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demonstrated improved OS and TSS compared to CRT alone; comparisons with docetaxel plus cisplatin (TP)-based IC+RT are unpublished.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.

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.

[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.

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.

Neutrophils in HNSCC Can Be Associated with Both a Worse or Favorable Prognosis.

The prognostic significance of tumor-infiltrating neutrophils in head and neck squamous cell carcinoma (HNSCC) is poorly understood. It is unclear how the presence of neutrophils affects prognosis due to their polarization into cytotoxic N1 or immunosuppressive N2. Therefore, we determined the number of CD66b+ neutrophil granulocytes separately in the stromal and epithelial compartments in cancer tissues from 397 patients with HNSCC. Tumor samples from six historical patient groups were processed into tissue microarrays and stained immunohistochemically. In total, 21.9% were HPV positive (p16+). Neutrophil counts were much lower in the stromal compartment (372 ± 812) than in the epithelial cancer compartment (1040 ± 1477) (p < 0.001), with large differences between groups. In three groups with high neutrophil infiltration, high rates were associated with a favorable prognosis, whereas in two groups, high rates were a negative prognostic factor. In p16- oropharyngeal and hypopharyngeal cancer high infiltration was associated with a favorable prognosis. Cancers with an exclusion of neutrophils in the epithelial compartment were associated with improved prognosis. In oropharyngeal and hypopharyngeal HPV-negative cancer high neutrophil infiltration rates were clearly associated with prolonged survival. Neutrophil granulocytes in HNSCC may contribute to a favorable or unfavorable prognosis.

[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.

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.

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.

A Large Adult Postcricoid Lymphatic Malformation: A Case Report and Literature Review.

Adult-onset lymphatic malformations arising at the postcricoid, a subsite of the hypopharynx, are sporadic. Only one case has been previously reported. In this study, we presented a 36-year-old female presented with globus sensation, dysphagia, and upper airway obstruction, requiring a tracheostomy. A computed tomography scan identified a 5 cm × 4.5 cm × 3 cm multilocular hypodense lesion in the postcricoid. Due to its considerable size, complete resection with function preservation was crucial, and a standard microscopic direct laryngoscopy approach may result in inadequate exposure, while an open transcervical approach may affect functional outcomes and increase surgical complications. We successfully performed an en bloc resection with a transoral endoscopic approach, using laryngeal suspension and a laparoscopic ultrasonic scalpel to preserve aerodigestive functions, ensure rapid recovery, and avoid neck scarring. The patient was decannulated within 2 weeks and remained disease-free after 1 year. The reported cases of adult-onset lymphatic malformations at the postcricoid and hypopharynx were reviewed and summarized for educational purposes.

Machine learning model to preoperatively predict T2/T3 staging of laryngeal and hypopharyngeal cancer based on the CT radiomic signature.

OBJECTIVES: To develop and assess a radiomics-based prediction model for distinguishing T2/T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) METHODS: A total of 118 patients with pathologically proven LHSCC were enrolled in this retrospective study. We performed feature processing based on 851 radiomic features derived from contrast-enhanced CT images and established multiple radiomic models by combining three feature selection methods and seven machine learning classifiers. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the models. The radiomic signature obtained from the optimal model and statistically significant morphological image characteristics were incorporated into the predictive nomogram. The performance of the nomogram was assessed by calibration curve and decision curve analysis. RESULTS: Using analysis of variance (ANOVA) feature selection and logistic regression (LR) classifier produced the best model. The AUCs of the training, validation, and test sets were 0.919, 0.857, and 0.817, respectively. A nomogram based on the model integrating the radiomic signature and a morphological imaging characteristic (suspicious thyroid cartilage invasion) exhibited C-indexes of 0.899 (95% confidence interval (CI) 0.843-0.955), fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on the radiomics model derived from contrast-enhanced CT images had good diagnostic performance for distinguishing T2/T3 staging of LHSCC. CLINICAL RELEVANCE STATEMENT: Accurate T2/T3 staging assessment of LHSCC aids in determining whether laryngectomy or laryngeal preservation therapy should be performed. The nomogram based on the radiomics model derived from contrast-enhanced CT images has the potential to predict the T2/T3 staging of LHSCC, which can provide a non-invasive and robust approach for guiding the optimization of clinical decision-making. KEY POINTS: • Combining analysis of variance with logistic regression yielded the optimal radiomic model. • A nomogram based on the CT-radiomic signature has good performance for differentiating T2 from T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma. • It provides a non-invasive and robust approach for guiding the optimization of clinical decision-making.

Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.

Squamous cell carcinoma is the most common form of head and neck cancer (SCCHN) and includes cancers of the lips, mouth, throat, tongue and voice box. It is called 'locally advanced' when the cancer has spread to nearby areas but not to other parts of the body. Few treatment options are available for people with locally advanced SCCHN who have had surgery and are unable to receive a type of chemotherapy called cisplatin. Xevinapant is being developed as a possible new type of cancer treatment. It is a liquid that is taken by mouth or given through a feeding tube. Adding xevinapant to the standard treatment ­ called radiotherapy ­ aims to make radiotherapy more effective against the cancer. Researchers have started a large, international, phase III study called XRay Vision to see if adding xevinapant to radiotherapy can help stop the cancer from coming back after surgery and help people live longer. Clinical Trial Registration: NCT05386550 (ClinicalTrials.gov).

