Efficacy of natural killer cell therapy combined with chemoradiotherapy in murine models of head and neck squamous cell carcinoma.

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.

Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer.

BACKGROUND: The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC). METHODS: NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors. RESULTS: The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function-associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC. CONCLUSIONS: Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.

Synergistic Antibacterial Activity of an Active Compound Derived from Sedum takesimense against Methicillin-Resistant Staphylococcus aureus and Its Clinical Isolates.

There are a growing number of reports of hospital-acquired infections caused by pathogenic bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). Many plant products are now being used as a natural means of exploring antimicrobial agents against different types of human pathogenic bacteria. In this research, we sought to isolate and identify an active molecule from Sedum takesimense that has possible antibacterial activity against various clinical isolates of MRSA. NMR analysis revealed that the structure of the HPLC-purified compound was 1,2,4,6-tetra-O-galloyl-glucose. The minimum inhibitory concentration (MIC) of different extract fractions against numerous pathogenic bacteria was determined, and the actively purified compound has potent antibacterial activity against multidrug-resistant pathogenic bacteria, i.e., MRSA and its clinical isolates. In addition, the combination of the active compound and ß-lactam antibiotics (e.g., oxacillin) demonstrated synergistic action against MRSA, with a fractional inhibitory concentration (FIC) index of 0.281. The current research revealed an alternative approach to combating pathogenesis caused by multi-drug resistant bacteria using plant materials. Furthermore, using a combination approach in which the active plant-derived compound is combined with antibiotics has proved to be a successful way of destroying pathogens synergistically.

Inhibitor of apoptosis protein Livin promotes tumor progression and chemoradioresistance in human anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is characterized by a rapid and aggressive course of progression. Despite significant advances in surgery, radiotherapy and chemotherapy, the disease­specific mortality due to ATC is approximately 100%. New strategies, such as molecular targeted therapies, are imperative for improving survival. Livin, a member of the human inhibitor of apoptosis protein family, has been found to be associated with tumor progression and poor prognosis in various human cancers. The aim of the present study was to evaluate the role of Livin in cancer progression and chemoradioresistance of ATC and to investigate its potential as a therapeutic target. Endogenous Livin expression in the human BHT101 ATC cell line was silenced by Livin­specific small interfering RNA. To assess the impact of Livin on cancer cell behavior in human ATC cells, various methods such as cell invasion, cell viability and cell apoptosis assays were applied. To assess the expression of Livin and the change of apoptosis­related proteins associated with Livin expression, reverse transcription­quantitative PCR and western blotting were performed. Immunohistochemistry was performed to detect Livin protein expression in human ATC tissues. The association between Livin expression and apoptotic/proliferation index was analyzed in human ATC cells. Livin­knockdown suppressed tumor cell invasion; and conversely, it enhanced cell apoptosis, with elevated expression levels of cleaved caspase­3 and ­7 and cleaved PARP. Livin­knockdown enhanced radiation­induced apoptosis, while reducing cell viability following radiotherapy, as well as lenvatinib treatment. In addition, human ATC tissues with high Livin­expression exhibited a high Ki­67 labeling index and low apoptotic index. In summary, these findings indicate the contribution of Livin to tumor progression and chemoradioresistance in ATC.

Comparison of long-term treatment outcomes of T2N0M0 laryngeal squamous cell carcinoma using different treatment methods.

