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Background: Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro-cancer inflammation and anti-cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain., Method: The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre-treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors., Results: A total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27-3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47-11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07-2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88-0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low-LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non-synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38-2.81, p < 0.001), a low-BMI (HR 0.96; 95% CI 0.93-0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10-2.22, p = 0.013) were independent prognostic factors for HNSCC patients., Conclusion: Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low-BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti-cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future., (© 2024 Wiley Periodicals LLC.)

Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC., Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan-Meier curves were plotted for outcomes estimation., Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB ( p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB ( p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS., Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.

Objectives: The 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)., Methods: Fifty 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 (V 1 -R 1 -R 2 -V 2 ) recorded by A-mode and B-mode were compared., Results: All EMG amplitudes of V 1 -R 1 -R 2 -V 2 signals recorded with B-mode were all above 500μV and significantly higher than those with A-mode (p<0.001). No false loss of signal, electrode dislodgement, or needle-related complications were noted during IONM. Postoperatively, all patients had symmetrical vocal cord movement. Lower EMG amplitudes were observed in older and male patients. Histopathology and laterality showed no significant differences in EMG amplitude., Conclusion: During using TCERM in thyroid surgery, the recording electrodes should be placed contra-laterally on the TC lamina. This approach ensures high and stable EMG signals, which are important for high-quality IONM of the RLN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chiang, Shih, Lien, Wang, Wang, Hwang, Huang, Wu, Yeh and Huang.)

Background: Little is known regarding the prognostication of the Pan-Immune-Inflammation Value (PIV) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)., Objectives: This study aimed to investigate the prognostic role of PIV in patients with R/M HNSCC receiving immune checkpoint inhibitors (ICI)., Patients and Methods: Patients who were diagnosed to have R/M HNSCC and treated with ICI were reviewed retrospectively. The cutoff value of PIV was set at the median. Patients were stratified into high PIV and low PIV. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS)., Results: A total of 192 patients were included in our study for oncologic outcomes evaluation. For the total population, the median PFS was 5.5 months and OS was 18.2 months. After stratification by PIV, median PFS was 11.7 months in the low PIV and 2.8 months in the high PIV groups (p < 0.001). The median OS was 21.8 months in the low PIV and 11.5 months in the high PIV groups (p < 0.001). Multivariate analysis demonstrated that PIV and PD-L1 were independent predictors associated with survival. A prognostic model using both PIV and PD-L1 was constructed. The median PFS was 12.2, 6.4, and 3.0 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001). The median OS was 23.7, 18.1, and 11.4 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001)., Conclusions: PIV is a prognostic biomarker in patients with R/M HNSCC treated with ICI. A prognostic model using PIV and PD-L1 could provide outcome prediction and risk stratification., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The prognosis of patients with hypopharyngeal cancer (HPC) remains poor. Our study aims to investigate the prognostic impact of cortactin in patients with HPC and its role for tegafur-uracil (UFUR) maintenance after adjuvant chemoradiotherapy (CRT). Patients who were diagnosed to have HPC and underwent laryngopharyngectomy followed by adjuvant CRT were enrolled into our study. Immunohistochemical staining was performed for cortactin evaluation. Kaplan-Meier curves were depicted for recurrence-free survival (RFS) and overall survival (OS). A total of 157 patients were enrolled into our study. After stratified by cortactin, 53 patients were cortactin (+) and 104 patients were cortactin (-). The median RFS was 86.7 months in cortactin (-) and 10.2 months in cortactin (+) (P < 0.001). The median OS was 93.4 months in cortactin (-) and 16.9 months in cortactin (+) (P < 0.001). Patients were further classified according to UFUR maintenance or not after adjuvant CRT. In cortactin (+) patients, the median RFS and OS were 13.6 months versus 7.0 months (P = 0.006) and 24.0 months versus 10.0 months (P < 0.001) in UFUR (+) and UFUR (-), respectively. In cortactin (-) patients, the median RFS and OS were 96.0 months versus 72.2 months (P = 0.262) and 98.5 months versus 105.0 months (P = 0.665) in UFUR (+) and UFUR (-), respectively. Cortactin has a significantly impact in HPC patients. UFUR maintenance provided survival benefits in patients with cortactin (+) after adjuvant CRT., Competing Interests: None., (AJCR Copyright © 2023.)

Objective: To investigate the beneficial outcomes of intraoperative enteral feeding in free-flap regeneration after extended head and neck cancer resection and flap reconstruction surgery., Study Design: A pilot randomized, double-blind, placebo-controlled clinical trial., Setting: Single tertiary care center., Methods: Patients with advanced head and neck cancers requiring radical tumor resections and free-flap reconstruction were randomly assigned to receive intraoperative enteral nutrition feeding (100 kcal/100 mL at 10-20 mL/h) via a nasogastric tube during free-flap reconstruction (n = 28) or continue fasting (n = 28). The primary outcome was impaired free-flap regeneration that required surgical reintervention within 90 days after the operation. Participants were enrolled between April 2020 and January 2022; the 90-day follow-up ended in April 2022., Results: The incidence of total or partial flap failure was similar between the 2 groups (14.2% or n = 4 in each group), but the rate of wound dehiscence or edge necrosis was significantly reduced in the feeding group (n = 6 vs 0 for fasting vs feeding; absolute risk reduction, 25.0% [95% confidence interval, 6.9-43.0]%; p = 0.022). Hospital stay length was shorter (p = 0.042) and hand grip strength was better preserved (p = 0.025) in the feeding group. Plasma concentrations of interleukin (IL)-6 and IL-8 after the operation increased significantly more in the fasting group. Perioperative adverse events did not differ between the 2 groups., Conclusion: Perioperative enteral feeding is a simple, safe, and effective approach to improve perioperative systemic catabolism and proinflammatory reactions, thereby enhancing early wound regeneration after major operations., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

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.

Concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nasopharyngeal carcinoma (NPC). Our study was a propensity-score-matching analysis and it aimed to investigate the oncologic outcomes of platinum plus tegafur−uracil versus platinum alone during CCRT in patient with nonmetastatic NPC. Patients with pathologic confirmed NPC in 2018−2022 were reviewed. Patients treated with platinum plus tegafur−uracil (CCRT-UP) or platinum alone (CCRT-P) during CCRT were recruited into this study. A propensity-score-matching analysis was conducted to diminish the selection bias. The recurrence-free survival (RFS) and overall survival (OS) were presented with Kaplan−Meier curves. The treatment-related adverse effects (AEs) were recorded according to the National Cancer Institute’s Common Terminology Criteria V3.0. A total of 44 patients with CCRT-UP and 44 patients with CCRT-P were identified after propensity score matching. The median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). The overall response rate and disease-control rate were insignificant between the CCRT-UP and CCRT-P groups. A subgroup analysis showed that the median OS was significantly longer in the CCRT-UP group than in the CCRT-P group, regardless of the clinical stage. A multivariate analysis exhibited that CCRT-UP was independently correlated with survival. The grade 3−4 AEs were insignificant between the CCRT-UP and CCRT-P arms. CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles. Further larger-scaled prospective randomized control trials are warranted to validate our conclusions.

