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Objective: The pathogenic mechanism underlying the effects of acidic pepsin in laryngeal cancer remains unclear. This study investigated whether acidic pepsin influences Glut‐1 expression and glycolytic activity in laryngeal carcinoma cells and whether it plays a role in the growth and migration of these cells through glycolysis. Study Design: In vitro study. Setting: A university‐affiliated hospital. Methods: Laryngeal carcinoma TU 212 and TU 686 cells were treated with acidic pepsin and 2‐deoxy‐d‐glucose (2‐DG), then transfected with Glut‐1 small interfering RNA (siRNA). Glucose uptake was detected by a radioimmunoassay counter, lactate secretion was detected by a lactic acid kit, and Glut‐1 expression was detected by western blotting. Cell viability, migration and invasion, and clonal formation were assessed using the Cell Counting Kit‐8, Transwell chamber, and clonal formation assays, respectively. Results: Acidic pepsin significantly increased Glut‐1 expression in laryngeal carcinoma cells compared with the control group (P <.01). It also significantly enhanced 18F‐fluorodeoxyglucose (Cin/Cout) uptake, lactate secretion, cell viability, migration, invasion, and clonal formation in laryngeal carcinoma cells compared with the control group (P <.01). The glycolytic inhibitor 2‐DG and Glut‐1 siRNA significantly reversed the effects of acidic pepsin on laryngeal carcinoma cells (P <.01). Conclusion: Acidic pepsin enhances the growth and migration of laryngeal carcinoma cells by upregulating Glut‐1, thus promoting glycolysis. [ABSTRACT FROM AUTHOR]

Purpose: The overall survival of laryngeal squamous cell carcinoma (LSCC) hasn't changed significantly in the last decades, leading to a negative prognosis in advanced stages. So, the immunotherapy takes space with the inhibition of PD-1/PD-L1 checkpoint, involved in suppression of immune response. Methods: A prospective study was conducted on LSCC patients, selected according to strict criteria. The study was approved by the ethics committee of our Hospital. Parameters were: sex, age, smoking and alcohol habits, C-reactive protein (CRP) level in the serum, laryngeal subsite involved, differentiation-based histopathologic grading of tumor, neck node involvement, tumor stage, expression levels of PD-L1 (as Combined Positive Score – CPS). P-value < 0.05 was statistically significant. Results: 58 patients were included: 31.03% were females, mean age 63.55±10.09. A statistically significant correlation between CPS and smoking habits and N stage was found. CRP resulted increased in 44.83% of patients with a statistically significant correlation with CPS. The most cases were glottic cancers (46.55%). 75.86% of tumors were moderately-differentiated, without correlation with CPS. Conclusion: PD-L1 expression levels are variables independent of sex, age, alcohol consumption, differentiation degree of LSCC. A statistically significant correlation between PD-L1 expression levels and smoking habits, neck node status and CRP was found. This last finding demonstrates the involvement of PD-1/PD-L1 checkpoint in immune response in case of cancer. However, these results need further studies to detect the best patients tailored for treatment with anti-PD-1/PD-L1 blocking antibodies. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments. Methods: Twenty-nine OPHL patients whose pathological exam was consistent with pT4aN0-x disease were enrolled and their clinical charts were retrospectively reviewed. The study analyzed oncological outcomes, such as local, regional, and distant recurrence rates (RR), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Additionally, functional results were analyzed, including decannulation rate, hospitalization time, and postoperative complication rate. Results: The study revealed and overall recurrence rate of 27%. The final rates for OS and DSS were 68% and 79%, respectively. Based on the univariate analysis the PTND was significantly associated with longer DFS. No significant differences inoncological outcomes were observed between pT4a patients who underwent adjuvant radio/radiochemotherapy and those who did not, in terms of RR, DFS, DSS or OS. However, adjuvant treatment was found to significantly increase decannulation time. Conclusions: In a properly super-selected subgroup of patients with pT4aN0 LSCC, OPHL may beconsidered as a conservative surgical option even without adjuvant treatment. However, for optimal oncological outcomes, it is strongly recommended to consider a central compartment dissection in cases of hypoglottic and anterior extra-laryngeal tumor extension. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the efficacy of two advanced Large Language Models (LLMs), OpenAI's ChatGPT 4 and Google's Gemini Advanced, in providing treatment recommendations for head and neck oncology cases. The aim is to assess their utility in supporting multidisciplinary oncological evaluations and decision-making processes. Methods: This comparative analysis examined the responses of ChatGPT 4 and Gemini Advanced to five hypothetical cases of head and neck cancer, each representing a different anatomical subsite. The responses were evaluated against the latest National Comprehensive Cancer Network (NCCN) guidelines by two blinded panels using the total disagreement score (TDS) and the artificial intelligence performance instrument (AIPI). Statistical assessments were performed using the Wilcoxon signed-rank test and the Friedman test. Results: Both LLMs produced relevant treatment recommendations with ChatGPT 4 generally outperforming Gemini Advanced regarding adherence to guidelines and comprehensive treatment planning. ChatGPT 4 showed higher AIPI scores (median 3 [2–4]) compared to Gemini Advanced (median 2 [2–3]), indicating better overall performance. Notably, inconsistencies were observed in the management of induction chemotherapy and surgical decisions, such as neck dissection. Conclusions: While both LLMs demonstrated the potential to aid in the multidisciplinary management of head and neck oncology, discrepancies in certain critical areas highlight the need for further refinement. The study supports the growing role of AI in enhancing clinical decision-making but also emphasizes the necessity for continuous updates and validation against current clinical standards to integrate AI into healthcare practices fully. [ABSTRACT FROM AUTHOR]