Early [stage I and II (T2N0M0)] laryngeal cancer types are currently recommended to be treated with a single modality, consisting of definitive radiation therapy or larynx-preserving surgery. Although the treatment outcomes of stage I are good, the frequency of successful outcomes decreases with T2N0M0. Therefore, the present study investigated the treatment outcomes of different treatment methods in T2N0M0 laryngeal cancer. In total, 83 patients with previously untreated T2N0M0 laryngeal squamous cell carcinoma were enrolled. Patients were grouped by treatment method: Radiation therapy (RT; 27 patients); chemoradiotherapy (CRT; 46 patients) with cisplatin base; and surgery-based therapy (SBT; ten patients). The recurrence rates of the RT, CRT and SBT groups were 44.4, 19.6 and 50%, respectively. Moreover, the local control rates of the RT, CRT and SBT groups were 55.6, 87.0 and 80%, respectively. The CRT group had a significantly lower recurrence rate and higher local control rate compared with the RT group (P<0.05). In the survival analysis, overall and disease-specific survival rate did not differ significantly among the treatment groups. However, 3- and 5-year disease-free survival rates (DFS) of the RT group were both 55%, those of the SBT group were both 50% and those of the CRT group were both 80%. Furthermore, the DFS was significantly higher in CRT group compared with the other groups (P=0.02). Using multivariate analysis with Cox regression, it was found that the treatment method was the most important factor for DFS and had a significant impact in the CRT group. In addition, in patients with glottic cancer with anterior commissure and subglottic invasion, the CRT group had significantly improved DFS compared with the RT group, whereas there was no significant difference between the two groups in patients without subglottic invasion. According to National Cancer Institution Common Toxicity Criteria (version 5.0), more patients had toxicity in the CRT group compared with the RT group. However, in the RT and CRT groups, no patients demonstrated mortality due to toxicity, and treatment-related toxicities were manageable. Collectively, although definitive conclusions could not be established, due to the limitations of this retrospective study, the results suggest that CRT had a positive impact on the local control and DFS rates with manageable toxicity in patients with T2N0M0 laryngeal cancer.

Gelatin Sponge Induced Maxillary Sinusitis After Transsphenoidal Pituitary Surgery.

Transsphenoidal pituitary surgery is a safe, well-established treatment method, but it is associated with several postoperative nasal complications. However, gelatin sponge induced maxillary sinusitis after transsphenoidal pituitary surgery has not been reported. In this study, we present an unusual case of gelatin sponge induced maxillary sinusitis after transsphenoidal pituitary surgery. Therefore, it should be recognized that gelatin sponge induced maxillary sinusitis may occur as a complication after transsphenoidal pituitary surgery.

Metastatic small cell neuroendocrine carcinoma of the submandibular gland from the lung: A case report.

RATIONALE: Small cell neuroendocrine carcinoma of the salivary gland is an extremely rare condition. To the best of our knowledge, metastasis of small cell neuroendocrine lung cancer to the submandibular gland has not been reported in the literature. PATIENT CONCERN: An 87-year-old female complained of a left neck mass that enlarged from one month ago. DIAGNOSIS: The final diagnosis was diagnosed as a metastatic small cell neuroendocrine carcinoma of the submandibular gland from lung by an immunohistochemistry. INTERVENTIONS: Left submandibular resection was performed under general anesthesia. OUTCOMES: We recommended further evaluation and treatment, but the patient and patient family support team rejected further treatment of her condition. It was confirmed that 3 months after this conclusive diagnosis, the patient died as a result of this condition and disease. LESSONS: Small cell neuroendocrine carcinoma of the salivary gland is an extremely rare condition. We report a case of metastatic small cell neuroendocrine carcinoma of the submandibular gland from the lung.

Computed tomography-based differential diagnosis of fungus balls in the maxillary sinus.

OBJECTIVE: We investigated the computed tomography (CT) features of the maxillary sinus fungus ball and compared them with those of other maxillary sinus diseases. STUDY DESIGN: The CT findings of 98 fungus ball lesions in 96 patients, with 35 cases of sinusitis confined to the maxillary sinus and 35 other sinus lesions confined to the maxillary sinus, were analyzed. RESULTS: The most common CT feature of maxillary sinus fungus balls was calcification within the maxillary sinus (n = 77 [78.6%]), followed by complete opacification (n = 57 [58.2%]), partial opacification with an irregular surface (n = 36 [36.7%]), bony sclerosis (n = 16 [16.3%]), and partial opacification (n = 5 [5.1%]). A high probability of maxillary sinus fungus ball was found when the CT scans showed calcification within the maxillary sinus and partial opacification with an irregular surface (P < .05). CONCLUSIONS: Maxillary sinus fungus balls show a higher frequency of calcification and partial opacification with an irregular surface on CT scans compared with maxillary sinusitis and other maxillary sinus lesions. Therefore, calcification and partial opacification with an irregular surface on preoperative CT scans suggest the maxillary sinus fungus ball as the first diagnostic consideration.

