A randomized comparison of three intubation techniques/tube materials for nasotracheal intubation.

PURPOSE: We sought to compare three intubation methods using different intubation techniques/tube materials for tube advancement from the nasal cavity into the oral cavity during nasotracheal intubation. METHODS: We conducted a randomized clinical trial with adult patients scheduled to undergo elective surgery requiring nasotracheal intubation for general anesthesia. Participants were randomly allocated to a polyvinyl chloride (PVC) tube group (group P), PVC tube attached to a rubber catheter group (group PR), or velvet-soft PVC tube group (group V). Tracheal intubation was then performed based on group allocation. The primary outcome was the first-attempt success rate of tube advancement into the oral cavity; secondary outcomes included the time required for tube advancement into the oral cavity, total intubation time, and the incidence of epistaxis. RESULTS: A total of 149 patients were included in the study. The first-attempt success rate in group V (90%) was significantly higher than that in group P (58%) (odds ratio, 6.5; 95% confidence interval [CI], 2.2 to 19.2), but similar to that in group PR (100%). The mean (standard deviation) time required for tube advancement into the oral cavity was significantly shorter in group V (16 [13] sec) than in group PR [40 (10) sec; 95% CI of mean difference, 17 to 30] and group P (26 [16] sec; 95% CI of mean difference, 3 to 16). Total intubation time was longest in group PR. Epistaxis occurred the least in group V. CONCLUSIONS: Among the three intubation techniques/tube materials for nasotracheal intubation, the velvet-soft PVC tube provided the highest first-attempt success rate, most expeditious advancement into the oral cavity, and lowest incidence of epistaxis. STUDY REGISTRATION: ClinicalTrials.gov (NCT04695444); first submitted 30 December 2020.

RéSUMé: OBJECTIF: Nous avons cherché à comparer trois méthodes d'intubation utilisant différentes techniques d'intubation / matériaux de sondes pour l'avancement de la sonde de la cavité nasale dans la cavité buccale pendant l'intubation nasotrachéale. MéTHODE: Des patient·es devant recevoir une intubation nasotrachéale ont été réparti·es au hasard dans un groupe avec sondes en polychlorure de vinyle (PVC) (groupe P), un groupe avec sondes en PVC attachées à un cathéter en caoutchouc (groupe PR) ou un groupe avec sondes en PVC doux comme du velours (groupe V). L'intubation trachéale a ensuite été réalisée en fonction de l'affectation du groupe. Le critère d'évaluation principal était le taux de réussite de la première tentative d'avancement de la sonde dans la cavité buccale; les critères d'évaluation secondaires comprenaient le temps nécessaire à l'avancement de la sonde dans la cavité buccale, la durée totale de l'intubation et l'incidence d'épistaxis. RéSULTATS: Au total, 149 patient·es ont été inclus·es dans l'étude. Le taux de réussite de l'intubation à la première tentative était significativement plus élevé dans le groupe V (90 %) que dans le groupe P (58 %) (rapport de cotes, 6,5; intervalle de confiance à 95 % [IC], 2,2 à 19,2), mais similaire à celui du groupe PR (100 %). Le temps moyen (écart type) nécessaire pour l'avancement de la sonde dans la cavité buccale était significativement plus court dans le groupe V (16 [13] sec) que dans le groupe PR (40 [10] sec; IC 95 % de la différence moyenne, 17 à 30) et dans le groupe P (26 [16] sec; IC 95 % de la différence moyenne, 3 à 16). La durée totale d'intubation était la plus longue dans le groupe PR. C'est dans le groupe V que l'épistaxis a été la moins fréquente. CONCLUSION: Parmi les trois techniques d'intubation/matériaux de sonde pour l'intubation nasotrachéale, le tube en PVC doux comme du velours a fourni le taux de réussite de première tentative le plus élevé, l'avancement le plus rapide dans la cavité buccale et l'incidence d'épistaxis la plus faible. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04695444); première soumission le 30 décembre 2020.