Objectives: Traction 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., Methods: 644 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., Results: 44/1142 (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., Conclusion: Early 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chiu, Lien, Wang, Wang, Hwang, Shih, Yu, Wu, Dionigi, Huang and Chiang.)

Head and neck squamous cell carcinoma (HNSCC) is a common cancer of the oral cavity. Cisplatin (CDDP) is the ideal chemo-radiotherapy used for several tumor types, but resistance to the drug has become a major obstacle in treating patients with HNSCC. 5-methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, reduces inflammation-mediated proliferation and metastasis. This study aimed to assess the anti-oral cancer activity of 5-MTP when used alone or in combination with CDDP. Results showed that CDDP dose dependently reduced the growth of SSC25 cells but not 5-MTP. The combination of CDDP and 5-MTP exerted additional inhibitory effect on the growth of SSC25 cells by attenuating the phosphorylation of STAT3. In the 4-nitroquinoline-1-oxide-induced oral cancer mouse model, 5-MTP sensitized the reduction effect of CDDP on tumorigenesis, which restricted the tongue tissue in hyperkeratotic lesion rather than squamous cell carcinoma. The combination of CDDP and 5-MTP may be a potent therapeutic strategy for HNSCC patients with radiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JT declared a shared affiliation, with no collaboration, with one of the authors, H-CC, and the reviewer LC declared a shared affiliation, with no collaboration, with several of the authors, Y-CS, C-CW, S-AY, T-ZH, to the handling editor at the time of the review., (Copyright © 2022 Su, Wang, Weng, Yeh, Chen, Hwang and Chen.)

Objectives: Intraoperative 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., Methods: In 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., Results: Nerve 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., Conclusion: Routinely 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Lien, Wang, Wang, Hwang, Shih, Wu, Dionigi, Huang and Chiang.)

Background: The prognosis was poor when patients had recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Herein, we conducted an observational study of cetuximab followed by immunotherapy (Cet-IO) versus immunotherapy followed by cetuximab (IO-Cet) in patients with R/M HNSCC., Methods: Patients who were diagnosed with R/M HNSCC and treated with a sequential cetuximab-containing regimen and immunotherapy-containing regimen were enrolled in our study. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS)., Results: A total of 75 patients were enrolled in our study for oncologic outcomes evaluation, with 40 patients in Cet-IO and 35 patients in IO-Cet. The median PFS1 was 5.1 months in Cet-IO and 4.5 months in IO-Cet ( p = 0.777) and the median PFS2 was 16.5 months in Cet-IO and 11.4 months in IO-Cet ( p = 0.566). The median OS was 23.7 months versus 22.8 months in Cet-IO and IO-Cet, respectively ( p = 0.484). The overall response rate (ORR) were 73% in Cet-IO versus 37% in IO-Cet ( p = 0.002). Multivariate analysis demonstrated that the treatment sequences, Cet-IO or IO-Cet, were insignificantly different with survival., Conclusion: Both Cet-IO and IO-Cet are effective in R/M HNSCC patients with insignificant survival differences. The higher ORR of Cet-IO might render it to be considered in patients with large tumor burdens and urgent needs for treatment responses. Further prospective studies are merited to validate our conclusions.

Introduction: Induction chemotherapy (IC) has a proven role in organ preservation and reducing distant failure. However, its ability to prolong survival remains controversy. Herein, our study aimed to investigate the impact of primary tumor location on survival in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with IC., Methods: Patients who were older than 18 years and diagnosed with LA-HNSCC between 2007 and 2016 were retrospectively identified from Taiwan National Health Insurance Research Database and Taiwan Cancer Registry. Patients were categorized into two group: IC group and CCRT group. In order to reduce the selection bias, IC patients were individually matched with the CCRT patients. The oncologic outcomes were presented with overall survival (OS)., Results: A total of 5547 patients were identified. After matching, 2208 patients were analyzed for outcomes comparison, including 1104 patients in each group. In general, median OS were 27.3 months versus 28.5 months in IC and CCRT group, respectively (p = 0.6151). Patients were stratified by primary tumor location. For patients with oral cavity cancers, the median OS was significantly inferior in IC group than those in CCRT group, while for patients with non-oral cavity cancer, the median OS was superior in IC group than those in CCRT group., Conclusions: Primary tumor location has a significant impact on survival in patients with LA-HNSCC treated with IC. Our study provides a strong evidence that primary tumor location should be taken into consideration during multidisciplinary approach., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Total thyroidectomy (TT) in patients with Graves' disease is challenging even for an experienced thyroid surgeon. This study aimed to investigate the accumulation of experience and applying newly developed devices on major complications and voice outcomes after surgery of a single surgeon over 30 years. This study retrospectively reviewed 90 patients with Graves' disease who received TT. Forty-six patients received surgery during 1990-1999 (Group A), and 44 patients received surgery during 2010-2019 (Group B). Major complications rates were compared between Group A/B, and objective voice parameters were compared between the usage of energy-based devices (EBDs) within Group B. Compared to Group B, Group A patients had higher rates of recurrent laryngeal nerve palsy (13.0%/1.1%, p = 0.001), postoperative hypocalcemia (47.8%/18.2%, p = 0.002), and postoperative hematoma (10.9%/2.3%, p = 0.108). Additionally, Group A had one permanent vocal cord palsy, four permanent hypocalcemia, and one thyroid storm, whereas none of Group B had these complications. Group B patients with EBDs had a significantly better pitch range ( p = 0.015) and jitter ( p = 0.035) than those without EBDs. To reduce the major complications rate, inexperienced thyroid surgeons should remain vigilant when performing TT for Graves' disease. Updates on surgical concepts and the effective use of operative adjuncts are necessary to improve patient safety and voice outcome.

Background: Oral mucositis (OM) is a common toxic side effect in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) that has a negative impact on treatment outcomes and patients’ survival. Our study aimed to evaluate the impact of parenteral glutamine supplement (dipeptiven) on oncologic outcomes in patients with NPC treated with CCRT. Methods: Patients who were diagnosed with pathologically proved NPC and treated with CCRT were enrolled into our study. Patients were classified as dipeptiven (+) and dipeptiven (−). Oncologic outcomes were measured, and multivariate regression analysis was performed. Grade 3−4 treatment related toxicities were also documented. Results: A total of 144 patients with NPC were recruited in this study to evaluate oncologic outcomes, with 41 dipeptiven (+) and 103 dipeptiven (−). CCRT interruption rate and severe adverse effect (SAE) rate were significant lower in the dipeptiven (+) group than in the dipeptiven (−) group. The median overall survival (OS) was not mature yet in the dipeptiven (+) group and 30 months in the dipeptiven (−) group (p < 0.01). Multivariate analysis demonstrated that dipeptiven supplementation and CCRT interruption were independent predictors associated with better survival. The OS was longest in patients with a dipeptiven supplement and patients who had CCRT interruption had significantly worst OS. As for safety profiles, grade 3 to 4 adverse effects were fewer in dipeptiven (+) than in dipeptiven (−). Conclusion: Dipeptiven supplementation is crucial in NPC patients treated with CCRT, which can ameliorate treatment-related toxicity and augment treatment efficacy. Further prospective clinical trials are warranted to validate our results.

This observational study investigated intraoperative electrophysiological changes and their correlation with postoperative facial expressions in parotidectomy patients with visual confirmation of facial nerve (FN) continuity. Maximal electromyography(EMG) amplitudes of the facial muscles corresponding to temporal, zygomatic, buccal and mandibular branches were compared before/after FN dissection, and facial function at four facial regions were evaluated before/after parotidectomy in 112 patients. Comparisons of 448 pairs of EMG signals revealed at least one signal decrease after FN dissection in 75 (67%) patients. Regional facial weakness was only found in 13 of 16 signals with >50% amplitude decreases. All facial dysfunctions completely recovered within 6 months. EMG amplitude decreases often occur after FN dissection. An amplitude decrease >50% in an FN branch is associated with a high incidence of dysfunction in the corresponding facial region. This study tries to establish a standard facial nerve monitoring (FNM) procedure and a proper facial function grading system for parotid surgery that will be useful for the future study of FNM in parotid surgery.

There are increasing incidences of elderly patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the treatment is not yet established. We conducted a propensity score matching analysis to evaluate the efficacy and safety of tegafur-uracil versus 5-fluorouracil in combination with cisplatin plus cetuximab in elderly patients with R/M HNSCC. Elderly patients with R/M HNSCC treated with cetuximab-containing chemotherapy were recruited into this study. In order to reduce the selection bias, propensity score matching was performed. Kaplan-Meier curves were plotted for progression-free survival (PFS) and overall survival (OS). Toxicities were graded according to the National Cancer Institute's Common Terminology Criteria V3.0. After propensity sore matching, 54 patients with tegafur-uracil, cisplatin plus cetuximab (UPEx), and 54 patients with 5-fluorouracil, cisplatin plus cetuximab (EXTREME) were identified. The median PFS was 5.4 months in UPEx and 5.8 months in EXTREME ( p = 0.451). The median OS was 10.8 months in UPEx and 10.2 months in EXTREME ( p = 0.807). The overall response rate (ORR) and disease control rate (DCR) were insignificant in both arms, accounting for 61% versus 59% ( p = 0.680) and 72% versus 70% ( p = 0.732) in the UPEx arm and the EXTREME arm, respectively. A multivariate analysis showed that age and ECOG PS were, independently, predictors. Grade 3/4 adverse events were much fewer in UPEx than in EXTREME ( p < 0.001). Both cetuximab-containing chemotherapies are effective in elderly patients with R/M HNSCC. Safety profiles are improved when tegafur-uracil is substituted for 5-fluorouracil. Further prospective studies are warranted to validate our conclusions.

Nasopharyngeal cancer shows a good response to intensity-modulated radiotherapy. However, there is no clear evidence for the benefits of routine use of image-guided radiotherapy. The purpose of this study was to perform a retrospective investigation of the treatment outcomes, treatment-related complications and prognostic factors for nasopharyngeal cancer treated with intensity-modulated radiotherapy and image-guided radiotherapy techniques. Retrospective analysis was performed on 326 consecutive nasopharyngeal cancer patients treated between 2004 and 2015. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. The 5-year overall survival and disease-free survival rates of these patients were 77.9% and 70.5%, respectively. Age, AJCC (American Joint Committee on Cancer) stage, retropharyngeal lymphadenopathy, treatment interruption and body mass index were independent prognostic factors for overall survival. Age, AJCC stage, retropharyngeal lymphadenopathy, image-guided radiotherapy and body mass index were independent prognostic factors for disease-free survival. In conclusion, intensity-modulated radiotherapy significantly improves the treatment outcomes of nasopharyngeal cancer. With the aid of image-guided radiotherapy, the advantage of intensity-modulated radiotherapy might be further amplified., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Wang, Wu, Lin, Lu, Chang, Lien, Wang, Hwang, Huang and Chiang.)

Approximately 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually. Radiation therapy is an important treatment for oral squamous cell carcinoma (OSCC). The survival rate of patients with HNSCC remained low (50%) in decades because of radiation therapy failure caused by the radioresistance of HNSCC cells. This study aimed to identify PI3K inhibitors that can enhance radiosensitivity. Results showed that pan-Phosphoinositide 3-kinases (PI3K) inhibitor BKM120 and class I α-specific PI3K inhibitor BYL719 dose-dependently reduced the growth of OSCC cells but not that of radioresistant OML1-R cells. The combination treatment of BKM120 or BYL719 with radiation showed an enhanced inhibitory effect on OSCC cells and radioresistant OML1-R cells. Furthermore, the enhanced inhibitory effect of the combination treatment was confirmed in patient-derived OSCC cells. The triple combination treatment of mTOR inhibitor AZD2014 and BKM120 or AZD2014 and BYL719 with radiation showed a significantly enhanced inhibitory effect on radioresistant OML1-R cells. These results suggest that the PI3K inhibitors are potential therapeutic agents with radiosensitivity for patients with OSCC., Competing Interests: The authors have declared that no competing interests exist.