Clinical difference between benign and malignant tumors of the hard palate.

OBJECTIVE: To determine the clinical characteristics and treatment results of benign and malignant tumors of the hard palate in our hospital. PATIENTS AND METHODS: A total of 25 patients who underwent surgical treatment for hard palate tumors between 2008 and 2018 were included in this study. Their demographic characteristics, smoking status, alcohol consumption, symptoms, duration of symptoms, size and localization of hard palate tumor, status of mucosal surface, radiologic examinations, surgery, reconstruction method, histopathologic results, treatment outcomes, oral intake start time, adjuvant treatment, postoperative complications, and recurrence were reviewed. RESULTS: Of the 25 patients with hard palate tumors, 15 (60.0%) had benign tumors and 10 (40.0%) had malignant tumors. Both benign and malignant tumors of the hard palate occurred more frequently in females than in the males. The most common symptom of hard palate tumor was palate mass. The most common benign tumor was pleomorphic adenoma (n = 13). The most common malignant tumors were squamous cell carcinoma and carcinoma ex pleomorphic adenoma (n = 3 for each). All patients were operated via transoral approach without external incision. We did not experience any recurrence in this study. The oral intake start time was late in malignant hard palate tumors (p < 0.05). CONCLUSION: The comparison of clinical features of benign and malignant hard palate tumors showed a statistical significance only for oral intake start time. Transoral surgical removal with clear margin is a safe and effective procedure for benign and malignant hard palate tumors.

Evaluation of Prognostic Factors for the Parotid Cancer Treated With Surgery and Postoperative Radiotherapy.

OBJECTIVES: To investigate the prognostic factors and treatment outcomes of primary parotid carcinoma treated with surgery and postoperative radiotherapy (PORT). METHODS: We reviewed retrospectively 57 patients with primary parotid carcinoma who were treated with surgery and PORT between 2005 and 2014. Superficial parotidectomy was performed in 19 patients, total parotidectomy in 10 patients, and total parotidectomy with lymph node dissection in 28 patients PORT on the tumor bed was performed in 41 patients, while PORT on tumor bed and ipsilateral cervical lymph nodes was performed in 16 patients. RESULTS: With a median follow-up of 66 months, the 5-year overall survival, disease-free survival, locoregional control, and distant control rates were 77.0%, 60.2%, 77.6%, and 72.8%, respectively. The 5-year overall survival by stage was 100%, 100%, 80.0%, and 46.4% in stage I, II, III, and IV, respectively. Recurrences at primary lesions were found in seven patients, while at cervical nodes in six patients. Distant recurrences were developed in 12 patients. No patient with the low and intermediate histologic grade developed distant failure. As prognostic factors, the histologic grade for overall survival (P=0.005), pathological T-stage (P=0.009) and differentiation grade (P=0.009) for disease-free survival, pathological T-stage for locoregional control (P=0.007), and lympho-vascular invasion (P=0.023) for distant recurrence were significant on multivariate analysis. CONCLUSION: This study revealed that differentiation grade, histologic grade, pathological T-stage, and lympho-vascular invasion were significant independent prognostic factors on clinical outcomes.

Nasal Septum Actinomycosis Mimicking Mucocele.

Actinomycosis commonly occurs in the cervicofacial region, but rarely in the paranasal sinus. The authors report an unusual case of nasal septum actinomycosis that was mistaken for a mucocele. The patient was treated accordingly using antibiotic therapy after endoscopic sinus surgery was performed. It is noteworthy that actinomycosis of the nasal septum could appear as a mucocele without central calcification or bony destruction in imaging studies.

Cavernous Lymphangioma in the Maxillary Sinus.

Lymphangioma in the maxillary sinus is rare. Herein, the authors report an unusual case of cavernous lymphangioma, in the maxillary sinus, with imaging examinations. Clinicians should be aware of the possibility of lymphangioma in the maxillary sinus, and be capable of distinguishing it, from other benign cystic lesions.

