferin, may be effective in preventing atherosclerosis by a similar molecular mechanism with different potency and efficacy.

Abstract This article reviews the literature on development of neuromuscular blockade management in thyroid surgery with intraoperative neural monitoring (IONM) in the past decade. Neuromuscular blockade management includes the choice of neuromuscular blocking agents (NMBAs) and reversal of neuromuscular blockade by sugammadex. A series of animal study and clinical trials showed NMBAs effect on IONM in thyroid surgery. We summarized five NMBA regimens for IONM: (a) relaxant‐free regimen, (b) depolarizing NMBA‐succinylcholine, (c) titration of nondepolarizing NMBA, and (d) rocuronium combined with sugammadex. The proper management of neuromuscular blockade during IONM has greatly developed over the past decade. The misuse of NMBAs is associated with false IONM interpretations to surgeons. A detailed understanding of NMBAs and neuromuscular blockade management by sugammadex may optimize IONM quality in patients receiving monitored thyroid surgery.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 μg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

BackgroundNeuromuscular blocking agents provide muscular relaxation for tracheal intubation and surgery. However, the degree of neuromuscular block may disturb neuromuscular transmission and lead to weak electromyography during intraoperative neuromonitoring. This study aimed to investigate a surgeon-friendly neuromuscular block degree titrated sugammadex protocol to maintain both intraoperative neuromonitoring quality and surgical relaxation during thyroid surgery.MethodsA total of 116 patients were enrolled into two groups and underwent elective thyroid surgery with intraoperative neuromonitoring. All patients followed a standardized intraoperative neuromonitoring protocol with continuous neuromuscular transmission monitoring and received 0.6 mg/kg rocuronium for tracheal intubation. Patients were allocated into two groups according to the degree of neuromuscular block when the anterior surface of the thyroid gland was exposed. The neuromuscular block degree was assessed by the train-of-four (TOF) count and ratio. Patients in group I received sugammadex 0.25 mg/kg for non-deep neuromuscular block degree (TOF count = 1~4). Patients in group II were administered sugammadex 0.5 mg/kg for deep neuromuscular block degree (TOF count = 0). The quality of the intraoperative neuromonitoring was measured using the V1 electromyography (EMG) amplitude. An amplitude less than 500 μV and greater than 500 μV was defined as weak and satisfactory, respectively.ResultsThe quality of the intraoperative neuromonitoring was not different between groups I and II (satisfactory/weak: 75/1 vs. 38/2, P = 0.14). The quality of surgical relaxation was acceptable after sugammadex injection and showed no difference between groups [55/76 (72.3%) in group I vs. 33/40 (82.5%) in group II, P = 0.23].ConclusionsThis surgeon-centered sugammadex protocol guided by neuromuscular block degree (0.5 mg/kg for deep block and 0.25 mg/kg for others) showed comparably high intraoperative neuromonitoring quality and adequate surgical relaxation. The results expanded the practicality of sugammadex for precise neuromuscular block management during monitored thyroidectomy.

BackgroundThe survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools.MethodsThis study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992-2003; Group B: 2004-2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups.ResultsGroup B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (pConclusionAmong patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.

In the past decade, the use of intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery has been widely accepted by surgeons as a useful technology for improving laryngeal nerve identification and voice outcomes, facilitating neurophysiological research, educating and training surgeons, and reducing surgical complications and malpractice litigation. Informing patients about IONM is not only good practice and helpful in promoting the efficient use of IONM resources but is indispensable for effective shared decision making between the patient and surgeon. The International Neural Monitoring Study Group (INMSG) feels complete discussion of IONM in the preoperative planning and patient consent process is important in all patients undergoing thyroid and parathyroid surgery. The purpose of this publication is to evaluate the impact of IONM on the informed consent process before thyroid and parathyroid surgery and to review the current INMSG consensus on evidence-based consent. The objective of this consensus statement, which outlines general and specific considerations as well as recommended criteria for informed consent for the use of IONM, is to assist surgeons and patients in the processes of informed consent and shared decision making before thyroid and parathyroid surgery.

