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.

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.

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.

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.

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.

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.

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.

Clinical Study of Second Branchial Cleft Anomalies.

OBJECTIVE: The objective of this study was to review the clinical characteristics and surgical treatment outcomes of second branchial cleft anomalies, and to evaluate the usefulness and accuracy of preoperative fine-needle aspiration cytology (FNAC) in the diagnosis of branchial cleft cysts. METHODS: A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2010 to December 2016. RESULTS: Among 25 patients with second branchial cleft anomalies, in 23 patients (92.0%), these anomalies presented as cysts, and in the remaining 2 patients (8.0%), these anomalies presented as fistulas. Fine-needle aspiration cytology had a diagnostic sensitivity of 100%, a positive-predictive value of 100%, and accuracy of 100% for diagnosing second branchial cleft cyst. All patients of second branchial cleft anomalies were treated surgically under general anesthesia. No recurrence of second branchial cleft anomalies was observed. CONCLUSION: Branchial cleft cysts were the most common type of second branchial cleft anomalies. Preoperative FNAC is a useful and accurate method for preoperative evaluation of branchial cleft cysts. Surgical excision of second branchial cleft anomalies is the treatment of choice without any complications and with no recurrence.

Surgical Treatment Outcomes of Vocal Process Granuloma After Endotracheal Intubation.

INTRODUCTION: The objective of this study was to review the clinical characteristics and surgical treatment outcomes of the vocal process granuloma after the endotracheal intubation. METHODS: A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2008 to December 2015. RESULTS: Twenty-one vocal process granulomas after endotracheal intubation were diagnosed in 13 patients. The most common symptom was hoarseness. Among 13 patients, bilateral vocal process granulomas were in 8 patients. For the remaining 5 patients, their unilateral vocal process granulomas were all left-sided. All the cases of vocal process granulomas after the endotracheal intubation were treated by laryngoscope microsurgery under general anesthesia. Recurrence of vocal process granulomas was identified in 1 lesion. CONCLUSION: This study suggests that surgery for vocal process granuloma after endotracheal intubation is a good treatment option for a rapid resolution of lesions and the associated symptoms, along with having low recurrence rates.

Sphenoid Sinus Mucocele Caused by Complications After Transsphenoidal Pituitary Surgery.

OBJECTIVE: The purpose of this study was to review the clinical characteristics, treatment methods, and surgical outcomes of sphenoid sinus mucocele after transsphenoidal pituitary surgery. PATIENTS AND METHODS: A total of 404 patients who underwent transsphenoidal pituitary surgery between January 2010 and December 2016 were identified. Among them, 5 patients with sphenoid sinus mucocele were included in this study. In our hospital, a single-nostril endonasal endoscopic wide sphenoidotomy is routinely used for pituitary tumor surgery. RESULTS: The occurrence rate of sphenoid sinus mucocele was 1.2% (5/404). Of the 5 patients, 2 were males and 3 were females. Four lesions (80.0%) were located in the right sphenoid sinus and 1 lesion (20.0%) was located in the left sphenoid sinus. Endoscopic marsupialization for sphenoid sinus mucocele was performed under local anesthesia in all patients. There were no major complications resulting from the surgical intervention, and there was no recurrence at the time of the last follow-up. CONCLUSION: Sphenoid sinus mucocele after endonasal transsphenoidal pituitary surgery is an extremely rare complication. Nasal endoscopy and MRI are useful for diagnosing this lesion. Endoscopic marsupialization is a safe and effective procedure for sphenoid sinus mucocele after endonasal transsphenoidal pituitary surgery.

Double Thyroglossal Duct Cysts in an Adult.

Double thyroglossal duct cysts (TDCs) are a very rare congenital malformation. Herein, we report a rare case of double TDCs, one below the hyoid bone and the other at the base of the tongue. Clinicians should be aware that TDCs can occur as multiple cystic lesions. Preoperative radiological examinations should be performed for an accurate diagnosis of double TDCs.

Congenital Salivary Fistula From Parotid Main Gland.