Surgical treatment strategy in Warthin tumor of the parotid gland / Estratégia de tratamento cirúrgico no tumor de Warthin de glândula parótida

Abstract Introduction: Warthin tumors are the second most common benign tumors of the parotid gland. We examined the clinical features of Warthin tumors in our hospital, and analyzed the consistency within the literatures. Objective: The aim of this study is to analyze the clinical features of Warthin tumors in our 10-year experience of 118 Warthin tumors undergoing surgery at a single institute. Methods: From December 2006 to December 2016, 110 patients who underwent surgical treatment for Warthin tumors were identified based on their medical records. Results: A total of 118 parotid gland operations were performed in 110 patients. Almost 90% of Warthin tumors were found in males, and average patient age was 66.1 ± 6.1 years. The prevalence of smoking history was 89.1% (98/110). Eight patients (7.3%) had bilateral Warthin tumors. Seventy-seven lesions (65.3%) were located in the parotid tail portion, followed by 34 lesions in the superficial lobe (28.8%) and 7 lesions in the deep lobe (5.9%). Conclusion: We determined the appropriate extent of surgery depending on the fine needle aspiration cytology and tumor location by computed tomography scans. Partial facial dysfunction after the operation was detected in 12 cases, and facial nerve function recovered within 3 months. Only one patient experienced a recurrence, and was disease free after the re-operation. We suggest that our treatment algorithm, depending on the location of tumors and the result of fine needle aspiration cytology, can be useful to determine the appropriate extent of surgery for Warthin tumors.

Resumo Introdução: Os tumores de Warthin são os segundos tumores benignos mais comuns da glândula parótida. Avaliamos as características clínicas dos tumores de Warthin em nosso hospital e analisamos a consistência com a literatura. Objetivo: Analisar as características clínicas dos tumores de Warthin em nossa experiência de 10 anos de 118 tumores de Warthin submetidos a tratamento cirúrgico em um único instituto. Método: De dezembro de 2006 a dezembro de 2016, 110 pacientes que receberam tratamento cirúrgico para tumores de Warthin foram identificados com base em seus prontuários médicos. Resultados: Foram feitas 118 cirurgias na glândula parótida em 110 pacientes. Quase 90% dos tumores de Warthin foram encontrados em homens e a média da idade dos pacientes foi de 66,1 ± 6,1 anos. A prevalência de tabagismo foi de 89,1% (98/110). Oito pacientes (7,3%) tinham tumores de Warthin bilaterais na glândula parótida. Das lesões, 77 (65,3%) localizavam-se na porção da cauda da parótida, seguidas por 34 no lobo superficial (28,8%) e 7 no lobo profundo (5,9%). Conclusão: Determinamos a extensão apropriada da cirurgia de acordo com a punção aspirativa com agulha fina e localização do tumor por tomografia computadorizada. Disfunção facial parcial após a cirurgia foi detectada em 12 casos e a função do nervo facial foi recuperada em 3 meses. Apenas um paciente apresentou recidiva e ficou livre da doença após reoperação. Sugerimos que nosso algoritmo de tratamento, a depender da localização dos tumores e do resultado da PAAF, pode ser útil para determinar a extensão apropriada da cirurgia para os tumores de Warthin.

Receptor tyrosine kinase, RON, promotes tumor progression by regulating EMT and the MAPK signaling pathway in human oral squamous cell carcinoma.

The receptor tyrosine kinase, recepteur d'origine nantais (RON), is known to be associated with the progression, metastasis, and prognosis of various types of cancers. Nevertheless, the role of RON in human oral squamous cell carcinoma (OSCC) is unclear. This study evaluated whether RON affects oncogenic behavior, oncogenic signaling pathways, and clinical outcomes, including survival, in human OSCC. Reverse transcription­PCR, quantitative PCR, western blotting and immunohistochemical staining were used to determine mRNA and protein expression levels of RON. Cell invasion, migration and apoptosis assays were used to assess the functional effects of small interfering RNA­mediated knockdown of RON or snail family transcriptional repressor 2 (SLUG). RON knockdown suppressed tumor cell invasion and migration and enhanced apoptosis in human OSCC cells. RON knockdown also decreased the phosphorylation of MAPK signaling proteins, such as ERK1/2, JNK and p38. In addition, RON knockdown suppressed the expression of the epithelial mesenchymal transition (EMT)­related transcription factor, SLUG. SLUG knockdown blocked the enhancement of cell invasion and migration induced by macrophage­stimulation protein (MSP)­mediated RON activation in OSCC cells. The cell morphology was changed to spindle­like shape under MSP­mediated RON activation in OSCC cells. RON was overexpressed in both fresh and paraffin­embedded human OSCC tissues. Taken together, these results indicate that RON contributed to tumor progression by regulating the EMT­related factor, SLUG, and the MAPK pathway in OSCC. This study may provide a theoretical basis for the application of RON­targeting agents, currently being studied in various cancer fields, for the treatment of OSCC.