ObjectivesIn patients with recurrent laryngeal nerve (RLN) injury after thyroid surgery, unrecovered vocal fold motion (VFM) and subjective voice impairment cause extreme distress. For surgeons, treating these poor outcomes is extremely challenging. To enable early treatment of VFM impairment, this study evaluated prognostic indicators of non-transection RLN injury and VFM impairment after thyroid surgery and evaluated correlations between intraoperative neuromonitoring (IONM) findings and perioperative voice parameters.Methods82 adult patients had postoperative VFM impairment after thyroidectomy were enrolled. Demographic characteristics, RLN electromyography (EMG), and RLN injury mechanism were compared. Multi-dimensional voice program, voice range profile and Index of voice and swallowing handicap of thyroidectomy (IVST) were administered during I-preoperative; II-immediate, III-short-term and IV-long-term postoperative periods. The patients were divided into R/U Group according to the VFM was recovered/unrecovered 3 months after surgery. The patients in U Group were divided into U1/U2 Group according to total IVST score change was 90% decrease in the injured RLN (p90% in the injured RLN (p=0.022) and thermal injury as the RLN injury mechanism (p=0.017). A large pitch range decrease in period-II was a prognostic indicator of a moderate/severe long-term postoperative subjective voice impairment.ConclusionThis study is the first to evaluate correlations between IONM findings and voice outcomes in patients with VFM impairment after thyroid surgery. Thyroid surgeons should make every effort to avoid severe type RLN injury (e.g., thermal injury or injury causing EMG decrease >90%), which raises the risk of unrecovered VFM and moderate/severe long-term postoperative subjective voice impairment. Using objective voice parameters (e.g., pitch range) as prognostic indicators not only enables surgeons to earlier identify patients with low voice satisfaction after surgery, and also enable implementation of interventions sufficiently early to maintain quality of life.

ObjectivesHigh-pitched voice impairment (HPVI) is not uncommon in patients without recurrent laryngeal nerve (RLN) or external branch of superior laryngeal nerve (EBSLN) injury after thyroidectomy. This study evaluated the correlation between subjective and objective HPVI in patients after thyroid surgery.MethodsThis study analyzed 775 patients without preoperative subjective HPVI and underwent neuromonitored thyroidectomy with normal RLN/EBSLN function. Multi-dimensional voice program, voice range profile and Index of voice and swallowing handicap of thyroidectomy (IVST) were performed during the preoperative(I) period and the immediate(II), short-term(III) and long-term(IV) postoperative periods. The severity of objective HPVI was categorized into four groups according to the decrease in maximum frequency (Fmax): 60%. Subjective HPVI was evaluated according to the patient’s answers on the IVST.ResultsAs the severity of objective HPVI increased, patients were significantly more to receive bilateral surgery (p=0.002) and have subjective HPVI (p0.05) and had higher Jitter, Shimmer, and IVST scores than patients in any of the objective HPVI groups; subjective HPVI lasted until period-IV.ConclusionThe factors that affect a patient’s subjective HPVI are complex, and voice stability (Jitter and Shimmer) is no less important than the Fmax level. When patients have subjective HPVI without a significant Fmax decrease after thyroid surgery, abnormal voice stability should be considered and managed. Fmax and IVST scores should be interpreted comprehensively, and surgeons and speech-language pathologists should work together to identify patients with HPVI early and arrange speech therapy for them. Regarding the process of fibrosis formation, anti-adhesive material application and postoperative intervention for HPVI require more future research.