Preoperative fasting aims to prevent pulmonary aspiration and improve bowel preparation, but it may induce profound systemic catabolic responses that lead to protein breakdown and insulin-resistant hyperglycemia after operation. However, the molecular mechanisms of catabolic reaction induced by prolonged preoperative fasting and surgical stress are undetermined. In this study, anesthetized rats were randomly assigned to receive a sham operation or laparotomy cecectomy. Fasting groups were restricted from food and water for 12 h before operation, while the feeding group had free access to food throughout the study period. Twenty-four hours after operation, the animals were sacrificed to collect blood samples and soleus muscles for analysis. Postoperative blood glucose level was significantly increased in the fasting group with elevated serum insulin and C-peptide. Continuous feeding reduced serum myoglobin and lactate dehydrogenase concentrations. Preoperative fasting activated inositol-requiring transmembrane kinase/endoribonuclease (IRE)-1α and c-Jun N-terminal kinase (JNK) mediated endoplasmic reticulum (ER)-stress, and reduced glucose transporter type 4 (Glut4) expression in the soleus muscle. Phospholamban phosphorylation was reduced and intracellular calcium levels were increased in the isolated skeletal muscle cells. Similar results were found in ER stress-induced C1C12 myoblasts. The expression of Glut4 was suppressed in the stressed C1C12, but was potentiated following inhibition of ER stress and chelation of intracellular free calcium. This study provides evidence demonstrating that prolonged preoperative fasting induces ER stress and generates insulin resistance in the skeletal muscle through suppression of Glut4 and inactivation of Ca 2+ -ATPase, leading to intracellular calcium homeostasis disruption and peripheral insulin resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This study aimed to estimate the effects of a supportive care program on the posttraumatic stress symptoms (PTSSs) of patients with oral cancer after surgery. Participants were divided into two groups. Outcome measurements included the Chinese version of the Davidson trauma scale to examine PTSSs at a clinical follow-up 1 week (T0), 1 month (T1), and 3 months (T2) after hospital discharge. The results indicated that the frequency and severity mean scores of PTSSs for the two groups at T0 were significantly higher than those at T1 and T2. Both the groups and times were significantly different; moreover, the supported group's PTSS score decreased more than that of the nonsupported group. These findings supported the effects of the supportive care program. Health care staff should be aware of the PTSS status of patients with oral cancer who undergo surgery and consider these issues in combination with patients' discharge care plans.

Objective: This study aimed to explore the influence of social support on the survival outcomes of patients with nasopharyngeal carcinoma (NPC). We examined whether the combined proxy influenced whether patients were more likely to receive radiotherapy., Methodology: data were collected from the 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The association between both insurance status and marital status and disease-specific survival rates were evaluated with a multivariate Cox proportional-hazards regression model to calculate the hazard ratios and associated confidence intervals. Odds ratio (OR) computed by logistic regression was also used to examine the relationship between the receipt of radiotherapy and insurance and marital status., Results: insured and uninsured patients differed significantly in T-stage, N-stage, M-stage, radiotherapy use, race, and marital status. The uninsured-non-married patients showed the lowest 5-year disease-specific survival rates. We further found unmarried patients with either Medicaid (OR, 0.40), or no insurance (OR, 0.24) had lower odds of receiving radiotherapy than those with insurance at diagnosis., Conclusions: uninsured-unmarried NPC patients had a significantly higher risk of distant metastasis at diagnosis, poorer 5-year disease-specific survival, and were less likely to receive radiotherapy than insured-married patients.

Background: Open thyroidectomy via conventional midline approach can be challenging in complex thyroid surgeries. This study proposes a U-shaped strap muscle flap (USMF) technique that provides adequately wide exposure of the surgical field., Methods: Strap muscles were cut close to the clavicle and along the anterior margin of both sternocleidomastoid muscles followed by total thyroidectomy in 20 patients as USMF group, and surgical outcomes were compared with 40 patients who had received total thyroidectomy via midline approach., Results: No patient had postoperative hematoma, vocal cord paralysis, permanent hypocalcaemia, wound infection or flap necrosis. At 2 months post-surgery, objective voice analysis and subjective assessment of voice and swallowing showed no significant difference between groups., Conclusions: USMF provides superb surgical field exposure, and the voice and swallowing functions after USMF are comparable to those obtained by midline approach. The USMF approach is a feasible option for selective difficult thyroid surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.02.20). Dr. Wu reports grants from Kaohsiung Medical University Hospital, Taiwan, during the conduct of the study. Dr. Huang reports grants from Kaohsiung Medical University Hospital, Taiwan, during the conduct of the study. The other authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Background: Surgery, the primary treatment for oral cancer, results in oral and facial structural defects that may cause difficulties in swallowing or mastication and thereby affect nutrition status and quality of life., Purpose: This study was designed to understand nutritional status and quality of life in oral cancer patients who had undergone surgery and to examine the effects of a dietary education program on nutritional status and quality of life in these patients., Methods: A quasi-experimental design was conducted. Eligible patients were enrolled immediately after they could sip water after surgery. The participants were randomized into the experimental group (n = 42) and the control group (n = 42). Both groups were provided guidance for swallowing exercise and performed a pre-test (T0) and three post-tests (T1-T3) for a total of three months. The experimental group additionally received a diet assessment and dietary education program intervention. The outcome measures included the nursing nutritional risk screening tool (NNRST) and oral health impact profile (OHIP-14T)., Results: The level of malnutrition risk (T0 vs. T3) was 47.6% vs. 4.8% in the experimental group and 35.7% vs. 42.9 in the control group. Generalized estimating equation (GEE) statistics were used to assess the effects of the dietary education program on nutritional status. Quality of life was found to be significantly better in the experimental group than in the control group (p < .001)., Conclusions / Implications for Practice: A dietary education program may be used to effectively improve the nutritional status and quality of life of patients after oral cancer surgery. We suggest that specialized nutritional support be provided during cancer treatment in order to achieve good nutritional status and improve quality of life.

How long esophageal screening should be performed for, and on which sub-groups of head and neck cancer (HNC) survivors, remains uncertain. This retrospective study analyzed data from the Taiwan National Health Insurance Research Database from 1999 to 2013. A total of 68,131 newly- diagnosed HNC patients were enrolled. Subjects who received esophageal endoscopic screening within 6 months after their diagnosis date of index HNC were identified. The incidence trends of secondary primary EC were analyzed using a Cochran-Armitage trend test. Among the 9,707 patients who received index esophageal endoscopy screening, 101 (1.0%) cases of synchronous EC were diagnosed. The 5- and 10-year cumulative incidence rates of metachronous ECs were 1.4% and 2.7%, respectively in those with an initial negative index endoscopic finding. Patients with oropharynx or hypopharynx cancers were at significantly higher risk of developing metachronous ECs compared with those with oral or larynx cancers (10-year incidence rate: 3.3% vs. 0.9%, respectively; hazard ratio: 2.15; 95% confidence intervals: 1.57-2.96). Metachronous EC continues to develop in patients with HNC even at 10-years after treatment for primary HNC. HNC patients, especially those with oropharynx or hypopharynx cancer, may require long-term endoscopic surveillance.

There is high risk of metastasis and recurrence in head and neck squamous cell carcinoma (HNSCC) patients, especially for patient who received definitive surgery and adjuvant radiotherapy. Aberrant activation of PI3K/AKT/mTOR signaling occurs in approximately 80% of HNSCC, which has been indicated to serve as prognostic biomarkers for patients suffer from recurrence or metastasis. Therefore, in this study, we focus on the relationship between the expression level of signaling factors in PI3K/AKT/mTOR pathway and recurrence tumor from HNSCC patients. A tissue microarray (TMA) was constructed from 54 cases of HNSCC patients who received definitive surgery and adjuvant radiotherapy, are followed more than 5 years, and with no previous malignancy and synchronous tumor. Slides were scored and dichotomized by two pathologists and scores. Based on the TMA block with IHC staining, the results showed that PI3K/AKT/mTOR signaling was highly activated both in recurrence and non-recurrence patients. Particularly, in the recurrence population, the results showed the low expression phospho-eukaryotic initiation factor 4E (p-eIF4E) or high expression eIF4E, phospho-eIF4E binding protein 1 (p-4EBP1), phospho-ribosomal protein S6 kinase beta-1 (p-S6K1) and phospho-40S ribosomal protein S6 (p-S6R) exhibited worse overall survival. The expression level of eIF4E and p-4EBP1 were significantly associated with tumor recurrence and recurrence-free survival. Furthermore, high expression level of eIF4E and p-4EBP1 had worse recurrence-free survival. In conclusion, the expression of eIF4E and p-4EBP1 should be considered as predictive biomarkers for the HNSCC patients. This may contribute to potential predictive biomarkers for HNSCC patient who receive adjuvant radiotherapy., Competing Interests: The authors have declared that no competing interests exist.

Objective: Hypopharyngeal carcinoma has a very poor prognosis. The high incidence of second esophageal neoplasia is one of the major causes. To establish an efficient follow-up scheme for increasing the diagnostic yield and reducing the adverse impact of second esophageal neoplasia on survival, the purpose of this study was to explore a biomarker to predict second esophageal neoplasia., Methods: In this retrospective cohort study, consecutive tissue specimens from those patients who underwent tumor resection between September 2007 and October 2015 were collected. Gene amplification was performed by real-time PCR. The expression of cortactin was evaluated by immunohistochemistry. The predictive risk factors of developing second esophageal neoplasia and prognostic factors related to survival were analyzed., Results: A total of 187 patients were included with a mean follow-up of 48months (12-118months). Second esophageal tumors were found in 53 (28.3%), including 41 (21.9%) esophageal squamous cell carcinoma and 12 severe dysplasia. The results of multivariate analyses revealed that age (OR 2.81, 95% CI 1.16-6.78), cortactin overexpression (OR 2.49, 95% CI 1.17-5.33), and stage IV versus I (OR 6.49, 95% CI 1.68-25.18) were independent predictors of second esophageal neoplasia, and second esophageal neoplasia (HR 1.78, 95% CI 1.05-3.01) was an independent predictor of overall survival., Conclusion: This is the first report to identify a potential biomarker for predicting second esophageal neoplasia in patients with hypopharyngeal carcinoma. In those patients with cortactin overexpression and younger age (≤60years old), close surveillance for second esophageal neoplasia is required. In addition, the real effect of cortactin overexpression on development of primary esophageal carcinoma is required to be validated in a large cohort study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Endothelin-converting enzyme-1 (ECE-1) primarily converts big endothelins (ETs) into active endothelin-1 (ET-1). However, the expression pattern and prognostication status of ECE-1 in head and neck cancer (HNC) are enigmatic. In this study, we investigated ECE-1 expression and assessed the roles of ECE-1 as a predictor for HNC differentiation and prognosis., Materials and Methods: ECE-1 expressions were evaluated by immunohistochemical analysis using a tissue microarray (TMA) composed of 100 cases of head and neck squamous cell carcinoma. The correlation of ECE-1 expression with clinicopathologic variables and patient outcomes was analyzed., Results: ECE-1 may be overexpressed in HNC carcinoma cells. Higher ECE-1 level was detected more frequently in moderately to poorly differentiated tumors and showed a lower differentiation category compared to the G1 cases (p = 0.015); this finding was further confirmed by an adjusted odds ratio (OR) of 4.071 (p = 0.042). Moreover, Kaplan-Meier survival analyses showed that a higher ECE-1 expression was associated with a poorer survival in patients with HNC (p < 0.0001). On multivariate Cox proportional hazards models analysis, ECE-1 of high expression proved to be an independent prognostic factor with a hazard ratio (HR) of 3.985 (p < 0.001)., Conclusion: Our data provide the first evidence that overexpression of ECE-1 in HNC is a predictor of poor tumor differentiation and prognosis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

The present study aimed to identify a feasible treatment strategy for hypopharyngeal cancer (HPC) with non-extensive invasion of the thyroid and/or cricoid cartilage. Between June 2008 and December 2014, patients with previously untreated HPC invading cartilage who had received either open partial laryngectomy (OPL) with tube-free tracheostomy or total laryngectomy (TL) with permanent tracheostomy and an artificial larynx (pneumatic tube) were retrospectively reviewed. The patients with extensive cartilage invasion and those with inoperable or T4b disease were excluded for OPL. Outcomes and quality of life were compared between the two treatment modalities. A total of 44 patients were included. The survival rates, complications, and Dysphagia Score were compared between the two treatment modalities. The outcome of the Voice Handicap Index (P=0.032), understandability of speech (P<0.001), normalcy of diet (P=0.041), senses (P=0.006), speech (P<0.001) and social contact (P=0.004) were significantly improved in the group receiving OPL compared with the group receiving TL. Therefore, OPL with tube-free tracheostomy may be a feasible option to treat patients with HPC with non-extensive invasion of the thyroid and/or cricoid cartilage.

Objectives: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis., Methods: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method., Results: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up., Conclusion: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis., (© 2018 John Wiley & Sons Ltd.)