Hany G Attia,1 Mai Abdelhalim Hamouda,2 Saeed Alasmari,3 Dalia F El-Telbany,4 Zaenah Zuhair Alamri,5 Safa H Qahl,5 Mohammad Y Alfaifi,6 Majid Mohammad Al-Sawahli,7 Sara Abd El Wahed8 1Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia; 2Department of Oral Pathology, Faculty of Dentistry, King Salman International University, El-Tur, Egypt; 3Department of Biology, College of Science and Arts, Najran University, Najran 1988, Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, Egypt; 5Department of Biological Science, College of Science, University of Jeddah, Jeddah, Saudi Arabia; 6Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf, Iraq; 8Department of Oral Pathology, Faculty of Dentistry, The British University in Egypt, Cairo, EgyptCorrespondence: Majid Mohammad Al-Sawahli, Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf, Iraq, Tel +201119925299, Email majidalsawahli@gmail.com Hany G Attia, Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia, Tel +966555857605, Email hgattia@nu.edu.saPurpose: : Polyvinyl alcohol-capped silver nanostructures (cAgNSs) were investigated in order to enhance the cytotoxicity, pro-apoptotic, and oxidant patterns of in human laryngeal carcinoma Hep-2 cells by employing a 50 mT electromagnetic field (LEMF) for 30 min.Methods: Wet chemical reduction was used to synthesize the cAgNSs, and after they had been capped with polyvinyl alcohol, they were specifically examined for particle size analysis and structural morphology. To visualize how the silver may attach to the protein targets, a molecular docking study was conducted. Estimation of cytotoxicity, cell cycle progression supported by mRNA expression of three apoptotic-promoting genes and one apoptotic-resisting.Results: Particle size analysis results were a mean particle size of 157.3± 0.5 nm, zeta potential value of − 29.6 mV± 1.5 mV, and polydispersity index of 0.31± 0.05. Significantly reduction of IC50 against Hep-2 cells by around 6-fold was concluded. Also, we obtained suppression of the proliferation of Hep-2 cells, especially in the G0/G1 and S phases. Significant enhanced mRNA expression revealed enhanced induced CASP3, p53, and Beclin-1 mediated pro-apoptosis and induced NF-κB mediated autophagy in Hep-2 cells. Augmented levels of GR, ROS and MDA as oxidative stress biomarkers were also obtained. HE staining of Hep-2 cells exposed to cAgNSs and LEMF confirmed the enhanced apoptotic potential comparatively.Conclusion: By conclusion, the developed nano-sized structures with the aid of extremely-low frequency electromagnetic field were successful to fortify the anti-cancer profile of cAgNSs in Hep-2 cells. Keywords: electromagnetic field, silver nanoparticles, apoptosis, laryngeal carcinoma

Laryngeal carcinoma is one of the malignancies in the head and neck region with high incidence and mortality. Despite advances in therapeutic modalities, the 5-year survival rate remains low. Wilms tumor 1-associated protein (WTAP) has been reported to regulate cancer progression, however, its role and mechanism in regulating laryngeal carcinoma development remain unclear. In this study, the expressions of WTAP, collagen triple helix repeat containing 1 (CTHRC1), and YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) and other molecules were detected by quantitative real-time polymerase chain reaction or western blotting. Cell viability and colony formation rate were determined by cell counting kit-8 assay and cell colony formation assay. Cell migration and invasion were investigated by transwell assay. The relationship between CTHRC1 and YTHDF1 was identified by RNA immunoprecipitation assay. The results showed that WTAP and CTHRC1 were upregulated in laryngeal carcinoma tissues and cells. WTAP or CTHRC1 silencing inhibited the proliferation, migration and invasion of laryngeal carcinoma cells. WTAP knockdown inhibited CTHRC1 mRNA stability by suppressing CTHRC1 m6A modification and YTHDF1 from recognizing CTHRC1 m6A sites. Moreover, CTHRC1 overexpression attenuated WTAP knockdown-mediated effects on laryngeal carcinoma cell phenotypes and the expression of β-catenin, C-myc and cyclinD1. Thus, WTAP facilitated CTHRC1 mRNA stability in an m6A-dependent manner to activate the Wnt/β-catenin pathway and promote laryngeal carcinoma cell malignant phenotypes. [ABSTRACT FROM AUTHOR]

Abstract Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.

Simple Summary: Advanced stage laryngeal squamous cell cancer (LSCC) continues to have poor prognosis, with 5-year survival from 50 to 60% and poor functional outcome. PD-L1 and tumor microenvironment (CD4, CD8, CD68 and CD163) expression were investigated in LSCC using immunohistochemistry. PD-L1 expression showed statistically significant positive correlation with all examined tumor microenvironment cells. Higher CD68 and CD163 expression represented significantly worse prognosticators for clinical outcome in patients with LSCC. To find out which LSCC patients will gain from immunomodulation therapies, it is important to understand the relationship between PD-L1 expression, immune cell distribution and prognosis in LSCC patients. Background: Despite the considerable advancement in the field of medicine over recent decades, laryngeal cancer continues to be a challenge. The field of immune oncology has generated promising immunomodulation therapies and opened up new ways of treatment. Methods: Our retrospective study included 102 patients diagnosed with laryngeal squamous cell cancer (LSCC). Immunohistochemistry was used to evaluate the expression of PD-L1 and tumor microenvironment cells (CD4, CD8, CD68 and CD163). Results: PD-L1 expression showed statistically significant positive correlations with all examined tumor microenvironment cells. Patients with high CD68 and CD163 expression intratumorally (p = 0.0005 and p = 0.006, respectively) had statistically significant shorter disease-specific survival. Moreover, a statistically shorter time to recurrence was found in patients with high CD68 intratumoral and CD8 overall counts (p = 0.049 and p = 0.019, respectively). Also, high CD8 overall (>23%) and CD68 intratumoral (>2.7%) expression were statistically significant predictors of recurrence (p = 0.028, OR = 3.11 and p = 0.019, OR = 3.13, respectively). Conclusions: Higher CD68 and CD163 expression represented significantly worse prognosticators for clinical outcomes in patients with LSCC. In order to determine which LSCC patients will benefit from anti-PD-1/PD-L1 inhibitors, it is crucial to elucidate the relationship between PD-L1 expression, immune cell distribution and prognosis in LSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current study was to evaluate the functional outcomes of stapler pharyngeal closure after total laryngectomy by the incidence of PCT and assessment of swallowing after surgery. In addition, the study aimed to evaluate the oncological outcomes in terms of patients' survival rates. Methods: This randomized clinical trial was conducted on 58 patients with advanced laryngeal carcinoma who underwent total laryngectomy. Patients were randomly assigned to two groups according to the method of pharyngeal repair after laryngectomy: manual closure group (n = 28), and stapler group (n = 30). Functional and oncological outcomes were assessed and compared. Results: The incidence of pharyngocutaneous fistula was significantly less in the stapler group. Additionally, operative time was significantly shorter and swallowing function was better in the stapler group compared to the manual group. There was no statistically significant difference between groups regarding survival rates. Conclusion: The stapler is a reliable method for pharyngeal closure after total laryngectomy if the limits of its indications regarding the primary tumor are considered. Stapler closure decreases the incidence of PCF and decreases the surgical time. Good swallowing outcomes are achieved without compromising the oncological outcomes. [ABSTRACT FROM AUTHOR]

Background: Narrow-band imaging is an advanced endoscopic technology used to detect changes on the laryngeal tissue surface, employing a comparative approach alongside white-light endoscopy to facilitate histopathological examination. Objective: This study aimed to assess the utility and advantages of NBI (narrow-band imaging) in identifying malignant laryngeal lesions through a comparative analysis with histopathological examination. Methods: We conducted a systematic literature review, utilizing databases such as PubMed, the CNKI database, and Embase for our research. Results: We analyzed the articles by reviewing their titles and abstracts, selecting those we considered relevant based on determined criteria; in the final phase, we examined the relevant studies according to the specific eligibility criteria. Conclusions: Narrow-band imaging is an advanced endoscopic technology that demonstrates its efficacy as a tool for diagnosing malignant laryngeal lesions and comparing them to premalignant lesions. The European Society of Laryngology has implemented a standardized classification system for laryngeal lesions to enhance data correlation and organization. [ABSTRACT FROM AUTHOR]

Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo. [ABSTRACT FROM AUTHOR]

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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 [ABSTRACT FROM AUTHOR]

Objectives: The lymph node status is crucial for guiding the surgical approach for patients with laryngeal and hypopharyngeal carcinoma (LHC). Nonetheless, occult lymph node metastasis presents challenges to assessment and treatment planning. This study seeks to develop and validate a diagnostic model for evaluating cervical lymph node status in LHC patients. Materials and methods: This study retrospectively analyzed a total of 285 LHC patients who were treated at the Department of Otolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University, from January 2015 to December 2020. Univariate and multivariate logistic regression analyses were employed to construct the predictive model. Discrimination and calibration were used to assess the predictive performance of the model. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the model, and validation was conducted using 10-fold cross-validation, Leave-One-Out Cross Validation, and bootstrap methods. Results: This study identified significant predictors of lymph node metastasis in LHC. A diagnostic predictive model was developed and visualized using a nomogram. The model demonstrated excellent discrimination, with a C-index of 0.887 (95% CI: 0.835-0.933). DCA analysis indicated its practical applicability, and multiple validation methods confirmed its fitting and generalization ability. Conclusion: This study successfully established and validated a diagnostic predictive model for cervical lymph node metastasis in LHC. The visualized nomogram provides a convenient tool for personalized prediction of cervical lymph node status in patients, particularly in the context of occult cervical lymph node metastasis, offering valuable guidance for clinical treatment decisions. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that miR-5189-3p plays a critical role in multiple diseases. This study aimed to investigate the function of miR-5189-3p in laryngeal squamous cell carcinoma (LSCC) and explore its underlying mechanisms. qRT-PCR was designed to determine the expression levels of miR-5189-3p and eukaryotic translation initiation factor 5A2 (EIF5A2), while CCK-8 assay was performed to measure the effects of miR-5189-3p on cell proliferation. Transwell assay was performed to evaluate cell invasion as well as migration, and wound healing assay was applied to demonstrate cell migratory ability. Target gene prediction and luciferase reporter assay were developed to screen the possible target gene of miR-5189-3p, and Western blot was designed to measure EIF5A2 protein expression. MiR-5189-3p was down-regulated in LSCC tissues and cell lines. Up-regulation of miR-5189-3p notably inhibited cell proliferation, invasion, and migration in HEP2 and FADU cells. EIF5A2 was the potential downstream gene of miR-5189-3p, and overexpression of miR-5189-3p apparently reduced EIF5A2 expression. Moreover, reintroduction of EIF5A2 rescued the tumor suppressive effects of miR-5189-3p. MiR-5189-3p functions as a tumor inhibitor in LSCC progression via directly regulating EIF5A2 and may be a potential therapeutic target for LSCC. [ABSTRACT FROM AUTHOR]

Purpose: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. Methods: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. Results: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. Conclusion: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision. [ABSTRACT FROM AUTHOR]

Abstract Depending on the source of the blastophore, there are various subtypes of laryngeal cancer, each with a unique metastatic risk and prognosis. The forecasting of their prognosis is a pressing issue that needs to be resolved. This study comprised 5953 patients with glottic carcinoma and 4465 individuals with non-glottic type (supraglottic and subglottic). Five clinicopathological characteristics of glottic and non-glottic carcinoma were screened using univariate and multivariate regression for CoxPH (Cox proportional hazards); for other models, 10 (glottic) and 11 (non-glottic) clinicopathological characteristics were selected using least absolute shrinkage and selection operator (LASSO) regression analysis, respectively; the corresponding survival models were established; and the best model was evaluated. We discovered that RSF (Random survival forest) was a superior model for both glottic and non-glottic carcinoma, with a projected concordance index (C-index) of 0.687 for glottic and 0.657 for non-glottic, respectively. The integrated Brier score (IBS) of their 1-year, 3-year, and 5-year time points is, respectively, 0.116, 0.182, 0.195 (glottic), and 0.130, 0.215, 0.220 (non-glottic), demonstrating the model's effective correction. We represented significant variables in a Shapley Additive Explanations (SHAP) plot. The two models are then combined to predict the prognosis for two distinct individuals, which has some effectiveness in predicting prognosis. For our investigation, we established separate models for glottic carcinoma and non-glottic carcinoma that were most effective at predicting survival. RSF is used to evaluate both glottic and non-glottic cancer, and it has a considerable impact on patient prognosis and risk factor prediction.

ABSTRACTNeurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

Objectives: The aim of this study was to investigate the degree of discrepancy between the clinical and pathological staging of laryngeal carcinoma, and the potential impact of this discrepancy on the outcomes and prognosis. Methods: This study was conducted on 127 patients who underwent total laryngectomy over five years (October 2016–October 2021). Data collected from pretherapeutic clinical staging regarding the extent of the tumor affection of different laryngeal subsites was compared to the postsurgical pathological assessment. Results: Overall, 12 out of 127 patients (9.4%) in the current study, were clinically over-staged from T3 to T4 due to radiological diagnosis of tumor infiltration of laryngeal cartilages that proved pathologically to be free of tumor. Additionally, discordance in the N stage was found in 12.6% (n = 16). However, stage discrepancy did not have a significant impact on the prognosis and survival. Conclusion: Discordance between clinical and pathological TNM staging of laryngeal carcinoma may affect the decision making and the choice of the treatment options. Some improvement can be probably achieved with advancements and higher accuracy of the preoperative diagnostic tools. [ABSTRACT FROM AUTHOR]

Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50–400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram's anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression. [ABSTRACT FROM AUTHOR]

Aims. To compare the efficacy of computed tomography from endoscopic examination in diagnosing and staging laryngeal carcinoma. Methods. From February 2019 to July 2020, we conducted a retrospective study on patients with laryngeal carcinoma. After receiving a clinical diagnosis of laryngeal masses, patients underwent indirect laryngoscopy evaluation before being referred for computed tomography (CT) scans. A postimaging biopsy was undertaken via direct laryngoscopy. Imaging features of the tumor, such as size, level of invasion, and tumor staging, were analyzed. Results. The mean age was 61±11, with 90% of male patients. The risk of laryngeal cancer for those patients who were active smokers (93.5%) and alcohol consumers (67.7%). The most common symptom was hoarseness (93.5%). In CT image, more than half of the cancers were carcinoma of the glottis (29%) and two regions, supraglottis and glottis (22.6%), while the less common cancers were the subglottic (3.2%) and all three regions (9.7%) carcinoma, especially true vocal cord (67.7%) is the most common site starting carcinoma. The percentage of tumor spreading to paraglottic space and pre-epiglottic space was 50% and 30.6%, respectively. The most common stage of laryngeal cancer in CT was the T3 stage (35.5%). Compared to laryngoscopy, there is a weak agreement (Kappa=0.518) in staging in laryngeal cancer in CT. Conclusion. MDCT is better in staging of laryngeal cancer in the T3 and T4 stages as compared to laryngoscopy. [ABSTRACT FROM AUTHOR]

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer—the process of tumor neoangiogenesis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Laryngeal neuroendocrine carcinomas are the most common non‐squamous neoplasm of the larynx. Due to the rarity of the tumor, pathological diagnosis should be confirmed by immunohistochemistry. Laryngeal neuroendocrine carcinomas (LNECs) are a rare cancer of the head and neck. Few case reports of poorly differentiated neuroendocrine carcinoma originating in the subglottic larynx exist within the literature. In this case, we discuss a 57‐year‐old patient with a history of four‐month hoarseness with a newly diagnosed of poorly differentiated neuroendocrine carcinoma in the subglottic larynx. Treatment and prognosis of the various NEC groups differ, so precise identification requires consideration of the microscopic findings and immunostaining analysis. immunohistochemistry staining demonstrated positive result for cytokeratin 7, synaptophysin, chromogranin, CD 56, with the Ki‐67 index of45%. Although surgery is usually the treatment for all tumor types, chemo radiotherapy is recommended for poorly differentiated NECs because surgery is ineffective. [ABSTRACT FROM AUTHOR]

Objective: In this study, we analyzed the correlation between the preoperative plasma lycopene levels, postoperative adverse complications of chemoradiotherapy, and nutritional risk scores in patients with laryngeal carcinoma. Methods: A total of 114 patients with laryngeal carcinoma and 114 healthy respondents were enrolled in this study. The patients with laryngeal carcinoma were divided into two groups: 62 patients with laryngeal carcinoma, with an NRS2002 score higher than 3 points and whose diet contained lycopene, were enrolled in the observation group, and 52 patients with laryngeal carcinoma during the corresponding time period, whose diet did not contain lycopene, were enrolled in the reference group. The immune indexes (CD4 + , CD8 + , IGA, IGM, IGG), nutritional indexes (albumin, prealbumin, transferrin), and postoperative adverse complications of chemo-radiotherapy in the two groups were recorded. Results: The lycopene levels were lower in patients with advanced tumor stage (III and IV). The diagnosis threshold of the plasma lycopene level for laryngeal carcinoma was 0.503 μmol/L. The area under the curve for plasma lycopene levels in cancer diagnosis was 0.96, with a clinical specificity of 0.943 and a sensitivity of 0.859. There was a significant negative correlation between the plasma lycopene levels and Nutrition Risk Screening (NRS) 2002 score (R2 = − 0.523, P < 0.001), which was related to the increase in NRS-2002 scores and nutritional hazards in patients with laryngeal carcinoma. The observation group showed a significant increase in nutritional and immune indices, as compared to the reference group, as well as a lower incidence of severe and serious adverse reactions to chemo-radiotherapy. Lycopene supplementation, tumor stage, NRS-2002 scores, nutritional and immune indices were all significant predictors of postoperative severe and serious adverse complications of chemoradiotherapy. Conclusion: Progression of laryngeal carcinoma and severity of the side effects of the adverse complications of chemo-radiotherapy are related to the levels of lycopene. [ABSTRACT FROM AUTHOR]

