Identification of a Novel Five-Gene Prognostic Model for Laryngeal Cancer Associated with Mitophagy Using Integrated Bioinformatics Analysis and Experimental Verification.

Laryngeal cancer (LC) is a prevailing tumor with a high mortality rate. The pivotal role of mitophagy in LC is acknowledged; however, a comprehensive analysis of the corresponding genes has not been conducted. In the present study, we proposed a prognostic model consisting of mitophagy-related genes in LC. Clinical information and transcriptome profiling of patients with LC and mitophagy-related genes were retrieved from open-source databases. Gene set variation analysis (GSVA) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify core mitophagy-related genes and construct gene co-expression networks. Functional enrichment analysis was employed to analyze the enriched regulatory pathways of the mitophagy-related genes. Kaplan-Meier curves (KM), Cox, and LASSO regression were applied to explore their prognostic effects. Finally, quantitative real-time PCR (RT-qPCR) further verified the bioinformatics prediction. A total of 45 genes related to mitochondrial pathways was collected. GSVA analysis demonstrated that these genes in tumor samples mainly referred to the mitochondrial pathway. Among these genes, five mitophagy-related-gene signatures (CERCAM, CHPF, EPHX3, EXT2, and MED15) were further identified to construct the prognostic model. KM and Cox regression analyses indicated that this model had an accurate prognostic prediction for LC. RT-qPCR showed that CERCAM, CHPF, EXT2, and MED15 expression were upregulated, and EPHX3 level was decreased in LC cells. The present study established a five-mitophagy-related-gene model that can predict the prognosis of LC patients, thus laying the foundation for a better understanding and potential advancements in clinical treatments for LC.

Experimental Verification of Erchen Decoction Plus Huiyanzhuyu Decoction in the Treatment of Laryngeal Squamous Cell Carcinoma Based on Network Pharmacology.

BACKGROUND: The prescription of Chinese herbal medicine (CHM) consists of multiple herbs that exhibit synergistic effects due to the presence of multiple components targeting various pathways. In clinical practice, the combination of Erchen decoction and Huiyanzhuyu decoction (EHD) has shown promising outcomes in treating patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanism by which EHD exerts its therapeutic effects in LSCC remains unknown. METHODS: Online databases were utilized for the analysis and prediction of the active constituents, targets, and key pathways associated with EHD in the treatment of LSCC. The protein-protein interaction (PPI) network of common targets was constructed and visualized using Cytoscape 3.8.1 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functional roles of core targets within the PPI network. Protein clustering was conducted utilizing the MCODE plug-in. The obtained results highlight the principal targets and pathways involved. Subsequently, clinical samples were collected to validate alterations in the levels of these main targets through Western blotting (WB) and immunohistochemistry (IHC). Furthermore, both in vivo and in vitro experiments were conducted to investigate the therapeutic effects of EHD on healing LSCC and elucidate its underlying mechanism. Additionally, to ensure experimental reliability and reproducibility, quality control measures utilizing HPLC were implemented for EHD herbal medicine. RESULTS: The retrieval and analysis of databases in EHD medicine and LSCC disease yielded a total of 116 overlapping targets. The MCODE plug-in methods were utilized to acquire 8 distinct protein clusters through protein clustering. The findings indicated that both the first and second clusters exhibited a size greater than 6 scores, with key genes PI3K and ErbB occupying central positions, while the third and fourth clusters were associated with proteins in the PI3K, STAT3, and Foxo pathways. GO functional analysis reported that these targets had associations mainly with the pathway of p53 mediated DNA damage and negative regulation of cell cycle in terms of biological function; the death-induced signaling complex in terms of cell function; transcription factor binding and protein kinase activity in terms of molecular function. The KEGG enrichment analysis demonstrated that these targets were correlated with several signaling pathways, including PI3K-Akt, FoxO, and ErbB2 signaling pathway. On one hand, we observed higher levels of key genes such as P-STAT3, P-PDK1, P-Akt, PI3K, and ErbB2 in LSCC tumor tissues compared to adjacent tissues. Conversely, FOXO3a expression was lower in LSCC tumor tissues. On the other hand, the key genes mentioned above were also highly expressed in both LSCC xenograft nude mice tumors and LSCC cell lines, while FOXO3a was underexpressed. In LSCC xenograft nude mice models, EHD treatment resulted in downregulation of P-STAT3, P-PDK1, PI3K, P-AKT, and ErbB2 protein levels but upregulated FOXO3a protein level. EHD also affected the levels of P-STAT3, P-PDK1, PI3K, P-AKT, FOXO3a, and ErbB2 proteins in vitro: it inhibited P-STAT3, P-AKT, and ErbB2, while promoting FOXO3a; however, it had no effect on PDK1 protein. In addition, HPLC identified twelve compounds accounting for more than 30% within EHD. The findings from this study can serve as valuable guidance for future experimental investigations. CONCLUSION: The possible mechanism of EHD medicine action on LSCC disease is speculated to be closely associated with the ErbB2/PI3K/AKT/FOXO3a signaling pathway.

DIAPH2 gene polymorphisms and laryngeal cancer risk in men.

BACKGROUND: The DIAPH2 gene is one of the genes commonly associated with laryngeal squamous cell carcinoma (LSCC). In our study, we considered the four polymorphisms of this gene, i.e. rs5920828, rs4322175, rs12851931 and rs5921830 as potential genetic risk factors for LSCC. METHODS: We determined the genotyping of the genetic variants of DIAPH2 in 230 male patients with histologically confirmed LSCC compared to the European population. Demographic and environmental exposure data of each subject were examined. To conduct the genetic tests, extraction of total DNA was performed. We genotyped all four variants in each patient and determined their frequencies. RESULTS: In the case of the rs12851931 polymorphism in the DIAPH2 gene, a significant difference was observed in the distribution of the T stage depending on the polymorphism. Heterozygotes were more often associated with T2 stage, while homozygotes were more likely to have higher tumor stages. The rs12851931 homozygotes of DIAPH2 were statistically significantly more prevalent in smokers. The results suggested that rs12851931 polymorphism in DIAPH2 could increase the onset risk of LSCC. CONCLUSIONS: Our results provide further information on the role of the DIAPH2 gene in the pathogenesis of LSCC.

PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.

Objective: This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Methods: Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. Conclusion: In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

Laryngeal and oropharyngeal adenocarcinoma with pulmonary metastases in a common raven (Corvus corax).

A captive 15-year-old male common raven (Corvus corax) was presented for post-mortem examination. It had been previously presented to a local veterinarian due to a 3-4 weeks long history of abnormal respiratory sounds. Upon admission, the bird demonstrated severe dyspnea and a massive amount of mucous in the oropharynx. After symptomatic treatment, dyspnea deteriorated dramatically, and euthanasia was elicited because of poor prognosis. The necropsy revealed a 2.65 x 2.15 x 2.18 cm expansile and poorly delineated cauliflower-shaped mass around the glottis and extending inside the tracheal lumen. Additionally, a dilated salivary gland in the adjacent tissue and multifocal reddish-fleshy areas in the lung parenchyma were detected. Histopathological examination identified the mass as moderately differentiated, tubular adenocarcinoma with invasive growth and moderate to marked cellular atypia and numerous mitoses. The presumptive origin of the neoplasia was one of the salivary glands. Multiple metastases were identified in the lung both macroscopically and histologically. Bacterial culture and molecular testing for West Nile and Usutu viruses were negative. To the authors' knowledge, this is the first report of metastatic laryngeal and oropharyngeal adenocarcinoma in a common raven.

Effects of rosiglitazone on quality of life and prognosis of patients with early stage glottic laryngeal carcinoma.

Early-stage glottic laryngeal carcinoma refers to Tis-T2 lesions without cervical lymph nodes involvement and distant metastasis. Rosiglitazone facilitates expression of anti-inflammatory substances in the body, protecting immune system and improving patient's treatment efficacy and prognosis. We aimed to clarify the influence of rosiglitazone on prognosis of early-stage glottic laryngeal carcinoma. The control group received low-temperature plasma radiofrequency ablation and the observation group additionally received rosiglitazone; 4 mg, 2 times/day for 6 months. After treatment, the observation group showed reduction in the fundamental frequency perturbation and amplitude perturbation and increase in the harmonic-to-noise ratio relative to the control group. Total effective rate was 80.31% and 77.14% for observation and control groups, respectively (P > 0.05). Peripheral blood immune makers were higher in the observation group. The incidence rates of adverse reactions were lower in the observation group. The median survival time was 33 months in control group and 47 months in observation group (P < 0.05). The five-year survival rate was 77.14% in the observation group and 54.29% in the control group (P < 0.05). Rosiglitazone can prolong the survival of early-stage glottic laryngeal carcinoma patients, improving immune function and reducing adverse reactions during treatment.