Objectives: Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical outcomes of Taiwanese patients with these two common oral cavity malignancies., Methods: Patients with first primary buccal or tongue SCC who were included in the Taiwanese Cancer Registry Database between 2004 and 2012 were eligible. The study sample consisted of 16,379 patients (7870 buccal SCC and 8509 tongue SCC) who received surgery with or without adjuvant therapy. The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the outcome measures., Results: Compared with tongue SCC, patients with buccal SCC had a higher prevalence of males (95.7% vs. 86.4%, p<0.0001), pT4 disease (21.4% vs. 12.7%, p<0.0001), and p-Stage IV (30.4% vs. 24.8%, p<0.0001) but a lower frequency of pN2 disease (15.2% vs. 18.5%, p<0.0001). The 5-year DSS and OS rates of buccal SCC patients were slightly higher than those of tongue SCC (78% vs. 77%, p=0.0297; and 71% vs. 69%, p=0.0231, respectively). Multivariate analysis identified tumor site (tongue vs. buccal SCC), sex (male vs. female), age (≥65 vs. <65years), pT classification (T4/T3/T2 vs. T1), and pN classification (N3/N2/N1vs. N0) as independent prognostic factors in the entire study cohort., Conclusions: The survival advantage of buccal SCC over tongue SCC appears significant in large clinical samples, despite a higher prevalence of p-Stage IV disease in the former., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: Human papillomavirus (HPV) is a risk factor for head and neck squamous cell carcinoma (HNSCC) as well as esophageal squamous cell carcinoma (ESCC). We aimed to investigate whether HPV infection underlies the field cancerization phenomenon over upper aerodigestive tract to develop synchronous multiple cancers., Study Design: A case control study., Methods: The presence and subtype of HPV-DNA sequence in cancers were examined by polymerase chain reaction and sequencing in a prospective cohort with 100 HNSCCs, 50 of which had synchronous ESCCs. The clinicopathologic characteristics were further analyzed according to the presence of HPV., Results: Twelve patients were HPV-positive, of which 11 were positive for HPV-16. The prevalence of HPV infection were not different between the synchronous and HNSCC alone groups (P = 0.357). Testing for HPV in paired HNSCC and ESCC tissues from the same patient revealed that none were concomitantly HPV-positive. Multivariate logistic regression showed drinking alcohol (odds ratio [OR], 18.75; P = 0.030), alcohol flushing (OR, 2.53; P = 0.041), and body mass index (OR, 0.77; P = 0.001) but not HPV infection were independent risk factors for synchronous phenotype. The patients with synchronous ESCCs had significantly poorer survival than those with HNSCC alone (5-year overall survival: 30% vs. 70%; log-rank P < 0.001). However, patients with HPV-positive HNSCC tend to have favorable outcome than those with HPV-negative HNSCC., Conclusions: HPV infection plays little role in field cancerization phenomenon to initiate synchronous SCC. The synchronous HNSCC and ESCC from the same patients had no clonal relationship. Routine endoscopic examination of the esophagus should be recommended for patients with risk factors identified., Levels of Evidence: NA. Laryngoscope, 126:1097-1102, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV-related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV-related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV-unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV-related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC. This suggests that similar to the Western world, HPV-related HNC is becoming an important public health issue in Taiwan., (© 2014 UICC.)

Background: The purpose of this study was to investigate whether the pretreatment total and differential leukocyte counts can predict the prognosis of patients with oral cavity cancer., Methods: In a retrospective analysis of patients treated between 2004 and 2011, medical records of 202 patients with oral cavity cancer were evaluated., Results: Patients with oral cavity cancer, the peripheral total white blood cell (WBC) count, monocyte, and neutrophil counts and neutrophil lymphocyte ratio increased with the advancement of clinical stage. In contrast, the lymphocyte count decreased. Further, total WBC, monocyte, and neutrophil counts were increased in those with pathologic stage T4 and poor tumor differentiation, and the monocyte count was also increased in those with lymph node metastasis. Moreover, the pretreatment circulating monocyte count was an independent prognostic factor for cancer-specific survival., Conclusion: A higher pretreatment circulating monocyte count can be considered as a useful prognostic marker in patients with oral cavity cancer., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: The totally implantable venous access port (TIVAP) is an important device for patients receiving chemotherapy. We have reported, to our knowledge, the first case of a metastatic tumor over a TIVAP implanted via the Seldinger technique with a subclavian vein puncture., Methods: Our patient, a 48-year-old man with hard palate cancer, had metastasis over the TIVAP. CT studies showed that the tumor had spread along the catheter from the neck to the chest wall., Results: The cause of death was multiple lung metastases and intractable tumor bleeding over the TIVAP., Conclusions: We present a novel case of metastasis over the TIVAP implanted by use of the Seldinger technique. This technique is used for patients receiving prolonged cytotoxic therapy for malignancy. Although the Seldinger technique is quick and more effective, we prefer the cephalic vein cut-down technique when an aggressive, advanced cancer of head and neck is involved., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Synchronous esophageal cancers can suppress the survival of patients with hypopharyngeal cancers. Esophageal screening with the image-enhanced endoscopy may identify more synchronous cancers while there is no evidence to support its benefit on survival., Methods: A total of 281 and 320 patients were diagnosed with hypopharyngeal cancer before and after the policy of routine esophageal screening. Primary outcome measures were overall survival., Results: Among those who received screening, 49 patients (49/180, 27.2%) had synchronous esophageal cancers; treatment planning was changed in 42 (23.3%). Before and after the policy, percentages of stage I-II synchronous cancers were 20% (3/15) and 53.1% (26/49), respectively. Adjunctive therapies for synchronous cancers have led to a better survival after the policy than before (P = 0.002). The Cox regression model quantified a survival benefit of 29% (95% CI: 11-43%) when adjusting for TNM stage of hypopharyngeal cancer. In post-policy period, the survival was better for those who chose screening than those who did not (HR: 0.57, 95% CI: 0.41-0.79). Among those without screening, there was no difference between the pre- and post-policy periods (HR: 0.96, 95% CI: 0.74-1.26)., Conclusions: Patients with hypopharyngeal cancers may benefit from the esophageal screening with image-enhanced endoscopy through the better detection of early-stage synchronous cancers., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: Oral squamous cell carcinoma (OSCC) has emerged as one of the major malignant tumors of the head and neck cancers. However, the molecular mechanism behind tumorigenesis of OSCC is not fully understood. The aim of this study was to investigate the role of calreticulin (CRT), an endoplasmic reticulum-resident protein, in OSCC cells., Materials and Methods: Sixteen paired samples of tumor and non-cancerous matched tissue (NCMT), six OSCC cell lines and normal human oral keratinocytes (NHOKs), and oral tissue microarray were used to reveal the expression of CRT by Western blotting and immunohistochemistry. Later, shRNA-mediated stable knockdown of CRT in OSCC cells was generated. The knockdown cell line was used to analyze cell proliferation, colony formation, anchorage-independent growth and cell migration in vitro., Results: CRT was differentially expressed in fresh tumor samples and six OSCC cell lines but not adjacent NCMTs and NHOKs. In oral tissue microarray, we showed that there was positive CRT staining in the vast majority of tumor cases (99/103), in sharp contrast to that in NCMT cases (29/92) (p<0.001). Stable knockdown of CRT in oral cancer cells resulted in significantly reduced growth rate, colony-forming capacity and anchorage-independent growth. This may be attributed to the induction of G0/G1 cell cycle arrest when CRT was depleted in the cells. Both horizontal and vertical movements of the CRT-knockdown stable line were markedly impaired. The phosphorylation levels of focal adhesion kinase (FAK), paxillin and ERK1/2 and the activity of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) were decreased in the CRT-knockdown cells. These results suggest that CRT can regulate oral cancer cell migration through activation of the FAK signaling pathway accompanied with proteolytic degradation of the extracellular matrix (ECM) by MMP-2 and MMP-9., Conclusion: Together, this study has defined a novel biological role for CRT in oral cancer. CRT is a potential biomarker and may contribute to the malignant phenotypes of OSCC cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report a woman presenting with unrelenting odynophagia and chest pain. Computed tomography identified a deep neck infection with acute phlegmonous esophagitis. However, esophageal intramural dissection with mucosal rupture occurred after routine nasogastric-tube insertion, and pus was vomited thereafter. The patient was treated with antibiotics and delayed endoscopic closure of the rupture site and made a full recovery. Although the definite pathogenesis remained unclear, esophageal intramural dissection with mucosal rupture, a possible and rare complication of nasogastric-tube insertion, eventually alleviated the acute phlegmonous esophagitis in our patient.