The Usefulness of Salivary Gland Organoids for Evaluation of the Potency of Botulinum Neurotoxin.

BACKGROUND AND OBJECTIVES: Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two-dimensional neuroblastoma cell line-based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three-dimensional organoid culture system. MATERIALS AND METHOD: We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland-related genes and proteins using real-time polymerase chain reaction (PCR) and immunofluorescence staining. RESULTS: The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of Aqp5 and Bhlha15, associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT/A was applied, as confirmed through real-time PCR. CONCLUSION: We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2697-2704, 2024.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.

Comprehensive Index of Vocal Fatigue (CIVF): Development and Clinical Validation.

OBJECTIVES: In this study, we sought to investigate whether auditory-perceptual and acoustic measures change after a passage-reading task and to develop a multidimensional index of performance fatigue in voice disorders. The clinical usefulness and cut-off scores of the newly developed index were also explored. METHODS: A total of 150 patients (age = 35.65 ± 11.44 years) with voice disorders and 100 healthy controls (age = 35.04 ± 11.26 years) were enrolled in the study. Overall severity (OS) and acoustic measures of sentence samples were obtained before and after a passage-reading task and compared between the two positions. Acoustic features included cepstral peak prominence (CPP), σCPP, L/H spectral ratio (SR), and σSR. Using the changes (Δ) in those acoustic measures and the scores of the Vocal Fatigue Index (VFI), a predictive model of the ΔOS was established. The clinical cut-off point of the index was also identified. RESULTS: For the patient group, OS was higher, but CPP and σCPP were lower for the rear position (after reading the passage) compared to the front position (before reading the passage). A significant portion (adjusted R2 = 77.7%) of the ΔOS was predicted by ΔCPP, tiredness score of the VFI, ΔσCPP, ΔσSR, and ΔSR. The area under the curve of the newly developed index was .864 (sensitivity, 78.67%; specificity, 78.00%), and the index's criterion was >2.6489. CONCLUSIONS: The newly developed Comprehensive Index of Vocal Fatigue (CIVF) can quantify vocal fatigue in voice disorders, reflecting both acoustic and auditory perceptual changes after a passage-reading task. Further studies should explore the responsiveness of the CIVF and the impact of related factors on the CIVF in various voice disorders.

Ductal delivery of extracellular vesicles promote the recovery from salivary gland inflammation.

Salivary gland dysfunction worsens the quality of life, but treatment for restoration of salivary gland function is limited. Although previous reports have demonstrated the therapeutic potentials of extracellular vesicles (EVs) in different preclinical models, the role of EVs in salivary glands remains elusive. Furthermore, little is known about the roles of salivary gland-derived EVs in tissue repair or regeneration compared to other EVs. In this study, EVs secreted from salivary gland-derived mesenchymal stem cells (sgMSCs) were comparatively analyzed with those from Wharton's jelly-derived MSC (wjMSCs). sgMSCs secreted more significant amounts of EVs than wjMSCs, and salivary gland epithelial cells showed a more efficient uptake of sgMSC-EVs than wjMSC-EVs. The possibility of immune regulation was tested via macrophage polarization and LPS-induced epithelial inflammation, resulting in an M1-to-M2 shift and reversal of acinar-to-ductal metaplasia by sgMSC-EV. Furthermore, the roles of sgMSC-EV-mediated immune regulation and tissue repair were clarified in vivo via retroductal delivery of sgMSC-EVs in a mouse model of obstructive sialadenitis. Collectively, our data demonstrate the superior role of sgMSC-EVs in the recovery from salivary gland inflammation and injury and suggest EVs as therapeutic tools for salivary gland dysfunction.

Correlations of MR Sialographic Gradings with the Clinical Measures of Sjögren's Syndrome.