Robotic and endoscopic trans-oral total laryngectomy, a systematic review and meta-analysis.

Trans-oral total laryngectomy (TOTL) is a novel minimally invasive approach to narrow-field laryngectomy. The objective of this study was to review published data on robotic and endoscopic-assisted TOTL to examine oncologic, functional, and adverse outcomes. MEDLINE, Web of Science, and Cochrane databases were searched between January 2009 and December 2023. PRISMA guidelines were used for data abstraction independently by two reviewers. Proportional meta-analysis (random effects model) was used for analysis. Main outcomes included oncologic outcomes (margin status, recurrence rate) and surgical complications (fistula, hemorrhage, need for second operation). Eight studies were included (total of 37 patients). Cases included 31 robotic-assisted, 3 endoscopic-assisted, and 3 robotic cases which required conversion to open approach. Most cases were performed for laryngeal SCC (22 patients, 59.5%). Primary closure was achieved in all patients. Negative margins were achieved in 20 of 21 patients with LSCC. Recurrence data was reported in 20 LSCC patients with disease recurrence in 4 patients (20%). Follow-up was described for 15 patients (mean of 3.5 years, range 1.6-5.8 years). Eleven complications occurred including fistula, bleed, and stomal stenosis with a pooled rate of 33.7% (95% CI: 16.4-53.0%, I2 = 0). Six fistulas occurred with a pooled rate of 23.2% (95% CI: 5.8-45.4%, I2 = 0). TOTL is an emerging treatment modality appropriate for select patients requiring TL and offers a minimally invasive approach with less tissue disruption. This is the first systematic review and meta-analysis to examine its oncologic outcomes and complications. Larger case series with adequate follow-up are needed to better characterize TOTL outcomes.

Accelerated Fractionated Radiation Therapy for Localized Glottic Carcinoma.

BACKGROUND: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma. METHODS: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80-100 mg per day). RESULTS: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring. CONCLUSIONS: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time.

The Relationship between miR-5682 and Nutritional Status of Radiotherapy-Treated Male Laryngeal Cancer Patients.

BACKGROUND: Nutritional deficiencies are frequently observed in patients with head and neck cancer (HNC) undergoing radiation therapy. microRNAs (miRNAs) were found to play an important role in the development of metabolic disorders throughout regulation of genes involved in inflammatory responses. This study aimed to explore the correlation between pre-treatment miR-5682 expression and parameters reflecting nutritional deficits in laryngeal cancer (LC) patients subjected to radiotherapy (RT). METHODS: Expression of miR-5682 was analyzed in plasma samples of 56 male LC individuals. Nutritional status of LC patients was assessed using anthropometric and laboratory parameters, bioelectrical impedance analysis (BIA) and clinical questionnaires. RESULTS: A high expression of miR-5682 was associated with significantly lower values of BMI, fat mass, fat-free mass and plasma albumin at selected periods of RT course. miR-5682 allowed us to distinguish between patients classified with both SGA-C and low albumin level from other LC patients with 100% sensitivity and 69.6% specificity (AUC = 0.820; p < 0.0001). Higher expression of studied miRNA was significantly associated with shorter median overall survival (OS) in LC patients (HR = 2.26; p = 0.008). CONCLUSIONS: analysis of miR-5682 expression demonstrates a potential clinical utility in selection of LC patients suffering from nutritional deficiencies developing as a consequence of RT-based therapy.

Transoral laser exoscopic surgery of the larynx: state of the art and comparison with traditional transoral laser microsurgery.

Objective: To evaluate the efficacy of transoral laser exoscopic surgery (TOLES) in a unicentric series of patients affected by benign and malignant glottic and supraglottic lesions, and compare outcomes with those of transoral laser microsurgery (TOLMS). Methods: To demonstrate the non-inferiority of TOLES in terms of operative time, margin status and complication rates, we compared outcomes of 93 patients treated by TOLES between July 2021 and July 2023 with those of a match-paired group of 107 historical patients treated by TOLMS. To perform a multiparametric ergonomic evaluation of TOLES vs TOLMS, we used observational methods for biomechanical overload risk assessment and wearable technologies comparing 15 procedures with TOLES vs a paired match of 13 surgeries performed with TOLMS by the same surgeon. Results: No significant differences were found in terms of surgical duration, positive margins, or complications between TOLES and TOLMS. Ergonomics assessment by inertial measurement units and electromyographic surface electrodes demonstrated a reduced biomechanical overload with TOLES compared to TOLMS. Conclusions: The many advantages of TOLES, such as its superior didactic value, better digital control of light even through small-bored laryngoscopes, improved binocular vision, and increase in surgical performance by 3 or 4-hand techniques, are difficult to be quantified. In contrast, its non-inferiority in terms of oncological results and better ergonomics compared to TOLMS are demonstrated herein.