Technological advances in thyroid surgery have rapidly increased in recent decades. Specifically, recently developed energy-based devices (EBDs) enable simultaneous dissection and sealing tissue. EBDs have many advantages in thyroid surgery, such as reduced blood loss, lower rate of post-operative hypocalcemia, and shorter operation time. However, the rate of recurrent laryngeal nerve (RLN) injury during EBD use has shown statistically inconsistent. EBDs generate high temperature that can cause iatrogenic thermal injury to the RLN by direct or indirect thermal spread. This article reviews relevant medical literatures of conventional electrocauteries and different mechanisms of current EBDs, and compares two safety parameters: safe distance and cooling time. In general, conventional electrocautery generates higher temperature and wider thermal spread range, but when applying EBDs near the RLN adequate activation distance and cooling time are still required to avoid inadvertent thermal injury. To improve voice outcomes in the quality-of-life era, surgeons should observe safety parameters and follow the standard procedures when using EBDs near the RLN in thyroid surgery

A recurrent laryngeal nerve (RLN) injury resulting in vocal fold paralysis and dysphonia remains a major source of morbidity after thyroid and parathyroid surgeries. Intraoperative neural monitoring (IONM) is increasingly accepted as an adjunct to the standard practice of visual RLN identification. Endotracheal tube (ET) surface recording electrode systems are now widely used for IONM; however, the major limitation of the clinical use of ET-based surface electrodes is the need to maintain constant contact between the electrodes and vocal folds during surgery to obtain a high-quality recording. An ET that is malpositioned during intubation or displaced during surgical manipulation can cause a false decrease or loss of electromyography (EMG) signal. Since it may be difficult to distinguish from an EMG change caused by a true RLN injury, a false loss or decrease in EMG signal may contribute to inappropriate surgical decision making. Therefore, researchers have investigated alternative electrode systems that circumvent common causes of poor accuracy in ET-based neuromonitoring. Recent experimental and clinical studies have confirmed the hypothesis that needle or adhesive surface recording electrodes attached to the thyroid cartilage (transcartilage and percutaneous recording) or attached to the overlying neck skin (transcutaneous recording) can provide functionality similar to that of ET-based electrodes, and these recording methods enable access to the EMG response of the vocalis muscle that originates from the inner surface of the thyroid cartilage. Studies also indicate that, during surgical manipulation of the trachea, transcartilage, percutaneous, and transcutaneous anterior laryngeal (AL) recording electrodes could be more stable than ET-based surface electrodes and could be equally accurate in depicting RLN stress during IONM. These findings show that these AL electrodes have potential applications in future designs of recording electrodes and support the use of IONM as a high-quality quantitative tool in thyroid and parathyroid surgery. This article reviews the major recent developments of newly emerging transcartilage, percutaneous, and transcutaneous AL recording techniques used in IONM and evaluates their contribution to improved voice outcomes in modern thyroid surgery.

Abstract Background The prognosis for patients with advanced differentiated thyroid carcinoma (ADTC) with disseminated distant metastases is very poor. Tyrosine kinase inhibitors targeting tumor angiogenesis have been shown to improve progression-free survival in patients with advanced thyroid carcinoma and progressive radioiodine-refractory thyroid carcinoma. Tyrosine kinase inhibitor has been reported as a successful neoadjuvant for total thyroidectomy to reduce tumor burden. However, the special indications for prompt treatment with lenvatinib as a rescue therapy to reduce tumor burden and prolong a durable response to radioiodine therapy have not been explored. Case presentation Here, we present two ADTC cases with distant metastases who were effectively treated by total thyroidectomy combined with lenvatinib to prolong a durable response to radioiodine therapy. Case 1 was a 66-year-old male diagnosed with ADTC and disseminated brain, lung, and bone metastases. Lenvatinib was initiated via compassionate access because of rapidly progressive tumor growth even after second doses of radioiodine therapy and external beam radiation therapy for his brain metastases. The result was a durable response to lenvatinib, slowing progressive tumor growth for 3 years and allowing a third course of radioiodine therapy to treat the bone metastases. Case 2 was a 45-year-old male diagnosed with ADTC and diffuse disseminated lung metastases. Respiratory failure ensued after total thyroidectomy, requiring mandatory support by respirator. Lenvatinib was started as a rescue therapy to reduce tumor burden rapidly. The patient was successfully weaned off the respirator only 1 week after using lenvatinib. The patient was then maintained on a low dose of lenvatinib, allowing three subsequent courses of radioiodine therapy. Currently, his lung metastasis remains well controlled with decreased lung infiltrating nodules and the patient can tolerate exercise well. Conclusion Our case experience indicated that lenvatinib has significant value as salvage therapy, reducing tumor burden, producing a durable response and maintaining quality of life. For ADTC patients with progressive life-threatening metastases, our experience suggests that lenvatinib treatment can be used as an urgent rescue therapy as well as a complement to radioiodine therapy to improve tumor eradication.

