Transoral robotic surgery (TORS) is a minimally invasive approach for treating early-stage malignant or benign tumors of the pharynx and larynx. This study represents the first real-world, single-arm, early feasibility evaluation of clinical performance and perioperative safety of da Vinci Single-Port (SP) for treating various benign or early-stage malignant tumors of the pharynx and larynx in Mainland Chinese population. A real-world, single-arm, single-center, early feasibility study (ChiCTR2300078809) enrolled 15 patients with a heterogeneous benign or early-stage malignant tumors of pharynx and larynx, who received da Vinci single port-assisted transoral robotic surgery (SP-TORS) from July 2023 to May 2024. The primary endpoint was intraoperative conversion rate, and the secondary endpoints included intraoperative bleeding, surgical duration, length of stay (LOS), ICU admission, postoperative pain score (VAS) and recovery of swallowing functions (MDADI). All 15 patients successfully completed SP-TORS without intraoperative conversion, ICU admission, intraoperative or postoperative massive bleeding. The median intraoperative bleeding volume and surgical duration were 5 ml and 60 min, respectively. The median LOS was 4 days with relatively low postoperative VAS. MDADI indicated all patients significantly recovered swallowing functions 1 month after surgery. Our preliminary institutional experience demonstrated clinical feasibility and acceptable perioperative safety for treating early-stage malignant or benign tumors of the pharynx and larynx in the Mainland Chinese population through SP-assisted transoral robotic surgeries.
Sequential triple primary malignancies are very uncommon. Distinguishing new primary tumors from metastases in cancer survivors is a diagnostic challenge. This case illustrates how comprehensive immunohistochemistry (IHC), particularly p53 expression patterns as a surrogate for TP53 gene status, can determine clonal independence. A 71-year-old male ex-smoker presented with three malignancies over 4 years. First, laryngeal squamous cell carcinoma (pT1bN0M0) showed complete loss of p53 staining (null pattern, truncating mutation). Four years later, lung adenocarcinoma (pT1bN1M0; TTF-1+/Napsin A+) showed strong, diffuse p53 nuclear positivity (missense mutation pattern). One month later, intrahepatic cholangiocarcinoma (pT1N0M0; CK7+/CK19+/TTF-1-) showed wild-type p53 (scattered weak positivity). Divergent p53 IHC patterns (two mutant phenotypes and one wild-type) indicated three independent primaries. The patient recovered well after each curative-intent surgery. Meticulous IHC profiling and careful interpretation of p53 staining patterns are crucial for distinguishing multiple primary cancers from metastatic disease.
Extramedullary plasmacytomas (EMPs) are uncommon neoplasms that rarely involve the feline larynx. This report details a solitary laryngeal EMP in a 12-year-old female domestic shorthair cat presenting with progressive dysphonia, dyspnea, and severe upper airway obstruction. Clinical and imaging examination revealed a mass originating from the epiglottis, causing severe chronic laryngeal stenosis. Due to the complexity and poor prognosis of the condition, euthanasia was elected. Histopathology demonstrated a non-encapsulated, submucosal proliferation of well-differentiated plasma cells within the epiglottis. The neoplastic cells exhibited mild to moderate cellular pleomorphism, characterized by anisocytosis, anisokaryosis, karyomegaly, occasional binucleation, and the presence of Mott cells. Immunohistochemistry (IHC) showed diffuse nuclear and cytoplasmic immunolabelling for MUM-1, confirming the plasma cell lineage. Based on the morphological and immunohistochemical findings, a diagnosis of solitary benign laryngeal EMP was established. This case emphasizes that while laryngeal EMPs are often histologically benign, their critical anatomical location can confer the potential for life-threatening obstructive respiratory disease. EMPs should thus be considered a key differential diagnosis for obstructive upper airway lesions in cats.
To compare antigen removal processing with conventional sodium dodecyl sulfate decellularization for generating laryngotracheoesophageal scaffolds, focusing on preservation of extracellular matrix integrity and removal of immunogenic material. Laryngotracheoesophageal complexes were harvested from C57BL/6 mice and processed using either antigen removal or sodium dodecyl sulfate-based protocols. Scaffolds were analyzed for residual double-stranded DNA content, collagen preservation, glycosaminoglycan retention, and ultrastructural integrity via histology, quantitative image analysis, and scanning electron microscopy. Both antigen removal and sodium dodecyl sulfate protocols achieved effective decellularization, with comparable dsDNA removal relative to native controls (p = 0.001; p < 0.001). Antigen removal scaffolds demonstrated better collagen preservation compared to sodium dodecyl scaffolds, which exhibited marked collagen depletion (Muscle: Collagen I, p < 0.001; Collagen III, p < 0.01; Cartilage: Collagen I, p < 0.05; Collagen III, p < 0.01). Both antigen removal and sodium dodecyl sulfate groups showed significant glycosaminoglycan depletion compared with controls (p < 0.001). Scanning electron microscopy confirmed superior ultrastructural preservation in antigen removal-treated scaffolds, characterized by intact fibrillar architecture and lacunar morphology, while sodium dodecyl sulfate scaffolds demonstrated collapsed lacunae and irregular extracellular matrix organization. Antigen removal processing generates laryngotracheoesophageal scaffolds with enhanced extracellular matrix preservation compared with conventional sodium dodecyl sulfate decellularization, while maintaining equivalent levels of antigen elimination. Retention of collagen and ultrastructure suggests antigen removal scaffolds may provide superior biomechanical and biologic performance for laryngeal tissue engineering. Although glycosaminoglycan depletion remains a limitation in both approaches, antigen removal scaffolds represent a promising pathway toward clinically translatable alternatives to immunosuppression-dependent laryngotracheoesophageal repair. Preclinical.
Anterior commissure exposure is the primary challenge in Wendler glottoplasty, often hindering successful suturing in narrow or prominent larynges. We describe a "scarless" hybrid technique for difficult cases. Following fiber-laser de-epithelialization, two 18-gauge trocars are inserted percutaneously through the thyroid cartilage. A suture is passed through the trocars, retrieved endoscopically, and tied externally over a Silastic sheet, bypassing endolaryngeal space constraints. Hyaluronic acid is injected to reduce suture tension. This combined approach salvages the procedure when endoscopic exposure is inadequate, ensuring a tight synechia without visible cervical scarring, optimizing outcomes for transgender patients.
The laryngotracheal junction (LTJ) is a functionally critical zone, due to its narrow anatomy, complex airflow dynamics, and proximity to the glottis and cricoid cartilage. Extensive stenoses, cricoid defects, and stomal anterior wall loss frequently exceed the possibilities of conventional resection and reconstruction. To outline the current role of microvascular reconstruction at the LTJ, with a focus on indications, techniques, and limitations from the perspective of otolaryngology and thoracic surgery. Narrative literature review of clinically established flap reconstruction techniques at the LTJ, including recent case series and key publications. For short, non-pretreated defects, cricotracheal resection and segmental tracheal resection with end-to-end anastomosis remain the standard of care. Microvascular reconstructions are mainly used for long, circumferential LTJ defects, extensive cricoid loss, previously irradiated or multiply operated regions, and complex treatment interventions. The radial forearm free flap is currently the best-established option for long tracheal and laryngotracheal defects and can be combined with cartilage reinforcement or a mucosal lining. Osseous flaps such as the medial femoral condyle flap and the thoracodorsal artery scapular tip flap allow larynx-preserving reconstruction, with restoration of a stable ring or posterior framework in selected cases. Prefabricated constructs, ALT-based flaps, jejunal grafts, and pedicled flaps play an adjunctive role in borderline and salvage situations. Microvascular reconstruction extends the therapeutic spectrum for LTJ surgery beyond conventional resection techniques and can provide a functional airway in highly complex situations and with acceptable morbidity. Given the limited evidence base from case series, interdisciplinary planning and centralisation of these procedures in experienced centres are essential. Der laryngotracheale Übergang (LTÜ) stellt aufgrund enger anatomischer Verhältnisse, komplexer Strömungsverhältnisse und der Nähe zu Glottis und Krikoid eine funktionell kritische Zone dar. Ausgedehnte Stenosen, Krikoiddefekte und ein suprastomaler Vorderwandverlust überschreiten häufig die Möglichkeiten konventioneller Resektions- und Rekonstruktionsverfahren.Darstellung der aktuellen Rolle mikrovaskulärer Rekonstruktionen am LTÜ mit Fokus auf Indikationen, Techniken und Grenzen aus Sicht von HNO- und Thoraxchirurgie.Narrative Literaturübersicht zu klinisch etablierten Verfahren der Lappenrekonstruktion am LTÜ.Für kurze, nicht voroperierte