Coexistence of Antrochoanal Polyp and Fibrous Dysplasia in the Maxilla.

The authors report an unusual case of coexistence of antrochoanal polyp (ACP) and fibrous dysplasia (FD) in the maxilla. To the best of our knowledge, this condition has never been reported in the literature. The complete removal of the ACP through endoscopic sinus surgery was attained and FD was ultimately diagnosed by histopathological examination. It is hypothesized that chronic inflammation or irritation due to FD has an effect on the occurrence of ACP.

Anthracofibrotic Lymph Node of Neck Mimicking Metastatic Malignant Melanoma in a Patient With Gastric Cancer.

Extrathoracic anthracofibrosis in head and neck region is of extremely rare occurrence and can be confused with malignancy. In this article, we report an unusual case of an anthracofibrotic lymph node of neck that was mistaken for metastatic malignant melanoma in a gastric cancer patient. Because the incidence of an anthracofibrotic lymph node of the neck is very low, it is important to distinguish it from other diseases, including malignancy or metastasis, especially in patients with a cancer history. Thus, pathological diagnosis of anthracofibrosis is necessary to make an accurate diagnosis and find appropriate treatment.

External Jugular Vein Aneurysm in a Child With Hemophilia A.

An external jugular vein (EJV) aneurysm is an extremely rare disease. Ultrasonography with color doppler methods is considered the criterion standard for diagnosis of a venous aneurysm. The treatment of choice for an EJV aneurysm is surgical excision. Herein, we report an unusual case of an EJV aneurysm in a child with hemophilia A. Because the incidence of an EJV aneurysm is low, it is important to distinguish it from other neck lesions, including congenital disease. In addition, it should be noted that in hemophilia patients, an EJV aneurysm may occur in a spontaneous or small trauma.

Guidelines for the Surgical Management of Oral Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

Surgical treatment strategy in Warthin tumor of the parotid gland.

INTRODUCTION: Warthin tumors are the second most common benign tumors of the parotid gland. We examined the clinical features of Warthin tumors in our hospital, and analyzed the consistency within the literatures. OBJECTIVE: The aim of this study is to analyze the clinical features of Warthin tumors in our 10-year experience of 118 Warthin tumors undergoing surgery at a single institute. METHODS: From December 2006 to December 2016, 110 patients who underwent surgical treatment for Warthin tumors were identified based on their medical records. RESULTS: A total of 118 parotid gland operations were performed in 110 patients. Almost 90% of Warthin tumors were found in males, and average patient age was 66.1±6.1 years. The prevalence of smoking history was 89.1% (98/110). Eight patients (7.3%) had bilateral Warthin tumors. Seventy-seven lesions (65.3%) were located in the parotid tail portion, followed by 34 lesions in the superficial lobe (28.8%) and 7 lesions in the deep lobe (5.9%). CONCLUSION: We determined the appropriate extent of surgery depending on the fine needle aspiration cytology and tumor location by computed tomography scans. Partial facial dysfunction after the operation was detected in 12 cases, and facial nerve function recovered within 3 months. Only one patient experienced a recurrence, and was disease free after the re-operation. We suggest that our treatment algorithm, depending on the location of tumors and the result of fine needle aspiration cytology, can be useful to determine the appropriate extent of surgery for Warthin tumors.

Intensity-modulated radiotherapy for stage I glottic cancer: a short-term outcomes compared with three-dimensional conformal radiotherapy.

PURPOSE: To investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). MATERIALS AND METHODS: We retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group. RESULTS: The 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080). CONCLUSION: IMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients.