Generation of tonsil organoids as an ex vivo model for SARS-CoV-2 infection

Palatine tonsil (hereinafter referred to as "tonsil") plays role in the immune systems first line of defense against foreign pathogens. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic since the infection was first reported in China in December 2019. The aim of this study was to establish tonsil epithelial cell-derived organoids and to examine their feasibility as an ex vivo model for SARS-CoV-2 infection. Using an optimized protocol, we achieved 3D tonsil organoid culture from human tonsil tissue that reflects the distinctive characteristics of the tonsil epithelium, such as its cellular composition, histologic properties, and molecular biological features. Notably, we verified that SARS-CoV-2 can infect tonsil organoids with a robust replication efficiency. Furthermore, treatment with remdesivir, an antiviral agent, effectively protected them from viral infection. Therefore, tonsil organoids could be available for investigation of SARS-CoV-2 infection-mediated pathology and for preclinical screening of novel antiviral drug candidates. One-sentence SummaryThis study established tonsil epithelial cell-derived organoids and demonstrated their feasibility as an ex vivo model for SARS-CoV-2 infection.

BRAF(V600E) Mutation is a Strong Preoperative Indicator for Predicting Malignancy in Thyroid Nodule Patients with Atypia of Undetermined Significance Identified by Fine Needle Aspiration / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). SUBJECTS AND METHOD: This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. RESULTS: The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: BRAFV600E gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p < 0.05). Multivariate analysis revealed that only BRAFV600E mutation was a statistically significant risk factor for malignancy (p < 0.05). When BRAFV600E mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. CONCLUSION: Patients with AUS thyroid nodules should undergo BRAFV600E gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.

Photodynamic Therapy for Recurrent Head and Neck Malignancy / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: As a preliminary study, authors tried to verify clinical and side effects of Radachlorin in a photodynamic therapy for recurrent head and neck malignancy. Radachlorin shows an absorption peak at 662 nm, which indicates that it penetrates up to 10 mm. SUBJECTS AND METHOD: We treated 12 sites for 9 treatments in 6 recurrent head and neck malignacies, 4 cases of squamous cell cancers and each of adenoid cystic cancer, and undifferentiated nasopharyngeal cancer. A dose of 1 mg/kg or 2-5 mL of Radachlorin was i.v. injected into the mass according to the mass size. We used a diode laser, MILON-662 (Milon Laser Company, Russia) and Medlight cylindrical 10/20 radial diffuser and frontal diffuser as light delivery devices. About 3 hrs after intravenous injection, or 30 min after intralesional injection, a light dose of 200-300 J/cm2 or cm of laser was irradiated onto the tumor or intralesionally with the light dose of 200-300 J/cm2, or cm. RESULTS: There was partial tumor regression in three of the five primary tumors. In one case of metastatic node treated by intralesional injection and irradiation, tumor showed complete necrosis. But there was no effect in 2 cases of subcutaneous metastases. There were no side effects such as fever, chill and photosensitivity in any of the cases. CONCLUSION: The clinical effect of photodynamic therapy (PDT) using Radachlorin with 662 nm of laser light is not clear yet, but it seems to be a safe treatment for head and neck malignancy. We need to investigate the effect of this PDT system in untreated head and neck malignancies.

Larynx-Preserving Partial Pharyngectomy via Lateral Pharyngotomy for the Treatment of Small (T1~2) Hypopharyngeal Squamous Cell Carcinoma

OBJECTIVES: To evaluate the oncologic and functional results of larynx-preserving partial pharyngectomy (LPP) via lateral pharyngotomy approach as a primary treatment for small (T1 or T2) hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: We performed a retrospective review of 23 patients who underwent LPP through lateral pharyngotomy approach for small HPSCC at the our department between January 1991 and June 2007. Fourteen (61%) patients had adjuvant postoperative radiotherapy. RESULTS: The 2-years and 5-years disease specific survival rate was 77% and 61%, respectively. Nine patients (39%) had tumor recurrence. The most common pattern of recurrence was isolated distant failure (n=4, 44%) followed by local (n=2, 22%) and loco-regional (n=3, 34%) recurrence. The ultimate cure rate of the primary tumor was 87% (20 of 23). Twenty-two of the 23 patients (95%) could be decannulated, tolerate an oral diet, and had acceptable postoperative phonatory function. CONCLUSION: LPP via lateral pharyngotomy approach appears to be a feasible procedure for selected small HPSCC patients in terms of both oncologic and functional outcomes.

Larynx-Preserving Partial Pharyngectomy via Lateral Pharyngotomy for the Treatment of Small (T1~2) Hypopharyngeal Squamous Cell Carcinoma

OBJECTIVES: To evaluate the oncologic and functional results of larynx-preserving partial pharyngectomy (LPP) via lateral pharyngotomy approach as a primary treatment for small (T1 or T2) hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: We performed a retrospective review of 23 patients who underwent LPP through lateral pharyngotomy approach for small HPSCC at the our department between January 1991 and June 2007. Fourteen (61%) patients had adjuvant postoperative radiotherapy. RESULTS: The 2-years and 5-years disease specific survival rate was 77% and 61%, respectively. Nine patients (39%) had tumor recurrence. The most common pattern of recurrence was isolated distant failure (n=4, 44%) followed by local (n=2, 22%) and loco-regional (n=3, 34%) recurrence. The ultimate cure rate of the primary tumor was 87% (20 of 23). Twenty-two of the 23 patients (95%) could be decannulated, tolerate an oral diet, and had acceptable postoperative phonatory function. CONCLUSION: LPP via lateral pharyngotomy approach appears to be a feasible procedure for selected small HPSCC patients in terms of both oncologic and functional outcomes.

Growth Inhibition and Apoptosis with H31 Metabolites from Marine Bacillus SW31 in Head and Neck Cancer Cells

OBJECTIVES: To determine whether a novel marine micro-organism with anticancer properties, H31, the metabolic product of Bacillus SW31, has anti-tumor effects on head and neck cancer, and potential for apoptotic-enhancing anti-cancer treatment of affected patients. METHODS: The cell viability and apoptosis assays were performed. Changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of H31 were explored in mouse xenograft model and drug toxicity of H31 was examined in zebrafish model. RESULTS: We identified the anticancer activity of H31, a novel metabolic product of Bacillus SW31. Bacillus SW31, a new marine micro-organism, has 70% homology with Bacillus firmus and contains potent cytotoxic bioactivity in head and neck cancer cells using MTT assay. Combined with c-JUN, p53, cytochrome C, and caspase-3, H31 induced apoptosis of KB cells, a head and neck cancer cell line. In a separate in vivo model, tumor growth in C3H/HeJ syngeneic mice was suppressed by H31. In addition, in a zebrafish model used for toxicity testing, a considerable dose of H31 did not result in embryo or neurotoxicity. CONCLUSION: Growth inhibition and apoptosis were achieved both in vitro and in vivo in head and neck cancer cells after exposure to H31, a metabolite from the marine Bacillus species, without any significant toxicity effects even at considerable H31 dose concentrations.

Surgical Treatment of Carotid Body Paragangliomas: Outcomes and Complications According to the Shamblin Classification

OBJECTIVES: The objective of this study was to review our experience in the surgical management of carotid body paragangliomas and evaluate the outcomes and complications according to the Shamblin classification. METHODS: Thirteen patients who had been diagnosed and surgically treated for carotid body tumors (CBTs) were enrolled in this study. We reviewed patient demographics, radiographic findings, and surgical outcomes collected from medical records. RESULTS: Fifteen CBTs were found in 13 patients and 13 tumors were resected. Selective preoperative tumor embolization was performed on six patients. The median blood loss, operation time, and hospital stay for these patients were not significantly reduced compared to those without embolization. The median tumor size was 2.3 cm in Shamblin I and II and 4 cm in Shamblin III. The median intraoperative blood loss was 280 mL and 700 mL, respectively (P<0.05). Internal carotid artery ligation with reconstruction was accomplished on three patients (23%), and they all belonged to Shamblin III (38%). One Shamblin III patient (8%) developed transient cerebral ischemia, and postoperative stroke with death occurred in another Shamblin III patient. Postoperative permanent cranial nerve deficit occurred in three patients (23%) who were all in Shamblin III (P=0.03). There were no recurrences or delayed complications at the median follow up of 29 months. CONCLUSION: Shamblin III had a high risk of postoperative neurovascular complications. Therefore, early detection and prompt surgical resection of CBTs will decrease surgical morbidity.

Occult Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The most significant prognosticator of survival for patients with squamous cell carcinoma of the oral tongue has been the association of neck nodal metastasis. However, no consensus exists as to whether an elective neck dissection should be performed in patients with early oral tongue squmous cell carcinoma with a clinically negative neck. SUBJECTS AND METHOD: A retrospective analysis was performed on 54 early oral tongue squamous cell carcinoma patients (T1=26 and T2=28) with clinically negative necks who were treated between 1992 to 2003. All patients had an ipsilateral neck dissection and 29 patients had a contralateral neck dissection. Surgical treatment was followed by postoperative radiotherapy in 20 patients. The follow-up period ranged from 3 to 110 months (mean, 56 months). Data were analyzed using the Kaplan-Meier method, log-rank test, and the chi-square test. RESULTS: Clinically occult, but pathologically positive ipsilateral lymph nodes were found in 26% (14/54) and contralateral lymph nodes in 3% (1/29). Based on the clinical staging of the tumor, 19% (5 of 26) of the cases showed lymph node metastases in T1 tumors, and 36% (10 of 28) in T2. All regional recurrences developed in the ipsilateral necks, there was no cases of contralateral neck recurrence. Patients with no evidence of occult nodal cancer have significantly improved disease-specific free survival rates over patients with any pathologically positive nodes (5 year disease specific survival rate, 90% vs 38%, p< or = 0.05). CONCLUSION: This study showed that ipsilateral elective neck dissection should be performed for early oral tongue cancers. On the other hand, our series suggests that it may not be harmful to observe the contralateral N0 neck in the treatment of early oral tongue cancer.

Evolution of Neck Dissection: Radical to Superselective / 대한이비인후과학회지

No abstract available.

Hereditary Angioneurotic Edema of the Larynx: A Case Report and Literature Review / 대한이비인후과학회지

Hereditary angioneurotic edema (HAE) is an autosomal dominant disease that results from the deficiency of C1 esterase inhibitor (C1-INH) function. Urgent proper intervention of the upper airway is warranted to save the life of patients with the disease, which often causes acute airway obstruction. We present, with a review of literature, a case of 37-year old woman with HAE of larynx.