The Value of the Endoscope-Holding Arm in Transoral Pharyngeal Surgery.

BACKGROUND: Transoral pharyngeal surgery is mainly feasible with the use of a microscope or robotic systems. Data about alternative methods, with lower costs and easier availability, are sparse. We intended to examine to what extent the endoscope-holding arm is a suitable alternative to the microscope or robotic systems. MATERIAL AND METHODS: We retrospectively reviewed subjects who underwent pharyngeal tumor resection with the endoscope-holding arm in our university department. RESULTS: We identified 13 subjects who underwent transoral pharyngeal surgery between November 2020 and November 2023. Most subjects presented with an oropharyngeal tumor (6/11 in the lateral wall or tonsil; 4/11 in the tongue base). The oropharyngeal lateral wall or tonsillar tumors were exposed with a standard mouth gag. The tongue-base tumors or hypopharyngeal tumors were exposed with an operating laryngoscope. Advantages over the microscope included an angled view. Advantages over robotic systems included haptic feedback and a faster setup. Advantages over both the microscope and robotic systems included lower costs and easier availability. Visualization with the endoscope was sufficient and similar to that of the microscope. Bimanual action was possible with surgical forceps and a monopolar electrode. CONCLUSIONS: Transoral pharyngeal surgery was feasible with the endoscope-holding arm. The endoscope-holding arm could be a cost-efficient alternative to the microscope or robotic systems.

Single-Port Robotic Removal of a Submucosal Foreign Body in the Distal Hypopharynx.

In this report, we present a 55-year-old female with cervical stenosis that underwent C5-C7 anterior cervical discectomy and fusion surgery complicated by hardware failure requiring removal. One screw remained after transcervical hardware removal due to operative difficulty with the risk of exposing the hypopharyngeal submucosal space. The retained screw caused the patient significant discomfort and dysphagia prompting a transoral attempt at removal. Using a hypopharynx blade on an oral retractor for access, the single-port surgical robot successfully removed the foreign body from the distal hypopharynx. In this case, a single-port surgical robot expanded access to the inferior hypopharynx. Laryngoscope, 134:588-591, 2024.

Comparison of three different image enhancement systems for detection of laryngeal lesions.

OBJECTIVE: Image enhancement systems are important diagnostic tools in the detection of laryngeal pathologies. This study aimed to compare three different image enhancement systems: professional image enhancement technology, Image1 S and narrow-band imaging. METHOD: Using the three systems, 100 patients with laryngeal lesions were investigated using a flexible and a 30° rigid endoscope. The lesions were diagnosed by three experts and classified using the Ni classification. The findings were compared. RESULTS: Lesions classified as 'benign' were histopathologically confirmed in 50 per cent of patients, malignant lesions were confirmed in 41 per cent and recurrent respiratory papillomatosis were confirmed in 9 per cent. There was no significant difference between the experts' assessments of each image enhancement system. CONCLUSION: The three systems give comparable results in the detection of laryngeal lesions. With two additional systems, more users can perform image-enhanced endoscopy, resulting in a broadly available tool that can help to improve oncological assessment.

Successful endoscopic resection for well-differentiated neuroendocrine tumor, Grade 1, in the hypopharynx.

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved.

Hypopharynx Cancer Incidence in Kazakhstan: 2017-2021.

OBJECTIVE: The article studies the geographical features of the incidence of hypopharynx cancer (HPC) in Kazakhstan. METHODS: The retrospective study was done for the period 2017-2021. Descriptive and analytical methods of ecoepidemiology were used. Crude (CR), age-specific (ASIR), age-standardized (ASR), equalized incidence rates and approximation were calculated. The dynamics of indicators was investigated using component analysis according to methodological recommendations. The method of drawing up a cartogram based on the determination of the standard deviation (σ) from the mean (x) was applied. RESULT: During the study period, 814 new cases of HPC were registered. The incidence rate decreased from 0.898 (2017) to 0.895 in 2021 and the overall decline was 0.003 per 100,000 population, including due to the age structure - ∑ΔA=+0.04, due to the risk of acquiring illness - ∑ΔR=-0.05 and their combined effect - ∑ΔRA=+0.01. The component analysis revealed that the increase in the number of patients with HPC was mainly due to the growth of the population (ΔP=+37.0%), changes in its age structure (ΔA=+106.1%) and changes associated with the risk of acquiring illness (ΔR=-133.4%). The cartograms were allocated according to the following criteria: low - up to 0.730/0000, average - from 0.73 to 1.180/0000, high - above 1.180/0000. The results of the spatial assessment showed the highest levels of HPC incidence in following regions: Atyrau (1.960/0000) and West Kazakhstan (1.580/0000). CONCLUSION: Thus, this is the first epidemiological study of HPC, which assessed the role of the influence of various factors, including demographic and risk of acquiring illness, on the dynamics of incidence, taking into account gender differences and geographical variability.