Defekte bleiben Krikotrachealresektion und segmentale Trachealresektion mit End-zu-End-Anastomose Standardverfahren. Mikrovaskuläre Rekonstruktionen kommen vor allem bei langen, zirkulären LTÜ-Defekten, ausgedehntem Krikoidverlust, vorbestrahlten oder mehrfach voroperierten Regionen sowie nach komplexen Vorinterventionen zum Einsatz. Der freie radiale Unterarmlappen ist in der aktuellen Literatur die am besten etablierte Option für lange tracheale und laryngotracheale Defekte und kann mit Knorpelverstärkungen und mukosaler Auskleidung kombiniert werden. Knochentragende Lappen wie der mediale Femurkondylenlappen (Medial femoral Condyle Flap, MFC) und der thorakodorsale Skapulaspitzenlappen (Thoracodorsal Artery scapular Tip Flap, TDAST) ermöglichen in ausgewählten Fällen larynxerhaltende Rekonstruktionen mit Wiederherstellung einer tragfähigen Ring- bzw. Posteriorstruktur. Präfabrizierte Konzepte, ALT-basierte Lappen, Jejunumtransplantate und gestielte Lappen spielen eine ergänzende Rolle in Grenz- und Salvage-Situationen.Die mikrovaskuläre Rekonstruktion erweitert das Spektrum der Chirurgie des laryngotrachealen Übergangs über konventionelle Resektionsverfahren hinaus und kann in hochkomplexen Situationen einen funktionsfähigen oberen Atemweg bei vertretbarer Morbidität wiederherstellen. Angesichts begrenzter Evidenz aus Fallserien ist eine interdisziplinäre Planung und Bündelung dieser Eingriffe in erfahrenen Zentren entscheidend.
In moderately advanced (T2-T3) glottic cancer, eligibility for organ-preserving surgery is limited by tumor extension into certain high-risk areas within the larynx that can be identified on preoperative imaging and serve as predictive factors for poorer outcomes. Their relevance in conservative treatment modalities, including (chemo)radiotherapy ([C]RT), remains unclear. The objective was to evaluate the impact of these predefined surgical high-risk zones in patients treated with (C)RT. This retrospective study included patients with T2-3, N0-3, M0 glottic carcinoma treated with primary (C)RT and with available diagnostic imaging from three academic medical centers between 2014 and 2018. Imaging was scored for tumor involvement of high-risk areas. The 5-year rates of locoregional control (LRC) and disease-specific survival (DSS) were compared using the log-rank test and Cox proportional hazards model. Imaging from 180 patients (mean age, 68 ± 11 years, 154 men) was assessed, with 173 entering the risk factor analysis after excluding unreliable scans. Significant findings were observed in the anterior larynx: vertical anterior commissure involvement negatively affected LRC and DSS, while horizontal anterior commissure and anterior paraglottic space reduced LRC. Deep vocal muscle infiltration showed negative trends. In multivariable analysis, vertical anterior commissure infiltration retained a trend toward lower DSS. Involvement of the anterior commissure, particularly vertical extension, which is a known predictive factor from surgical studies, likely predicts poorer outcomes after (C)RT for T2-T3 glottic carcinoma. Involvement of the anterior paraglottic space and depth of tumor infiltration carry potential predictive value. Question Can radiological risk factors proven in surgically treated patients with T2-T3 glottic carcinoma also predict treatment failure in patients treated with (chemo)radiotherapy? Findings On multivariable analysis, vertical anterior commissure involvement showed a trend toward poorer disease-specific survival. Clinical relevance Our findings contribute to the search for harmonized prognostic factors across treatment modalities for glottic carcinoma and provide a basis for integrating these risk factors into staging and treatment counseling.
Obesity is a recognised risk factor for brachycephalic obstructive airway syndrome (BOAS) in pugs; however, the mechanisms linking obesity to BOAS remain unclear. Previous veterinary studies have primarily focused on tongue fat, with limited evaluation of other airway regions. This study aimed to investigate the associations between body condition score (BCS) and regional airway fat, and their relationship with BOAS functional grades. Client-owned pugs undergoing BOAS assessment and pre-operative head and neck computed tomography (CT) were enrolled. Fat volumes within the tongue (T), pharynx (P), larynx (L), and total upper airway (V) were measured and normalised using a skull size index (S). Dogs were classified as non-obese (BCS = 4-5/9) or obese (BCS = 7-9/9), and BOAS severity was classified as grade II (moderate) or grade III (severe). Forty-nine BOAS-affected pugs (31 females and 18 males) were included, of which 17 were non-obese and 32 were obese. The median age was 45 months (range: 10-174 months). A significant positive association was identified between BCS and tongue fat (T/S) (p = 0.028). Moreover, pugs with grade III BOAS exhibited significantly greater laryngeal fat (L/S) than those with grade II BOAS (p = 0.034). These findings suggest that weight management and strategies aimed at reducing regional fat accumulation may help mitigate upper airway obstruction in obese pugs, particularly by targeting excess laryngeal fat, which was significantly associated with severe BOAS. Further research is warranted to investigate whether genetic factors influence regional airway fat distribution and to develop targeted treatment strategies aimed at reducing fat accumulation around the larynx.
To evaluate the clinical response, survival outcomes, and organ-preservation potential in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients treated with neoadjuvant immunochemotherapy (NIC) followed by definitive radiotherapy (DRT). We retrospectively reviewed patients with stage III-IVb HNSCC treated with NIC followed by DRT between 2021 and 2023. Tumor response was assessed after NIC and after completion of DRT according to RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Toxicities were graded according to CTCAE 5.0 criteria. A total of 74 patients were included, with hypopharyngeal tumors accounting for 47.3%. All patients completed at least two cycles of NIC. After NIC, the objective response rate was 89.2%, with clinical complete response (cCR) and clinical partial response (cPR) rates of 1.4% and 87.8%, respectively. After DRT, the corresponding rates shifted to 17.6% and 77.0%, respectively. With a median follow-up of 24 months (range: 5-38 months), the estimated 2-year OS and PFS rates were 83.2% and 61.7%. Among patients with laryngeal or hypopharyngeal carcinoma, the larynx-preservation rate was 95.2% and the 2-year larynx-preservation OS reached 73.6%. NIC-related adverse events were predominantly grades 1-3 (90.0%). NIC followed by DRT was associated with high response rates, encouraging survival outcomes, and manageable toxicities in this retrospective cohort. While organ-preservation rates are promising, the modest PFS highlights the need for further investigation in larger or selective cohorts.
Preoperative assessment of Head and Neck Squamous Cell Carcinoma (HNSCC) aggressiveness is often hindered by the sampling errors of incisional biopsies. While Contrast-Enhanced Computed Tomography (CECT) is the standard for staging, its potential to serve as a non-invasive complementary radiological tool of the entire tumor volume remains underutilized. To evaluate the predictive performance of preoperative CECT-derived tumor volume, densitometric values, and morphological features as predictors of histopathological grade and lymph node metastasis (pN) in HNSCC. The primary outcome was predicting lymph node metastasis (pN+), and the secondary outcome was predicting histopathological grade. This retrospective observational study analyzed 42 patients with SCC of the oral cavity, larynx, or maxilla. Quantitative (3D volume, Hounsfield Units [HU], HU Delta) and qualitative (margins, lobulations, necrosis) CT parameters were correlated with definitive histopathology. Diagnostic performance was assessed using Receiver Operating Characteristic (ROC) curve analysis and Spearman's rank correlation. High-grade tumors (G2/G3) demonstrated significantly larger median volumes (18.1 vs. 2.9 cm3, p = 0.006), lower contrast density (55 vs. 68 HU, p = 0.010), and reduced vascular wash-in (23 vs. 30 HU Delta, p = 0.008) compared to G1 lesions. ROC analysis identified a volume threshold of ≥9.43 cm3 for high-grade disease (AUC = 0.865; sensitivity 67.6%, specificity 100%). For regional metastasis (pN+), tumor volume was the only significant predictor (25.4 vs. 6.2 cm3, p = 0.036), with an optimal cut-off of ≥6.76 cm3 (AUC = 0.769; sensitivity 100%). Strong negative correlations were observed between contrast enhancement and internal necrosis (r = -0.812, p < 0.001). Preoperative CECT parameters show promise as non-invasive imaging surrogates of HNSCC aggressiveness. A paradoxical reduction in contrast enhancement characterizes high-grade biology, reflecting disorganized neo-angiogenesis and internal hypoxia. Integrating 3D volumetric analysis and morphological markers shows potential as a complementary exploratory tool that, pending future prospective validation, may support risk stratification and surgical planning alongside traditional histopathological assessment.
Congenital laryngeal webs are rare laryngeal anomalies resulting from incomplete re-canalization of the primitive larynx. They present a significant therapeutic challenge, requiring a delicate balance between establishing a patent airway and preserving vocal function. This study details a ten-year, single-surgeon experience at a tertiary care centre to evaluate the efficacy of a graded management protocol and long-term outcomes. A retrospective chart review was conducted for 23 pediatric patients managed for congenital laryngeal webs between 2015 and 2025. Data regarding demographics, Cohen's classification, presenting symptoms, surgical management, and postoperative outcomes were analyzed. Treatment choice was dictated by web severity: endoscopic release for thin webs, open web release with keel placement for thick webs without subglottic extension and open reconstruction for thick webs with subglottic extension. The cohort included 23 patients (10 males, 13 females) with a mean age of 4.5 years. The study population presented with severe pathology; Type III webs were the most prevalent (65.2%). Consequently, respiratory symptoms (82.6%) were more common than isolated voice abnormalities (78.2%). Management strategies included endoscopic web release (17.4%), endoscopic web release and keel placement (21.7%), open web release with keel placement (8.7%) and open laryngotracheal reconstruction (LTR) (34.8%). Post-operative airway patency was achieved in all tracheostomized patients, yielding a 100% decannulation rate (8/8). Revision surgery was required in 2 patients (1 in Type III and 1in Type IV), (8.7%). Perceptual voice analysis yielded a mean GRBAS score of G2R1B1A1S1. Congenital laryngeal webs are rare but clinically significant airway anomalies that may present with a wide spectrum of respiratory and phonatory symptoms. A tailored algorithm-reserving endoscopic techniques for thin webs and open LTR for thick webs-results in excellent decannulation rates. Overall, a multidisciplinary approach with careful surgical technique and long-term follow-up is essential to optimize both airway stability and voice outcomes in children with congenital laryngeal webs.
Background/Objectives: Management of cervical esophageal cancer after induction therapy remains unsettled. Definitive chemoradiotherapy is the guideline default, but a subset of patients with residual but resectable disease may still benefit from surgery. No validated multidisciplinary selection framework exists for this subsite. Methods: We conducted a systematic review registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261369102) and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, using searches of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library from inception through 14 April 2026. We identified 1779 records, removed 873 duplicates, and screened 906 records; 87 full-text reports were assessed, of which 67 were excluded at the full-text stage (66 on population grounds-disease not cervical esophageal; and 1 because cervical-direct outcomes were not separable within a mixed cervical/thoracic cohort), leaving 20 cervical-direct studies included in the primary synthesis. Thoracic and meta-analytic sources are cited for indirect comparison and biological rationale but are not counted in the included set. Included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I); certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Formal meta-analysis was not performed because study design, treatment approach, and outcome reporting were too heterogeneous. Results: Cervical-specific evidence is predominantly retrospective but consistent in direction. Available cervical-specific observational data suggest benefit mainly in patients with biopsy-confirmed incomplete response, resectable residual disease, preserved performance status, and access to experienced centers. Larynx-preserving resection is feasible in 90% of T1-2 tumors and 54% of T3-4 responders. In thoracic esophageal squamous cell carcinoma, neoadjuvant chemoimmunotherapy yields pathologic complete response rates of approximately 29-48%; in cervical disease, the SCENIC trial has reported interim clinical response of approximately 50% in 28 patients, but pathology-confirmed response is not yet available. We present a proposed multidisciplinary selection framework integrating response depth, post-induction stage, laryngeal preservation feasibility, sarcopenia, circulating tumor DNA dynamics, and programmed death-ligand 1 (PD-L1) expression. The framework has not been prospectively validated and is presented as a hypothesis-generating, conceptual tool for multidisciplinary discussion rather than a clinically validated instrument. Adjuvant nivolumab is recommended for residual pathologic disease after margin-negative (R0) resection when surgery follows preoperative chemoradiotherapy; after PD-1-based induction, adjuvant checkpoint inhibition remains investigational. Conclusions: The available cervical-direct evidence is predominantly retrospective and selection-prone, and several inputs supporting the framework are extrapolated from thoracic ESCC cohorts; conclusions about the survival benefit of surgery should therefore be read as associations rather than causal claims. Surgery has a role after induction therapy in carefully selected incomplete responders. The proposed framework is designed for multidisciplinary use and requires prospective validation before routine clinical application.
Laryngeal conservation in advanced disease is possible with chemo-radiation (CTRT); however, it is at the expense of significant toxicity. There is sparse data from the Indian subcontinent addressing the same. A retrospective cohort study of Stage III-IVa/b patients treated between May 2011 and April 2022. We assessed survival outcomes, organ preservation rates, and toxicities. 300 patients, with a median age of 63 years (57;69), were identified. Median follow-up was 4.1 years (3.5; 4.4). Dysphagia was the most common grade 3 toxicity (119; 40%). The 5-year overall survival (OS) was 61% (55%; 69%). Sitewise, laryngeal cancers (64% (55%; 74%)) fared better than hypopharyngeal cancers (55% (45%; 67%)) with respect to 5-year OS. The larynx preservation rate was 84% (79%; 90%) at 5 years. Functional laryngeal preservation is achievable in locally advanced laryngeal and hypopharyngeal cancers with definitive CTRT. Outcomes aligned with established and published data.
Existing epidemiological evidence on breastfeeding and cancer risks is inconsistent, and no studies have thoroughly examined the relationship between breastfeeding and each site-specific cancer in China. We aimed to investigate these associations among parous Chinese women. A total of 157,454 participants aged 40-75 years from 2012 to 2021 were recruited. Cox proportional hazards model was applied to explore the association between breastfeeding behaviors and cancer risks by hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). 5,542 incident cancer cases were identified with a median follow-up of 4.81 years. The history of breastfeeding was statistically significantly associated with lower risk of breast cancer in the multivariate-adjusted model (HR = 0.78, 95%CI: 0.65-0.94). In addition, the risk of gallbladder cancer increased with increasing months of total breastfeeding (P-trend = 0.039), with a 51% increase in risk for each additional 12 months of breastfeeding (HR = 1.51, 95%CI: 1.12-2.02). The risk of breast cancer decreased with increasing months of total breastfeeding (P-trend = 0.015), with a 15% reduction in risk for each additional 12 months of breastfeeding (HR = 0.85, 95%CI: 0.76-0.95). The subgroup analyses according to menopausal status shows significant separations for colon-rectum cancer, uterus cancer, oesophagus cancer, and larynx cancer (all P-interaction < 0.05). In addition, significant linear associations were suggested concerning gallbladder cancer (P-overall = 0.0302, P-nonlinear = 0.6558) and breast cancer (P-overall = 0.0175, P-nonlinear = 0.5544). This study provides further support for the role of breastfeeding behavior in overall cancer and its 24 site-specific cancers.
Laryngeal injuries, especially cricoid cartilage fractures, are rare but may present with airway emergencies, and appropriate airway management is vital. A 24-year-old man admitted to the emergency room with isolated blunt cervical trauma after a motorcycle accident. The patient presented dysphonia, stridor, hemoptysis, cervical subcutaneous emphysema, and increasing respiratory distress. Oral intubation was initially successful, however, worsening subcutaneous emphysema and loss of effective ventilation suggested airway disruption. Emergency cricothyrotomy was performed, but persistent air leakage from the incision site prompted bronchoscopy, which revealed a 7-mm tracheal laceration on the right side of the larynx. The patient was reintubated under bronchoscopy. Computed tomography showed a cricoid cartilage fracture. Tracheostomy and complete repair were performed 2 days after the injury. The cricoid cartilage was fractured fully circumferentially, with the anterior part deviated toward the caudal side, and its deepest part had perforated the right side of the trachea. The cricoid cartilage was repaired, and the tracheal perforation was dilated to create a laryngo-cutaneous fistula. Persistent hoarseness after fistula closure was associated with scar formation of the left vocal fold and arytenoid cartilage dislocation. Although symptoms gradually improved with voice rehabilitation, increased vocal demand after a job change led to thyroplasty 2 years after injury. Cricoid cartilage fractures associated with blunt laryngeal injuries may cause tracheal injury. This case highlights the challenges of managing concurrent cricoid fracture and tracheal injury, where the surgical airway site coincided with the traumatic defect. Rapid decision-making balancing exploration and stabilization was critical.
Chronic laryngitis is a persistent inflammatory disorder that has recently been linked to air pollution. Fine particulate matter (PM2.5) is a major air pollutant capable of inducing pyroptosis, a caspase-1-dependent inflammatory form of programmed cell death characterized by gasdermin D cleavage, plasma membrane rupture, and the release of proinflammatory cytokines. However, the mechanisms underlying PM2.5-induced pyroptosis in the larynx and the potential therapeutic strategies remain unclear. In this study, we investigated the protective effects of human turbinate mesenchymal stromal cell-derived exosomes (hTMSC-exos) on PM2.5-induced pyroptosis in human vocal fold fibroblasts (hVFFs). PM2.5 exposure triggered pyroptotic cell death, as evidenced by increased LDH release, PI positivity, GSDMD-N expression, and IL-1β and IL-18 secretion. It also induced excessive reactive oxygen species (ROS) production, disrupted mitochondrial function, and impaired mitophagy, as indicated by p62 accumulation and suppressed PINK1/Parkin expression. Treatment with hTMSC-exos significantly alleviated these effects, reducing pyroptosis markers, lowering ROS production, and preserving mitochondrial membrane potential. Mechanistically, hTMSC-exos restored mitophagy activity suppressed by PM2.5, as demonstrated by increased LC3-II, PINK1, and Parkin expression and decreased p62 levels. Fluorescence imaging further confirmed enhanced co-localization of mitochondria with LC3-II. Importantly, the protective effects of hTMSC-exos were abolished by the mitophagy-specific inhibitor cyclosporin A, confirming that mitophagy activation is essential for exosome-mediated protection. These findings suggest that hTMSC-exos attenuate PM2.5-induced pyroptosis through a mitophagy-dependent mechanism, providing new insight into the pathogenesis of environmentally induced laryngeal injury and highlighting the therapeutic potential of exosome-based approaches for chronic laryngitis.
Cancer is the second leading cause of death worldwide, including in Georgia. This study aimed to evaluate the number of new cancer cases, identify the most common cancer sites, analyze sex differences, and evaluate age-standardized rates (ASR) and age-specific rates from 2015 to 2019 in Georgia. We used the Georgia National Cancer Registry data for all registered cancer cases, excluding non-melanoma of skin, and the National Statistics Office of Georgia population data. ASRs per 100,000 population were calculated using the direct standardization method, with the WHO's world standard population as a reference. Between 2015 and 2019, 50,098 cancer cases (ICD-10 codes C00-96 exc. C44) were diagnosed in Georgia, including 21,802 in men (ASR 175.5/100,000) and 28,296 in women (ASR 192.8/100,000). Among men, the most common cancer sites were lung (16%, ASR 28.0/100,000); prostate (14%, ASR 22.0/100,000); bladder (10%, ASR 16.3/100,000); colorectal (10%, ASR 16.2/100,0000); and larynx (6%, ASR 10.9/100,000). Among women, the most common cancer sites were breast (34%, ASR 64.5/100,000), thyroid (14%, ASR 34.3/100,000), colorectal (7%, 10.3/100,000), cervix (6%, ASR 12.6/100,000) and corpus uteri (6%, ASR 11.4/100,000), respectively. This is the first comprehensive evaluation of cancer incidence in Georgia. Beyond sex-specific cancers such as breast and prostate, lung cancer was more common in men, while thyroid cancer was more common in women. The overall cancer incidence in Georgia was lower than the 2022 GLOBOCAN-estimated ASR for the 27 EU countries. Differences in healthcare infrastructure, screening uptake, or reporting accuracy may explain these disparities.
To describe the frequency and distribution of Human Papillomavirus (HPV) infection in patients with Head and Neck Squamous Cell Carcinoma (HNSCC) treated at a tertiary hospital in Colombia. A descriptive cross-sectional study was conducted in 81 patients diagnosed with HNSCC between 2015 and 2021 at Fundación Santa Fe de Bogota, Colombia, as part of the Colombian cohort of the InterCHANGE and HEADSpace study. Formalin-Fixed Paraffin-Embedded (FFPE) tumor samples were analyzed for HPV DNA detection and genotyping. Fifty-nine samples were processed using the HPV-Direct Flow CHIP assay (Master Diagnóstica, Seville, Spain), and 22 with the INNO-LiPA HPV Genotyping Extra assay (Fujirebio, Gothenburg, Sweden). Both techniques identify high- and low-risk HPV genotypes through PCR amplification and reverse hybridization. Immunohistochemistry for p16 was performed in all cases using the anti-p16INK4a (E6H4 clone) antibody, considering strong nuclear and cytoplasmic staining in ≥ 70% of tumor cells as positive. Descriptive statistics included absolute and relative frequencies. The mean age was 66-years (±11), and 64.2% were male. The oropharynx was the most frequent tumor location (50.6%, n = 41), followed by the oral cavity (35.8%, n = 29) and larynx (13.6%, n = 11). Overall, 51.9% (n = 42) of tumors were HPV DNA-positive. HPV infection was more frequent in oropharyngeal carcinomas (92.7%, n = 38) than in the oral cavity (6.9%, n = 2) or larynx (18.2%, n = 2). HPV-16 was the predominant genotype (79.4%), followed by HPV-35, HPV-18, and HPV-33. p16 overexpression was observed in 49.4% (n = 40) of cases, mainly in oropharyngeal carcinomas (87.8%, n = 36). Among HPV DNA-positive tumors, 92.5% (n = 37) were also p16-positive. This study demonstrates a high prevalence of HPV, predominantly HPV-16, in oropharyngeal carcinomas compared with other head and neck sites in our cohort. These results provide baseline data for Colombia and highlight the need for multicenter studies including more heterogeneous populations to guide future prevention and control strategies. 4 (According to the Oxford Centre for Evidence-Based Medicine, 2011).
Background: Fatal sand burial is a rare and diagnostically challenging entity in forensic practice. In such cases, death may result from thoracic or thoracoabdominal compression, airway obstruction by particulate material, massive inhalation of sand or soil, or a combination of these mechanisms. External signs may be subtle or absent, making postmortem interpretation highly dependent on a comprehensive, multilevel assessment. Case Presentation and Methods: We report the case of a 17-year-old male who died following accidental sand burial caused by the collapse of a self-excavated beach tunnel. External examination, autopsy, histological and toxicological analyses were performed. A review of the literature was also conducted to identify published forensic cases of fatal sand or soil burial and to compare circumstantial, macroscopic, microscopic, and ancillary findings. Results: Autopsy revealed marked pulmonary edema and congestion, multivisceral congestion, scattered sand granules within the larynx, and epicardial petechiae. Histological examination demonstrated acute pulmonary emphysema, edema, vascular congestion, and hemorrhagic laterocervical lymph nodes. Overall, the findings were considered most consistent with mechanical asphyxia due to thoracic compression. The literature review identified six eligible studies describing eight fatal cases. Despite the limited sample size and marked heterogeneity, two main diagnostic patterns emerged: compression-related deaths, usually associated with tunnel or beach-hole collapse and minimal or absent particulate material within the airways, and aspiration-/obstruction-related deaths, characterized by abundant or compact sand or soil material within the airways. In cases without massive aspiration, mixed mechanisms may coexist. Pulmonary edema and congestion were the most frequently reported autopsy findings. When available, histological examination appeared useful in distinguishing antemortem from postmortem burial. Conclusions: Fatal sand burial should not be regarded as a uniform forensic entity. External examination alone is often insufficient, and accurate diagnosis requires a comprehensive, multidisciplinary approach integrating scene reconstruction, autopsy data, histopathological findings, and ancillary analyses. Hemorrhagic involvement of the laterocervical lymph nodes may represent a potentially relevant but currently underexplored finding, whose diagnostic significance warrants further investigation in analogous cases.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and is associated with an extremely poor prognosis. Multimodal therapy, combining surgery, radiation therapy, and chemotherapy, is recommended. Although paclitaxel and lenvatinib have been used as drug treatments, combination therapy with dabrafenib and trametinib has recently been reported to be effective. This combination therapy is generally associated with few serious adverse events, although rare cases of cardiac dysfunction have been reported. Here, we report the case of an 84-year-old woman with BRAF V600E mutation-positive ATC who developed cardiac dysfunction during combination therapy with dabrafenib and trametinib. The patient had no significant medical history and was referred to our department with left vocal cord paralysis and a thyroid mass. Histological examination of the right thyroid lobe tumor revealed components of undifferentiated carcinoma. Imaging studies showed invasion of the larynx and trachea, leading to total thyroidectomy, total laryngectomy, and paratracheal lymph node dissection. Postoperative pathological examination confirmed ATC (pT4aN0). Postoperative imaging revealed no distant metastases, and adjuvant radiotherapy was administered. Four months after the completion of radiotherapy, a cervical lymph node recurrence and right lung metastases were observed. As the tumor tested positive for BRAF V600E mutation using the MEBGEN™ BRAF kit, combination therapy with dabrafenib and trametinib was initiated. At week five of treatment, pitting edema developed in both lower limbs, and a decrease in the left ventricular ejection fraction (LVEF) was noted, prompting the discontinuation of therapy. By week six, the LVEF recovered, and dabrafenib was restarted at the same dose, whereas trametinib was resumed at a one-step reduced dose. Follow-up CT at week six demonstrated a partial response (PR). Treatment was continued at these doses; however, tumor enlargement was observed at week 26, leading to treatment discontinuation and a transition to palliative care. ATC remains extremely challenging to treat because of its rapid progression and low sensitivity to drug therapies. Furthermore, lenvatinib, a molecularly targeted agent, shows limited efficacy against ATC and is associated with frequent adverse events. In contrast, combination therapy with dabrafenib and trametinib is considered an effective therapeutic option for patients with BRAF V600E mutation-positive ATC, when appropriate management and monitoring are implemented.