The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy.

OBJECTIVES: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC. METHODS: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders. RESULTS: A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately. CONCLUSIONS: Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification.

Evaluation of different methods of transoral minimally invasive surgery for supraglottic laryngeal carcinoma.

BACKGROUND AND OBJECTIVES: To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. METHODS: Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence-free survival (RFS), and postoperative functions were analyzed. RESULTS: Sixty-two patients were early-stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty-eight patients were scored Grade-1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan-Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki-67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. CONCLUSIONS: The positive margin, Ki-67 index ≥40% and P53(+)&Ki-67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.

Alaryngeal Speech Enhancement for Noisy Environments Using a Pareto Denoising Gated LSTM.

Loss of the larynx significantly alters natural voice production, requiring alternative communication modalities and rehabilitation methods to restore speech intelligibility and improve the quality of life of affected individuals. This paper explores advances in alaryngeal speech enhancement to improve signal quality and reduce background noise, focusing on individuals who have undergone laryngectomy. In this study, speech samples were obtained from 23 Lithuanian males who had undergone laryngectomy with secondary implantation of the tracheoesophageal prosthesis (TEP). Pareto-optimized gated long short-term memory was trained on tracheoesophageal speech data to recognize complex temporal connections and contextual information in speech signals. The system was able to distinguish between actual speech and various forms of noise and artifacts, resulting in a 25% drop in the mean signal-to-noise ratio compared to other approaches. According to acoustic analysis, the system significantly decreased the number of unvoiced frames (proportion of voiced frames) from 40% to 10% while maintaining stable proportions of voiced frames (proportion of voiced speech frames) and average voicing evidence (average voice evidence in voiced frames), indicating the accuracy of the approach in selectively attenuating noise and undesired speech artifacts while preserving important speech information.

A Systematic Review Evaluating the Diagnostic Efficacy of Narrow-Band Imaging for Laryngeal Cancer Detection.

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.

Significance of PD-L1 and Tumor Microenvironment in Laryngeal Squamous Cell Cancer.

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.

Cancer and immune response: The role of PD-1/PD-L1 checkpoint in laryngeal carcinoma. Preliminary results.

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.

Boron neutron capture therapy as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: A preliminary report.

OBJECTIVE: Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. PATIENTS AND METHODS: This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8-22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. RESULTS: The median hospital stay after BNCT was 2 days (1-6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. CONCLUSIONS: BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.

Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis.

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.

LncRNA BBOX1-AS1 Contributes to Laryngeal Carcinoma Progression by Recruiting SRSF1 to Maintain EFNB2 mRNA Stability.

Laryngeal cancer is a common malignancy of the larynx with a generally poor prognosis. This study systematically assessed the functional role of lncRNA BBOX1-AS1 in laryngeal carcinoma progression and associated molecular regulatory mechanisms. The proliferation, migration, and invasion of laryngeal carcinoma cells were detected by Cell Counting Kit-8, wound healing, clonal formation, and transwell assays. In addition, the interaction between BBOX1-AS1, Serine/Arginine Splicing Factor 1 (SRSF1), and Ephrin-B2 (EFNB2) mRNA was examined employing RNA immunoprecipitation and RNA pull-down experiments. Furthermore, western blotting, and RT-qPCR assays were adopted to detect the expression levels of BBOX1-AS1, SRSF1, and EFNB2. The impact of BBOX1-AS1 and SRSF1 on EFNB2 mRNA stability was examined using the RNA stability assay. BBOX1-AS1 was highly expressed in human laryngeal carcinoma tissues and cell lines. BBOX1-AS1 knockdown suppressed the growth, proliferation, migration, and invasion of laryngeal carcinoma cells. BBOX1-AS1 maintained the stability of EFNB2 mRNA in laryngeal carcinoma cells by recruiting SRSF1. EFNB2 knockdown inhibited the growth and metastatic function of laryngeal carcinoma cells in vitro. EFNB2 overexpression reversed the influence of BBOX1-AS1 knockdown on laryngeal cancer tumorigenesis. BBOX1-AS1 maintained EFNB2 mRNA stability by recruiting SRSF1, thereby aggravating laryngeal carcinoma malignant phenotypes. BBOX1-AS1 might be a new theoretical target for the treatment of laryngeal carcinoma.

