IgG4-related disease with nasopharyngeal malignancy-like manifestations.

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.

Next-generation sequencing identified that RET variation associates with lymph node metastasis and the immune microenvironment in thyroid papillary carcinoma.

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA. METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism. RESULTS: Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways. CONCLUSION: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

Application of Platysma Myocutaneous Flap in Surgical Repair after T2-3 Glottic Carcinoma Resection.

OBJECTIVE: Numerous methods and materials are available for vertical partial laryngectomy. In this study, the reparative effects of the platysma myocutaneous flap (PMF) and ribbon myocutaneous flap (RMF) on the postoperative voice quality of patients were compared to provide a reference for selecting a method conducive to improving postoperative voice quality. METHODS: A retrospective analysis was performed on patients with unilateral T2-3 glottic carcinoma. Following vertical partial laryngectomy, the defect was repaired with a PMF or simple RMF. Twelve months after surgery, voice quality was assessed according to voice acoustics, aerodynamics, and subjective perceptual evaluation, and glottic morphology was recorded using a laryngeal stroboscopy. RESULTS: A total of 70 patients were identified, including 54 in the PMF group and 16 in the RMF group. The PMF group was superior to the RMF group in terms of voice quality assessed by voice acoustics, aerodynamics, and subjective perceptual evaluation. In the PMF group, 72.2% of patients performed phonation with their vocal cords, and approximately 27.8% of patients were affected by supraglottic compression. In the RMF group, 81.3% of patients were affected by supraglottic compression. No significant difference was found in the 5-year survival rate between the two groups. CONCLUSION: For defect repair following vertical partial laryngectomy, a PMF can allow better postoperative voice quality to be achieved than an RMF because a PMF can provide more tissue (including strap muscle under the flap) for padding, which enables the glottic portion corresponding to the vocal cord to close well. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3181-3186, 2024.

Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer.

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K-AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

The prognostic value of lymphatic metastatic size in head and neck squamous cell carcinoma.

BACKGROUND: Lymphatic metastatic size was proved to predict prognosis in different types of carcinomas, except in head and neck squamous cell carcinoma (HNSCC) located in hypopharynx, oropharynx and supraglottic region et al. The aim of this study is to evaluate the prognostic value of lymphatic metastatic size in HNSCC, which may guide clinical decision-making in practice. METHODS: From 2008 to 2022, 171 patients, who were diagnosed as HNSCC in our center, were included. The demographic data, clinicopathological characteristics and lymphatic metastatic size were recorded and analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS: Among 171 patients, 107 cases were hypopharyngeal cancer, 38 cases supraglottic cancer and 26 cases oropharyngeal cancer. The median of lymphatic metastatic size was 8 mm (range 0-46). According to lymphatic metastatic size, the patients were assigned to three subgroups: Group I (0 mm), Group II ( ≤ 10 mm) and Group III (> 10 mm). Kaplan-Meier analysis with log rank test revealed that Group I and Group II had similar locoregional control rate, distant metastasis free probability, disease-free survival and overall survival (all p > 0.05), whereas Group III had significant worse prognosis. Adjusted for demographic and other clinicopathological characteristics, lymphatic metastatic size was an independent predictor of disease-free survival and overall survival in HNSCC. CONCLUSIONS: Lymphatic metastatic size was an independently prognostic factor in HNSCC, which may assist in postoperative adjuvant treatment decisions.

A risk stratification system developed to predict contralateral incidental malignant foci in early papillary thyroid carcinoma preoperatively.

BACKGROUND: In clinical practice, contralateral incidental malignant foci (CIMFs) can be found in some early (cT1N0M0) papillary thyroid carcinomas (PTCs) on postoperative pathological examination. To screen out the patients with high risk of CIMF preoperatively would help in determining the extent of thyroid surgery. METHODS: From October 2016 to February 2021, 332 patients diagnosed with early (cT1N0M0) PTC who underwent total thyroidectomy were included and randomly allocated into a training dataset (n = 233) and a test dataset (n = 99). Demographic and clinicopathological features were recorded and analyzed using logistic regression analysis. A coefficient-based nomogram was developed and validated. RESULTS: Logistic regression analyses revealed that the predictive model including BRAF V600E mutation, multifocality and margin of the contralateral nodule achieved the best diagnostic performance. The nomogram showed good discrimination, with AUCs of 0.795 (95 % CI, 0.736-0.853) for the training set and 0.726 (95 % CI, 0.609-0.843) for the test set. The calibration curve of the nomogram presented good agreement. CONCLUSION: The risk stratification system can be used to quantify the probability of CIMF and may assist in helping the patients choose total thyroidectomy or thyroid lobectomy with early (cT1N0M0) PTC.

[Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma].

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2.

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48's function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

Gasless endoscopic thyroidectomy via the anterior chest approach: the experience with 1500 cases.

BACKGROUND: Conventional thyroidectomy leaves an eye-catching scar in the anterior neck region. Endoscopic thyroidectomy may achieve a better esthetic effect and improve quality of life postoperatively. The aim of this study was to undertake a complete review of a large cohort of the patients undergoing gasless endoscopic thyroidectomy (GET) via anterior chest approach (ACA) with a long-term follow-up period, and evaluate the results and limits of this procedure. METHODS: Between 2003 and 2022, 1413 patients undergoing GET via ACA in our department were included. The demographic, clinicopathological characteristics, oncologic and esthetic outcomes were summarized and analyzed. RESULTS: The indication for surgery was papillary thyroid carcinoma in 686 (48.5%) patients and benign thyroid diseases in 727 (51.5%) patients. Among them, 802 (56.8%) patients took hemithyroidectomy, and 611 (43.2%) patients did sub-total/total thyroidectomy. Meanwhile, 598 (42.3%) ones had central neck dissection, while 88 (6.2%) lateral neck dissection. The most common complication was transient hypoparathyroidism with an incidence of 2.9%. During the follow-up period of 2 to 232 months, three patients were confirmed locoregional recurrence. Most of the patients were satisfied with the cosmetic results. CONCLUSION: Gasless endoscopic thyroidectomy via anterior chest approach is a safe and feasible procedure, which could achieve excellent oncologic and esthetic outcomes.

[Clinical analysis of gasless transoral vestibular robotic resection of thyroglossal duct cysts].

Objective:This study aimed to explore the safety and feasibility of gasless transoral vestibular robotic resection of thyroglossal duct cysts. Methods:The clinical data of patients who underwent gasless transoral vestibular robotic resection of thyroglossal duct cysts at the Department of otolaryngology, Sun Yat-sen Memorial Hospital, Sun yat-sen university from September 2020 to May 2022 were analyzed. The operative time, blood loss, postoperative complications, postoperative pain score, postoperative aesthetic score, and recurrence were prospectively evaluated. Results:All patients completed the operation successfully and no case conversed to an open operation. The operation time was 104.00（95.00, 131.25） minutes, and the surgical blood loss was 15.00（10.00, 16.25） mL. The drainage volume was（59.71±9.20） mL. Postoperative pathology was consistent with thyroglossal duct cysts. There was no local reswelling, subcutaneous hematoma, emphysema, skin flap necrosis, infection and other complications. The postoperative hospital stay was 3.00（2.00, 3.00） days. Six patients had mild sensory abnormalities of the lower lip 3 months after surgery, and all patients were satisfied with the cosmetic outcomes. No recurrence was found during the 5-26 months follow-up. Conclusion:gasless transoral vestibular robotic resection of thyroglossal duct cysts is safe and feasible, with hidden postoperative scars and good cosmetic outcomes. It can provide a new choice for patients with thyroglossal duct cysts.

Comparison of 980-nm/1470-nm Dual-Wavelength Fiber Laser Versus Ultrasonic Scalpel Device in Open Thyroidectomy.

Background: To investigate the application value of 980-nm/1470-nm dual-wavelength fiber laser in thyroidectomy. Methods: The clinical data of 130 patients undergoing thyroid surgery from March 2017 to December 2018 were retrospectively analyzed. According to the use types of energy devices, the patients were divided into laser group and ultrasonic scalpel group, with 65 patients in each group. The baseline data, operation-related indicators, operation complications, postoperative pathological conditions, and follow-up results of the two groups were compared. Results: The operations were successfully completed in both groups. The median operative time of total thyroidectomy (TT), lobectomy+central lymph node dissection (CLND), TT+CLND in the laser group were longer than that in the harmonic scalpel group, and the difference was statistically significant (p < 0.05). The incidence of parathyroid gland congestion in the laser group (10.3%) was lower than that in the harmonic scalpel group (19.2%), and the difference was statistically significant (p < 0.05). No significant differences were found in operative type, intraoperative blood loss, postoperative drainage volume, operative complications, postoperative hospital stay, and lymph node metastasis rate between the two groups (p > 0.05). No incidence was noted of recurrence, metastasis, or death in both groups. Conclusions: The 980-nm/1470-nm dual-wavelength fiber laser had an efficacy in open thyroidectomy similar to that of the harmonic scalpel, was safe and feasible, and less damage to the parathyroid gland blood supply than a scalpel. It can be used as a new option for thyroid surgery.

Identification of a distinct tumor endothelial cell-related gene expression signature associated with patient prognosis and immunotherapy response in multiple cancers.

BACKGROUND: Tumor endothelial cells (TECs) play a significant role in regulating the tumor microenvironment, drug response, and immune cell activities in various cancers. However, the association between TEC gene expression signature and patient prognosis or therapeutic response remains poorly understood. METHODS: We analyzed transcriptomics data of normal and tumor endothelial cells obtained from the GEO database to identify differentially expressed genes (DEGs) associated with TECs. We then compared these DEGs with those commonly found across five different tumor types from the TCGA database to determine their prognostic relevance. Using these genes, we constructed a prognostic risk model integrated with clinical features to develop a nomogram model, which we validated through biological experiments. RESULTS: We identified 12 TEC-related prognostic genes across multiple tumor types, of which five genes were sufficient to construct a prognostic risk model with an AUC of 0.682. The risk scores effectively predicted patient prognosis and immunotherapeutic response. Our newly developed nomogram model provided more accurate prognostic estimates of cancer patients than the TNM staging method (AUC = 0.735) and was validated using external patient cohorts. Finally, RT-PCR and immunohistochemical analyses indicated that the expression of these 5 TEC-related prognostic genes was up-regulated in both patient-derived tumors and cancer cell lines, while depletion of the hub genes reduced cancer cell growth, migration and invasion, and enhanced their sensitivity to gemcitabine or cytarabine. CONCLUSIONS: Our study discovered the first TEC-related gene expression signature that can be used to construct a prognostic risk model for guiding treatment options in multiple cancers.

[Reliability and validity of the Chinese version of URICA-Voice scale].

Objective:To translate the University of Rhode Island Change Assessment of voice scale（URICA-Voice） into Chinese and test its reliability and validity. Methods:The URICA-Voice scale was converted into Chinese by literal translation, cultural adjustment, expert consultation, pre-investigation, and back translation. Convenience sampling was used to recruit patients at four speech therapy centers from February to May 2022. Then the Chinese version of the scale was distributed to them, and the reliability and validity of the scale were tested after data collection. Cronbach ɑ was used to evaluate the reliability. The critical ratio method and Pearson correlation coefficient were used for item analysis. Item-level content validity, scale-level content validity, and confirmatory factor analysis were used to test the validity of the scale. Results:A total of 247 valid questionnaires were collected. ①Item analysis: the critical ratios between a high-score and low-score groups of 32 items were all statistically significant（P<0.01） and all the critical ratios were above 3.00. The Pearson correlation between 32 items and the total score was significant（P<0.01）. ②Validity analysis: I-CVI=1.00, S-CVI/Ave=1.00, χ²/df=2.30, RMSEA=0.07. Except for item 9 and 23, the standardized factor loading coefficients of other items were all above 0.50. AVE of the four dimensions of the scale was all above 0.50, and the combined reliability of the four dimensions was all above 0.70. The correlation coefficients between dimensions were less than the square root of the AVE of the dimension itself. ③Reliability analysis: the Cronbach ɑ of the whole scale was 0.94, and the Cronbach ɑ of the four dimensions were 0.88, 0.92, 0.94, and 0.88 respectively. Conclusion:The Chinese version of URICA-Voice has good reliability and validity, and can be used as a specific measurement tool for evaluating the compliance of voice training in China.

Prognostic Significance of a Model Based on Acetaldehyde Dehydrogenase 2 Genetic Polymorphisms in Laryngeal Carcinoma.

OBJECTIVE: Because of the high costs associated with early-stage laryngeal carcinoma diagnosis and prognosis prediction, this study attempts to find valuable targets to establish a novel predictive model by focusing on the aldehyde dehydrogenase 2 (ALDH2) genotype and other peripheral blood markers. STUDY DESIGN: Retrospective study. SETTING: Tertiary comprehensive hospital. METHODS: From January 2011 to January 2021, 362 cases of laryngeal carcinoma were included and divided into 2 groups in this retrospective analysis. Information on medical history, alcohol, and tobacco consumption habits, ALDH2 genotypes, and other peripheral blood markers was collected. Endpoints of the current study included disease-free survival and overall survival. A nomogram model for overall survival was established and evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 236 patients were included in the training cohort, and the other 126 were included in the validation cohort. The median follow-up of the patients was 9.6 years (interquartile range: 7.5-12.5 years). Peripheral fibrinogen, hemoglobin, and ALDH2 genotypes were significantly associated with an increase in laryngeal carcinoma mortality rate on Kaplan-Meier curves. The ROC curve showed that the effectiveness of overall survival prediction by the nomogram model was better than that of traditional clinical staging. CONCLUSION: A prognostic nomogram of laryngeal carcinoma patients involving ALDH2 and peripheral blood markers and T and N stages was constructed and validated.

Role of immune-inflamed phenotype in the prognosis of hypopharyngeal carcinoma following primary surgery.

BACKGROUND: The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined. METHODS: We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand-1 (PD-L1), and interferon (IFN)-γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non-inflamed tumors based on the presence or absence of parenchymal CD8+ T cells. RESULTS: We found that 74% of HPSCC cases in our cohort were characterized by an immune-inflamed TME. Immune-inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163+ tumor-associated macrophages and Foxp3+ regulatory T cells. Additionally, the inflamed tumor showed increased expression of PD-L1, without IFN-γ upregulation. CONCLUSIONS: The immune-inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.

CO2 transoral laser microsurgery for early glottic carcinoma with anterior commissure involvement.

OBJECTIVE: Anterior commissure (AC) involvement is an unfavorable factor for transoral laser microsurgery (TLM) treatment of early glottic carcinoma (EGC). This study aimed to evaluate the therapeutic efficacy of TLM treatment for EGC with AC involvement. METHODS: From 2008 to 2017, 177 patients with T1-T2 EGC with AC involvement were retrospectively included and divided into the TLM group (n=115) receiving CO2 laser TLM and the control group undergoing open surgery (n=62). The survival outcomes, postoperative complications, laryngeal preservation rate, recurrence and the phonological results were compared between groups. RESULT: The TLM group had significantly reduced hospital stay, hospitalization costs, and intraoperative blood loss as compared with the control group. The tracheotomy rate was significantly higher in the control group (96.8% vs. 0%). The 5-year overall survival (OS) was 89.6% and 85.5% in the TLM group and control group, respectively. Log-rank test showed no difference in survival rate between the two groups. There was no significant difference in laryngeal preservation rate and overall recurrence rate between groups. In postoperative vocal function evaluation, there were significant differences in the overall grade (G), the roughness (R), the breathiness (B), Voice Handicap Index-10 (VHI-10), Jitter, Shimmer, noise/harmonic ratio (NHR), maximum phonation time (MPT), phonation threshold pressure (PTP) between the two groups. CONCLUSION: For EGC with AC involvement, TLM has similar survival outcomes with the open surgery, but has better postoperative voice outcomes. Meanwhile, TLM can effectively reduce intraoperative blood loss, hospitalization time, hospitalization costs and postoperative complications.

Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas.

Background: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. Methods: To identify N6-methyladenosine (m6A) regulators that are involved in regulating the HNSCC TME, a computational screen was applied to The Cancer Genome Atlas (TCGA) HNSCC patient samples. The effects of mutation, copy number variation (CNV), and transcriptional regulation on YTHDF1 expression were analyzed. We analyzed the TME infiltration, cancer-immunity cycle activities, and YTHDF1-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: Among the 24 m6A regulators, 3 factors (YTHDF1, ELAVL1, and METTL3) were highly correlated with TME infiltration. As the top candidate, YTHDF1 was up-regulated and amplified in HNSCC. YTHDF1 promoter gains active histone marks and high chromatin accessibility, which might be transcriptionally activated by SOX2 and TP63. Moreover, YTHDF1 expression significantly associates with tumor malignant phenotype in HNSCC, which has a positive correlation with CD4+ T cells and a negative correlation with CD8+ T cells infiltration. Specifically, YTHDF1 expression is negatively associated with the cancer-immunity cycle and immune checkpoint inhibitors. In terms of the underlying biological mechanisms, YTHDF1 may interact with YTHDF2/3 to regulate several vital immune-related pathways. Conclusions: We identify YTHDF1 associated with TME and elucidate an underlying mechanism of immune escape in HNSCC, which might be used as a predictive marker in guiding immunotherapy.