We evaluate the role of intraoperative neuromonitoring (IONM) in thyroidectomy performed for Graves’ disease (GD) with an emphasis on recurrent laryngeal nerve (RLN) management and completeness of resection. The study is a retrospective series comprising 55 thyroidectomy (control group) versus 82 procedures with intermittent IONM (I-IONM) and 72 by means of continuous IONM (C-IONM). In the control group the laryngeal nerves have been identified by visualization solely. In the I-IONM group both vagal nerve (VN) and RLN have been localized and monitored during thyroid resection. C-IONM was achieved with a vagal stimulation probe. I-IONM group had shorter operating times (P = 0.032). RLN morbidity, meaning palsy rate, was 2.7% in the C-IONM group, 3.6% in I-IONM and 5.4% in the control group (P = 0.058). The proportion of complete procedures (total or near total resections) were significantly higher using monitoring technology (P = 0.049). Persistent positive serum TBII values were found in 25 (45%), 25 (30%) and 20 (27%) patients at 12 months in the control, I-IONM and C-IONM groups respectively (P = 0,04). IONM is an effective technology in GD patients. Keywords: Thyroid surgery, Graves’ disease, Neural monitoring, Recurrent laryngeal nerve, Morbidity

Intraoperative facial nerve monitoring (FNM) has been widely accepted as an adjunct during parotid surgery to facilitate identification of the facial nerve (FN) main trunk, dissection of FN branches, confirmation of FN function integrity, detection of FN injury and prognostication of facial expression after tumor resection. Although the use of FNM in parotidectomy is increasing, little uniformity exists in its application from the literature. Thus, not only are the results of many studies difficult to compare but the value of FNM technology is also limited. The article reviews the current literature and proposes our standardized FNM procedures during parotid surgery, such as standards in FNM setup, standards in general anesthesia, standards in FNM procedures and application of stimulus currents, interpretation of electrophysiologic signals and prediction of the facial expression outcome and pre-/post-operative assessment of facial expressions. We hope that the FNM standardized procedures will provide greater uniformity, improve the quality of applications and contribute to future research.

Intraoperative neural monitoring (IONM) is now an integral aspect of thyroid surgery in many centers. Interest in IONM and the number of institutions that perform monitored thyroidectomies have increased throughout the world in recent years. For surgeons considering the introduction of IONM in their practice, specific training in IONM devices and procedures can substantially shorten the learning curve. The International Neural Monitoring Study Group (INMSG) has been at the forefront of IONM technology and procedural adoption since the introduction of neural monitoring in thyroid and parathyroid surgery. The purpose of this document is to define the INMSG consensus on essential elements of IONM training courses. Specifically, this document describes the minimum training required for teaching practical application of IONM and consensus views on key issues that must be addressed for the safe and reliable introduction of IONM in surgical practice. The intent of this publication is to provide societies, course directors, teaching institutions, and national organizations with a practical reference for developing IONM training programs. With these guidelines, IONM will be implemented optimally, to the ultimate benefit of the thyroid and parathyroid surgical patients.

