Seong Keun Kwon

PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma

Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC). Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.

Vocal Fold Augmentation with Injectable Polycaprolactone Microspheres/Pluronic F127 Hydrogel: Long-Term In Vivo Study for the Treatment of Glottal Insufficiency

There is increasing demand for reconstruction of glottal insufficiency. Several injection materials have been examined for this purpose, but all had limitations, such as poor long-term durability, migration from the injection site, inflammation, granuloma formation, and interference with vocal fold vibration due to viscoelastic mismatch. Here, we developed a novel injection material, consisting of polycaprolactone (PCL) microspheres, which exhibits better viscoelasticity than conventional materials, and Pluronic F127 carrier, which decreases the migration of the injection materials. The material was injected into rabbits with glottal insufficiency and compared with the FDA-approved injection material, calcium hydroxylapatite (CaHA). Endoscopic and histological examinations indicated that PCL/Pluronic F127 remained at the injection site with no inflammatory response or granuloma formation, whereas CaHA leaked out and migrated from the injection site. Therefore, vocal fold augmentation was almost completely retained during the 12-month follow-up period in this study. Moreover, induced phonation and high-speed recording of vocal fold vibration showed decreased vocal fold gap area in the PCL/Pluronic F127 group. Our newly developed injection material, PCL/Pluronic F127, permits efficient augmentation of paralyzed vocal fold without complications, a concept that can be applied clinically, as demonstrated by the successful long-term follow-up.

Treatment of intraoral ranulas with micromarsupialization: Clinical outcomes and safety from a phase II clinical trial

Micromarsupialization of an oral ranula has been introduced to clinical practice. However, the technical feasibility, indications, and safety of the procedure were not fully studied. In this study, we report the results of a prospective phase II clinical trial to evaluate the clinical outcomes.

Role of surgical salvage for regional recurrence in laryngeal cancer.

Objectives: The aims of this study were to analyze the pattern of regional recurrence in laryngeal cancer, evaluate the role of surgical salvage, and identify factors affecting salvage outcome.

Laser-assisted endoscopic submucosal medial arytenoidectomy (LESMA).

INTRODUCTION Various surgical techniques have been proposed for the management of patients with bilateral vocal fold paralysis (VFP) or posterior glottic stenosis (PGS), which make use of external and endoscopic approaches. The purpose of these surgical treatments is to restore an adequate airway without disturbing voice quality and swallowing. It has been known that medial arytenoidectomy and cordotomy using laser, which partially resects the medial portion of the arytenoids, can preserve the airway and voice quality without damage on the membranous vocal fold.1 However, laser arytenoidectomy and cordotomy may result in granulation or scar tissue formation after surgery, which could fail to restore the adequate airway. Submucous medial arytenoidectomy can prevent granulation tissue formation, thus accelerating healing processes and improving treatment outcomes. We herein describe our experiences in the management of bilateral VFP and PGS by combining posterior transverse partial cordotomy, as described by Dennis and Kashima,2 with modified method of submucosal medial arytenoidectomy, as described by Crumley.1

Evaluation of the Poly(lactic-co-glycolic acid)/Pluronic F127 for Injection Laryngoplasty in Rabbits:

Objective Poly(lactic-co-glycolic acid) (PLGA) is an aliphatic polyester and one of the most commonly used synthetic biodegradable polymers for tissue engineering. The objectives of this study were to evaluate the biocompatibility of PLGA/Pluronic F127 in the vocal fold. Study Design A randomized, prospective, controlled animal study. Setting University laboratory. Subjects and Methods We used 18 New Zealand white rabbits, which were divided into 5% PLGA solution (n = 9) and 10% PLGA solution (n = 9) groups. The PLGA/Pluronic F127 solutions were injected into the rabbit vocal fold. Laryngoscopic exams were performed at 1, 4, and 8 weeks after implantation; then larynx specimens were sampled. High-speed video camera examination was performed for functional analysis of vocal mucosa vibration at 8 weeks after implantation. Also, we evaluated the amplitude of the mucosal wave from the laryngeal midline on high-speed recording. Histologic study of larynx specimen was performed at 4 and 8 weeks. Results All animals survived until the scheduled period. Laryngoscopic analysis showed that both 5% and 10% PLGA/Pluronic F127 maintained after 8 weeks after injection without significant inflammatory response. On functional analysis, high-speed camera examination revealed regular and symmetric contact of vocal fold mucosa without a distorted movement by injected PLGA/Pluronic F127. Histologically, no significant inflammation was observed in the injected vocal fold. Conclusion As a vocal fold injection material, PLGA/Pluronic F127 showed a good bio-compatibility without significant inflammatory response. Further experiment will follow to elucidate its role for drug or gene delivery into the vocal fold.

Comparison of treatment modalities for Contact granuloma: A Nationwide Multicenter Study

This study evaluated the efficacy of commonly used treatment modalities and determined predictors of treatment outcome for contact granuloma.

Identification of genomic mutations associated with clinical outcomes of induction chemotherapy in patients with head and neck squamous cell carcinoma

PurposeWe performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response.MethodsPatients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10xa0%.ResultsOf the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2xa0% of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95xa0% confidence interval 2.07–20.10, Pxa0<xa00.001).ConclusionsComprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.

Effect of induction chemotherapy on survival in locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy: Single center experience

Although induction chemotherapy can reduce distant metastases in locally advanced head and neck squamous cell carcinoma (HNSCC), overall survival (OS) improvement because of induction chemotherapy has not been confirmed.