Hypopharyngeal Squamous Cell Carcinoma Research Articles

Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma.

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

The Association Between the Change of Soluble Programmed Cell Death Ligand-1 (sPD-L1) and the Radiosensitivity in Patients With Hypopharyngeal Squamous Cell Carcinoma

The aim of this study was to evaluate the change of sPD-L1 in the plasma of hypopharyngeal squamous cell carcinoma (HSCC) patients before and after radiotherapy (RT) and to explore their relationship with the sensitivity to radiotherapy.A total of 50 patients and 12 healthy individuals were enrolled. All blood samples were collected before RT and 38 blood samples were obtained after RT. Twenty-three matched formalin-fixed, paraffin-embedded (FFPE) specimen from patient tumor biopsies were examined PD-L1 immunohistochemistry, and the sPD-L1 levels were quantified by enzyme-linked immunosorbent assay (ELISA).The level of plasma sPD-L1 in patients were higher than healthy individuals. Plasma sPD-L1 levels at diagnosis correlated positively with T stage, but no association and difference between baseline sPD-L1 levels and other factors, including gender, age, N stage, prognostic stage and blood cell counts. The level of sPD-L1 in plasma had moderate correlations with PD-L1 expression on tumor cells. Notably, it is classified into decreased or increased groups depending on change of the concentration of sPD-L1 after RT, and the study found the sensitivity to radiotherapy of decreased group were higher than increased group.The study reported that sPD-L1 can be detectable in the plasma of HSCC. Besides, the change of plasma sPD-L1 following radiotherapy might be of guided significance for predicting the sensitivity to radiotherapy.

Radical Surgery vs. Definitive Concurrent Chemoradiotherapy for Locally Advanced Hypopharyngeal Cancer

Debates have always been around the superiority of radical surgery or definitive concurrent chemoradiotherapy (CCRT) for locally advanced hypopharyngeal cancer. The aim of this study is to retrospectively evaluate clinical outcomes and long-term adverse effects of patients treated in two methods and try to figure out this question.We retrospectively reviewed patients with locally advanced hypopharyngeal squamous cell carcinoma, as stage III-IV, between June 2013 and June 2019 in our hospital, who were treated with radical surgery plus adjuvant radiotherapy (SRT, n = 52) or definitive CCRT (n = 21). The overall survival (OS) and disease-free survival (DFS) were calculated and compared by the Kaplan-Meier method with SPSS 26.0 software, and the long-term adverse effects were compared with the chi-square test between two groups.We finally included 73 patients in this study, among whom 52 received SRT and 21 received CCRT. The 3-year OS rate and DFS rate for all patients (n = 73) were 69.1% and 76.9%, respectively. The 1-year OS rate of the CCRT group was better than the SRT group (95.2% v 84.6%, P = 0.049), while the 1-year DFS rates between two groups were similar. However, the 3-year OS rate of CCRT group was lower than SRT group (57.1% v 72.2%), even though it showed no statistical significance (P = 0.074). Besides, the feeding tube rate and tracheotomy rate after two years were both 23.8% of the CCRT group, which were significantly higher than the SRT (both were 5.8%) (P = 0.039).For patients with locally advanced hypopharyngeal cancer, definitive CCRT has a better OS than radical surgery in a short time, but the advantage shrank as time goes by. This may be related to the long-term adverse effects which are more prevalent during the latter follow-up period in the CCRT group. We need more prospective studies in the future to demonstrate it.

An MRI-based radiomics-clinical nomogram for the overall survival prediction in patients with hypopharyngeal squamous cell carcinoma: a multi-cohort study.

