Search Results (52)

Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these treatments. Methods: This prospective observational cohort study was conducted at the ENT Clinic, Victor Babeș University of Medicine and Pharmacy, Timișoara; recruitment was conducted between October 2019 and January 2024. Seventy-five patients diagnosed with laryngeal squamous cell carcinoma (LSCC) were initially enrolled but only 15 patients (20%) completed the 12-month follow-up, with an attrition rate of 80%. Tumor stages ranged from T1 to T4a, with TL patients having a higher proportion of advanced-stage disease (Stage III–IV: 76%) compared to PL (45%) and CRT (50%). Validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Voice Handicap Index-30 (VHI-30), the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Outcome and Severity Scale (DOSS), were used to assess QoL, voice function, swallowing function, and psychological impact. Results: At 12 months, the global QoL score from the EORTC QLQ-H&N35 was lowest in TL patients (49.8 ± 10.9), significantly lower than both PL (61.2 ± 9.6, p = 0.002) and CRT (64.1 ± 7.8, p < 0.001). Post hoc Bonferroni analysis confirmed significant pairwise differences between TL vs. PL (p = 0.002) and TL vs. CRT (p < 0.001), while the difference between PL and CRT was non-significant (p = 0.14). TL patients had higher speech-related disability (VHI: 88.3 ± 12.6) and dysphagia prevalence (DOSS: 4.0 ± 1.2), with 16% remaining enteral feeding-dependent. Anxiety (HADS-A: 7.5 ± 2.9) and depression (HADS-D: 9.0 ± 3.2) were highest in TL patients, with 36% meeting clinical depression criteria at 12 months. Multivariable regression identified TL (OR = 3.92, 95% CI: 2.14–5.79, p < 0.001) and advanced tumor stage (OR = 2.85, 95% CI: 1.79–4.21, p = 0.002) as strong predictors of poor QoL. Kaplan–Meier analysis showed no significant OS differences (p = 0.12), but CRT patients had lower DFS (78%) compared to TL (82%) and PL (85%) (p = 0.048). Conclusions: TL patients experience the most significant impairments in QoL, speech, and social reintegration despite rehabilitation. CRT patients show higher recurrence rates but better QoL, while PL offers the best balance of function and survival. These findings highlight the need for long-term survivorship support tailored to treatment type. Full article

Early-stage laryngeal cancer (T1-T2) is commonly treated with organ-preserving techniques such as transoral laser microsurgery (TOLMS) or radiation therapy (RT), both providing comparable oncological outcomes but differing in functional results. Local recurrence occurs in approximately 10% of cases, making salvage surgery a crucial therapeutic option. This multi-institutional study investigates the efficacy of open partial horizontal laryngectomy (OPHL) as a salvage treatment, following recurrent laryngeal squamous-cell carcinoma (LSCC) after failed TOLMS. This analysis includes 66 patients who underwent OPHL between 1995 and 2017, reporting favorable oncological outcomes with overall survival (OS) of 87.4%, disease-specific survival (DSS) of 93.4%, and disease-free survival (DFS) of 85.5%. A recurrence rate of 10.6% was observed post-salvage OPHL, with vascular invasion and advanced pathological staging identified as significant predictors of recurrence. OPHL emerged as an effective organ-preserving alternative to total laryngectomy (TL) in select patients, especially those with limited tumor spread and preserved laryngeal function. The study highlights the importance of careful patient selection and thorough preoperative assessment to improve outcomes, positioning OPHL as a key option in treating recurrent laryngeal cancer and offering oncological control while preserving laryngeal functions. Full article

(1) Background: Laryngeal surgery due to carcinoma leads to significant tissue disruption, cellular injury, and inflammation. This leads to increased levels of reactive oxygen species (ROS), causing oxidative damage that can influence quality of life (QOL) and recovery and complicate the postoperative course. The aim of this study was to compare how postoperative quality of life and surgical complication occurrence interacted with the biomarker levels of oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; glutathione peroxidase 1, GPX1; and catalase, CAT) and inflammation (interleukin 1, IL-1; interleukin 6, IL-6; C-reactive protein, CRP) in patients treated with conservative and radical laryngeal surgery. (2) Methods: The study included 56 patients who underwent surgical treatment for laryngeal cancer. Blood samples were collected to analyze oxidative stress and inflammation parameters before surgery and on the first and seventh days postoperatively. Serum concentrations of MDA, SOD, GPX, CAT, IL-1, IL-6, and CRP were measured using coated enzyme-linked immunosorbent assay (ELISA) kits. EORTC QLQ-H&H43 questionnaire was used to measure the QOL of patients. (3) Results and Conclusions: T stage, pain intensity, and the extent of the surgical procedure were established as significant predictive factors for QOL in multivariate analysis. There was a significant positive correlation between surgical complication occurrence and preoperative values of GPX and MDA, but significant predictors of surgical complication occurrence on the 7th postoperative day were SOD and MDA values (p < 0.05). Full article

Head and neck cancer is the seventh leading cancer diagnosis worldwide. One of the most common cancers in the head and neck region is laryngeal cancer. In past years, the incidence of laryngeal squamous cell carcinoma has risen by 23%, and despite progress in treatment modalities, the survival rate has not changed. It is well known that genetic alterations may contribute to individuals’ susceptibility to cancer. Research of genetic alterations, such as single nucleotide polymorphisms, is essential to understanding carcinogenesis and susceptibility of laryngeal squamous cell carcinoma. A total of 200 LSCC patients and 200 controls were included in this retrospective case-control study; both groups were matched by age and sex. In the present study, we analyzed six SNPs in genes essential for apoptosis regulation: TP53 (rs9895829, rs17884306), BCL2 (rs1564483, rs4987855), BAX (rs704243), NOXA (PMAIP1) (rs1041978, rs78800940). We evaluated their associations with the risk of LSCC development, its pathomorphological manifestation, and patients’ overall survival rate. Genotyping was carried out using RT-PCR. The AG genotype of rs9895829 was more prevalent in controls than in cancer patients, leading to lower susceptibility to LSCC (OR = 0.301; 95%CI 0.096–0.940; p = 0.039). None of the analyzed SNPs showed an association with pathomorphological features of LSCC, but NOXA rs1041978 T allele carriers were found to be diagnosed with LSCC at an older age (OR = 1.962; 95%CI 1.072–3.592; p = 0.031). There was no statistically significant association between investigated SNPs and patient OS. The present study indicates that the AG genotype of rs9895829 provides a protective effect against LSCC development. Full article

Background: Surgical site infection (SSI) in laryngeal cancer (LC) patients significantly increases morbidity and may postpone adjuvant therapy. Additionally, SSI can prolong hospitalization, thus representing a burden for the healthcare system. Most of the published studies refer to SSI after salvage laryngectomy. Methods: The present prospective cohort study aimed to clarify the incidence and factors associated with SSI in patients after primary open surgery for LC. Through regular hospital surveillance of patients who underwent primary partial or total laryngectomy, we gathered 24 putative factors and identified SSI from 2013 to 2022. Patients with SSI were compared with patients without SSI. Results: SSI was observed in 21 (6.6%) of 319 patients. ULRA showed that the occurrence of SSI was significantly associated with the American Society of Anesthesiologists (ASA) score, other postoperative healthcare-associated (HAI) infection, T classification, N classification, advanced clinical stage (III–IV), length of stay (LOS), duration of drainage, and the National Healthcare Safety Network (NHSN) risk index. Multivariate logistic regression analysis identified two independent factors associated with SSI occurring in these patients: duration of drainage (RR (relative risk) 1.593; 95% CI 1.159–2.189; p = 0.004) and LOS (RR: 1.074; 95% CI: 1.037–1.112; p < 0.001). Conclusions: Our study provided insight into the burden of SSI in LC patients, highlighting several priority areas and targets for quality improvement. Full article

According to recent research, inflammatory STAT4 and its protein impact may be important factors in developing cancerous diseases. Still unanalyzed is this effect in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated four single nucleotide variants (SNVs) of STAT4 (rs10181656, rs7574865, rs7601754, and rs10168266) and STAT4 serum levels to determine their link between LSCC development and its clinical manifestations. A total of 632 men (324 LSCC patients and 338 healthy individuals) were involved in this study. The genotyping was carried out using real-time PCR. Additionally, we measured 80 study subjects’ (40 LSCC patients and 40 control subjects) STAT4 protein concentrations using an enzyme-linked immunosorbent assay (ELISA). In our study, the T allele of STAT4 rs7574865 significantly increases the likelihood of LSCC occurrence by 1.4-fold. Additionally, this SNV is associated with higher odds of early-stage disease, T1 size LSCC development, absence of metastasis to neck lymph nodes, and well-differentiated carcinoma. The G allele of rs10181656 is significantly associated with various clinical characteristics of LSCC, increasing the odds of early- and advanced-stage disease by 2.8-fold and 1.9-fold, respectively. Additionally, this allele is linked to an increased likelihood of developing tumors of different sizes and non-metastasized LSCC, as well as poorly differentiated carcinoma, highlighting its potential impact on the development and features of LSCC. Conclusion: The analysis of the STAT4 rs7574865 SNV revealed that the G allele is linked to a more favorable prognosis in LSCC. Additionally, it is hypothesized that the G allele of rs10181656 may be associated with the occurrence of LSCC but may not serve as a sensitive prognostic biomarker for distinguishing between disease stages, cell differentiation, or tumor size. Full article

Background/Objectives: Positive margins are associated with locoregional recurrence in early laryngeal cancer. The aim of this study was to evaluate the impacts of specimen-driven (ex vivo) positive margins on patients with early-stage laryngeal cancer whose tumor bed (defect-driven) margins had been negative. Methods: A retrospective study was performed on 60 consecutive T1b/T2 glottic cancer patients who underwent open frontolateral laryngectomy. The intraoperative margins were obtained from the tumor bed. Their recurrence and disease-free survival were evaluated. In all cases, negative margins were obtained from the surgical bed. The impact of positive margins from the specimen was evaluated in a paraffin study. Results: Among 10 patients with positive margins in the specimen, six experienced local relapse, and among 50 patients with negative margins in the specimen, three developed recurrence. The 5-year disease-free survival rates were 37.5% and 93.9%, respectively (p < 0.001; log-rank). Even with negative margins in the surgical bed, patients with positive margins in the specimen at the final histopathological examination had a 3.5-fold higher chance of developing local recurrence than those with negative margins (HR = 13.993; 95% CI: 3.479–56.281; p < 0.001; univariate Cox regression). Conclusions: Specimen-driven positive margins represent a significant risk factor for local recurrence, even under negative margins at the tumor bed. Full article

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. Full article

There is still much to learn about the epigenetic mechanisms controlling gene expression during carcinogenesis. When researching aberrant DNA methylation, active proliferative tumor cells from head and neck squamous cell cancer (HNSCC) can be used as a model. The aim of the study was to investigate the methylation status of CDKN1, CDKN2A, MYC, Smad3, SP1, and UBC genes in tumor tissue (control-normal tissue) in 50 patients (37 men and 13 women) with HPV-negative HNSCC. Methods: Bisulfite conversion methods and methyl-sensitive analysis of high-resolution melting curves were used to quantify the methylation of genes. In all patients and across various subgroups (tongue carcinoma, laryngeal and other types of carcinomas T2, T3, T4 status; age before and after 50 years; smoking and non-smoking), there are consistent differences in the methylation levels in the SP1 gene in tumor DNA compared to normal. Results: The methylation of the SP1 gene in tumor DNA suppresses its expression, hinders HNSCC cell proliferation regulation, and could be a molecular indicator of malignant cell growth. The study of DNA methylation of various genes involved in carcinogenesis is promising because hypermethylated promoters can serve as potential biomarkers of disease. Full article

Objectives. The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. Methods. This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a “protocol” of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. Results. A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran’s Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). Conclusions. PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy. Full article