OBJECTIVES: Sjögren syndrome (SS) features salivary gland architectural changes such as ductal deformities and fat deposition secondary to inflammatory cell infiltrates; however, the anatomical and pathophysiological correlations of SS remain to be determined. This study aimed to determine the correlations of imaging findings based on the magnetic resonance (MR) sialography with the clinical and laboratory aspects of SS patients. METHODS: We evaluated the MR sialographic findings of two pairs of parotid glands (PGs) and submandibular glands (SMGs) from 41 SS patients. The distinct MR sialographic features were then compared with the clinical symptoms, biological (anti-SSA/Ro antibody positivity), histological (labial gland focus score), and functional (salivary flow and scintigraphy) data. RESULTS: Ductal deformities such as sialectasis in the PG ducts were exclusively observed in SS, and fat replacement in SMGs was more distinct in patients with SS than in non-SS sicca patients. Of the 82 PGs and SMGs from 41 SS patients, the grade of sialectasis in PGs on MR sialographic images and fat stage in SMGs showed strong correlations with anti-SSA/Ro-positivity. PG sialectasis was found more frequently in patients with dry mouth and decreased salivary gland function. A significant correlation was found between fat deposition in PGs and SMGs and decreased salivary gland function. CONCLUSION: These results suggest that MR sialography is a reliable, adjunctive anatomical and functional study to assess SS. Detail aspects of sialectasis and fat accumulation encountered on MR sialography in SS patients can help physicians assume the disease status in SS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:307-316, 2023.

Long-term outcomes of early stage oral tongue cancer: Main cause of treatment failure and second primary malignancy.

Objective: We attempted to investigate the long-term outcomes, prognostic factors, treatment failures, second primary malignancies, and salvage therapies in early (pT1-2N0) oral tongue squamous cell carcinoma (OTSCC). Methods: We retrospectively analyzed the medical records of 295 early stage OTSCC patients. Results: Two hundred ninety-five patients were enrolled. The average follow-up period was 64.5 months (range, 1-190 months). Five-year recurrence-free survival rate was 84.8% and disease-specific survival rate was 91.2%. On multivariate analysis, only the depth of invasion (DOI) exhibited significant correlations with the disease recurrence. Patient's age and DOI demonstrated a significant association with survival. A total of 53 recurrence and 35 death events occurred, with the main cause of treatment failure being regional or local recurrence. In recurrent cases, the success rate of salvage treatment was 42% at 5 years. During the follow-up period, second primary malignancy occurred in 13 patients, and 8 (61.5%) of those patients were successfully treated. Conclusions: In pT1-2N0 OTSCC, regional or local recurrence is the main recurrence pattern, whereas age and DOI >5 mm are significant prognostic factors related to recurrence and survival. Since several patients experienced second primary malignancies in the head and neck, careful and thorough surveillance may be required to detect second primary lesions. Level of Evidence: 4.

Reliability of Acoustic Measures in Dysphonic Patients With Glottic Insufficiency and Healthy Population: A COVID-19 Perspective.

OBJECTIVES: The COVID-19 pandemic has affected the voice assessment protocols for dysphonic patients. In this study, we compared the changes in acoustic measures of the healthy population as well as dysphonic patients due to glottic insufficiency between the pandemic period requiring face masks and the prepandemic period when the masks were not essential. The clinical reliability of the acoustic measures with and without face masks was explored. METHODS: A total of 120 patients (age = 42.3 ± 11.9 yrs) with glottic insufficiencies such as UVFP and sulcus vocalis and 40 healthy population (age = 40.5 ± 11.2 yrs) cohorts were enrolled during the pandemic period. Age- and gender-matched 120 patients and 40 healthy population cohorts who underwent voice assessment without face masks before the pandemic were enrolled as prepandemic controls. Acoustic measures and overall severity estimates of vowel and speech samples were compared, which included cepstral peak prominence (CPP), L/H spectral ratio (SR), their standard deviations, F0, jitter percent (Jitt), shimmer percent (Shim), noise-to-harmonic ratio (NHR), Cepstral Spectral Index of Dysphonia (CSID), and Acoustic Psychometric Severity Index of Dysphonia. RESULTS: Both patients and healthy cohorts showed higher SRv and SRs but lower CSIDv during the pandemic compared to the prepandemic period. F0 of the healthy male controls during the pandemic was higher than during the prepandemic periods, while the CSIDs was lower for the pandemic period. The pandemic patient cohort showed lower σSRs compared to the prepandemic patient cohort. When the acoustic measures of patients were compared to the healthy population cohort, the patient cohort showed lower CPP and σCPPs, while higher σCPPv, Jitt, Shim, and NHR during both pandemic and prepandemic period. Overall, the area under the curve of the acoustic measures and overall severity estimates was similar between the mask and non-mask groups, although the AUC of the SR measures was poor. CONCLUSIONS: Wearing face masks during the pandemic did not compromise the overall reliability of the acoustic analysis in patients with glottic insufficiency, suggesting the current protocol of acoustic analysis can be carried out reliably while wearing a mask to ensure safety in the pandemic era.

Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands.

Salivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.

Correlation Between Salivary Microbiome of Parotid Glands and Clinical Features in Primary Sjögren's Syndrome and Non-Sjögren's Sicca Subjects.

Recent studies have demonstrated that the oral microbiome in patients with Sjögren's syndrome (SS) is significantly different from that in healthy individuals. However, the potential role of the oral microbiome in SS pathogenesis has not been determined. In this study, stimulated intraductal saliva samples were collected from the parotid glands (PGs) of 23 SS and nine non-SS subjects through PG lavage and subjected to 16S ribosomal RNA amplicon sequencing. The correlation between the oral microbiome and clinical features, such as biological markers, clinical manifestations, and functional and radiological characteristics was investigated. The salivary microbial composition was examined using bioinformatic analysis to identify potential diagnostic biomarkers for SS. Oral microbial composition was significantly different between the anti-SSA-positive and SSA-negative groups. The microbial diversity in SS subjects was lower than that in non-SS sicca subjects. Furthermore, SS subjects with sialectasis exhibited decreased microbial diversity and Firmicutes abundance. The abundance of Bacteroidetes was positively correlated with the salivary flow rate. Bioinformatics analysis revealed several potential microbial biomarkers for SS at the genus level, such as decreased Lactobacillus abundance or increased Streptococcus abundance. These results suggest that microbiota composition is correlated with the clinical features of SS, especially the ductal structures and salivary flow, and that the oral microbiome is a potential diagnostic biomarker for SS.

Thermoresponsive fiber-based microwells capable of formation and retrieval of salivary gland stem cell spheroids for the regeneration of irradiation-damaged salivary glands.

Three-dimensional spheroid culture enhances cell-to-cell interactions among stem cells and promotes the expression of stem cell properties; however, subsequent retrieval and delivery of these cells remain a challenge. We fabricated a thermoresponsive fiber-based microwell scaffold by combining electrospinning and hydrogel micropatterning. The resultant scaffold appeared to facilitate the formation of cellular spheroids of uniform size and enabled the expression of more stem cell-secreting growth factor genes (EGF, IGF-1, FGF1, FGF2, and HGF), pluripotent stem cell-related genes (SOX2 and NANOG), and adult epithelial stem cell-related genes (LGR4, LGR5, and LGR6) than salivary gland stem cells in a monolayer culture (SGSCmonolayer). The spheroids could be retrieved efficiently by decreasing temperature. SGSC-derived spheroid (SGSCspheroid) cells were then implanted into the submandibular glands of mice at 2 weeks after fractionated X-ray irradiation at a dose of 7.5 Gy/day. At 16 weeks post-irradiation, restoration of salivary function was detected only in SGSCspheroid-implanted mice. The production of submandibular acini specific mucin increased in SGSCspheroid-implanted mice, compared with PBS control. More MIST1+ mature acinar cells were preserved in the SGSCspheroid-implanted group than in the PBS control group. Intriguingly, SGSCspheroid-implanted mice exhibited greater amelioration of tissue damage and preservation of KRT7+ terminally differentiated luminal ductal cells than SGSCmonolayer-implanted mice. The SGSCspheroid-implanted mice also showed less DNA damage and apoptotic cell death than the SGSCmonolayer-implanted mice at 2 weeks post-implantation. Additionally, a significant increase in Ki67+AQP5+ proliferative acinar cells was noted only in SGSCspheroid-implanted mice. Our results suggest that a thermoresponsive fiber-based scaffold could be of use to facilitate the production of function-enhanced SGSCspheroid cells and their subsequent retrieval and delivery to damaged salivary glands to alleviate radiation-induced apoptotic cell death and promote salivary gland regeneration.