[Predictive value of strobovideolaryngoscopy, acoustic and aerodynamic measures in the prognosis of temporally unilateral vocal fold paralysis after thyroidectomy].

Objective:To investigate the strobovideolaryngoscopy, acoustic and aerodynamic characteristics of transient unilateral vocal ford paralysis（UVFP） after thyroidectomy. Methods:A retrospective analysis was made of 11 patients with temporary UVFP after thyroidectomy who were treated in Department of Otolaryngology and Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2013 to March 2021; 8 patients with permanent UVFP after thyroidectomy during the same period were included as a control group. The differences in baseline strobovideolaryngoscopy, acoustic and aerodynamic measures were compared between the two groups. Results:The tones of patients with temporary UVFP after thyroidectomy were all normal, and the proportions of abnormal vocal fords（vocal ford bowing, atrophy, and shortening）, ventricular adduction and glottic insufficiency were significantly lower than those of permanent UVFP patients; arytenoid cartilage stability and height mismatch of vocal ford tended to be better than permanent UVFP. The maximal phonation time（MPT） in patients with temporary UVFP was （8.5±4.1） s, which was significantly longer than （3.9±2.1） s in patients with permanent UVFP; fundamental frequency, mean airflow（MeAF） and mean subglottic pressure（SGP） were better in temporary UVFP than those in patients with permanent UVFP, but the difference did not reach statistical significance. Conclusion:None and mild glottic insufficiency, normal tone, ventricular adduction, and vocal ford appearances without vocal fold bowing, atrophy, and shortening, can be served as the predictors for the early recovery of vocal ford movement in temporary UVFP after thyroidectomy. The MPT less than 4 s, and MeAF, and SGP remarkably increased is the predictor of poor prognosis for vocal ford recovery.

Near complete response to a pembrolizumab-based therapeutic strategy in an abdominal metastatic head and neck squamous cell carcinoma case.

Metastasis of head and neck squamous cell carcinoma rarely occurs in hepatic cancer and has a poor prognosis (median survival of 4 months). The efficacy of immunotherapy for these patients remains unknown. Herein, we present a patient with hypopharyngeal carcinoma metastasis to the liver with TERT and TP53 mutations together with a combined positive score of 70. The tumor invaded the abdominal wall, liver, inferior vena cava and retroperitoneal lymph nodes. The patient was treated with pembrolizumab combined with cisplatin and 5-FU for four cycles and has been maintained on pembrolizumab monotherapy until now. The patient achieved a near complete response of hepatic and subcutaneous metastases, and the tumor thrombus disappeared completely. The patient developed grade I rashes on the trunk, which were considered immune-related adverse events; thus, the patient presented a significant tumor response and good tolerance to the therapeutic strategy. On the basis of this observation, pembrolizumab-based therapeutic strategies may be an effective alternative for metastatic hypopharyngeal carcinoma and may prolong overall survival and progression-free survival, which should be confirmed by more patients in the future. Immune-related adverse events also need attention.

A 25-gene panel predicting the benefits of immunotherapy in head and neck squamous cell carcinoma.

Tumor mutation burden high (TMB-H) is widely used in the guidance of immune checkpoint blocking (ICB) therapy for head and neck squamous cell carcinoma (HNSCC) patients. However, a few patients still had a poor response. Therefore, it is necessary to investigate a better model to guide ICB therapy. We constructed a genomic mutation model conducive to ICB therapy using an available HNSCC dataset. Moreover, treatment procedures for patients with HNSCC from our internal cohort confirmed this model. Here, a genomic mutation signature based on a list of 25 candidate genes that are favorable for immunotherapy was established. Patients with combined mutation had a respectable clinical outcome under ICB treatment. Notably, compared with patients who obtained TMB-H (TMB ≥ 10, but did not have combined mutation), those patients with TMB-L (TMB < 10) and combined mutation acquired remarkably beneficial overall survival. Moreover, the combined mutation signature predicting the survival status of patients was superior to TMB, with a Youden index of 0.55. Furthermore, higher immune cell infiltration levels, more active cancer-immunity cycle activities and immune response pathways were observed in patients with combined mutation. Finally, our internal cohort further confirmed that combined mutated patients can benefit from ICB therapy rather than any other patients.