Myrtol standardized affects mucociliary clearance.

BACKGROUND: Myrtol standardized (Gelomyrtol forte) has been shown to be effective in controlling nasal symptoms of rhinosinusitis by promoting mucociliary clearance. Our aim was to evaluate the short- and long-term effects of myrtol on ciliated columnar cells and goblet cells in an in-vitro setting. METHODS: Nasal epithelial cells were harvested (42 days) from an air-liquid interface (ALI) culture of human nasal epithelial stem/progenitor cells (hNESPCs), which was derived from biopsies of nasal inferior turbinate mucosa. Myrtol 0.1% was applied to the ALI culture system at 2 different time-points (day 0 and day 35) on progenitor and differentiated cells. Ciliary beat frequency (CBF), supernatant fluid, and ciliated and goblet cell markers were evaluated after short- (7 days) and long-term (42 days) treatment. RESULTS: In the long-term treatment with myrtol, there was an increase in cilia area (type IV ß-tubulin+ , 1.53-fold, p = 0.031) and ciliogenesis-related markers (Foxj1 and CP110) with no change in CBF, as compared with control. In addition, the short-term myrtol treatment group exhibited greater mucin secretion compared with control. CONCLUSION: This study demonstrates, through cellular and molecular mechanisms, that myrtol standardized enhances the mucus production from goblet cells in the short term, and promotes ciliated cell differentiation in the long term.

Comparison of the distribution of intranasal steroid spray using different application techniques.

BACKGROUND: Optimizing the intranasal distribution of nasal steroid spray (NS) is important in managing patients with allergic rhinitis (AR). Using a 3-dimensional computational model of the human nose, we found that inspiratory airflow improved particle distribution by 86%. We hence designed a study to determine if the intranasal distribution of NS is improved by (1) simultaneous gentle inspiration or (2) nasal decongestion. METHODS: Twenty patients with AR were recruited. Colored triamcinolone nasal spray Nasacort®, was applied to 1 side of the nasal cavity with simultaneous gentle inspiration (technique1) and the other side with no inhalation (technique 2). Flexible nasoendoscopy with video documentation was performed immediately after each application. The same procedures were repeated 30 minutes after nasal decongestion. The nasal cavity was divided into 10 different regions and presence of the colored medication in each region was given 1 point. RESULTS: Prior to decongestion, the mean total score was significantly higher using technique 1 (4.61 ± 0.25) compared to technique 2 (3.80 ± 0.24), (p = 0.03). Following decongestion, the mean total score for techniques 1 and 2 was (5.20 ± 0.40) and (4.30 ± 0.32), respectively. The differences in total score for both techniques before and after decongestant were not significant. CONCLUSION: The presence of inspiratory airflow, using the gentle inspiration technique, improves the intranasal distribution of NS in patients with AR. The use of correct technique is more important than nasal decongestion in the distribution of nasal spray particles.

Endoscopic Endonasal Resection of Recurrent Nasopharyngeal Mucoepidermoid Carcinoma.

Nasopharyngeal mucoepidermoid carcinoma is a rare entity, for which surgical resection is the treatment of choice. The open technique is considered the standard approach, but this often results in significant morbidities such as trismus, dysphagia, and neurologic deficits. The advent of endoscopic endonasal techniques has made endoscopic resection a viable alternative to the open approach in terms of access, adequacy of resection, and lesser surgical morbidity. The authors describe a patient of recurrent nasopharyngeal mucoepidermoid carcinoma that was resected entirely endoscopically. The authors also present a literature review of this little-known disease and a comparison between the endoscopic and open approach.

Relapse status as a prognostic factor in patients receiving salvage surgery for recurrent or residual nasopharyngeal cancer after definitive treatment.

BACKGROUND: The purpose of this study was to determine the prognostic value of relapse status (recurrent vs residual disease) in patients receiving surgical salvage for nasopharyngeal carcinoma (NPC). METHODS: Retrospective review was conducted on 52 patients who underwent salvage surgery for locoregional relapse of NPC. Univariate and multivariate analyses were used to investigate the prognostic value of relapse status. RESULTS: Median follow-up duration was 44.4 months. Mean overall survival (OS) and disease-free survival (DFS) for patients with NPC with residual and recurrent disease after surgical salvage were 107.4 and 54.4 months, and 83.6 and 34.6 months, respectively (p < .001). This improved survival was demonstrated regardless whether the relapse was at the primary or nodal site. Multivariate analysis revealed that recurrent disease status and nodal disease relapse were independent poor prognostic factors for survival in patients receiving salvage surgery for NPC. CONCLUSION: In patients undergoing surgical salvage for NPC relapse, residual disease carries a better prognosis than recurrent disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1393-1400, 2016.

Clinical Outcome among Nasopharyngeal Cancer Patients in a Multi-Ethnic Society in Singapore.

BACKGROUND: Nasopharyngeal cancer (NPC) is endemic among Chinese populations in Southeast Asia. However, the outcomes of non-Chinese NPC patients in Singapore are not well reported. AIM: To determine if non-Chinese NPC patients have a different prognosis and examine the clinical outcomes of NPC patients in a multi-ethnic society. METHODS: Retrospective chart review of 558 NPC patients treated at a single academic tertiary hospital from 2002 to 2012. Survival and recurrence rates were analysed and predictive factors identified using the Kaplan-Meier method and Cox regression model. RESULTS: Our cohort comprised 409 males (73.3%) and 149 females (26.7%) with a median age of 52 years. There were 476 Chinese (85.3%), 57 Malays (10.2%), and 25 of other ethnic groups (4.5%). Non-Chinese patients were more likely to be associated with advanced nodal disease at initial presentation (p = 0.049), compared with the Chinese. However, there were no statistical differences in their overall survival (OS) or disease specific survival (DSS) (p = 0.934 and p = 0.857 respectively). The 3-year and 5-year cohort OS and DSS rates were 79.3%, 70.7%, and 83.2%, 77.4% respectively. Advanced age (p<0.001), N2 disease (p = 0.036), N3 disease (p<0.001), and metastatic disease (p<0.001) at presentation were independently associated with poor overall survival. N2 disease (p = 0.032), N3 disease (p<0.001) and metastatic disease (p<0.001) were also independently associated with poor DSS. No predictive factors were associated with loco-regional recurrence after definitive treatment. Advanced age (p = 0.044), N2 disease (p = 0.033) and N3 disease (p<0.001) were independently associated with distant relapse. CONCLUSION: In a multi-ethnic society in Singapore, non-Chinese are more likely to present with advanced nodal disease. This however did not translate into poorer survival outcomes. Older patients with N2 or N3 disease are associated with a higher risk of distant relapse and poor overall survival.

Impairment of cilia architecture and ciliogenesis in hyperplastic nasal epithelium from nasal polyps.

BACKGROUND: Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown. OBJECTIVE: We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro. METHODS: Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation. RESULTS: Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 µm [5.51-7.43 µm] vs control subjects: 3.73 µm [3.50-4.27 µm], P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 µm vs control subjects 4.89 ± 0.24 µm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 µm vs control subjects: 5.21 ± 0.37 µm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro. Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 [CP110], forkhead box J1 [Foxj1], and P73 isoform with an N-terminal transactivation domain [TAp73]) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length. CONCLUSION: For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis.

En bloc resection concept for endoscopic endonasal nasopharyngectomy: surgical anatomy and outcome.

BACKGROUND: Nasopharyngeal carcinoma (NPC) patients have a 19%-56% locoregional recurrence rate after primary therapy. For those recurrent NPC (rNPC) patients, re-irradiation may cause some complications. In recent years, endoscopic endonasal nasopharyngectomy (EEN) has become a surgical option for rNPC patients. Here we introduce the concept of en bloc excision (EBE) technique for EEN, including the surgical technique and clinical outcomes. METHODS: A retrospective study was conducted covering September 2009 to May 2013, involving the collection of locoregional rNPC cases from two institutions (Kuang-Tien General Hospital (KTGH) in Taiwan and National University Health System (NUHS) in Singapore). These patients failed prior therapy and then underwent EEN. We reported the 2-year overall survival rate, the 2-year disease-free survival rate, and related complications. RESULTS: Nine patients (five from KTGH and four from NUHS) completed this study, with five, two, and two patients of recurrence tumors (rT1), rT2, and rT3, respectively. The mean age was 46.4 years (range 32-63); the mean follow-up period was 24.9 months (range 10-45). The 2-year survival rate and the 2-year disease-free rate were 100% and 80%, respectively, in five patients. No significant complications or cases of mortality occurred. CONCLUSIONS: The EBE concept of EEN is suitable for early rT1 and has relatively encouraging short-term outcomes. In selected rT2, careful EBE can be performed by expanding the surgical field. A clear view of the internal carotid artery-related anatomy is indispensable. In the future, more series may be needed to determine the role of EEN in rNPC patients.

Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro.

Basal cells in nasal epithelium have stemness/progenitor characters and play essential roles in the epithelial remodeling in nasal polyps (NP). We investigate whether the human nasal epithelial stem/progenitor cells (hNESPCs) from patients with NP are inherently distinct from those obtained from healthy controls. Epithelial basal cells were isolated and cultured for four passages from NP tissues and control nasal mucosa. hNESPCs from controls were stained positively with stem cell marker p63 and KRT5 and presented a consistent high Ki67 expression level over four passages. In contrast, hNESPCs from NP patients showed: i). a reduced growth and proliferation rate at each passage by evaluating colony-forming efficiency and doubling time; ii). a lower percentage of Ki67(+) cells among p63(+) cells in the colonies in late passages, which was also confirmed by immunostaining in the NP tissues. Thus reduced growth/proliferation dynamics in hNESPCs from NP could be an important pathological phenomenon in NP development.

Live human nasal epithelial cells (hNECs) on chip for in vitro testing of gaseous formaldehyde toxicity via airway delivery.

Cell models based on human nasal epithelial stem/progenitor cells (hNESPCs) are developed to obtain functional ciliated cells on modified Transwell inserts. The live hNECs are integrated into microfluidic platforms to mimic the 3D features of the human upper airway for in vitro testing of gaseous formaldehyde toxicity via airway delivery.

Efficacy of computed tomographic scans in the evaluation of patients with esophageal foreign bodies.

OBJECTIVES: This study aimed to determine whether computed tomographic (CT) scans on which foreign body impaction cannot be detected can be relied upon to decide whether a patient requires further investigation by esophagoscopy. This information might minimize unnecessary esophagoscopy without incurring the risk of a missed impacted foreign body. METHODS: In a retrospective chart review of all patients admitted to National University Hospital, Singapore, over the period 2004 to 2011 for an ingested foreign body, case files of patients who underwent preoperative CT scanning followed by esophagoscopy were identified and reviewed. The results of the CT scan and the findings of esophagoscopy in these patients were analyzed. RESULTS: A total of 376 patients underwent rigid esophagoscopy for an ingested foreign body during this period. Of these, 119 patients had CT scans performed before the endoscopy. Based on our analysis, the sensitivity of CT scanning was 100%, and the specificity was 70.6%. The positive predictive value was 89.5%, and the negative predictive value was 100%. None of the patients who had CT scans with no detectable foreign body had complications on follow-up. CONCLUSIONS: CT scanning appeared to be sensitive and specific in investigation of patients with an ingested foreign body. It also has a high negative predictive value, which may allow it to be the only preliminary investigation in these patients. Based on these data, a prospective study with close monitoring of patients who have CT scans with no detectable foreign body can be designed to accrue more patients to answer this query.

The use of nasal epithelial stem/progenitor cells to produce functioning ciliated cells in vitro.

BACKGROUND: Although epithelial stem/progenitor cells have been isolated from many parts of the human airway epithelium such as lung and trachea, there is limited information in regard to stem cells in nasal epithelium. The aim of this study was to determine if (1) human nasal epithelial stem/progenitor cells (hNESPCs) can be isolated and propagated in vitro and (2) allogeneic adult primary human fibroblasts can serve as a feeder layer for hNESPCs expansion under serum-free conditions. METHODS: Primary cells taken from inferior turbinate biopsy specimens (n = 3) were enzymically dissociated and plated on either allogeneic human fibroblasts or murine NIH 3T3 fibroblasts, in a chemical-defined medium supplemented with growth factors. Self-renewal, proliferation, and differentiation potential were compared. RESULTS: The optimized media were capable of supporting the undifferentiated growth and expansion of hNESPCs on both feeder cells. The doubling time and cloning efficiency of hNESPCs cultured on a human feeder layer were comparable with that cultured on 3T3 feeders. Significantly, the hNESPCs on both feeder layers could be cultured for four passages, and they can differentiate into ciliated columnar cells and goblet cells at the air-liquid interface, resembling the in vivo mucociliary airway epithelium. CONCLUSION: Our results showed the feasibility of expanding hNESPCs for clinical purpose by using human feeder layer, avoiding components of animal source, while preserving their self-renewal and differentiation potential. This study represents an early step toward a better understanding of hNESPCs, and serum -free media plus human feeder potentially would be an ideal method for making clinical grade hNESPCs on a large scale.

Anaplastic myoepithelial carcinoma of the sinonasal tract: an underrecognized salivary-type tumor among the sinonasal small round blue cell malignancies? Report of one case and a review of the literature.

We present a 45 year old female patient with a nasal carcinoma showing high-grade/anaplastic histomorphological features and with a distinct myoepithelial immunohistochemical phenotype including positivity for smooth muscle actin, p63, S100 protein with no sustentacular pattern, calponin, cytokeratin 14, vimentin and cytokeratins (AE1-3 and CK5/6). A minority (<5%) of the cells showed focal and variable immunoreactivity for EMA with no cuticular/canalicular pattern. Bcl-2, CD99, CD117 and CD56 were variously positive, but chromogranin and synaptophysin were negative. Weak to moderate nuclear p53 immunoreactivity was seen in 50% of tumor cells. Mib-1/Ki-67 showed an average proliferation of 60-70%. Fluorescent in situ hybridization revealed no EWS-gene translocation. In situ hybridization for EBER was negative.

Role of fine-needle aspiration cytology in the evaluation of parotid tumours.

BACKGROUND: The aim of this study was to evaluate the accuracy of fine-needle aspiration cytology in the diagnosis of parotid tumours. METHODS: A retrospective review was conducted to examine the preoperative cytological and final histological results of patients who underwent parotidectomies at our institution. RESULTS: Sensitivity and specificity for diagnosing malignant and benign tumours were 80%, 100%, and 98.5%, 87.5%, respectively, and 85.1% of benign tumours were accurately typed on fine-needle aspiration cytology compared with only 40% in the malignant group. Using the clinical parameters of associated facial nerve palsy or presence of cervical lymphadenopathy to indicate the presence of malignancy, the diagnostic yield was only 30%. CONCLUSION: Fine-needle aspiration cytology is useful in the preoperative assessment of parotid tumours as it is more reliable than clinical examination to diagnose malignant parotid tumours. Although it may not accurately type the malignant tumours, the diagnosis of malignant tumours preoperatively may allow for appropriate surgical planning by the surgeon.

Cysteinyl leukotriene 1 receptor expression in nasal polyps.

OBJECTIVES: The pathogenesis of nasal polyps, thought to involve complex interactions between different factors, is currently not fully understood. Recent studies have suggested the involvement of cysteinyl leukotrienes (CysLTs) in nasal polyp development. To further understand the role of CysLTs in polyp pathogenesis, we studied the expression of CysLT1 receptors in nasal polyps. METHODS: The study group comprised polyps removed endoscopically from 20 consecutive patients. Samples of ethmoid mucosa from 4 patients who underwent orbital decompression for Graves' ophthalmopathy were used as controls. The presence of CysLT1 receptors was determined with a rabbit anti-human anti-CysLT1 receptor polyclonal antibody. Cells with and without CysLT1 receptor expression were counted within the epithelial layer and stroma by means of light microscopy (40x magnification). RESULTS: There were significantly more cells expressing CysLT1 receptors in the stroma than in the epithelium in both nasal polyps and control specimens. The stroma of polyps also contained more CysLT1 receptor-expressing cells than did controls (29 x 10(3) +/- 7 x 10(3) versus 3 x 10(3) +/- 3 x 10(3) cells per square millimeter; p < .01). In the epithelium of polyps, there was significantly higher expression of CysLT1 receptors than in controls (7 x 10(3) + 3 x 10(3) versus 0 cells per square millimeter; p = .02). No significant differences in polyps were found between patients with and patients without Samter's triad and asthma. CONCLUSIONS: The significant up-regulation of CysLT1 receptors we found in both the stroma and the epithelium of nasal polyps suggests the presence of an inflammatory component in the pathogenesis of polyps, and possibly explains the efficacy of leukotriene modifiers in their treatment.

Pseudocyst of the auricle: a histologic perspective.

OBJECTIVE: The aim of the study is to describe the histologic spectrum in the pseudocyst of the auricle and to identify any consistent histologic features of this condition. STUDY DESIGN: A prospective study was performed in which the tissue specimen from patients with pseudocyst of the auricle treated at the Department of Otolaryngology, Singapore General Hospital during a 1-year period was sent for histology. METHODS: Consecutive patients with pseudocyst of the auricle who were treated had their tissue specimen sent for histology. These specimens were independently reviewed by one consultant pathologist. RESULTS: All 16 specimens revealed an intracartilaginous cyst devoid of epithelial lining. Interestingly, there were consistent perivascular mononuclear infiltrates of lymphocytes evident in the connective tissue layer just superficial to the anterior segment of the cartilage. CONCLUSION: Pseudocyst of the auricle is a benign condition predominantly affecting young Asian males. Histology characteristically reveals an intracartilaginous cyst devoid of epithelial lining, and there are no pathognomonic features. We postulate that an inflammatory response is crucial to the development of this condition on the basis of a consistent perivascular inflammatory response seen in all our specimens.

Management of pharyngoesophageal spasm with Botox.

Pharyngoesophageal spasm following laryngectomy can result in failure of tracheoesophageal (TE) speech and dysphagia. Chemical denervation with Clostridium botulinum toxin (Botox) is effective in relieving pharyngeal constrictor spasm, thereby facilitating TE speech production. This article reviews the technique, results,and complications regarding the use of Botox in the management of TE speech failure associated with pharyngoesophageal spasm.

Modalities of surveillance in treated nasopharyngeal cancer.

OBJECTIVE: We sought to assess the efficacy of different modalities in the detection of disease during the early posttreatment period of nasopharyngeal carcinoma (NPC). Study design and setting We prospectively evaluated 57 patients with NPC who were treated with radiation. A postnasal space (PNS) biopsy, an endoscopic examination, and computed tomography (CT) scans were performed 4 months after treatment. RESULTS: Four patients had evidence of disease in the PNS biopsy specimen. The sensitivity, specificity, and positive and negative predictive values of the endoscopic examination were 75%, 94.3%, 50%, and 98%, respectively, while those of the CT scan were 50%, 49.1%, 6.9%, and 92.9%, respectively. CONCLUSION: In the early postradiation period for patients with NPC, an endoscopic examination is a suitable surveillance modality, but routine CT scanning has no added clinical benefit. SIGNIFICANCE: When an endoscopic examination of the PNS yields normal results, a biopsy is not necessary because the likelihood of disease is low.

Parotid gland surgery: 4-year review of 118 cases in an Asian population.

BACKGROUND: To determine the presentation and management of parotid lesions requiring excision in a largely Chinese Asian population. METHODS: Retrospective study of 118 consecutive parotidectomies. RESULTS: Thirty-seven percent were Warthin's tumor (WT), 33% pleomorphic adenoma (PA), 21% other benign disease (OBD), and 9% malignant tumor (MT). Mean age was significantly different between benign (51 years) and malignant (40 years) lesions. MT decreased above 50 years, but increased five times with pain and two times with a noninferior pole lesion. Sensitivity of fine-needle aspiration (FNA) for differentiating benign from MT = 78%, for WT =5 8%, for PA =82%, for OBD = 28%, and for MT = 38%. CT scans did not alter WT management. Facial nerve (FN) paresis was not associated with histology, tumor size, site, or parotidectomy type. CONCLUSIONS: This is the first report documenting that most benign parotid tumors are WT and not PA. MT risk is greater in those less than 50 with pain and a noninferior pole lesion. Cystic lesions such as WT require great care in the evaluation of FNA findings.