Deep learning model for tongue cancer diagnosis using endoscopic images.

In this study, we developed a deep learning model to identify patients with tongue cancer based on a validated dataset comprising oral endoscopic images. We retrospectively constructed a dataset of 12,400 verified endoscopic images from five university hospitals in South Korea, collected between 2010 and 2020 with the participation of otolaryngologists. To calculate the probability of malignancy using various convolutional neural network (CNN) architectures, several deep learning models were developed. Of the 12,400 total images, 5576 images related to the tongue were extracted. The CNN models showed a mean area under the receiver operating characteristic curve (AUROC) of 0.845 and a mean area under the precision-recall curve (AUPRC) of 0.892. The results indicate that the best model was DenseNet169 (AUROC 0.895 and AUPRC 0.918). The deep learning model, general physicians, and oncology specialists had sensitivities of 81.1%, 77.3%, and 91.7%; specificities of 86.8%, 75.0%, and 90.9%; and accuracies of 84.7%, 75.9%, and 91.2%, respectively. Meanwhile, fair agreement between the oncologist and the developed model was shown for cancer diagnosis (kappa value = 0.685). The deep learning model developed based on the verified endoscopic image dataset showed acceptable performance in tongue cancer diagnosis.

Machine learning and magnetic resonance imaging radiomics for predicting human papilloma virus status and prognostic factors in oropharyngeal squamous cell carcinoma.

BACKGROUND: We attempted to predict pathological factors and treatment outcomes using machine learning and radiomic features extracted from preoperative magnetic resonance imaging (MRI) of oropharyngeal squamous cell carcinoma (OPSCC) patients. METHODS: The medical records and imaging data of 155 patients who were diagnosed with OPSCC were analyzed retrospectively. RESULTS: The logistic regression model showed that the area under the receiver operating characteristic curve (AUC) of the model was 0.792 in predicting human papilloma virus (HPV) status. The LightGBM model showed an AUC of 0.8333 in predicting HPV status. The performance of the logistic model in predicting lymphovascular invasion, extracapsular nodal spread, and metastatic lymph nodes showed AUC values of 0.7871, 0.6713, and 0.6638, respectively. In predicting disease recurrence, the LightGBM model showed an AUC of 0.8571. In predicting patient death, the logistic model showed an AUC of 0.8175. CONCLUSIONS: A machine learning model using MRI radiomics showed satisfactory performance in predicting pathologic factors and treatment outcomes of OPSCC patients.

Care and Management of Voice Change in Thyroid Surgery: Korean Society of Laryngology, Phoniatrics and Logopedics Clinical Practice Guideline.