Background This study was conducted to investigate the clinico-epidemiological and histopathological profiles of laryngeal and hypopharyngeal cancer. Methods This was a descriptive cross-sectional study carried out over the course of 18 months in 65 patients who underwent direct laryngoscopy and biopsy, as well as additional histopathological examination, at the Department of Otorhinolaryngology at the Government T.D. Medical College Hospital in Alappuzha, Kerala. The study was approved by the institutional ethics committee, and the participant's written informed consent was obtained. Results Based on the TNM staging that was done after coordinating clinical and radiological results, out of the 65 cases, 48 cases were diagnosed with carcinoma larynx and 17 cases were hypopharyngeal cancers. Most cases of carcinoma supraglottis showed up in stage III (9 cases), then stage II (7 cases), stage I (5 cases), and finally stage IVA (3 cases). Compared to supraglottic cancer, glottic cancer which had 14 cases in stage I and 4 in stageII manifested at an earlier stage. There were just six cases which presented in the advanced stage, four of them were in stage III, and one in each of the stages IVA and IVB. There were six cases of carcinoma hypopharynx in stage II and six in stage III, three cases in stages IVA, and just one case in stageI. There was one case of in-situ cancer in the hypopharynx (stage 0). All hypopharynx carcinomas had dysphagia and most had nodal metastasis. None had subglottic extension. Minor cartilage erosion seen in12%. The histological diagnosis of squamous cell carcinoma was found in all of our patients. Moderately differentiated squamous cell carcinoma was the most often encountered histological grade followed by well differentiated and then poorly-differentiated. Prevertebral space involvement or carotid encasement were absent. Conclusion Early detection is challenging for hypopharyngeal tumors, which also have a high risk of metastasis and recurrence. Patients with cancer of the larynx and hypopharynx may have an unfavorable prognosis if they have an airway compromise necessitating a tracheostomy. The public's knowledge of the signs, risk factors, and need to seek medical care as soon as symptoms appear can help significantly reduce the morbidity and death rate from laryngeal and hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of TRIB3 activation of Wnt/β-catenin signaling pathway on the growth and proliferation of laryngeal carcinoma TU686 cells in vitro and expression of peripheral immunosuppressive molecules in transplanted mice. Methods: Protein and RNA expressions of TRIB3 were detected in vitro cells (human immortalized epidermal cell line HaCat and laryngeal carcinoma cell line TU686) and tissues (laryngeal carcinoma and adjacent tissues), respectively. Laryngeal carcinoma TU686 cells were cultured in vitro and divided into negative control group (NC group) and TRIB3 knockdown group (sh-TRIB3 group), total protein and RNA of cells were extracted to verify the expression level of TRIB3 in two groups. After successful verification, proliferation ability of TU686 cells was detected by CCK-8, colony cloning and flow cytometry. Protein expression levels of Wnt, Cyclin-D1, C-myc，β-catenin and p-β-catenin in two groups were detected by Western blot. Correlation analysis verified the correlation between TRIB3 and Wnt, Cyclin-D1, C-myc，β-catenin, p-β-catenin protein expressions. TRIB3-low expressing nude mouse transplanted tumor model (TRIB3 sgRNA group) was constructed by knockdown the TRIB3 core plasmid, and a parallel control group (Control sgRNA group) was set up, tumor growth volume and weight were observed, and serum immunosuppressive molecules expressions was determined by ELISA. Results: Compared with HaCat cells and normal paracarcinoma tissues, TRIB3 was highly expressed in TU686 cells and laryngeal carcinoma tissues. Compared with negative control group, proliferation ability of TU686 cells was significantly inhibited after TRIB3 knockdown, and cell growth was blocked in G1/S phase. Expressions of Wnt, Cyclin-D1, C-myc and β-catenin protein in Wnt/β-catenin signaling pathway were decreased significantly, while expression of p-β-catenin was increased significantly. TRIB3 was significantly correlated with protein expression levels of Wnt, Cyclin-D1，β-catenin and p-β-catenin. The in vivo results showed that compared with Control sgRNA group, tumor growth volume and weight of mice in TRIB3 sgRNA group were significantly decreased, and expressions of serum immunosuppressive molecules IL-4, IL-6, IL-10, TGF-β and PGE2 were significantly decreased. Conclusion: TRIB3 is highly expressed in TU686 cells, and TRIB3 can inhibit growth and proliferation of TU686 cells and transplanted tumors by activating Wnt/β-catenin-related signaling pathways, and reverse tumor immunosuppressive microenvironment, suggesting that TRIB3 may be an effective target for laryngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Pretherapeutic discussion in the head and neck tumor board (HNT) has been mandatory at the University Medical Center Freiburg since 01/2015, and it is intended to contribute to a survival benefit through interdisciplinary decision making. Prior to 2015, an optional HNT existed in which mainly advanced tumor stages were discussed. The aim of this study was to determine the effect of a pretherapeutic HNT on treatment and survival in laryngeal cancer. Methods: A retrospective data analysis of 412 laryngeal carcinoma patients treated at the Head and Neck Cancer Center of the University Medical Center Freiburg between 01/2010 and 12/2020 was conducted. Differences regarding TNM status, UICC classification, tumor localization, gender and age at initial diagnosis, recurrence, secondary tumors, therapy, 5-year survival, and 5-year recurrence-free survival (5YSR/5Y-RFS) were assessed for therapy initiation with or without a pretherapeutic HNT. Results: In total, 314 patients underwent a pretherapeutic HNT, and 98 received therapy initiation without an HNT. The HNT group showed significantly more advanced T stages and UICC classifications (p < 0.001; p = 0.003) and more frequent primary chemo/radiotherapy (p < 0.001). There was no significant difference regarding 5YSR (43 vs. 47 months, p = 0.96) or 5Y-RFS (48 vs. 52 months, p = 0.16). The time between initial diagnosis and therapy initiation was significantly longer when an HNT was performed (38 vs. 20 days, p = 0.008). Conclusions: The HNT group showed significantly more advanced tumor stages, suggesting that even before it became mandatory, it was frequently used for interdisciplinary case discussion in more complex cases. Due to the small number of T3/4 patients in the non-HNT group, a survival advantage of an HNT cannot be validly demonstrated in our study. However, the HNT led to broader patient counselling regarding their therapy options. At the same time, a significant delay in therapy initiation could be seen, suggesting that workflows between diagnosis, HNT presentation, and therapy initiation should be optimized. [ABSTRACT FROM AUTHOR]

Accurate staging of laryngeal carcinoma can inform appropriate treatment decision-making. We developed a radiomics model, a deep learning (DL) model, and a combined model (incorporating radiomics features and DL features) based on the venous-phase CT images and explored the performance of these models in stratifying patients with laryngeal carcinoma into stage I–II and stage III–IV, and also compared these models with radiologists. Three hundreds and nineteen patients with pathologically confirmed laryngeal carcinoma were randomly divided into a training set (n = 223) and a test set (n = 96). In the training set, the radiomics features with inter- and intraclass correlation coefficients (ICCs) > 0.75 were screened by Spearman correlation analysis and recursive feature elimination (RFE); then support vector machine (SVM) classifier was applied to develop the radiomics model. The DL model was built using ResNet 18 by the cropped 2D regions of interest (ROIs) in the maximum tumor ROI slices and the last fully connected layer of this network served as the DL feature extractor. Finally, a combined model was developed by pooling the radiomics features and extracted DL features to predict the staging. The area under the curves (AUCs) for radiomics model, DL model, and combined model in the test set were 0.704 (95% confidence interval [CI]: 0.588–0.820), 0.724 (95% CI: 0.613–0.835), and 0.849 (95% CI: 0.755–0.943), respectively. The combined model outperformed the radiomics model and the DL model in discriminating stage I–II from stage III–IV (p = 0.031 and p = 0.020, respectively). Only the combined model performed significantly better than radiologists (p < 0.050 for both). The combined model can help tailor the therapeutic strategy for laryngeal carcinoma patients by enabling more accurate preoperative staging. [ABSTRACT FROM AUTHOR]

Key Clinical Message Laryngeal neuroendocrine carcinomas are the most common non‐squamous neoplasm of the larynx. Due to the rarity of the tumor, pathological diagnosis should be confirmed by immunohistochemistry. Abstract Laryngeal neuroendocrine carcinomas (LNECs) are a rare cancer of the head and neck. Few case reports of poorly differentiated neuroendocrine carcinoma originating in the subglottic larynx exist within the literature. In this case, we discuss a 57‐year‐old patient with a history of four‐month hoarseness with a newly diagnosed of poorly differentiated neuroendocrine carcinoma in the subglottic larynx. Treatment and prognosis of the various NEC groups differ, so precise identification requires consideration of the microscopic findings and immunostaining analysis. immunohistochemistry staining demonstrated positive result for cytokeratin 7, synaptophysin, chromogranin, CD 56, with the Ki‐67 index of45%. Although surgery is usually the treatment for all tumor types, chemo radiotherapy is recommended for poorly differentiated NECs because surgery is ineffective.

Objective: Laryngeal cancer (LC) is one of the most common squamous cell carcinomas of the head and neck in clinical practice, and its incidence has been increasing in recent years, but the prognosis of the patients is not favorable. Hence, it is critical to re-understand and deeply study the causes and mechanisms of LC and explore new effective treatment methods and strategies. In this study, we analyzed the effect of Dihydroartemisinin (DHA) on the pathological progression of LC through the periostin (POSTN)/Yes-associated protein (YAP)/interleukin (IL)-6 pathway, which can provide new clinical references and guidelines. Methods: POSTN, YAP, and IL-6 levels in 18 pairs of fresh LC tissues and adjacent counterparts in our hospital were detected. Additionally, LC TU686 cell line was purchased for DHA treatment of various concentrations to detect changes in cell biological behavior. Finally, we built a tumor-bearing mouse model with C57BL/6 mice and intragastrically administrated DHA to the animals to observe the growth of living tumors and to measure POSTN, YAP, and IL-6 expression in tumor tissues. Results: As indicated by PCR, Western blotting, and immunohistochemistry, POSTN, YAP, and IL-6 presented higher expression in LC tissues than in adjacent counterparts. In cell experiments, the cloning rate of LC cells decreased and the apoptosis rate increased after DHA intervention, with 160 μmol/L DHA contributing to the most significant effect on LC activity inhibition. Furthermore, DHA-intervened cells exhibited markedly reduced POSTN, YAP, and IL-6 levels. Finally, the tumorigenesis experiment in nude mice showed inhibited tumor growth after DHA administration. And consistently, the expressions of POSTN, YAP, and IL-6 in living tumors decreased. Conclusions: DHA can inhibit POSTN/YAP/IL-6 transduction, accelerate LC cell apoptosis, and alleviate the malignant progression of LC.

Background: Pretherapeutic discussion in the head and neck tumor board (HNT) has been mandatory at the University Medical Center Freiburg since 01/2015, and it is intended to contribute to a survival benefit through interdisciplinary decision making. Prior to 2015, an optional HNT existed in which mainly advanced tumor stages were discussed. The aim of this study was to determine the effect of a pretherapeutic HNT on treatment and survival in laryngeal cancer. Methods: A retrospective data analysis of 412 laryngeal carcinoma patients treated at the Head and Neck Cancer Center of the University Medical Center Freiburg between 01/2010 and 12/2020 was conducted. Differences regarding TNM status, UICC classification, tumor localization, gender and age at initial diagnosis, recurrence, secondary tumors, therapy, 5-year survival, and 5-year recurrence-free survival (5YSR/5Y-RFS) were assessed for therapy initiation with or without a pretherapeutic HNT. Results: In total, 314 patients underwent a pretherapeutic HNT, and 98 received therapy initiation without an HNT. The HNT group showed significantly more advanced T stages and UICC classifications (p < 0.001; p = 0.003) and more frequent primary chemo/radiotherapy (p < 0.001). There was no significant difference regarding 5YSR (43 vs. 47 months, p = 0.96) or 5Y-RFS (48 vs. 52 months, p = 0.16). The time between initial diagnosis and therapy initiation was significantly longer when an HNT was performed (38 vs. 20 days, p = 0.008). Conclusions: The HNT group showed significantly more advanced tumor stages, suggesting that even before it became mandatory, it was frequently used for interdisciplinary case discussion in more complex cases. Due to the small number of T3/4 patients in the non-HNT group, a survival advantage of an HNT cannot be validly demonstrated in our study. However, the HNT led to broader patient counselling regarding their therapy options. At the same time, a significant delay in therapy initiation could be seen, suggesting that workflows between diagnosis, HNT presentation, and therapy initiation should be optimized.

Objective·To compare the effects and complications of carbon dioxide laser laryngectomy and open partial laryngectomy in the treatment of laryngeal carcinoma.Methods·Clinical data of 101 patients with stage Ⅰ-Ⅲ laryngeal squamous cell carcinoma admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2018 were selected and divided into open surgery group and minimally invasive group according to different surgical methods. The open surgery group received open partial laryngectomy (57 cases), and the minimally invasive group received carbon dioxide laser laryngectomy (44 cases). Follow-up visits were made by telephone and outpatient visits, and the operation time, postoperative laryngeal mucosa edema time, length of stay, 5-year survival rate, complication rate and recurrence rate of the two groups were compared in the different clinical stages (stage Ⅰ, stage Ⅱ, and stage Ⅲ) and tumor locations (glottic type and non-glottic type).Results·The operation time, postoperative laryngeal mucosa edema time and length of stay of the minimally invasive group were shorter than those of the open surgery group (P0.05); while comparison of the 5-year survival rates of patients with non-glottic type between the two groups (62.5% in the open surgery group vs 0 in the minimally invasive group) showed a statistically significant difference (P0.05).Conclusion·Compared with open partial laryngectomy, carbon dioxide laser laryngectomy has faster postoperative recovery and lower complication rate in the treatment of early and middle laryngeal malignant tumors, so it is worth promoting.

Minghua Li,1,&ast; Jiawei Gui,1,&ast; Hao Wang,2 Jun An,3 Ruoqing Wu,1 Xiaotong Liu,1 Bo Wu,1 Hui Xiao1 1Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210019, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, Xuzhou Central Hospital, Xuzhou, 221009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Xiao, Email 13946129836@163.comBackground: Laryngeal cancer was one of the most common malignancies of the head in those years. It has become one of the most common causes of death due to its high recurrence rate and high metastasis rate. It was well known that platelets, especially activated platelets, promote the proliferation, division, and invasion of tumor cells. Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet aggregation function in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet aggregation function in laryngeal cancer.Materials and Methods: Between January 2015 and December 2016, we conducted a retrospective analysis of 203 patients who were diagnosed with laryngeal cancer consecutively. The patients were stratified by platelet aggregation function into two groups: low “adenosine diphosphate induced light transmittance aggregometry (ADP-induced LTA) ≤ 15.1” and high (ADP-induced LTA > 15.1). Pathological tissues from different parts of the operation were collected and the pathologist determined the pathological type. We assessed the prognostic significance of platelet aggregation function using Kaplan-Meier curves and Cox regression.Results: The low cohort had a significantly higher lymphocyte count than the high cohort. Compared with the high cohort, the low cohort had significantly lower levels of platelet-to-lymphocyte ratio (PLR), ADP-induced LTA, and Interleukins (IL)-6. The ADP-induced LTA (hazard ratio, 1.212; P < 0.001) was independently related with 5-year overall survival rate.Conclusion: Patients with ADP-induced LTA > 15.1 experience poor outcomes. Platelet aggregation function, when elevated, could be a new prognostic indicator for laryngeal cancer.Keywords: laryngeal carcinoma, platelet aggregation function, platelet-to-lymphocyte ratio, inflammation, overall survival rate

Background: Narrow-band imaging is an advanced endoscopic technology used to detect changes on the laryngeal tissue surface, employing a comparative approach alongside white-light endoscopy to facilitate histopathological examination. Objective: This study aimed to assess the utility and advantages of NBI (narrow-band imaging) in identifying malignant laryngeal lesions through a comparative analysis with histopathological examination. Methods: We conducted a systematic literature review, utilizing databases such as PubMed, the CNKI database, and Embase for our research. Results: We analyzed the articles by reviewing their titles and abstracts, selecting those we considered relevant based on determined criteria; in the final phase, we examined the relevant studies according to the specific eligibility criteria. Conclusions: Narrow-band imaging is an advanced endoscopic technology that demonstrates its efficacy as a tool for diagnosing malignant laryngeal lesions and comparing them to premalignant lesions. The European Society of Laryngology has implemented a standardized classification system for laryngeal lesions to enhance data correlation and organization.

Objective To investigate the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin C2 (mTORC2) signal signaling and human cholesterol modulator junction albumin 2 (SREBP2) in laryngeal carcinoma tissue. Methods A total of 60 primary laryngeal cancer patients with tumor and adjacent noncancerous tissue samples were collected and compared for PI3K, AKT, mTORC2, and SREBP2 expression by immunohistochemistry. Results The positive expressions of ΡΙ3Κ (88, 3%ις. 40.0%), ΑΚΤ (76.7% vs. 31.7%), mTORC2 (78,3% vs. 21.7%), and SREBP2 (65.0% vs. 8.3%) were higher in cancer tissues than those in adjacent tissues. the differences were statistically significant(P<0.05). The positive expressions of AKT, mTORC2 and SREBP2 were higher in patients whose tumors were ≥3 cm in diameter than in those whose tumors were <3 cm in diameter, the differences were statistically significant (P<0.05). The positive expression rates of AKT and SREBP2 in patients with stages III to IV disease were higher than those with stages I to Il disease (P<0.05). The positive expression rate of mTORC2 and SREBP2 was different between patients with different degrees of differentiation (P<0.05). The 2-year survival rate of patients with positive expression of PI3K, AKT.mTORC2, and SREBP2 was lower than that with negative expression, although the differences were not statistically significant (P>0.05). Conclusion PI3K/AKT/mTORC2 are highly expressed in the cancerous tissues of laryngeal cancer, which are related to the tumor diameter, clinical stage and differentiation degree, and they are potential targets for metabolic reprogramming therapy of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Objective To analyze the factors influencing the recurrence of laryngeal cancer (LC) after treatment and to construct a predictive model for LC recurrence. Methods Eighty patients with LC who had been treated (with surgical resection, radiotherapy, chemotherapy, or targeted therapy) were divided into the recurrence group (17 cases) and non-recurrence group (63 cases) according to whether a relapse occurred during the follow-up period. The information on the patients' age, sex, body mass index, smoking history, alcohol consumption history, LC family history, underlying diseases, tumor staging, tumor location, tumor pathological classification, tumor diameter, tumor infiltration depth, treatment plan, and other factors was collected. Serum mRNA levels of cytoskeletal protein 4 (CKAP4), polypeptide N-acetylgalactosamine transferase 2 (pp-GalNAc-T2), and transmembrane protein 2 (TMEM2) were measured using qRT PCR. Cox regression analysis was performed to analyze the influencing factors for LC recurrence. Logistic regression analysis was performed to construct a predictive model for LC recurrence, and the predictive value of the model for LC recurrence was evaluated using the receiver operating characteristic (ROC) curve. Results The recurrence group showed a significantly higher proportion of tumors of stages III-IV and significantly higher relative mRNA expression of serum CKAP4, pp-GalNAc-T2, and TMEM2 than the non-recurrence group (all P<0. 05). The relative mRNA expression levels of CKAP4, ppGalNAc-T2, and TMEM2 in serum were influencing factors for the recurrence of patients with LC after treatment (all P< 0. 05). We constructed a predictive model for LC recurrence after treatment: predictive probability=−8. 967+0. 724×the relative expression level of serum CKAP4 mRNA+0. 081×the relative expression level of serum pp-GalNAc-T2 mRNA+ 1. 132×the relative expression level of serum TMEM2 mRNA. The ROC curve analysis revealed that the model showed good predictive value for LC recurrence (AUC=0. 872, 95%CI：0. 779–0. 962, the cut-off value ≥0. 229, P<0. 001). The sensitivity, specificity, negative predictive value, and positive predictive value of this model in predicting LC recurrence were 88. 23%, 79. 36%, 96. 13%, and 53. 57%, respectively. Conclusion The relative serum expression levels of CKAP4 mRNA, pp-GalNAc-T2 mRNA, and TMEM2 mRNA are factors affecting the recurrence of patients with LC after treatment, and the model constructed based on these factors has high predictive value for LC recurrence [ABSTRACT FROM AUTHOR]

Objective· To compare the effects and complications of carbon dioxide laser laryngectomy and open partial laryngectomy in the treatment of laryngeal carcinoma. Methods· Clinical data of 101 patients with stage Ⅰ-Ⅲ laryngeal squamous cell carcinoma admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2018 were selected and divided into open surgery group and minimally invasive group according to different surgical methods. The open surgery group received open partial laryngectomy (57 cases), and the minimally invasive group received carbon dioxide laser laryngectomy (44 cases). Follow-up visits were made by telephone and outpatient visits, and the operation time, postoperative laryngeal mucosa edema time, length of stay, 5-year survival rate, complication rate and recurrence rate of the two groups were compared in the different clinical stages (stage Ⅰ, stage Ⅱ, and stage Ⅲ) and tumor locations (glottic type and non-glottic type). Results· The operation time, postoperative laryngeal mucosa edema time and length of stay of the minimally invasive group were shorter than those of the open surgery group (P<0.05). Comparison of the 5-year survival rates of patients with the same clinical stage and glottic type between the two groups showed no statistically significant difference (both P>0.05); while comparison of the 5-year survival rates of patients with non-glottic type between the two groups (62.5% in the open surgery group vs 0 in the minimally invasive group) showed a statistically significant difference (P<0.05). In the minimally invasive group, there were 3 cases of complications, including 1 case of fever and 2 cases of lung infection; in the open surgery group, there were 14 cases of complications, including 5 cases of fever, 7 cases of lung infection and 2 cases of pharyngeal fistula. The complication rate of patients in the minimally invasive group (6.82%, 3/44) was lower than that in the open surgery group (24.60%, 14/57), and the difference was statistically significant (P<0.05); the complication rate of patients with stage Ⅱ and glottic type in the minimally invasive group was significantly lower than that in the open surgery group (P< 0.05). Comparing the recurrence rate of patients in the two groups (10.53% in the open surgery group vs 2.27% in the minimally invasive group), the difference was not statistically significant (P>0.05). Conclusion· Compared with open partial laryngectomy, carbon dioxide laser laryngectomy has faster postoperative recovery and lower complication rate in the treatment of early and middle laryngeal malignant tumors, so it is worth promoting. [ABSTRACT FROM AUTHOR]

Objective To determine the affection of Mucin 13 (MUC13) on the biological behaviors such as proliferation, drug sensitivity, cell cycles, apoptosis, migration, and invasion of cells of human laryngeal squamous cell carcinoma. Methods MUC13-RNAi sequence was packaged into lentivirus and transfected into human laryngeal squamous cell carcinoma cell line TU177. CCK-8 assay, tablet cloning assay, transwell assay, and flow cytometry were applied to confine the affection of MUC13 expression inhibition on the proliferation, drug sensitivity, cycle, migration, invasion behaviors of TU177 cells. Results Compared with the Blank control (Blank) TU177 cells and the meaningless sequence transfected negative control (NC), the OD value variation rate of CCK-8 test of TU177 cells in the MUC13-RNAi group decreased with culture time, cytotoxicity of 5-Fluorouracil to TU177 cells increased. The relative clone formation rate of Tu177 cells in the NC group was 78.9% and that of TU177 cells in the MUC13-RNAi group was 54.1% compared with that in the blank group (P<0.05). In the migration experiment, the relative migration rate of TU177 cells in the MUC13-RNAi group was 56.3% when compared with that of NC group, with statistical significance (P<0.05). In the invasion experiment, the relative migration rate of laryngeal cancer cells in the MUC13-RNAi group was 69.2% when compared with that of NC group, the differences were statistically significant (P<0.05). At the same time, TU177 cells in the MUC13-RNAi group experienced G1 phase arrest and increased tendency of early apoptosis. Conclusions After the specific inhibition of MUC13 expression in the laryngeal squamous cell carcinoma line TU177, the proliferation ability, cytotoxicity of 5-Fluorouracil to TU177 cells, and migration ability of the cells were decreased, the cells were slightly G1 blocked and the apoptotic tendency was increased, suggesting that MUC13 is involved in the regulation of a variety of biological behaviors of laryngeal squamous cell carcinoma cells. [ABSTRACT FROM AUTHOR]

Aims: This study aims to make a comparative analysis of disease-free survival (DFS) and overall disease-specific survival (OS) in patients with laryngeal carcinoma. Materials and methods: The study was designed retrospectively. Sixteen patients with postoperative PSM and 30 with negative surgical margins (NSM) were included. Survival analysis and Long-Rank comparisons was performed for DFS and OS between groups. Results: PSM was a significant independent risk factor for loco-regional recurrence and disease-related mortality (p = 0.004, HR: 1.6, p = 0.002, HR: 3.2, respectively). DFS and OS were significantly longer in NSM group (p = 0.001 and 0.003, respectively). For PSM group, 2- and 5-year DFS rates were 57%; OS rates were 80% and 34% respectively. In NSM group, 2- and 5-year DFS rates were 96% and 83%; OS rates were found to be 96%. Conclusion: PSM had significant relation with poor prognosis. [ABSTRACT FROM AUTHOR]

A meta‐analysis study to assess the effect of possible risk factors for pharyngocutaneous fistula (PCF) after total laryngectomy of laryngeal carcinoma. A comprehensive literature examination till January 2023 was implemented and 1794 linked studies were appraised. The picked studies contained 3140 subjects with total laryngectomy of laryngeal carcinomas in the picked studies' baseline, 760 of them were PCF, and 2380 were no PCF. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of possible risk factors for PCF after total laryngectomy of laryngeal carcinomas and surgical wound infection after total laryngectomy of laryngeal carcinoma by the dichotomous and continuous styles and a fixed or random model. The PCF had a significantly higher surgical wound infection (OR, 6.34; 95% CI, 1.89–21.27, P =.003) compared with the no PCF in total laryngectomy of laryngeal carcinomas. The smoking (OR, 1.73; 95% CI, 1.15–2.61, P =.008), and preoperative radiation (OR, 1.90; 95% CI, 1.37–2.65, P <.001) had significantly higher PCF as a risk factor in total laryngectomy of laryngeal carcinomas. The preoperative radiation had a significantly lower spontaneous PCF closure (OR, 0.33; 95% CI, 0.14–0.79, P =.01) compared with the no preoperative radiation in total laryngectomy of laryngeal carcinomas. However, the neck dissection (OR, 1.34; 95% CI, 0.75–2.38, P =.32), and alcohol intake (OR, 1.95; 95% CI, 0.76–5.05, P =.17), had no significant effect on PCF in total laryngectomy of the PCF had a significantly higher surgical wound infection, and preoperative radiation had a significantly lower spontaneous PCF closure in total laryngectomy of laryngeal carcinomas. Smoking and preoperative radiation were shown to be risk factors for PCF, however, neck dissection and alcohol intake were not shown to be risk factors for PCF in total laryngectomy of laryngeal carcinomas. Although precautions should be taken when commerce with the consequences because some of the picked studies for this meta‐analysis was with low sample sizes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]