Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma.

BACKGROUND: The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx. RESULTS: Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed. CONCLUSIONS: Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.

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.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25-30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC. METHODS: A retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates. RESULTS: Of the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event. CONCLUSION: The Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

[Clinical application of Visual throat forceps in the removal of hypopharyngeal foreign body].

Objective:To explore the feasibility of using self-made visual throat forceps to remove hypopharyngeal foreign bodies. Methods:The throat forceps were combined with the endoscope and connected to a monitor via a data cable resulting in a visual throat forceps apparatus. This device was utilized to examine and treat the hypopharyngeal foreign bodies. Results:Among 53 patients, foreign bodies were detected in 51,with 48 cases involving hypopharyngeal foreign bodies. All were successfully extracted using the visual throat forceps. Three cases, diagnosed as esophageal foreign bodies by electronic gastroscopy, were treated using the same method. Conclusion:Visual throat forceps can be used to examine the hypopharynx and remove foreign bodies. It has the advantages of simple operation, rapid operation, and high success rate of foreign body removal from the hypopharynx. It is worthy of clinical application.

[Feasibility and efficacy of pre-management of superior laryngeal artery in endoscopic surgery for hypopharyngeal cancer].

Objective: To explore the feasibility and efficacy for the dissection and ligation of the superior laryngeal artery in endoscopic surgery for hypopharyngeal cancer. Methods: Eight cadaveric heads were selected, and the laryngopharynxes were harvested. The positions of the superior laryngeal arteries entering the larynxes were dissected and observed under endoscopic vision, and their anatomical characteristics were summarized. Twenty-nine patients (all were male, aged 39-74 years old) with hypopharyngeal cancer who underwent transoral endoscopic surgery at the Department of Otorhinolaryngology Head and Neck Surgery of the Second Xiangya Hospital, Central South University from January 2018 to December 2019 were selected, and the patients were randomly divided into two groups by drawing lots, namely, the superior laryngeal artery was actively dissected and occluded during surgery in observation group (n=15) or not in control group (n=14). The differences in surgical time, bleeding volume, postoperative complications, and postoperative disease-free survival rate were compared between the two groups. Statistical analysis was conducted using SPSS 25.0 software. Results: The entry point of the superior laryngeal artery into the larynx was approximately at the level of the superior edge of the thyroid cartilage, and entered the larynx at the posterior one-third of the lateral wall of the pyriform fossa. The superior laryngeal artery might be determined through endoscopic exploration in all patients of observation group. The endoscopic surgery time [(40.00±7.56) minutes] and intraoperative bleeding volume [(24.00±8.28) ml] in the observation group were respectively less than those [(48.57±14.06) minutes and (42.86±15.41) ml] in the control group, and the differences were statistically significant (t=-2.064, P=0.049; t=-4.064, P=0.001). There was no case with postoperative bleeding in the observation group, but with one case of postoperative bleeding in the control group. Total disease free survival rate was 86.2% and there was no significant difference in disease free survival rates between the two groups during a follow-up period of at least 36 months (P=0.986). Conclusion: Dissection of the superior laryngeal artery during endoscopic surgery for hypopharyngeal cancer is feasible, and pre-management and occlusion of the superior laryngeal artery can effectively reduce intraoperative bleeding.

[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.

Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

Fasciocutaneous and jejunal free flaps for circumferential hypopharyngeal defect reconstruction: A 22-year multicenter cohort study.

BACKGROUND: It remains unclear whether a tubed fasciocutaneous or jejunal free flap (FCFF and JFF) is preferable for reconstruction of circumferential pharyngolaryngoesophageal defects. METHODS: All consecutive patients with circumferential pharyngolaryngoesophageal defects reconstructed with an FCFF or JFF between 2000 and 2022 were included. Outcomes of interest were rates of fistulas, strictures, and donor-site complications. RESULTS: In total, 112 patients were included (35 FCFFs and 77 JFFs). Fistula and stricture rates were significantly lower following JFF compared to FCFF reconstructions, with 12% versus 34% (p = 0.008) and 29% versus 49% (p = 0.04), respectively. Severe donor-site complications leading to surgical intervention or ICU admittance only occurred after JFF reconstructions (18%, p = 0.007). CONCLUSIONS: The high fistula and stricture rates in FCFF reconstructions and the rate of severe abdominal complications in JFF reconstructions illustrate inherent procedure-specific advantages and disadvantages. Relative pros and cons should be carefully weighed when tailoring treatments to the individual needs of patients.

Transoral robotic vertical partial laryngectomy (hemilaryngectomy) extended to the hypopharynx.

Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.

Pedicled flaps reconstruction of hypopharynx and laryngeal defects: Successful preservation of laryngeal function in patients with advanced hypopharyngeal cancer.