Voice change is a common complaint after thyroid surgery and has a significant impact on quality of life. The Korean Society of Laryngology, Phoniatrics and Logopedics assembled a task force to establish guideline recommendations on education, care, and management related to thyroid surgery. The guideline recommendations encompass preoperative voice education, management of anticipated voice change during surgery, and comprehensive voice care after thyroid surgery, and include in-depth information and up-to-date knowledge based on validated literature. The committee constructed 14 key questions (KQs) in three categories-preoperative (KQ 1-2), intraoperative (KQ 3-8), and postoperative (KQ 9-14) management-and developed 18 evidence-based recommendations. The Delphi survey reached an agreement on each recommendation. A detailed evidence profile is presented for each recommendation. The level of evidence for each recommendation was classified as high-quality, moderate-quality, or low-quality. The strength of each recommendation was designated as strong or weak considering the level of evidence supporting the recommendation. The guidelines are primarily targeted toward physicians who treat thyroid surgery patients and speech-language pathologists participating in patient care. These guidelines will also help primary care physicians, nurses, healthcare policymakers, and patients improve their understanding of voice changes and voice care after thyroid surgery.

Predictive Factors Affecting the Outcomes Of angiolytic Laser-Assisted Glottoplasty for Sulcus Vocalis.

OBJECTIVE: Glottoplasty using an angiolytic laser is an option for the surgical treatment of sulcus vocalis. In this study, we sought to evaluate the clinical outcomes of using a 532-nm diode laser in sulcus vocalis patients and to identify predictive factors of improved voice outcomes after angiolytic laser-assisted glottoplasty. METHODS: A total of 66 patients with sulcus vocalis who underwent laser-assisted glottoplasty with a 532-nm diode laser were included in this study. RESULTS: 3 months after surgery, GRBAS scores, patient-reported outcome measures, fundamental frequency (F0), jitter percent, and noise-to-harmonic ratio decreased significantly, while cepstral peak prominence (CPP) of vowel and sentence production increased. Patients with auditory-perceptual improvements showed greater improvement in the Voice Handicap Index (VHI) scores, F0, and CPP of vowel and sentence production compared to those with no improvement. While young male patients with preoperatively high F0 were predicted to have favorable outcomes, the type of sulcus vocalis was not predictive of treatment outcomes. Patients treated with lower laser power showed better improvement in the VHI scores postoperatively than those who received higher laser power per vocal fold. Combined injection laryngoplasty with laser glottoplasty was effective in lowering the F0, especially in male patients with high F0. CONCLUSION: A 532-nm diode laser is useful for treating sulcus vocalis. Young male patients and individuals with preoperatively high F0 showed better voice outcomes after laser glottoplasty. Laser power and combined injection laryngoplasty are considered to affect improvement in the VHI and lowering F0 after laser glottoplasty in sulcus vocalis.

Treatment outcomes of neoadjuvant chemotherapy and transoral robotic surgery in locoregionally advanced laryngopharyngeal carcinoma.

BACKGROUND: We aimed to identify the optimal indications of neoadjuvant chemotherapy (NACT) and transoral robotic surgery (TORS) in patients with locoregionally advanced (T3-4 or N2-3) head and neck cancer (HNC). METHODS: A total of 50 patients were included in the study. RESULTS: T1 was identified in seven cases, T2 in 19, T3 in 22, and T4 in 2. N0 was identified in nine cases, N1 in 18, N2 in 22, and N3 in 1. There were 25 patients (50%) with complete remission of the primary lesion and 25 patients (50%) with partial remission. On pathologic examination of surgical specimens after neoadjuvant chemotherapy and TORS, 2 patients (4%) had a positive surgical margin, and 48 patients (96%) had a negative margin. Pathologic metastatic lymph nodes (LNs) were not observed in 39 cases (78%), and one metastatic LN was observed in 11 cases (22%). The 3-year recurrence-free survival (RFS) of all patients was 85.4%. On multivariate analysis, lymphovascular invasion showed a significant correlation with RFS. CONCLUSIONS: In patients with locoregionally advanced HNC, NACT and TORS achieved favorable oncologic and functional outcomes.

3D Organoid Culture From Adult Salivary Gland Tissues as an ex vivo Modeling of Salivary Gland Morphogenesis.