To explore whether radiomics features extracted from pre-treatment magnetic resonance imaging (MRI) can predict the overall survival (OS) in patients with hypopharyngeal squamous cell carcinoma. A total of 190 patients with hypopharyngeal squamous cell carcinoma were eligibly enrolled from two institutions. Radiomics features were extracted from contrast-enhanced axial T1-weighted (CE-T1WI) sequence. The least absolute shrinkage selection operator (LASSO) algorithm was applied to establish a radiomics score correlated with OS. Multivariate logistic regression analysis was applied to determine the independent risk factors, which was combined with radiomics score to build the final radiomics nomogram. A radiomics score with 6 CE-T1WI features for OS prediction was constructed and validated; its integration with specific clinicopathologic factors (N stage) showed a better prediction performance in the training, internal validation, and external validation cohorts (C-index 0.78, 0.75, and 0.75). Calibration curves determined a good agreement between the predicted and actual overall survival. The radiomics-clinical nomogram and radiomics score might be non-invasive and reliable methods for the risk stratification in patients with hypopharyngeal squamous cell carcinoma. • An MRI-based radiomics model was constructed to evaluate of OS in patients with hypopharyngeal squamous cell carcinoma. • A radiomics-clinical nomogram that combined radiomics features and clinical characteristics was established. • Multi-cohort study validated the predictive performance of the radiomics-clinical nomogram to stratify patients with high risk in clinical practice.

Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUNDIn recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC).AIMTo clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy.METHODSThis is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann–Whitney U test. Pearson’s χ2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan–Meier method was used to estimate the cumulative patient survival rates.RESULTSIn our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE (P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE (P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively.CONCLUSIONGastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.

Nomograms predicting prognosis for locally advanced hypopharyngeal squamous cell carcinoma.

This study aimed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with locally advanced hypopharyngeal squamous cell carcinoma (HSCC). 864 patients with locally advanced HSCC during 2010-2015 from the surveillance, epidemiology and end results (SEER) database were selected. After classifying continuous data by risk, Cox regression analyses were applied to detect significant independent prognostic factors, with which nomograms were established. To evaluate the value of nomograms, concordance index (C-index), area under the receiver-operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA), Kaplan-Meier analysis was adopted. The efficacy of surgery in different risk groups was also studied to figure out people who can benefit from surgery. A total of 864 locally advanced HSCC patients were randomized into the training cohort (n = 608) and the validation cohort (n = 256). Age, race, tumor size, T stage, N stage, primary site, radiotherapy, and chemotherapy were independent prognostic factors for OS and CSS (except race) and formed the nomograms. The nomograms revealed satisfied performance in C-index, AUC, DCA, and calibration curves, and prevailed over American Joint Committee on Cancer (AJCC) TNM staging system in predicting OS and CSS. After risk stratification, patients of low-risk group resulted in the best outcomes. Patients in moderate-risk may benefit from surgery. Convenient and well-calibrated nomograms to predict OS and CSS for III/IVA/IVB-stage HSCC patients were set up and assessed and may do a favor to make clinical decisions.

Utility of the Modified and High-Sensitivity Modified Glasgow Prognostic Scores for Hypopharyngeal Squamous Cell Carcinoma.

ObjectiveTo determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC).Study DesignRetrospective cohort study.SettingAffiliated university hospital.MethodsWe reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS).ResultsThe 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05).ConclusionOur study suggests that the HS-mGPS is useful as prognostic factor in HSCC.

Total Laryngectomy: A Review of Surgical Techniques.

Since the first total laryngectomy was performed in the late 18th century, several improvements and variations in surgical techniques have been proposed for this procedure. The surgical techniques employed in total laryngectomy have not been comprehensively discussed to date. Thus, the main objective of this article was to address controversial aspects related to this procedure and compare different surgical techniques used for a total laryngectomy procedure from the beginning to the end.Although the management paradigms in laryngeal and hypopharyngeal squamous cell carcinomas have shifted to organ-preserving chemoradiotherapy protocols, total laryngectomy still plays a prominent role in the treatment of advanced and recurrent tumors. The increased incidence of complications associated with salvage total laryngectomy has driven efforts to improve the surgical techniques in various aspects of the operation. Loss of voice and impaired swallowing are the most difficult challenges to be overcome in laryngectomies, and the introduction of tracheoesophageal voice prostheses has made an enormous difference in postoperative rehabilitation and quality of life. Advancements in reconstruction techniques, tumor control, and metastatic management, such as prophylactic neck treatments and paratracheal nodal dissection (PTND), as well as the use of thyroid gland-preserving total laryngectomy in selected patients have all led to the increasing success of modern total laryngectomy. Several conclusions regarding the benchmarking of surgical techniques cannot be drawn. Issues regarding total laryngectomy are still open for discussion, and the technique will continue to require improvement in the near future.

Hirsute hypopharynx and esophagus presenting with refractory cough and successfully treated with hot biopsy method

A 56-year-old man had a history of hypopharyngeal squamous cell carcinoma (stage T2N0M0) and had undergone partial pharyngolaryngectomy with submental flap reconstruction for the pharyngeal defect. After an initial uneventful 6 months after treatment, he began to have a severe cough and a frequent itching throat sensation. These symptoms were aggravated after swallowing or eating. Frequent choking episodes also occurred. Endoscopy showed some hair growth over the left pyriform sinus and esophageal orifice (A).

Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study

Voltage-dependent calcium channel subunit alpha-2/delta-1 (α2δ1) has been identified as a marker of cancer stem cells in multiple malignant tumor types. However, α2δ1’s role in the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) was not reported. In our study, ten pairs of HSCC and peritumoral normal tissues were used for immunohistochemistry assessment. And α2δ1 expression levels of 34 more HSCC samples were also evaluated, represented by the integral optic density using Image-Pro Plus. Clinicopathological associations and prognostic value of α2δ1 were analyzed. As a result, α2δ1 expression was frequently increased in HSCC tissues. Although the correlation between patients’ clinicopathological characteristics and their α2δ1 expression levels was not significant, α2δ1 expression was significantly correlated with unfavorable overall survival (OS) (P = 0.018) and progression-free survival (PFS) (P = 0.023). Univariate and multivariate cox regression analyses suggested α2δ1’s prognostic role for both OS and PFS (P = 0.013 and 0.011, respectively). This study specifically demonstrated that α2δ1 regularly increased in HSCC compared with peritumoral tissues, and α2δ1 could act as a promising prognostic marker in HSCC patients.

Pathological Level VI Lymph Node Metastasis in Clinical N3b Pyriform Sinus Squamous Cell Carcinoma.

The frequency of metastasis to level VI lymph nodes in advanced pyriform sinus squamous cell carcinoma (PSSCC) is unknown. We intended to analyze the clinical features and pathological presence or absence of level VI lymph node metastasis in patients with PSSCC. The data of 270 patients with previously untreated hypopharyngeal squamous cell carcinoma from 2006 to 2016 were obtained. Patients who underwent pharyngolaryngectomy for the pyriform sinus subsite with a curative intent with level VI dissection were included. We retrospectively analyzed the clinical Tumor-Node (TN) status (TNM classification of malignant tumors, eighth edition) and the presence or absence of pathological level VI lymph node metastasis. A total of 34 patients were included. Eight patients (24%) had pathological level VI lymph node metastasis. The rate of pathological level VI lymph node metastasis was directly proportional to the clinical N status (P = .0002, Chi-square test for trend). In all, 5 patients with cN2b- 3 were classified as cN3b. Ipsilateral pathological level VI lymph node metastasis was observed in 1 patient, and bilateral metastasis was observed in 3 patients. There was no association between clinical T status or pyriform sinus apex invasion and pathological level VI metastasis (both P > .99, Fisher's exact test). PSSCC with cN3b is prone to bilateral level VI metastasis. We recommend that patients with PSSCC with cN3b should undergo bilateral level VI lymph node dissection.

Improvement in recurring nivolumab-induced pneumonitis with repetitive administration of infliximab in a patient with head and neck cancer: A case report

Severe pneumonitis induced by nivolumab, an anti-programmed cell death-1 monoclonal antibody, is a rare but potentially fatal immune-related adverse event. In cases of steroid-refractory pneumonitis, an appropriate therapeutic strategy using anti-tumor necrosis factor-α (TNF-α) antibody has not been established. A 59-year-old female was diagnosed with hypopharyngeal squamous cell carcinoma. Previous therapies including chemoradiotherapy and throat laryngectomy were performed, but metastatic recurrence appeared in the intrapulmonary and mediastinal lymph nodes. The patient was administered nivolumab. On the 14th day of nivolumab administration, the patient experienced dyspnea and computed tomography of the chest showed multiple consolidations in the right lung. She was diagnosed with nivolumab-induced pneumonitis. Because the pneumonitis was refractory to steroid therapy, she was administered infliximab, and the pneumonitis improved. On the 72nd and 101st days of nivolumab administration, nivolumab-induced pneumonitis re-appeared with an elevated serum TNF-α concentration. In each occurrence of pneumonitis, repetitive administration of infliximab improved the pneumonitis. Repetitive administration of infliximab may be effective for treating recurrent nivolumab-induced pneumonitis that is associated with an increased serum TNF-α concentration.

Survival analysis of patients with advanced hypopharyngeal cancer comparing patients who received primary surgery to those who received chemoradiation: An analysis of the NCDB

IntroductionThe objective of this study was to use the American College of Surgeons’ National Cancer Database (NCDB) to examine the association between primary treatment and overall survival (OS) among patients with locoregionally advanced hypopharyngeal cancer. Methods6,055 adult patients diagnosed between 2004 and 2015 with stage III or IV, M0, hypopharyngeal squamous cell carcinoma were identified within the NCDB. Patients who received primary chemoradiation (CRT) were compared to those that received surgery with adjuvant radiation or chemoradiation (S + Adj). OS was compared between treatment groups using Kaplan-Meier analyses, propensity score adjustment, and Cox regression analyses. ResultsThe median survival was 22.7 months (IQR 11.0–49.0). The S + Adj group had a significantly higher comorbidity score, higher grade disease, and more advanced stage disease than the CRT group. S + Adj was associated with significantly improved survival when compared to CRT (p < 0.0001). A propensity score adjusting for facility type, facility location, care at multiple facilities, histology, and T stage was developed. S + Adj was associated with longer survival (HR: 0.72, 95% CI: 0.64–0.80) when compared to CRT in a multivariable Cox regression analysis (adjusting for age, race and ethnicity, insurance status, a comorbidity index, diagnosis year, treatment delay, N stage, and the propensity score). S + Adj was associated with significantly improved survival among those with T2 disease (p = 0.02), T3 disease (p = 0.02), and T4 disease (p < 0.0001) in sensitivity analyses examining these subcohorts independently. ConclusionsAmong patients with advanced hypopharyngeal cancer reported in NCDB, treatment with S + Adj was associated with longer survival compared to those treated with primary CRT.

Basaloid squamous cell carcinoma of the hypopharynx: an analysis of 213 cases.

Basaloid squamous cell carcinoma (BSCC) is a rare aggressive variant of squamous cell carcinoma (SCC) with a poor prognosis. No large series of exclusively hypopharyngeal BSCC patients have been previously reported. Therefore, this retrospective population-based study aims to explain the patient demographics, clinicopathologic characteristics, incidence, and survival outcomes of hypopharyngeal BSCC and how it relates to conventional-type SCC. The National Cancer Institute's Surveillance, Epidemiology, and End Results database registry was queried for patients diagnosed with hypopharyngeal BSCC and conventional-type SCC between 2001 and 2016. The incidence of hypopharyngeal BSCC from 2001 to 2016 was 0.0161 per 100,000 individuals. The BSCC group comprised 213 patients, and the SCC group 7958 patients. The majority of BSCCs were considered high grade (Grade III/IV, 89.58%). Most BSCC patients were diagnosed at an advanced stage (American Joint Committee on Cancer [AJCC] stage IV, 65.38%). The 1-, 5-, and 10-year disease-specific survival (DSS) rates for hypopharyngeal BSCC were 84.10%, 57.40%, and 46.20%, respectively. Multivariate analysis, after adjustment for sex, age, race, tumor location, grade, and AJCC stage, showed that patients with BSCC had significantly better DSS than those with conventional-type SCC. Surgery with radiation contributed to a favorable DSS for BSCC patients in comparison with other treatments. This analysis of the largest hypopharyngeal BSCC series indicates a better prognosis for this pathologic type compared with conventional-type hypopharyngeal SCC. Multimodality treatment with surgery and radiation may result in a favorable prognosis for hypopharyngeal BSCC patients.

Image-enhanced endoscopy for detection of second primary esophageal neoplasms in patients with hypopharyngeal cancer: Prevalence, risk factors, and characteristics.

Esophageal second primary neoplasms (ESPNs) are common in hypopharyngeal squamous cell carcinoma (HPSCC) patients and are associated with poor prognoses. The effectiveness of image-enhanced endoscopy (IEE) has not been well established. We reviewed the patients between April 2016 and April 2018 with HPSCC receiving ESPNs screening via white-light imaging, narrow-band imaging, and Lugol chromoendoscopy. Of 99 eligible patients, ESPNs prevalence was 31%. Of the 69 patients assigned to the follow-up group, 23 with positive findings showed significantly increased previous histories of second primary malignancies in the upper aerodigestive tract. Among them, patients without symptoms at the time of IEE screening showed less advanced T stages and higher percentages of receiving minimal invasive therapy. The present study represented the clinical utility of routine IEE screening in HPSCC patients and proposed routine surveillance may help identify and properly manage early-stage ESPN.

Validation of the risk factors for primary control of early T-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma by transoral surgery: a prospective observational study

We had previously identified the following risk factors for insufficient control of early T-stage head and neck cancer by transoral surgery (TOS): (1) tumor thickness > 7mm on enhanced computed tomography (CT), and (2) poor differentiation in pathological examination. We subsequently used a different patient cohort to validate the usefulness of these factors in determining the need for adaptation of TOS. A prospective observational study METHODS: Patients who received TOS as a definitive treatment between April 1, 2016 and September 30, 2020 were included. Primary control rates (by single TOS and TOS alone) in relation to the above-mentioned risk factors were calculated. Overall (O), recurrence-free (RF), and disease-free (DF) survival (S) outcomes were evaluated. A combination analysis based on the number of risk factors was also performed. Patients with tumor thickness > 7mm had a 2.88-fold [95% confidence interval (CI) 1.01-8.51] higher risk of incomplete primary resection by single TOS, while patients who showed poor differentiation on pathological assessments had a 13.14-fold (95% CI 3.66-47.14) higher risk of insufficient primary control by TOS alone. The 3year OS, RFS, and DFS rates were 99%, 83%, and 63%, respectively. Patients with both risk factors had a 93.00-fold (95% CI 4.99-1732.00) higher risk of incomplete primary control by TOS alone. Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, primary control by TOS alone may not be achieved in patients with both risk factors, that is, tumor thickness > 7mm as measured by enhanced CT and poor differentiation on pathological examination.

Cetyltrimethylammonium Bromide Attenuates the Mesenchymal Characteristics of Hypopharyngeal Squamous Cell Carcinoma Through Inhibiting the EGFR/PI3K/AKT Signaling Pathway.

Cetyltrimethylammonium bromide (CTAB), a quaternary ammonium surfactant, was shown to have antitumor effects in a cellular mode of head and neck squamous cell carcinoma (HNSCC), modulating apoptotic and cytotoxic processes. However, the mechanisms by which CTAB exerts its effects against the epithelial- mesenchymal transition in HNSCC remain poorly understood. In the present study, we investigated whether CTAB inhibits cellular mobility and invasiveness of hypopharyngeal squamous cell carcinoma (HPSCC) cells. WST-1, cell-cycle phase distribution, and wound healing, as well as transwell assays were conducted. Changes in protein expression patterns and related signaling pathways involved in effects of CTAB on HPSCC cell lines were evaluated by western blotting. Treatment of human HPSCC cell lines with CTAB significantly altered their morphology from spindle-like to cobblestone-like by diminishing mesenchymal-like phenotypic characteristics. CTAB also hindered cell functional properties, including migration and invasion, independently of cell viability. In addition, western blot results demonstrated that treatment with CTAB reduced expression of mesenchymal markers. Further investigation showed that CTAB treatment suppressed the phosphorylation of extracellular-regulated kinase 1/2, mechanistic target of rapamycin kinase and AKT serine/threonine kinase 1. CTAB also repressed the expression and phosphorylation levels of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the partial restoration of mesenchymal phenotype by EGF addition confirmed that CTAB inhibited migration and invasion in HPSCC cells by blocking the EGFR signaling pathway. Our results suggest that CTAB is involved in the suppression of EGFR-mediated mesenchymal phenotype and the molecular mechanism by which CTAB obstructs HPSCC cell metastasis may represent a promising strategy for use in HPSCC treatment.

Use of Supraclavicular Flap by End to Side Technique in Pharyngeal SCC: A Case Report and Review of Literature

Objectives In recent years, conservation laryngeal surgeries, including partial pharyngectomy, have been introduced as an alternative procedure for selected cases of hypopharyngeal squamous cell carcinoma (HSCC). Reconstruction of these defects presents a considerable challenge for the surgeon after partial pharyngectomy due to its circumferential nature. In this case report, we represent the innovative “End to side” technique to reconstruct hypopharyngeal defect using the rolled supraclavicular flap after laryngeal-preserving partial pharyngectomy. Methods and Results A 70-year-old female presented with a history of progressive dysphagia and odynophagia. The evaluations revealed a T3N0M0 SCC of pyriform sinus. The mass was successfully resected through partial pharyngectomy, and the hypopharyngeal defect reconstruction was achieved using the rolled supraclavicular flap via the “End to side” technique. The patient was discharged after decannulation on day 10. The 3-week barium swallow was performed with no evidence of anastomotic leakage, and the oral feeding was started after NG tube removal. At week 5, complete movement of the true vocal cord on the one side and good phonation and deglutition was observed. There was no evidence of recurrence after 1 year. Conclusions Laryngeal-preserving partial pharyngectomy and hypopharyngeal reconstruction with the rolled supraclavicular flap via the “End to side” technique could lead to good oncological and functional outcomes in selected cases of pyriform sinus.

Metformin Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma through Circ_0003214-Mediated MiR-489-3p-ADAM10 Pathway.

Purpose This study aims to explore the function of metformin in hypopharyngeal squamous cell carcinoma (HSCC) and the underlying mechanism. Methods Cell viability, colony formation, cell apoptosis, and cell cycle were investigated using cell counting kit-8 assay, colony formation, and flow cytometry assay. Gene expression was detected by quantitative real-time polymerase chain reaction and western blot. The target relationship was validated by dual-luciferase reporter assay or RNA immunoprecipitation assay. An animal study was implemented to clarify the effect of metformin in vivo. Results Metformin suppressed HSCC cell viability and colony formation ability and induced cell cycle arrest and apoptosis, and circ_0003214 overexpression weakened these effects. Circ_0003214 regulated A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression via targeting miR-489-3p. Besides, miR-489-3p restoration reversed the role of circ_0003214, and ADAM10 knockdown reversed miR-489-3p inhibition-mediated effect. Moreover, metformin blocked tumor growth via the circ_0003214-miR-489-3p-ADAM10 axis in vivo. Conclusion Metformin inhibits HSCC progression through the circ_0003214/miR-489-3p/ADAM10 pathway.

Functional Larynx Preservation in Patients With Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated With Induction Chemotherapy vs. Concurrent Chemoradiation Alone.

ObjectivesChemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates.MethodsRecords for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher’s exact test.ResultsWe included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19).ConclusionIn this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.