Search Results (316)

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy with unsatisfactory survival rates, highlighting the need for reliable biomarkers to improve its diagnosis and prognosis. Growth differentiation factor 15 (GDF15), a protein implicated in various cancers, has not been thoroughly investigated in LSCC. This study aimed to evaluate the significance of GDF15 expression in LSCC by integrating immunohistochemical analysis of archival tissue samples with RNA sequencing data from public databases (TCGA and GEO) to provide comprehensive clinical insights. Methods: We analyzed archival tissue samples from 65 patients with LSCC using immunohistochemistry and evaluated GDF15 expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Statistical analyses included Kaplan–Meier survival analysis and Cox proportional hazards regression to assess the correlation between GDF15 expression, clinicopathological variables, and survival outcomes. Results: GDF15 expression did not significantly differ between tumor and adjacent normal tissues. However, in the tissue macroarray (TMA) cohort, high GDF15 expression was significantly associated with a lower TNM stage and less advanced pT status. Kaplan–Meier analysis revealed that high GDF15 expression correlated with reduced overall survival in the TMA cohort, suggesting its utility in risk stratification. Multivariate analysis identified GDF15 as an independent prognostic factor for disease-free survival in LSCC. Conclusions: Our findings suggest that GDF15 may serve as a prognostic biomarker for LSCC, particularly in early-stage disease. Elevated GDF15 levels, which are associated with poorer overall survival, could be integrated into diagnostic panels to enhance risk stratification and inform treatment decisions. Furthermore, GDF15 may be a promising target for therapeutic intervention. Further research is warranted to validate these results and explore their potential in clinical practice. Full article

Background/Objectives: Laryngeal cancer (LC) accounts for 1–3% of all malignant neoplasms. The aim of this study was to analyze temporal trends in the incidence and mortality of LC in Central Serbia over a 25-year period (1999–2023). Methods: Data on newly diagnosed cases and deaths, stratified by sex and age group, were obtained from the Serbian Cancer Registry. Crude, age-specific, and age-standardized incidence and mortality rates were calculated. Joinpoint regression analysis was used to estimate average annual percent changes (AAPCs) and assess their statistical significance. Results: The average annual age-standardized incidence rate (ASR-W) was 11.1 per 100,000 in men and 1.4 in women, with corresponding mortality rates of 5.4 and 0.5, respectively. The highest incidence was observed in the 60–69 age group for both sexes (61.1/100,000 in men; 7.4/100,000 in women), while the highest mortality was recorded in individuals aged ≥70 (35.7/100,000 in men; 3.8/100,000 in women). A statistically significant annual decline among men was observed in both incidence (ASR-W: −0.7%) and mortality (ASR-W: −2.0%). In contrast, trends among women were not statistically significant, indicating overall stability. Conclusions: Although the Cancer Registry in Serbia faces limitations primarily due to data quality issues, it is a key tool for understanding LC trends, guiding health policies, and effectively allocating resources. Given the substantially higher burden among men, it is essential to strengthen tobacco and alcohol control, improve occupational safety, and promote early detection and timely treatment to reduce the disease burden. Full article

Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article

Laryngeal cancer significantly affects not only survival but also core functions such as speech, swallowing, and breathing. These impairments often result in substantial psychological distress and reduced health-related quality of life (HRQoL). This review aims to synthesize current evidence regarding the psychological impact, quality of life outcomes, and system-level challenges faced by laryngeal cancer patients while identifying strategies for integrated survivorship care. Anxiety and depressive symptoms are highly prevalent among laryngeal cancer patients, particularly those undergoing total laryngectomy or chemoradiotherapy. HRQoL outcomes vary significantly depending on treatment modality, with long-term deficits noted in domains such as voice, swallowing, and emotional well-being. Access to psychological support and rehabilitation remains inconsistent, hindered by institutional, socioeconomic, and cultural barriers. Structured survivorship models, psychological screening, and patient-centered rehabilitation have demonstrated benefits but are not universally implemented. Comprehensive care for laryngeal cancer must extend beyond tumor control to address persistent functional and psychological sequelae. A multidisciplinary, anticipatory, and personalized approach—centered on integrated rehabilitation and mental health support—is essential to optimize survivorship outcomes and improve long-term quality of life. Full article