Purpose: This study aimed to evaluate the oncologic and functional results of pharyngeal defect reconstruction using a submental island flap in hypopharyngeal cancer patients., Methods: Functional and oncologic results were assessed in 14 patients based on a retrospective chart review. Speech function grading was as follows: 1 = excellent (>70% intelligibility); 2 = good (40-70% intelligibility), and 3 = poor (<40% intelligibility). Swallowing function score was stratified as 1 = full diet (excellent), 2 = soft diet (excellent-good), 3 = liquid diet (good), 4 = combined oral and gastric tube (good-poor), and 5 = gastric tube-dependent (poor)., Results: All flaps survived well. Salivary fistula with infection was found in 1 patient and treated conservatively. The mean length of hospitalization, and speech and swallowing scores according to laryngeal invasion in 11 patients after partial pharyngectomy were 21.63 ± 4.31 versus 11 ± 2.00 (p = 0.003), 2.38 ± 0.5 versus 1.67 ± 1.16 (p = 0.18) and 3.88 ± 0.84 versus 3.33 ± 1.53 (p = 0.46), respectively. Speech and swallowing returned to good-excellent in 63.6% and good in 45.5% of patients after surgery., Conclusions: The submental island flap is reliable for reconstructing laryngopharyngeal defects after ablation of hypopharyngeal cancer. Speech and swallowing are restored to good function in half of the patients. Laryngeal involvement of the cancer is predictive of longer hospitalization., (Copyright © 2012 S. Karger AG, Basel.)

Background: This study investigated the risk factors for synchronous esophageal neoplasia in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: All 315 consecutive patients with newly diagnosed HNSCC received endoscopic esophageal screening with image-enhanced endoscopy., Results: Sixty-nine patients (21.9%) had synchronous esophageal neoplasia, 37 (53.6%) with superficial neoplasia and 21 (30.4%) with multiple esophageal lesions. Univariate analysis revealed age <50 years, drinking alcohol, and location of index HNSCC were significant risk factors for developing synchronous esophageal neoplasia. In multivariate analysis, drinking alcohol (odds ratio [OR], 3.792; p = .0035), index oropharynxgeal cancers (OR, 3.618; p = .0045) and hypopharyngeal cancers (OR, 2.627; p = .0029) were independent risk factors. Drinking alcohol was clearly dose-response related (p = .001)., Conclusion: Alcohol consumption and index tumor location are associated with the development of synchronous esophageal neoplasia in patients with HNSCC. Because of the high prevalence, routine endoscopic examination of the esophagus should be recommended, especially in patients with the risk factors identified., (© 2010 Wiley Periodicals, Inc. Head Neck, 2011.)

Background and Study Aim: Although narrow-band imaging (NBI) in endoscopy can improve detection of early-stage esophageal malignancies in patients with head and neck cancers, false-positive results may be obtained in areas with nonspecific inflammatory changes. This study evaluated the feasibility of primary screening with NBI and magnification for the presence of esophageal malignancies in these cancer patients., Patients and Methods: Sixty-nine patients with documented head and neck cancers were enrolled from April 2008 to January 2009. All patients underwent a meticulous endoscopic examination of the esophagus using a conventional white-light system followed by re-examination using the NBI system and final confirmation with NBI plus magnification., Results: Twenty-one patients (30.4 %) were confirmed to have esophageal neoplasia. Among these 21, 16 (76.2 %) had synchronous lesions, 9 (42.9 %) were asymptomatic, and 10 (47.6 %) had early-stage neoplasia. The incidence of multiple esophageal neoplasia was 57.1 %. NBI was more effective than conventional endoscopy in detecting neoplastic lesions (35 lesions in 21 patients vs. 22 lesions in 18 patients) and was particularly effective in patients with dysplasia (13 lesions in 9 patients vs. 3 lesions in 3 patients). The sensitivity and accuracy of detection were 62.9 % and 64.4 % for conventional endoscopy, 100 % and 86.7 % for NBI alone, and 100 % and 95.6 % for NBI with high magnification, respectively., Conclusions: Compared with current approaches, NBI followed by high magnification significantly increases the accuracy of detection of esophageal neoplasia in patients with head and neck cancers. The result warrants conducting prospective randomized controlled study to confirm its efficacy., ((c) Georg Thieme Verlag KG Stuttgart . New York.)