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT. Full article

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. Full article

Introduction: CD24 is often overexpressed in human tumors as a regulator of cell migration, invasion and proliferation. It has been associated with poor prognosis and chemoresistance in laryngeal cancer. In oral cavity tumors, it was correlated with better overall survival. In this study, we aimed to evaluate the role of CD24 in peripheral blood leukocytes (PBLs) as a potential marker for head and neck malignancies. Materials and Methods: CD24/CD11b expression in peripheral blood leukocytes (PBLs) of head and neck cancer patients and matched healthy controls was analyzed via flow cytometry. Tumors and healthy tissues were immune-stained for CD24 expression and the intensity of stain was ranked. Clinical data including tumor site, size, locoregional or metastatic spread, histopathological characteristics and recurrence events were analyzed. Results: CD24 expression in PBLs was significantly higher in a cohort of 101 head and neck cancer patients compared with 101 matched healthy controls (26.9 ± 12.9 vs. 22.4 ± 13.8; p = 0.02). No significant differences in CD24 levels in PBLs were found between different head and neck subsites involved with malignancy. Higher CD24 levels did not correlate with any adverse feature, i.e., perineural invasion or lymphovascular invasion, advanced T stage or regional spread. Immunohistochemistry analysis demonstrated that CD24 was highly expressed in tumor tissue in comparison to healthy surrounding tissue. Conclusions: CD24 is a possible uprising marker for tumor identification, overexpressed in PBLs and is intensely stained in tumor tissue and pre-malignant lesions. Tumor–PBLs should be further studied. Full article

Background: Despite recommendations for upfront total laryngectomy (TL), many patients with cT4a laryngeal cancer (LC) instead undergo definitive chemoradiation, which is associated with inferior survival. Sociodemographic and oncologic characteristics associated with TL utilization in this population are understudied. Methods: This retrospective cohort study utilized hospital registry data from the National Cancer Database to analyze patients diagnosed with cT4a LC from 2004 to 2017. Patients were stratified by receipt of TL, and patient and facility characteristics were compared between the two groups. Logistic regression analyses and Cox proportional hazards methodology were performed to determine variables associated with receipt of TL and with overall survival (OS), respectively. OS was estimated using the Kaplan–Meier method and compared between treatment groups using log-rank testing. TL usage over time was assessed. Results: There were 11,149 patients identified. TL utilization increased from 36% in 2004 to 55% in 2017. Treatment at an academic/research program (OR 3.06) or integrated network cancer program (OR 1.50), male sex (OR 1.19), and Medicaid insurance (OR 1.31) were associated with increased likelihood of undergoing TL on multivariate analysis (MVA), whereas age > 61 (OR 0.81), Charlson–Deyo comorbidity score ≥ 3 (OR 0.74), and clinically positive regional nodes (OR 0.78 [cN1], OR 0.67 [cN2], OR 0.21 [cN3]) were associated with decreased likelihood. Those undergoing TL with post-operative radiotherapy (+/− chemotherapy) had better survival than those receiving chemoradiation (median OS 121 vs. 97 months; p = 0.003), and TL + PORT was associated with lower risk of death compared to chemoradiation on MVA (HR 0.72; p = 0.024). Conclusions: Usage of TL for cT4a LC is increasing over time but remains below 60%. Patients seeking care at academic/research centers are significantly more likely to undergo TL, highlighting the importance of decreasing barriers to accessing these centers. Increased focus should be placed on understanding and addressing the additional patient-, physician-, and system-level factors that lead to decreased utilization of surgery. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may increase the risk of cancer development and a poor cancer prognosis. TAMs of the M2 phenotype, together with the intermittent hypoxic environment within the tumor, drive tumor aggressiveness. However, the mechanism of TAMs in IH remains unclear. In our study, IH induced the recruitment of macrophages, and IH-induced M2-like TAMs promoted glycolysis in laryngeal cancer cells through hexokinase 1. The hexokinase inhibitor 2-deoxy-D-glucose and HK1 shRNA were applied to verify this finding, confirming that M2-like TAMs enhanced glycolysis in laryngeal cancer cells through HK1 under intermittent hypoxic conditions. Comprehensive RNA-seq analysis disclosed a marked elevation in the expression levels of the transcription factor ZBTB10, while evaluation of a laryngeal cancer patient tissue microarray demonstrated a positive correlation between ZBTB10 and HK1 expression in laryngeal carcinoma. Knockdown of ZBTB10 decreased HK1 expression, and overexpression of ZBTB10 increased HK1 expression in both laryngeal cancer cells and 293T cells. The luciferase reporter assay and Chromatin immunoprecipitation assay confirmed that ZBTB10 directly bound to the promoter region of HK1 and regulated the transcriptional activity of HK1. Finally, the CLEC3B level of the M2 supernatant is significantly higher in the IH group and showed a protumor effect on Hep2 cells. As ZBTB10-mediated regulation of HK1 affects glycolysis in laryngeal cancer, our findings may provide new potential therapeutic targets for laryngeal cancer. Full article