Congenital parotid fistulas are extremely rare diseases. Herein, the authors report a patient with congenital salivary fistula from parotid main gland in a 15-year-old boy. Therefore, clinicians should consider the possibility of congenital parotid fistula form parotid main gland. Surgical excision of the fistula and parotid gland can be effective treatment option of congenital parotid fistula.

Bronchogenic Cyst in the Head and Neck Region.

OBJECTIVE: The objective of this study was to review the clinical characteristics and surgical treatment outcomes of patients with bronchogenic cysts in the head and neck region. METHODS: A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2006 to May 2016. RESULTS: Eight patients with a final diagnosis of bronchogenic cyst in the head and neck region were identified based on their medical records. The most common location for the head and neck lymphatic malformations was the neck (4 patients), followed by the soft palate (1 patient), the posterior pharyngeal wall (1 patient), the floor of mouth (1 patient), and the arytenoid (1 patient). The size of the lymphatic malformations ranged from 1 to 6 cm. Bronchogenic cysts recurred in 2 patients. Both these patients were disease-free after the revision operation. No major complications resulting from the surgical intervention were observed. CONCLUSION: Bronchogenic cysts are rare congenital malformations and they can occur at various sites in the head and neck region. Bronchogenic cyst should be considered in the differential diagnosis of midline and lateral neck masses or intraoral cysts.

Surgical Treatment Outcomes of Head and Neck Lymphatic Malformations in Patients With a Variety of Ages and Unusual Sites.

OBJECTIVE: The objective of this study was to review the clinical characteristics and surgical treatment outcomes of head and neck lymphatic malformations and to define the risk factors for recurrence. METHODS: A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2010 to February 2015. RESULTS: The unusual sites for a head and neck lymphatic malformation were tonsil, buccal space, nasopharynx, and the vallecula. No recurrence of lymphatic malformations was observed when the lesion was removed completely. Recurrence was more common in patients with the infiltrative type and incomplete excision. CONCLUSIONS: Lymphatic malformations occurred in patients with a variety of ages and unusual sites. Surgical excision could become the treatment of choice if the malformation can be excised completely without serious complications. Recurrence was more common in patients in whom an infiltrative type malformation was incomplete excised.

Pedunculated Primary Mucosal Malignant Melanoma Originated From the Posterior Nasal Septum.

Primary mucosal malignant melanoma of the nasal cavity is a rare disease. The authors present the patient of a pedunculated primary mucosal malignant melanoma originated from the posterior nasal septum, which was successfully removed via the endoscopic approach. Clinicians should consider the possibility that a primary mucosal malignant melanoma may originate in the nasal cavity, mimicking the other more frequently observed lesions.

A Huge Ancient Schwannoma of the Epiglottis.

Ancient schwannoma of the epiglottis is extremely rare. The authors report the first case of a patient with a huge ancient schwannoma of the epiglottis. Clinicians should consider the possibility that ancient schwannoma may originate in the epiglottis mimicking the other more frequently observed lesions.

The cyclic peptide ecumicin targeting ClpC1 is active against Mycobacterium tuberculosis in vivo.

Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.

SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma.

BACKGROUND: In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). METHODS: We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. RESULTS: SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. CONCLUSIONS: SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC.

Predictive factors of recurrence and malignant transformation in vocal cord leukoplakia.

The aim of this study was to define the predictive risk factors of vocal cord leukoplakia recurrence and malignant transformation. From January 2009 to December 2013, 63 patients with a diagnosis of vocal cord leukoplakia were identified based on their medical records. The 63 patients comprised 62 males and one female. This study showed that the extent of vocal cord leukoplakia resulted in statistically significant differences for both the recurrence of vocal cord leukoplakia and malignant transformation (p < 0.05). In addition, this study revealed that the degree of dysplasia resulted in statistically significant differences for both the recurrence of vocal cord leukoplakia and malignant transformation (p < 0.05). We suggest that the extent of lesion and the degree of dysplasia are predictive factors for the risk of recurrence and malignant transformation.