Over the past decade, the use of neuromonitoring in thyroid surgery has become well established and is increasing accepted across the world. In addition, new developments in energy devices have significantly improved efficacy in achieving hemostasis in thyroid surgery. Few studies focused on the complication rates in energy device-assisted sutureless neuro-monitored thyroidectomy. This study investigates a novel LigaSure Small Jaw (LSJ) technique for sutureless thyroidectomy and compares the surgical complication rates between LSJ and conventional clamp-and-tie technique in one thousand consecutive neuro-monitored thyroidectomy patients. Five hundred patients received sutureless thyroidectomy performed with LSJ (Group L), and 500 patients received surgery performed with conventional clamp-and-tie technique (Group C). Complication rates of postoperative hematoma, hypocalcemia and recurrent laryngeal nerve (RLN) palsy were compared between groups. The overall complication rates of hematoma, hypocalcemia (temporary/ permanent), and RLN (temporary/ permanent) palsy were 0.9%, 24.9% (24.6%/0.3%), and 1.7% (1.5%/0.2%), respectively. Group L and Group C significantly differed in postoperative hematoma rate (0.0% vs. 1.8%, respectively; p = 0.0026) and in postoperative hypocalcemia rate (20.1% vs. 30.0%, respectively; p = 0.0032). The incidence of RLN palsy did not significantly differ between Group L and Group C (1.38% vs. 2.08%; p = 0.2652). The overall surgical complication rates are low in neuro-monitored thyroidectomy. The LSJ is feasible for performing completely sutureless thyroidectomy and obtains superior outcomes of postoperative hematoma and hypocalcemia in comparison with clamp-and-tie hemostatic technique. The novel LSJ technique using double or overlapped sealing is useful for sutureless thyroidectomy. However, surgeons must carefully observe the tissue contraction that may reduce the LSJ-RLN distance and increase the risk of thermal injury during the LSJ activation.

Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cell that is investigated in bone tissue engineering (BTE). Osteoblasts are the main cells responsible for bone formation in vivo and directing ADSCs to form osteoblasts through osteogenesis is a research topic in BTE. In addition to the osteogenesis of ADSCs into osteoblasts, the crosstalk of ADSCs with osteoblasts through the secretion of extracellular vesicles (EVs) may also contribute to bone formation in ADSC-based BTE. We investigated the effect of ADSC-secreted EVs (ADSC-EVs) on osteoblast function. ADSC-EVs (size ≤ 1000 nm) were isolated from the culture supernatant of ADSCs through ultracentrifugation. The ADSC-EVs were observed to be spherical under a transmission electron microscope. The ADSC-EVs were positive for CD9, CD81, and Alix, but β-actin was not detected. ADSC-EV treatment did not change survival but did increase osteoblast proliferation and activity. The 48 most abundant known microRNAs (miRNAs) identified within the ADSC-EVs were selected and then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GO analysis revealed that these miRNAs are highly relevant to skeletal system morphogenesis and bone development. The KEGG analysis indicated that these miRNAs may regulate osteoblast function through autophagy or the mitogen-activated protein kinase or Ras-related protein 1 signaling pathway. These results suggest that ADSC-EVs enhance osteoblast function and can contribute to bone regeneration in ADSC-based BTE.

Objectives: The objective of this study is to evaluate the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) under special programmatic management in Eastern Taiwan over the past 10 years. Materials and Methods: All newly diagnosed MDR-TB patients and MDR-TB patients enrolled previously with persistent positive cultures were included in this study, from May 2007 to April 2017, in Eastern Taiwan. A panel of pulmonologists designed the initial MDR-TB regimens. Subsequently, regimens were adjusted according to drug susceptibility test results for second-line drugs. Mobile teams were organized for treatment support, and several measures were adapted to safeguard effective treatment support. Results: A total of 178 patients with bacteriological confirmed pulmonary MDR-TB were identified, of whom 167 had treatment outcomes when the study was conducted. Of these 167 patients, 120 (71.9%) were cured, 11 (6.5%) completed therapy (78.4% had successful treatment), 25 (15.0%) died, 9 (5.4%) had treatment failure, none were transferred out, and 2 (1.2%) were lost to follow-up. Surgery was performed on 8 (4.8%). Conclusions: This is an analysis of the treatment outcomes after adopting the Directly Observed Treatment, Short-course Plus program to treat MDR-TB patients in Eastern Taiwan. We had a low proportion of loss-to-follow-up, resulting in a high treatment success rate. This program serves as an effective model in providing quality care to patients with MDR-TB.