Lumen formation of salivary glands has been investigated using in vivo or ex vivo rudiment culture models. In this study, we used a three-dimensional (3D) salivary gland organoid culture system and demonstrated that lumen formation could be recapitulated in mouse SMG organoids. In our organoid culture system, lumen formation was induced by vasoactive intestinal peptide and accelerated by treatment with RA. Furthermore, lumen formation was observed in branching duct-like structure when cultured in combination of fibroblast growth factors (FGF) in the presence of retinoic acid (RA). We suggest RA signaling-mediated regulation of VIPR1 and KRT7 as the underlying mechanism for lumen formation, rather than apoptosis in the organoid culture system. Collectively, our results support a fundamental role for RA in lumen formation and demonstrate the feasibility of 3D organoid culture as a tool for studying salivary gland morphogenesis.

Single clonal glandular stem cells derived from human parotid glands do not attain malignant phenotype during long-term in vitro culture.

Mesenchymal stem cells (MSCs) are being intensively investigated as future therapeutics for various human diseases. One of the most important challenges to the clinical application of MSCs is the possibility of malignant transformation during long-term in vitro culturing. However, there have been no reports on the tumorigenicity of salivary gland-derived MSCs following long-term in vitro culturing. Here, we isolated a single clonal glandular stem cells from human parotid gland stem cells (hpGSCs) using a modified sub-fractionation culturing method. The possibility of malignant transformation of these cells following long-term culturing was evaluated under in vitro and in vivo culture conditions. Single clonal glandular stem cells from the human parotid gland have unique multipotent MSCs traits. hpGSCs at passage 18 stained strongly for ß-galactosidase expression and the long-term culture of hpGSCs led to a reduction in telomerase activity. hpGSCs could not survive in a soft agar environment and did not cause tumor formation in a xenograft mouse model. In addition, the expression of salivary cancer-related oncogenes was not elevated in hpGSCs following the long-term culture. In conclusion, we demonstrated that there is no possibility of acquiring a malignant transformation during long-term in vitro cell expansion of hpGSCs.

Effect of human acellular dermal matrix (Megaderm™) on infra-auricular depressed deformities, Frey's syndrome, and first bite syndrome following parotidectomy: a multi-center prospective study.

BACKGROUND: Parotidectomy is the primary treatment for parotid gland tumors. However, complications may include a prominent facial scar or infra-auricular depressed deformity, Frey's syndrome, first bite syndrome, or other facial pain, numbness, and paralysis. Acellular dermal matrix (ADM) has been widely used to prevent these complications in parotid surgery, but there have been no prospective, multi-center trials documenting its efficacy. This study evaluates the effectiveness of ADM implantation in preventing infra-auricular depressed deformity, Frey's syndrome and first bite syndrome after parotidectomy. METHODS: We analyzed 51 cases of standard parotidectomy and 58 cases of parotidectomy with implantation of Megaderm™ ADM through prospective multicenter trial. Acute complications including infection, seroma, hematoma, skin necrosis, and acute parotid area pain were evaluated 1 week postoperatively. Clinician grading of Frey's syndrome and blinded clinician evaluation of infra-auricular depressed deformities were conducted at 3, 6, and 12 months. Patients evaluated subjective satisfaction with neck appearance, Frey's syndrome quality, and acute parotid area pain at 3, 6, and 12 months. RESULTS: There was a higher incidence of seroma in the Megaderm™ group than in the control group at week 1. The incidence and total clinician-evaluated Frey's syndrome scores were significantly lower in the Megaderm™ group than in the control group at 3, 6, and 12 months. Both the objective and subjective evaluations of the facial contour showed a better outcome in the Megaderm™ group compared to the control group at 3, 6, and 12 months. There were no significant differences between the groups in the patient-reported Frey's syndrome quality scores at 3, 6, and 12 months, but the Megaderm™ group reported significantly less acute pain than the control group. CONCLUSIONS: ADM implantation can effectively reduce the occurrence of Frey's syndrome, infra-auricular depressed deformity, and first bite syndrome after parotidectomy. ADM may be especially advantageous in complex parotidectomy cases when significant complications are expected.