The role of central neck dissection and adjuvant treatment in pT4aN0 laryngeal carcinoma treated with open partial horizontal laryngectomy.

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.

Epigenetic mechanism of RBM15 in affecting cisplatin resistance in laryngeal carcinoma cells by regulating ferroptosis.

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.

Can initial apparent diffusion coefficient and tumour volume predict future metastases in treatment-naive patients with laryngeal squamous cell carcinoma.

Purpose: To evaluate the predictive capability of the apparent diffusion coefficient (ADC) at initial diagnosis in treatment-naive patients with laryngeal squamous cell carcinoma (LSCC) for the development of future metastases. Material and methods: Magnetic resonance images of patients with pathologically proven non-metastatic, treatmentnaive LSCC were retrospectively evaluated. Follow-up positron emission tomography scans were assessed for the scanning of metastases. Results: A total of 37 patients (32 males and 5 females) with a mean age of 62.8 ± 8.9 years were enrolled. Mean tumour volume and ADC were 4.8 ± 62 cm3 and 0.72 ± 0.51 × 10-3 mm2/s, respectively. Six local and 8 distant metastases were detected in a mean follow-up period of 17.5 ± 10.2 months. A significant association between ADC and the presence distant metastases (p = 0.046) and local metastases (p = 0.042) was found. The difference in mean ADC values between future metastatic and non-metastatic initial tumours was significant (p = 0.017). Conclusions: Pre-treatment ADC values and volume of the initial tumour might provide early information about the development of future metastases in patients with LSCC in this series.

Expression and clinical significance of NKG2A and HLA-E in advanced laryngeal carcinoma.

OBJECTIVES: The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance. MATERIAL AND METHODS: We analyzed the expression levels of HLA-E and NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance. RESULTS: KLRC1 (the coding gene of NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients. CONCLUSIONS: The findings suggest that the expression levels of HLA-E and NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.

The clinical utility of diffusion-weighted imaging in diagnosing and predicting treatment response of laryngeal and hypopharyngeal carcinoma: A systematic review and meta-analysis.

PURPOSE: Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC. METHODS: A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies. RESULTS: A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 103 mm2/s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes. CONCLUSION: DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI's reliability in predicting prognosis and treatment response in patients with LC/HPC.

Pan-immune-inflammation value: a new prognostic index in operative laryngeal and pharyngeal carcinomas.

PURPOSE: This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors. METHODS: A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters. RESULTS: We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756. CONCLUSIONS: Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis. REGISTRATION INFORMATION: Registration number: KYLL-202307-001, date: July 2023.

Negative Pressure Wound Therapy in Pharyngocutaneous Fistula.

Pharyngocutaneous fistula (PCF) is an abnormal connection between the pharynx and skin that can occur after laryngectomy surgery. It can have a significant negative impact on patient recovery, delaying wound healing, requiring prolonged nil-per-oral (NPO) status, and reducing quality of life. Traditionally, the management of PCF has relied on conservative measures or surgical intervention. However, negative pressure wound therapy (NPWT) offers a promising alternative approach. This case study involves three patients who underwent laryngectomy and developed postoperative PCF. All patients received NPWT with a modified suction catheter and low negative pressure (20-40 mmHg). With NPWT, all patients achieved complete wound closure, with healing times ranging from two weeks to six weeks. This suggests that NPWT may significantly accelerate PCF healing compared to traditional methods. However, maintaining an airtight dressing on the neck region can be challenging. This study highlights the potential of NPWT for faster PCF closure after laryngectomy. Further research is needed to optimize NPWT application techniques, explore the impact on long-term outcomes, and establish guidelines for broader clinical use.

Development and validation of a diagnostic model for predicting cervical lymph node metastasis in laryngeal and hypopharyngeal carcinoma.

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.

Reliability of large language models for advanced head and neck malignancies management: a comparison between ChatGPT 4 and Gemini Advanced.

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.

Stapler versus conventional pharyngeal repair after total laryngectomy: a randomized clinical trial.

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.

Citalopram, an antipsychotic agent, induces G1/G0 phase cell cycle arrest and promotes apoptosis in human laryngeal carcinoma HEP-2 cells.

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.