The aim of this study was to assess the treatment results and toxicity profiles of post-operative conventional radiotherapy (Conv-RT) and intensity-modulated radiotherapy (IMRT) for stage III and IV oral cavity cancer. During the period from April 2002 to December 2005, a total of 49 patients with stage III and IV squamous cell carcinoma of the oral cavity were treated with radical surgery followed by post-operative RT. Twenty-seven patients received Conv-RT while 22 received IMRT. Only three patients received adjuvant chemotherapy. With a median follow-up time of 3.3 years, the 3-year overall survival and disease-free survival rates for patients who received Conv-RT vs IMRT were comparable. There was no significant difference in acute toxicity between the two different RT techniques. However, in terms of late toxicity, patients receiving IMRT had significantly less moderate to severe xerostomia and dysphagia than those receiving Conv-RT (36% vs 82%, p=0.01 for xerostomia and 21% vs 59%, p=0.02 for dysphagia). Post-operative Conv-RT and IMRT are equally effective in terms of tumor control for locally advanced oral cavity cancer. Patients receiving IMRT had comparable acute and significant less late toxicity than those receiving Conv-RT.

This study was aimed at identifying acoustic and physiological measures useful for monitoring voice changes in postnasopharyngeal patients with nonlaryngeal malignancies, and providing evidences of vocal tract effect on voice through comparisons between individuals with and without intact vocal tract. Simultaneous acoustic-electroglottographic signals recorded during phonation of vowels /i/ and /a/ sustained at habitual, high, and low pitch levels were compared among 10 postradiotherapy patients with nasopharyngeal carcinoma (NPC), 10 voice patients (VPs) with intact vocal tract, and 10 healthy individuals with normal voice (NORM). Results from a series of discriminant analyses revealed that the NPC group generally exhibited lower signal-to-noise (SNR) and open quotient (OQ) and higher Formant 1 frequency (F(1)) and speed quotient (SQ) than the NORM group. Unlike both VP and NORM groups, the NPC group failed to show a pitch effect on all voice measures, including OQ, SQ, percent jitter, percent shimmer, and SNR, suggesting an effect of radiotherapy and/or vocal tract on laryngeal behaviors. For the vowel /i/, on the other hand, only the NPC and NORM groups showed a pattern of pitch-dependent F(1) raising, a reflection of increased pharyngeal narrowing. These findings suggested that the pitch effect on laryngeal behaviors differed not only between individuals with intact vocal tract and those without but also between those with structural and dynamic changes of vocal tract.

Background: This study was undertaken to determine the status of cyclooxygenase-2 (COX-2) in nasopharyngeal cancer (NPC) in Taiwanese patients and its relationship to survival after radiotherapy (RT). In addition, the effect of NS-398, a potent selective COX-2 inhibitor, was tested in vitro alone and in combination with radiation on NPC-BM1 human NPC cells as a prelude to using this drug along with RT in the treatment of patients with NPC., Methods: Thirty-seven patients diagnosed with T4N0-3M0 NPC were enrolled into this study. COX-2 expression was determined by immunohistochemical staining of formalin-fixed, paraffin-embedded tumor tissue. Patient survival was the clinical end point. The effects of COX-2 expression on cell survival and radioresistance was tested in vitro using the selective COX-2 inhibitor NS-398 in conjunction with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) and clonogenic assays., Results: COX-2 immunoreactivity was detected in 62% of NPC tumors, and expression levels were high in 43%. Survival analysis showed the 5-year overall survival rates for patients who had high COX-2 expression was 27% compared with 60% for those with low/absent expression (p = .047). Pattern of failure analysis showed no significant difference between high and low COX-2 expression in locoregional failure (27% vs 25%, p = .91). However, patients with N0 to N1 disease and high COX-2 expression had a significantly higher incidence of distant metastasis compared with patients with stage N0 to N1 disease and low COX-2 expression (83% vs 15%, p = .004). This difference was not observed in patients with N2 to N3 disease. This difference contributed to worse survival of patients whose tumors had high COX-2 expression levels. The selective COX-2 inhibitor NS-398 was directly cytotoxic to NPC-BM1 cells in vitro, as judged in an MTT assay (viable cells decreased from 92% to 76%, 52%, and 22%, with increases of NS-398 from 20 to 40, 60, and 80 microM, respectively). Radiation-induced cell death was also increased by treatment with NS-398. At a 10% survival level, 40 microM NS-398 increased radiation cytotoxicity by a factor of 1.37, whereas 60 microM increased it by a factor of 4.9., Conclusions: COX-2 overexpression is a predictor for poor survival for advanced stage NPC. In vitro, NS-398 radiosensitizes the NPC-BM1 cell line, providing a basis for testing the combination of COX-2 inhibitors with radiation in the treatment of patients with NPC., ((c) 2005 Wiley Periodicals, Inc.)

Acute frontal sinusitis can be a serious condition because of its potential life-threatening complications. These complications, including spread of infection to the frontal bone and intracranially, require prompt diagnosis and intervention to avoid morbidity and mortality. We report a case of acute frontal sinusitis in a 16-year-old girl who presented with fever, severe headache, and vomiting of 3 days' duration. Generalized fluctuant swelling of the nasal root, and bilateral supraorbital and frontoparietal regions was noted. Computed tomography (CT) demonstrated left pansinusitis, extensive subgaleal abscess and epidural empyema with osteomyelitis of the frontal bone. External frontoethmoidectomy with mucoperiostectomy were performed. Endoscopic sinus surgery was then conducted for intranasal ethmoidectomy. Intraoperative cultures grew viridans streptococci, coagulase-negative staphylococci and Peptostreptococcus micros. The patient received 3 weeks of treatment with intravenous antibiotics (penicillin 3 MU 4-hourly, ceftriaxone 500 mg 12-hourly, metronidazole 500 mg 6-hourly) and was discharged uneventfully and prescribed additional oral antibiotics for 5 weeks (clindamycin 150 mg 6-hourly and chloramphenicol 250 mg 6-hourly). CT revealed complete resolution of the abscess and clear maxillary and ethmoid sinuses at 7 weeks posttreatment. The patient was free of sinus infection at 4-years follow-up, without noticeable cosmetic deformity.

Fourth branchial cysts are quite rare. A neonate with a left lateral neck mass and respiratory distress was found to have a fourth branchial cyst, which was diagnosed with computed tomography and endoscopy. The characteristic computed tomography findings included an air-containing neck cyst, which was located at the anteromedial site of the common carotid artery with mediastinal extension. Endoscopic examination revealed an internal opening at the apex of the pyriform sinus, communicating with the cyst. Total excision of the cyst was performed, and the specimen, which showed ciliated columnar epithelium with a subepithelial lymphoid infiltrate, thyroid follicles, and thymic tissue, histologically confirmed the diagnosis.