The application of intraoperative neural monitoring (IONM) has been widely accepted to improve surgical outcomes after thyroid surgery. The malfunction of an IONM system might interfere with surgical procedures. Thus, the development of anesthesia modalities aimed at ensuring functional neuromonitoring is essential. Two key issues should be taken into consideration for anesthetic management. Firstly, most patients undergo recurrent laryngeal nerve monitoring via surface electrodes embedded in an endotracheal tube. Thus, advanced video-assisted devices might optimize surface electrode positioning for improved neuromonitoring signaling accuracy. Secondly, neuromuscular blocking agents are routinely used during thyroid surgery. The ideal neuromuscular block should be deep enough for surgical relaxation at excision and recovered enough for an adequate signal f nerve stimulation. Proper neuromuscular block management could be achieved by titration doses of muscle relaxants and reversal agents.

A variety of electromyography (EMG) recording methods were reported during intraoperative neural monitoring (IONM) of recurrent laryngeal nerve (RLN) in thyroid surgery. This study compared two surface recording methods that were obtained by electrodes on endotracheal tube (ET) and thyroid cartilage (TC). This study analyzed 205 RLNs at risk in 110 patients undergoing monitored thyroidectomy. Each patient was intubated with an EMG ET during general anesthesia. A pair of single needle electrode was inserted obliquely into the TC lamina on each side. Standard IONM procedure was routinely followed, and EMG signals recorded by the ET and TC electrodes at each step were compared. In all nerves, evoked laryngeal EMG signals were reliably recorded by the ET and TC electrodes, and showed the same typical waveform and latency. The EMG signals recorded by the TC electrodes showed significantly higher amplitudes and stability compared to those by the ET electrodes. Both recording methods accurately detected 7 partial loss of signal (LOS) and 2 complete LOS events caused by traction stress, but only the ET electrodes falsely detected 3 LOS events caused by ET displacement during surgical manipulation. Two patients with true complete LOS experienced temporary RLN palsy postoperatively. Neither permanent RLN palsy, nor complications from ET or TC electrodes were encountered in this study. Both electrodes are effective and reliable for recording laryngeal EMG signals during monitored thyroidectomy. Compared to ET electrodes, TC electrodes obtain higher and more stable EMG signals as well as fewer false EMG results during IONM.

The use of neuromuscular blocking agent (NMBA) during anesthesia may interfere with facial nerve monitoring (FNM) during parotid surgery. Sugammadex has been reported to be an effective and safe reversal of rocuronium-induced neuromuscular block (NMB) during surgery. This study investigated the feasibility and clinical effectiveness of sugammadex for NMB reversal during FNM in Parotid surgery. Fifty patients undergoing parotid surgery were randomized allocated into conventional anesthesia group (Group C, n = 25) and sugammadex group (Group S, n = 25). Group C did not receive any NMBA. Group S received rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at skin incision. The intubating condition and influence on FNM evoked EMG results were compared between groups. The intubation condition showed significantly better in group S patients than C group patients (excellent in 96% v.s. 24%). In group S, rapid reverse of NMB was found and the twitch (%) recovered from 0 to >90% within 10 min. Positive and high EMG signals were obtained in all patients at the time point of initial facial nerve stimulation in both groups. There was no significant difference as comparing the EMG amplitudes detected at the time point of initial and final facial nerve stimulation in both groups. Implementation of sugammadex in anesthesia protocol is feasible and reliable for successful FNM during parotid surgery.

Objective. Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. Methods. Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. Results. Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 μV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 μV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 μV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 μV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. Conclusion. The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.