Flexible endoscopic phonosurgery for treatment of functional sequelae after laryngeal oncologic surgery: a narrative review.

Flexible endoscopic phonosurgery (FEPS) is one of the most recent and constantly evolving operative techniques in the field of minimally invasive laryngeal surgery. Thanks in part to the possibility of using new technologies, such as digital endoscopes, laser fibres, and different laryngeal injection materials, its fields of application have rapidly expanded. This narrative review describes the current possible indications of FEPS ranging from injection laryngoplasties in cases of vocal cord paralysis or mass defect, to the correction of dysphagia after open partial horizontal laryngectomies. Use of microscissors, microforceps, and laser fibres also allows this technique to be applied for removal of superficial vocal cord lesions, avoiding general anaesthesia in an increasing number of patients.

Transoral robotic surgery for supraglottic cancer. A review of oncological and functional outcomes compared to open surgery.

Objective: Supraglottic squamous cell carcinoma (SCC) represents a major surgical challenge in organ-preserving treatment. Type I open partial horizontal laryngectomy (OPHL I) is considered the most popular. To date, minimally-invasive approaches such as laser microsurgery and transoral robotic surgery (TORS) have gained increasing relevance. The aim of this narrative review is to obtain a descriptive comparison of functional and oncological outcomes from studies on patients with supraglottic SCC treated with OPHL I and TORS, respectively. Material and methods: A computerised search was performed using the Pubmed database for articles published from 2000 to 2023. A comparative analysis on functional and oncological outcomes of patients treated by TORS and OPHL I was performed. Results: The present narrative review shows a superiority of TORS compared to open surgery for supraglottic SCC in terms of functional outcomes, while maintaining comparable oncological outcomes. Conclusions: Although recently introduced in the treatment of laryngeal pathology, TORS has been shown to be a reliable technique not only for functional but also for oncological outcomes, ensuring good overall survival, disease-free survival, and disease control rates comparable to OPHL I.

Evolution of the quality of life of total laryngectomy patients using electrolarynx.

OBJECTIVE: Therapy and vocal rehabilitation in laryngeal cancer impact patients' quality of life. The objective of this study was to evaluate the evolution of the quality of life of patients with laryngeal cancer submitted to total laryngectomy and using electrolarynx. METHODS: This is an observational study with a cross-sectional design and a quantitative approach. It was conducted between April 2022 and January 2023 in a Brazilian cancer hospital. For data collection, a quality of life questionnaire, validated for patients with head and neck cancer at the University of Washington, was applied in two phases: from 7 days after total laryngectomy and, subsequently, from 70 days after surgery using electronic larynx for at least 60 days. The inclusion criteria were patients undergoing total laryngectomy included on the Aldenora Bello Cancer Hospital's election list to receive the electronic larynx. Patients who did not sign the informed consent form were not included. RESULTS: The sample consisted of 31 patients, of which approximately 84% were men and approximately 93% at the age of 50 years or older. When comparing the phases, it is possible to observe that the item speech had the greatest progress, while chewing had the least. Only the item recreation, swallowing, taste, and saliva did not show any statistical significance. The score for the general quality of life questions increased. CONCLUSION: Electronic larynx is a viable and useful method of voice rehabilitation. Our data suggest that the use of the electrolarynx as a postlaryngectomy method of verbal communication is responsible for positive effects on patients' quality of life.

[Epidemiological features papillomatosis of the larynx in adults: a literature review]. / Epidemiologicheskie osobennosti papillomatoza gortani u vzroslykh (obzor literatury).

The literature review presents current data on the epidemiology, drug, and surgical treatment of laryngeal papillomatosis in adults. Possible prospects for further study of the prevalence and incidence of the disease and provoking factors of recurrence of the disease for the development of possible preventive measures are considered.