The European Larynx Organ Preservation Study [MK-3475-C44].

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS ≥ 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/α/ß = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL. Clinical Trial Registration: clinicaltrials.gov, identifier NCT06137378.

Efficacy of Minor Salivary Glands as Indicators of Depth of Resection for Superficial Hypopharyngeal Carcinoma.

Objective: This study aimed to investigate the utility of minor salivary glands in the hypopharynx as novel indicators for safe resection of superficial hypopharyngeal carcinomas with fewer complications. Study Design: Cadaveric study. Setting: Cadavers were stored in the pathology laboratory at Kansai Medical University. Methods: Twenty-three cadaveric specimens were examined for minor salivary glands in the pyriform sinus, posterior wall, and postcricoid regions of the hypopharynx. Their count, size, and depth were assessed. Resected specimens from 5 consecutive patients with superficial hypopharyngeal carcinomas were pathologically analyzed to determine the positional relationship between cancer and minor salivary glands. Results: Minor salivary glands were present in more than 70% of patients in each region during autopsy, with the postcricoid region having a larger count and size. The glands were universally present, regardless of sex, height, or body mass index. Minor salivary glands in the pyriform sinus and postcricoid region were present at a depth of 30% from the bottom of the submucosal layer, whereas those in the posterior wall were present in the shallow muscularis. During surgery, endoscopic findings revealed minor salivary glands as small white nodules in the submucosal layer. Pathological examination of the resected specimen confirmed that the white nodule was a minor salivary gland. In addition, tumor position in relation to minor salivary glands provided an adequate margin for resection. Conclusion: Minor salivary glands may serve as reliable indicators for determining adequate deep safety margins during surgery for superficial hypopharyngeal carcinoma.

Non-adherence to recommended adjuvant radiation after total laryngectomy.

OBJECTIVES: Investigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). METHODS: Previously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. RESULTS: Among 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72-0.93) analysis. CONCLUSIONS: Within the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Female Classical Singers Apply Different Resonatory Strategies Than Male: Insights from an MRI-Based Analysis.

INTRODUCTION: The morphology of the vocal tract plays a crucial role in singing. Adjustments of the lower part of the vocal tract are essential for voice quality and timbre. Structured investigations of this region are challenging due to the small extent of the morphological modifications. MATERIAL AND METHODS: This study analyzed the morphology of the endolaryngeal tube and parts of the surrounding hypopharynx for the sustained vowels /a/, /e/, /i/, //, and // by 11 female singer subjects who were at the beginning of their academic singing studies. As in a previous study with male subjects, analysis was based on two phonatory conditions: a natural, speech-like phonation and a singing phonation, like in classical singing. By means of 3D image processing from magnetic resonance imaging, multiple measures were derived. The data were statistically analyzed using linear mixed effects models and ANOVA. RESULTS: The female singers enlarged the ratio of the endolaryngeal tube to the adjacent hypopharynx for singing. DISCUSSION: In contrast to the findings of the male singers in a previous study, the ratios of the laryngeal volumes to the neighboring hypopharynx increased while singing. The female singer subjects of the present study increased those ratios, mediated by an over-proportional enlargement of the endolaryngeal tube. Existing acoustic differences to male singers are thus given a morphological basis. CONCLUSION: The study gives insight into the characteristic adjustments of the vocal tract of female classical singers. The resonatory strategies for females in classical singing differ from those found in males.

Discovering an uncommon site of angioleiomyoma origin: a rare case report.

Background: Angioleiomyoma, a benign tumour of the smooth muscles of blood vessels, primarily affects individuals aged 30-50 years, with a higher incidence in females. While it commonly affects the lower extremities, it can also develop in the head and neck. However, hypopharyngeal angioleiomyomas are extremely rare, with only one documented case in world literature. Methods: The authors present a rare case of a 70-year-old male with symptoms of voice change and deglutition discomfort. Imaging studies indicated a hypopharyngeal mass. Direct laryngoscopy showed a well-defined mass originating from the left lateral pharyngeal wall, obstructing the left vallecula and pyriform sinus. The patient underwent anterolateral pharyngotomy with mass excision. Results: After a successful anterolateral pharyngotomy, the patient experienced significant improvement in symptoms. Conclusion: Diagnosing and managing hypopharyngeal angioleiomyoma is challenging due to its unusual location. Its rarity emphasizes the importance of considering it as a possible differential when evaluating hypopharyngeal masses.

Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Synovial Sarcoma of the Hypopharynx in a Filipino Female: A Case Report.

Synovial sarcoma of the hypopharynx is an uncommon malignancy, with less than 100 cases reported in available journals. We report a case of a 22-year-old female presenting with dysphagia and enlarging hypopharyngeal mass, clinically diagnosed as hypopharyngeal malignancy, right, at least stage III. Histopathologic examination including immunohistochemistry study with TLE1 and SS18 Fluorescence In Situ Hybridization (FISH) confirm the diagnosis of synovial sarcoma. This is the first reported case of synovial sarcoma of the hypopharynx in the Philippines confirmed by SS18 FISH. Due to the size of the mass, chemoradiotherapy followed by surgery is the current plan of management for this patient.

A case of hypopharyngeal amyloidosis by digestive endoscopy. / æ¶ˆåŒ–å† é•œæ£€æŸ¥å‘çŽ°ä¸‹å’½éƒ¨æ·€ç²‰æ ·å˜æ€§1例.

Amyloidosis is a rare disease. This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom. The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough, sputum production, acid reflux, belching, and abdominal pain. Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis. Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx. Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue. The patient tested positive for anti-amyloid A antibodies, Congo red staining (+), and periodate Schiff staining (+). Amyloidosis commonly affects the digestive system and may have various etiologies, often presenting with symptoms that overlap with other digestive system diseases, leading to frequent misdiagnosis and missed optimal treatment opportunities. The hypopharynx, a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts, can be effectively evaluated for amyloidosis using digestive endoscopy.

Improved survival of locoregional-advanced larynx and hypopharynx cancer patients treated according to the DeLOS-II protocol.

Introduction: Larynx organ preservation (LOP) in locoregional-advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-LHSCC) being only R0-resectable (clear margins > 5 mm) by total laryngectomy (TL) is desirable. Based on tumor-specific survival (TSS) and overall survival (OS) data from the RTOG 91-11 trial and meta-analyses of randomized clinical trials (RCTs), cisplatin-based concurrent radiochemotherapy (CRT) is discussed being superior to cisplatin-based induction chemotherapy followed by radiotherapy (IC+RT) and TL followed by postoperative RT (TL+PORT) or radiochemotherapy (TL+PORCT). Outside of RCTs, T4 LHSCC treated with TL+PORCT demonstrated improved OS and TSS compared to CRT alone; comparisons with docetaxel plus cisplatin (TP)-based IC+RT are unpublished. Head-to-head comparisons in RCTs of these four alternatives are missing. Materials and methods: We utilized monocentric registry data to compare the outcome in the LOP trial DeLOS-II (NCT00508664) and propensity score (PS)-matched LHSCC patients. DeLOS-II utilized endoscopic tumor staging after one cycle of TP-based IC for selecting TL+R(C)T for non-responders versus IC+RT for responders. Main risk factors for survival (localization hypopharynx, T4, N+, tobacco smoking >30 pack years, alcohol consumption >60 g/day, age, sex) were used to calculate the individual PS for each DeLOS-II patient and 330 LHSCC patients suitable for DeLOS-II according to eligibility criteria in Leipzig by CRT (78), TL+PORT (148), and TL+PORCT (104). We performed PS matching with caliper width 0.2. Results: The 52 DeLOS-II patients (whole intent-to-treat cohort) and three PS-matched cohorts (52 LHSCC patients each) had equal distribution regarding risk factors including Charlson comorbidity score (CS; all p > 0.05) but differed in outcome. During 12,498.6 months of follow-up, 162 deaths (36/41/43/42 in DeLOS-II/TL+PORCT/TL+PORT/CRT, p = 0.356) occurred; DeLOS-II patients had superior OS and TSS. Compared to DeLOS-II, the HR (95% CI) observed in TL+PORCT, TL+PORT, and CRT for OS and TSS were 1.49 (0.92-2.43), 1.49 (1.15-3.18), and 1.81 (1.11-2.96) for OS; and 2.07 (0.944-4.58), 3.02 (1.32-6.89), and 3.40 (1.58-7.31) for TSS. Conclusion: In addition potential LOP, LA-LHSCC suitable for LOP according the DeLOS-II protocol may achieve improved survival.

[Cervicogenic dysphagia: a case report]. / Tservikogennaya disfagiya: sluchai iz praktiki.

The article presents a case of pharyngeal dysphagia and obstructive sleep apnea syndrome caused by degenerative-dystrophic changes in the cervical spine with the formation of large cervical osteophytes at the C3-C6 level. Osteophytes caused deformation of the posterior wall of the hypopharynx and narrowing of its lumen by 20-25% from the level of the arytenoid cartilages to the upper parts of the epiglottis. CT scan also showed the intervertebral disc heights lost, as well as osteophytes at the posterolateral margins of the vertebral bodies (disc osteophyte complex). Osteosclerosis in combination with facet arthrosis caused spinal and foraminal stenosis.

Squamous cell papilloma of the hypopharynx with elongated villous projections.

Squamous cell papilloma with elongated villous projections may occur in the hypopharynx and present with symptoms observable on physical examination.

Salvage surgery for recurrent or residual hypopharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aggregates the data of studies that include site-specific analyses of patients undergoing salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma. METHODS: The primary outcomes are disease-free, disease-specific, and overall survival (DFS, DSS, and OS, respectively). Secondary outcomes include complications and postoperative feeding requirements. RESULTS: Fifteen studies met the inclusion criteria with a total of 442 patients. Two-year DFS is reported from 30.0 to 50.0% and 5-year DFS ranges from 15.0 to 57.1%. Five-year DSS ranges from 28.0 to 57.1%. Two-year OS ranges from 38.8 to 52.0% and 5-year OS ranges from 15.5 to 57.1%. Complications include pharyngocutaneous fistula (0.0-71.4%), carotid artery rupture (2.9-13.3%), and stomal stenosis (4.2-20.0%). Complete oral feeding achieved following surgery ranges from 61.9 to 100.0%, while complete gastrostomy tube dependence ranges from 0.0 to 28.6%. CONCLUSIONS: Salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma has a relatively high complication rate and should be offered to patients with the understanding of a guarded prognosis.

Lymphoepithelial Carcinoma: A rare Presentation in the Hypopharynx.

Hypopharyngeal origin of lymphoepithelial carcinoma is extremely rare. We report a case of 74 years old male presented with Globus sensation in the throat for 2 months. He underwent total laryngectomy with partial pharyngectomy after clinico-radiological evaluation and biopsy. His final diagnosis was lymphoepithelial carcinoma and IHC was positive for pancytokeratin and p63.

Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma.

BACKGROUND: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. MATERIALS AND METHODS: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. RESULTS: lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). CONCLUSIONS: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.

Neuroendocrine Carcinoma of the Hypopharynx - An Elusive Clinical Rarity.

Neuroendocrine carcinoma originating from neuroendocrine cells is typically linked to unfavourable survival rates. We are introducing an exceptional case of neuroendocrine carcinoma occurring in the hypopharynx. To date, only a handful of instances involving primary neuroendocrine carcinoma of the hypopharynx have been documented. Advanced age, being male, a history of chronic alcoholism, smoking, and previous radiation are all risk factors associated with this condition. The majority of patients present with distant metastases and are not amenable to a complete cure. As there are no guidelines for the treatment of this rare tumour, various treatment modalities have been tried. Here, we are reporting one such case which was diagnosed as small-cell neuroendocrine carcinoma of the hypopharynx on the basis of histopathological cues and received concurrent chemoradiotherapy.

CT and MR anatomy of the larynx and hypopharynx.

Imaging of the larynx and hypopharynx is frequently requested to assess the extent of neoplasms beyond the field of view of endoscopic evaluation. The combination of optical and cross-sectional imaging allows tumors to be classified according to AJCC/UICC guidelines. A thorough understanding of laryngeal and hypopharyngeal anatomy is crucial to guide the radiological eye along the possible pathways of the spread of diseases and to guide differential diagnoses. Computed tomography (CT) has been the first cross-sectional imaging technique used to evaluate the larynx and hypopharynx; its spatial resolution combined with volumetric capability and the use of injectable contrast medium made CT the working horse in the assessment of neoplastic and inflammatory diseases. In the last two decades, magnetic resonance (MR) supported CT in the most challenging cases, when the optimal contrast resolution due to the multisequence portfolio is needed to assess the neoplastic involvement of laryngeal cartilages, paraglottic space(s), and extra laryngeal spread. The aim of this paper is to give a comprehensive radiological overview of larynx and hypopharynx complex anatomy, combining in vivo images, anatomical sections, and images of ex vivo specimens.

[Transoral robotic surgery in the management of solitary fibrous tumor at the entrance of the hypolaryngeal esophagus: a case report and literature review].

To explore the clinical diagnosis and treatment experience of isolated fibrotic tumor （SFT） occurring in the larynx, hypopharynx and esophageal inlet with a wide range.The patient, admitted to the Department of Otolaryngology-Head and Neck Surgery of Tangdu Hospital of Air Force Medical University was a female aged at 78 years, who was diagnosed with SFT primarily occured at laryngeal, hypopharynx and esophageal entrance. The clinical data, surgical methods, histopathology characteristics of the patient were analyzed respectively. It's proved that a tumor sized about 3.8 cm×2.8 cm×2.0 cm with slippy surface was found at the entrance of the laryngeal, hypopharynx and esophageal entrance, covering the laryngeal vestibule, glottis and right piriform fossa, which was completely resected by transoral robotic surgery. The postoperative pathological diagnosis was SFT. The patient recovered well after surgery and showed no recurrence within 16-month follow-up. SFT occurring in the larynx, hypopharynx, and esophageal inlet is very rare, and transoral da Vinci robotic surgical resection of the tumor in this area is feasible, and has the advantages of clear field of vision, less bleeding, less trauma, fewer complications, and quicker postoperative recovery.

Effects of Marital Status on Hypopharynx Squamous Cell Carcinoma Survival Stratified by Demographic and Pathological Factors: A Retrospective Study.

Objectives: Understanding the interaction between marital status and gender, race, and age is important for developing tailored interventions aimed at improving socio-emotional support for patients. Therefore, the objective of this study is to explore the correlation between marital status and hypopharynx squamous cell carcinoma (SCC) and whether the association varied by age, race, and gender. Methods: We examined the clinicopathological variables using chi-squared tests and we evaluated the association between survival and different variables using the methods of Kaplan-Meier. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. Results: A total of 1686 patients were analyzed. The rate of being married was lower among African American, and this rate decreased with higher tumor stage. While both married male and female survivors benefit from their marital status, subgroups analysis shows a differential in overall survival (OS) based on gender, with males benefiting more than females. Patients who were divorced/separated [male hazard ratio (HR) = 1.214, 95% confidence interval (CI): 0.985-1.495; female HR = 1. 159, 95% CI: 0.691-1.945], never married (male HR = 1.476, 95% CI: 1.234-1.765; female HR = 1.422, 95% CI: 0.901-2.245), and widowed (male HR = 1.795, 95% CI: 1.390-2.317; female HR = 1.663, 95% CI: 1.081-2.559) had increased hazard of OS compared with married/partnered patients. The effect of marital status was significantly associated with treatment outcome only in Caucasian patients who harbored well/moderately differentiated and nonmetastatic disease (P < .001). Conclusion: While there are survival benefits for married patients with hypopharynx SCC, married/partnered males may benefit more than females. Age, race, and gender could affect the correlation between marital status and survival.