BACKGROUND: Preserving laryngeal function and reconstructing the hypopharynx in advanced hypopharyngeal cancer pose significant challenges for head and neck surgeons. METHODS: A 48-year-old male patient was diagnosed with advanced hypopharyngeal cancer originating from the left pyriform sinus. The tumor extended into the hypopharynx, left vocal cord, ventricular fold, partial aryepiglottic fold, and a segment of the cervical esophagus. A curative tumor resection was performed, and a well-thought-out strategy was employed for hypopharyngeal repair and laryngeal reconstruction. RESULTS: Following the surgery, the patient demonstrated exceptional flap survival, and the tracheostomy tube was removed at the 6-month mark. No surgery-related complications were observed, and both swallowing and vocal functions exhibited a robust recovery. CONCLUSION: Our reconstruction strategy proves effective in preserving laryngeal function among patients with advanced hypopharyngeal cancer.

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.

The Time-Point Distribution Characteristics of Laryngopharyngeal Reflux in Elderly Patients.

OBJECTIVE: To identify the characteristics of the time-point distribution of the occurrence of hypopharyngeal-proximal reflux episodes (HREs) in elderly and younger patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Retrospective cohort study. SETTING: Analysis of data from patients with LPR-related symptoms and 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-hour HEMII-pH) monitoring from February 2017 to September 2022 at Sixth Medical Center of PLA General Hospital. METHODS: Patients were divided into 2 age groups: the elderly group (>60 years) and the younger group (≤60 years). The time series of HREs and meals within 24 hours were analyzed based on HEMII-pH. RESULTS: A total of 305 patients were included (126 elderly patients). In younger patients, except for nonacid-gas HREs, the incidence of the remaining types of HREs tended to increase within 2 hours after meals, especially after dinner. The incidence of all types of HREs pre- and postmeal was not significantly different in the elderly group (χ2 = 0.080, P = .777). The incidence of nighttime HREs in elderly patients was statistically higher than in younger patients (6.23% vs 3.96%, P = .030), particularly acid-/nonacid-liquid HREs. CONCLUSION: HREs tend to increase within 2 hours after meals in younger LPR patients, except for nonacid-gas HREs. In elderly LPR patients, the incidence of all types of HREs pre- and postmeal were not significantly different, and nighttime fluid HREs was more prone to occur than in younger patients.

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.

Salvage total laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: Validated prognostic nomograms predicting oncological outcomes.

BACKGROUND: Salvage total laryngectomy (STL) is a preferred treatment for patients with residual, recurrent, and second primary squamous cell carcinoma of the larynx/hypopharynx after (chemo)radiation. To individually estimate postoperative oncological outcomes, we designed and validated prognostic nomograms. METHODS: We used a dataset of 290 patients who underwent STL. Nomograms predicting 2- and 5-year OS, DFS, and DSS were developed, using variables which are identified pre- or postoperatively. The nomograms were externally validated on a dataset of 109 patients. RESULTS: The nomograms based on postoperative variables performed better than those based on preoperative variables (OS: C = 0.68 vs. 0.64; DFS: C = 0.70 vs. 0.64; DSS: C = 0.74 vs. 0.64). The nomogram predicting DSS based on postoperative variables performed best. CONCLUSIONS: The presented prognostic nomograms for predicting oncological outcomes in patients who undergo STL are tools which allow for a reliable prognostic assessment.

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.

Hypopharyngeal Diffuse Large B-Cell Lymphoma in a 74-Year-Old Man Presenting with Dysphagia: A Case Report.

BACKGROUND Malignant lymphomas can occur at various sites. Hypopharyngeal tumors are at risk for airway obstruction and require rapid diagnosis and treatment. Most hypopharyngeal malignancies are squamous cell carcinomas; other tumors are rare. To date, only a few cases of malignant hypopharyngeal lymphoma have been reported, and its specific characteristics are unknown. Herein, we report a case of right hypopharyngeal diffuse large B-cell lymphoma (DLBCL) in a 74-year-old man with dysphagia. CASE REPORT A 74-year-old man presented to our hospital with dysphagia. He had no relevant medical history. Endoscopic examination revealed a right hypopharyngeal tumor. The surface of the tumor was smooth, with no evidence of hemorrhage. Computed tomography revealed a 40-mm mass located in the hypopharynx. We performed a tracheotomy and biopsy of the tumor. Histopathological examination revealed a diffuse proliferation of large atypical B cells with negative staining for Epstein-Barr virus by in situ hybridization. Immunohistochemical staining was positive for CD20 but negative for CD3 and CD10. The patient was administered chemotherapy. The tumor reduced in size, and the patient recovered completely. During the two-year follow up, no recurrence of cancer was observed. CONCLUSIONS Although most hypopharyngeal tumors are squamous cell carcinomas (SCCs), the possibility of other types of tumors should also be considered. Malignant lymphoma of the hypopharynx is rare, and more cases need to be studied and reported in the future.