(1) Background: The early detection of laryngeal cancer is crucial for achieving superior patient outcomes and preserving laryngeal function. Artificial intelligence (AI) methodologies can expedite the triage of suspicious laryngeal lesions, thereby diminishing the critical timeframe required for clinical intervention. (2) Methods: We included all studies published up to February 2025. We conducted a systematic search across five major databases: MEDLINE, EMCARE, EMBASE, PubMed, and the Cochrane Library. We included 15 studies, with a total of 17,559 patients. A risk of bias assessment was performed using the QUADAS-2 tool. We conducted data synthesis using the Meta Disc 1.4 program. (3) Results: A meta-analysis revealed that AI demonstrated high sensitivity (78%) and specificity (86%), with a Pooled Diagnostic Odds Ratio of 53.77 (95% CI: 27.38 to 105.62) in detecting laryngeal cancer. The subset analysis revealed that CNN-based AI models are superior to non-CNN-based models in image analysis and lesion detection. (4) Conclusions: AI can be used in real-world settings due to its diagnostic accuracy, high sensitivity, and specificity. Full article

Despite advancements in multidisciplinary treatment, esophagectomy remains the primary curative treatment for esophageal cancer. Given that lymph node metastases can spread from the cervical to abdominal regions, three-field lymph node dissection has been established as a standard approach. However, this highly invasive procedure involves multiple anatomical regions—thoracic, abdominal, and cervical—leading to significant surgical burden. To reduce surgical invasiveness, minimally invasive esophagectomy (MIE) has become increasingly common worldwide. With its adoption and advancements in multidisciplinary therapy, discussions have emerged regarding the potential omission of lymph node dissection in selected cases. Since the introduction of robot-assisted minimally invasive esophagectomy (RAMIE) in 2004, this technique has progressively replaced conventional MIE. Robotic systems—equipped with a magnified 3D camera, articulated instruments, and tremor filtering—allow surgeons to perform complex procedures with greater precision than manual techniques. One randomized controlled trial (RCT) has demonstrated fewer postoperative complications with RAMIE compared to open esophagectomy. Additionally, RAMIE has been shown to enable more extensive lymph node dissection around the left recurrent laryngeal nerve than conventional MIE. However, the long-term oncological benefits of RAMIE remain unproven, as no RCTs have definitely confirmed its impact on long-term survival in esophageal cancer patients. Ongoing randomized trials are expected to provide further insights into its prognostic benefits. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

Background: Previous studies have shown that ventilation strategies used in general anesthesia influence perioperative outcomes of video-assisted thoracoscopic surgery (VATS). This study investigated the perioperative effects of non-intubated anesthesia (NIA) versus intubated anesthesia (IA) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing VATS. Methods: This retrospective cohort study analyzed patients who underwent elective VATS for early-stage NSCLC between January 2015 and December 2022. Patients were categorized into the NIA and IA groups based on the ventilation strategies during general anesthesia. Comprehensive outcome data, including intraoperative and postoperative variables, were compared between the two groups. Univariate and multivariate logistic regression models were used to assess the odds ratios for conversion from NIA to IA. Results: A total of 372 patients who received NIA and 1560 who received IA for VATS were eligible for analysis. After propensity score matching, 336 patients were included in each group. In the matched analysis, patients who received NIA demonstrated favorable perioperative outcomes, including reduced opioid consumption, lower postoperative complication rates, and shorter hospital stays, compared to those who received IA. Additionally, patients with a lower baseline oxygen saturation and those who experienced intraoperative pulmonary and cardiovascular adverse events had a higher risk of conversion from NIA to IA. Conclusions: NIA during VATS in patients with early-stage NSCLC was associated with superior perioperative outcomes. Prospective studies are warranted to further evaluate the impact of NIA on perioperative outcomes in this patient population. Full article

Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes. Full article

Nectin-2 and Nectin-4 are cell adhesion molecules associated with the progression of various cancers. The main goal of this pilot study was to evaluate the expression patterns of Nectin-2 and Nectin-4 in laryngeal squamous cell carcinoma (LSCC). A retrospective study was conducted on tissue microarray (TMA) samples derived from 31 patients who underwent total laryngectomy. The findings revealed heterogenous expression of both Nectin-2 and Nectin-4 in tumor cells and surrounding stroma, with Nectin-4 expression being significantly higher than Nectin-2 expression. Specifically, 74% of cases showed weak cytoplasmic staining for Nectin-2, while 41.93% exhibited strong cytoplasmic staining for Nectin-4. Both Nectin-2 and Nectin-4 expressions were more pronounced at the invasive tumor margins. Although no significant differences in Nectin-4 expression were observed across tumor grades (W = 83.500; z = −0.463; p = 0.658), differences in expression patterns were noted. Well-differentiated tumors (Grade 1), 80.65% of cases, showed predominantly membranous Nectin-4 staining, including in squamous epithelial cells of the mucosal surface. Conversely, in less-differentiated tumors (Grade 2 and 3), a shift toward cytoplasmic staining was evident. Specifically, 74.19% of Grade 2 tumors and 100% of Grade 3 tumors showed a predominant cytoplasmic localization of Nectin-4. This transition from membranous to cytoplasmic localization was also evident in the progression from normal superficial epithelium to malignant tissue. These observations suggest that alterations in the expression and subcellular localization of Nectin-4 may be associated with carcinogenesis and could serve as potential markers for the assessment of precancerous lesions and the aggressiveness of laryngeal tumors. Full article

Objectives: This study evaluates the potential of high-speed videoendoscopy (HSV) in differentiating between benign and malignant glottic lesions, offering a non-invasive diagnostic tool for clinicians. Moreover, a new parameter derived from high-speed videoendoscopy (HSV) had been proposed and implemented in the analysis for an objective assessment of the vocal fold stiffness. Methods: High-speed videoendoscopy (HSV) was conducted on 102 participants, including 21 normophonic individuals, 39 patients with benign vocal fold lesions, and 42 with glottic cancer. Laryngotopographic parameter describing the stiffness of vocal fold (SAI) and kymographic parameters describing amplitude, symmetry, and glottal dynamics were quantified. Statistical differences between groups were assessed using receiver operating characteristic (ROC) analysis and lesion classification was performed using a machine learning model. Results: Univariate receiver operating characteristic (ROC) analysis revealed that SAI (AUC = 0.91, 95% CI: 0.839–0.962) and weighted amplitude asymmetry (AUC = 0.92, 95% CI: 0.85–0.974) were highly effective in distinguishing between normophonic and organic lesions (p < 0.01). Further multivariate analysis using machine learning models demonstrated improved accuracy, with the SVM classifier achieving an AUC of 0.93 for detecting organic lesions and 0.83 for distinguishing benign from malignant lesions. Conclusions: The study demonstrates the potential value of parameter describing the pliability of infiltrated vocal fold (SAI) as a non-invasive tool to support histopathological evaluation in laryngeal lesions, with machine learning models enhancing diagnostic performance. Full article

The synthetic cortisol analog budesonide (BUD) is an essential drug employed to manage chronic inflammatory diseases in humans, mainly those involving gastroenteric and airway mucosa, such as rhinitis, laryngitis, bronchitis, esophagitis, gastritis, and colitis, with high levels of success. As a glucocorticoid, BUD prevents the expression of pro-inflammatory cytokines/chemokines and the recruitment of immune cells into the inflamed mucosa. However, emerging evidence indicates that BUD, unlike classical glucocorticoids, is also a potent modulator of stem and cancer cell behavior/plasticity. Certainly, BUD stabilizes cell–cell adhesions, preventing embryonic stem cell differentiation and inhibiting the development of 3D gastruloids. In addition, BUD inhibits the motile/invasive propensity of different cancer cells, including breast, lung, and pancreatic cancer. Finally, it prevents the infection of positive single-stranded human-infecting RNA viruses such as SARS-CoV-2. At a molecular level, BUD induces epigenetic changes and modifies the transcriptome of epithelial, stem, and cancer cells, providing molecular support to the immune cell-independent activity of BUD. Here, we performed an in-depth review of these unexpected activities of BUD, identified by unbiased drug screening programs, and we emphasize the molecular mechanisms modulated by this efficacious drug that deserve further research. Full article

Spontaneous ventilation lung surgery (SVLS) without intubation is aimed at avoiding adverse effects of mechanical ventilation lung surgery (MVLS) entailing one-lung mechanical ventilation through a double-lumen tracheal tube. This innovative strategy has evolved following the publication of a small randomized study of thoracoscopic pulmonary wedge resection carried out under spontaneous ventilation without tracheal intubation in fully awake patients. It now entails target-controlled sedation, the use of a laryngeal mask, and thoracic analgesia by intercostal or paravertebral blocks and has shown promise both in unicenter and multicenter studies, resulting in optimal feasibility and safety and highly satisfactory results, particularly in patients undergoing lung cancer resection and metastasectomy, lung biopsy for undetermined interstitial lung disease, lung volume reduction surgery for end-stage emphysema, and bullectomy for primary and secondary spontaneous pneumothorax. However, concerns and unresolved issues still exist regarding the advantages and disadvantages of SVLS as well as the identification of optimal indications. This perspective is aimed at providing a critical overview of the current knowledge about SVLS with emphasis on recent data comparing the results with those of MVLS published in the last 10 years. Full article

Background and Objectives: Despite notable advances in diagnosing and managing laryngeal cancer, the disease continues to present challenges, particularly in the advanced stages. Circulating microRNAs (miRNAs) are increasingly recognized as accessible biomarkers for cancer detection and follow-up. This exploratory study centers on identifying and evaluating miRNAs that are specifically downregulated in laryngeal carcinoma patients, aiming to clarify their clinical relevance in distinguishing pre- and post-therapeutic states. Methods: A total of 30 patients with laryngeal cancer provided paired blood samples before and after undergoing surgical or non-surgical treatment. To reduce variability and resource demand, each set of 10 samples was pooled into three pre-treatment groups (P1, P2, and P3) and three corresponding post-treatment groups (C1, C2, and C3). Total RNA, including miRNAs, was isolated from both plasma and exosomes, followed by qPCR-based profiling (Qiagen platform). Downregulated miRNAs were singled out through statistical comparisons using Mann–Whitney U tests; receiver operating characteristic (ROC) analyses and logistic regression were further applied to assess diagnostic utility. Results: Seven miRNAs demonstrated significant downregulation in the pre-treatment samples (fold changes ranging from 0.20 to 0.64, p < 0.05). Notably, hsa-miR-107 and hsa-let-7a-5p both showed marked reductions of approximately fivefold (p < 0.01), suggesting a strong association with active tumor presence. In ROC analysis, hsa-miR-107 achieved an area under the curve (AUC) of 0.78 (95% CI: 0.62–0.90) with 72% sensitivity and 74% specificity in differentiating pre- from post-treatment states. A logistic regression model incorporating downregulated candidates produced odds ratios between 0.52 and 0.64 (p < 0.05), pointing to their potential additive value in clinical decision-making. Conclusions: These preliminary findings indicate that certain miRNAs, when suppressed in circulation, may be linked to the oncogenic milieu of laryngeal cancer. Confirming these observations in larger, multicenter investigations is critical, but this pilot work underscores the promise of downregulated miRNAs as biomarkers of disease activity and potential guides to therapy response. Full article