Recurrent laryngeal nerve (RLN) injury is a significant morbidity associated with thyroid surgery. Surgeons have increasingly used intraoperative neural monitoring (IONM) as an adjunct technique for identifying the RLNand predicting the outcome of vocal cord function. Many animal studies have investigated limits, adjournments and new applications of IONM. The advent of animal studies has substantially improved understanding of IONM technology and the electrophysiology of RLN. Lessons learned from animal studies have clinical applications in establishing proper strategies for preventing nerve injury.

Directing adipose-derived stem cells (ADSCs) toward chondrogenesis is critical for ADSC-based articular cartilage regeneration. Simvastatin (SIM) was reported to promote both chondrogenic and osteogenic differentiation of ADSCs by upregulating bone morphogenetic protein-2 (BMP-2). We previously found that ADSC chondrogenesis is initiated and promoted in a hyaluronan (HA) microenvironment (HAM). Here, we further hypothesized that SIM augments HAM-induced chondrogenesis but not osteogenesis of ADSCs. ADSCs were treated with SIM in a HAM (SIM plus HAM) by HA-coated wells or HA-enriched fibrin (HA/Fibrin) hydrogel, and chondrogenic differentiation of ADSCs was evaluated. SIM plus HAM increased chondrogenesis more than HAM or SIM alone, including cell aggregation, chondrogenic gene expression (collagen type II and aggrecan) and cartilaginous tissue formation (collagen type II and sulfated glycosaminoglycan). In contrast, SIM-induced osteogenesis in ADSCs was reduced in SIM plus HAM, including mRNA expression of osteogenic genes, osteocalcin and alkaline phosphatase (ALP), ALP activity and mineralization. SIM plus HAM also showed the most effective increases in the mRNA expression of BMP-2 and transcription factors of SOX-9 and RUNX-2 in ADSCs, while these effects were reversed by CD44 blockade. HAM suppressed the levels of JNK, p-JNK, P38 and p-P38 in ADSCs, and SIM plus HAM also decreased SIM-induced phosphorylated JNK and p38 levels. In addition, SIM enhanced articular cartilage regeneration, as demonstrated by implantation of an ADSCs/HA/Fibrin construct in an ex vivo porcine articular chondral defect model. The results from this study indicate that SIM may be an enhancer of HAM-initiated MSC-based chondrogenesis and avoid osteogenesis.

During conventional intermittent intraoperative neuromonitoring (IONM) in thyroidectomy, recurrent laryngeal nerve (RLN) injury is detected by an electromyographic (EMG) loss of signal (LOS) after the nerve dissection. Exclusive continuous monitoring during the phase of RLN dissection may be helpful in detecting adverse EMG changes earlier. A total of 208 RLNs at risk were enrolled in this study. Standardized IONM procedures were followed. We continuously stimulated the RLN at the lower exposed end with a stimulator to exclusively monitor the real-time quantitative EMG change during RLN dissection. Once the amplitude decreased by more than 50% of the initial signal, the surgical maneuver was paused and the RLN was retested every minute for 10 minutes to determine amplitude recovery before restarting the dissection. The procedure was feasible in all patients. No LOS was encountered in this study. Nineteen RLNs had an amplitude reduction of more than 50%. Eighteen nerves showed gradual amplitude recovery (16 nerves had a traction injury and two nerves had a compression injury). After 10 minutes, the recovery was complete (i.e., >90%) in eight nerves, 70–90% in seven nerves, and 50–70% in three nerves. Among these 18 nerves, only one nerve developed temporary vocal palsy because it was exposed to unavoidable repeated nerve traction after restarting the dissection. Another nerve showed no gradual recovery from thermal injury, and developed temporary vocal palsy. The temporary and permanent palsy rates were 1% and 0%, respectively. During intermittent IONM, exclusive real-time monitoring of the RLN during dissection is an effective procedure to detect an adverse EMG change, and prevent severe RLN injuries that cause LOS.

Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers.