Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways.

Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.

Curcumin inhibits tongue carcinoma cells migration and invasion through downregulation of matrix metallopeptidase 10.

Squamous cell carcinoma (SCC) of tongue is an aggressive head and neck cancer with high propensity of regional spreading and invasion. Tongue carcinoma cells treated with curcumin, the major curcuminoid of the turmeric, demonstrated reduction in adhesion, migration, and invasion ability. High-throughput microarray analysis indicated that curcumin treatment suppressed matrix metallopeptidase 10 (MMP10) expression. MMP10 is overexpressed in tongue carcinoma tissues in comparison with the normal epithelia. Curcumin treatment on tongue carcinoma cell lines suppressed MMP10 expression at both mRNA and protein levels. Our results suggested that curcumin is a promising inhibitor to tongue cancer cells migration and invasion.

Long-term hearing results and otological complications of nasopharyngeal carcinoma patients: comparison between treatment with conventional two-dimensional radiotherapy and intensity-modulated radiotherapy.

OBJECTIVE: To assess the long-term audiological outcome and otological complications of nasopharyngeal carcinoma patients who have received intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2 DRT). STUDY DESIGN: Prospective study on the audiological outcome and otological complications 5-9 years after radiotherapy. METHODOLOGY: Patients had pure-tone audiogram before radiotherapy and 5 years after radiotherapy. Otological examination was performed 5-9 years after radiotherapy by an otolaryngologist. RESULTS: There is a significant deterioration of the hearing threshold 5 years after radiotherapy but there is no statistically significant difference in the deterioration of hearing between IMRT and 2 DRT. Six patients in the 2 DRT group and 1 patient in the IMRT group had osteoradionecrosis of the external auditory canal (p = 0.042). CONCLUSION: There are fewer incidences of osteoradionecrosis of the external auditory canal in patients treated with IMRT. There is no difference in bone conduction threshold in patients treated with IMRT or 2 DRT.

Biomarkers for use in monitoring responses of nasopharyngeal carcinoma cells to ionizing radiation.

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer. The incidence rate is higher in southern China and Southeast Asia in comparison with the Western countries. Radiotherapy is the standard treatment of NPC as the cancer cells are sensitive to ionizing radiation. Radiation treatment has good local control to patients with early NPC. It is essential to monitor the response of the NPC cells to radiation treatment in advance in order to select suitable treatment choice for the patients. This review aims to discuss the potential use of biomarkers in monitoring the responsiveness of NPC cells to radiation treatment.

Long-term results of robotic-assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy. METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow-up period for all patients were 38 months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively. CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.

Mature miR-184 and squamous cell carcinoma of the tongue.

Human microRNA 184 (miR-184) is overexpressed in squamous cell carcinoma (SCC) of the tongue. In vitro inhibition of miR-184 levels could induce apoptosis and hinder proliferation of tongue SCC cells. Patients with tongue SCC have high plasma miR-184 levels. Plasma miR-184 is likely associated with the tumor load. Surgical removal of the primary tumor reduced plasma miR-184 levels significantly. The data suggested that miR-184 is linked to the pathogenesis of tongue SCC. Further studies are warranted to evaluate the use of microRNA-based serological markers in monitoring tongue SCC.

Management of the N0 neck--reference or preference.

For patients with squamous cell carcinoma of the upper aerodigestive tract, appropriate management of the regional lymph nodes is an important and often controversial issue that has significant influence on survival. Over the years radical treatment either by surgery or radiotherapy contributed to improvement in prognosis. Recently, a more conservative approach has achieved a similar level of cancer control with less morbidity. This review considers the issues of selection of patients for treatment of the neck, choice of modality and extent of therapy, treatment of the contralateral neck, management of recurrence and influence of the site and status of the primary lesion.

Use of transoral nasopharyngeal brush biopsy for Epstein-Barr virus DNA detection of local recurrence of nasopharyngeal carcinoma after radiotherapy.

BACKGROUND: The purpose of this study was to evaluate the use of transoral nasopharyngeal brush biopsies and quantitative polymerase chain reaction (qPCR) Epstein-Barr virus (EBV) DNA detection system in surveillance of local recurrence of nasopharyngeal carcinoma (NPC). METHODS: A prospective cohort study was performed to compare the nasopharyngeal epithelial EBV DNA levels of patients with recurrent NPC and the control group of postirradiated patients with NPC disease in remission. RESULTS: Fourteen patients with recurrent NPC and 15 postirradiated patients in disease remission were recruited for transoral brush biopsies. There was a statistically significant difference between the mean EBV detection level (EDL) of the recurrence group (EDL = 2.38) and the control group (EDL = 0.17; p < .0001). There was no significant correlation between the EDL and the recurrence of T classification disease. CONCLUSION: The transoral brush biopsy and qPCR EBV DNA detection system may provide an additional surveillance strategy for recurrence of NPC. Further study is required to validate its sensitivity, specificity, and cost-effectiveness. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1301-E1304, 2016.

The clinical association of programmed cell death protein 4 (PDCD4) with solid tumors and its prognostic significance: a meta-analysis.

BACKGROUND: Programmed cell death protein 4 (PDCD4) is a novel tumor suppressor protein involved in programmed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical significance and prognostic value of PDCD4 in solid tumors. METHODS: A systematic literature review was performed to retrieve publications with available clinical information and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta-analysis Of Observational Studies in Epidemiology group. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's tests. RESULTS: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was significantly associated with the differentiation status of head and neck cancer (OR 4.25, 95% CI 1.87-9.66) and digestive system cancer (OR 2.87, 95% CI 1.84-4.48). Down-regulation of PDCD4 was significantly associated with short overall survival of patients with head and neck (HR: 3.44, 95% CI 2.38-4.98), breast (HR: 1.86, 95% CI 1.36-2.54), digestive system (HR: 2.12, 95% CI 1.75-2.56), and urinary system cancers (HR: 3.16, 95% CI 1.06-9.41). CONCLUSIONS: The current evidence suggests that PDCD4 down-regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be confirmed by large-scale prospective studies.

Long-term performance of indwelling tracheoesophageal speaking valves in Chinese patients undergoing laryngectomy.

OBJECTIVES: To assess the use of indwelling tracheoesophageal speaking valves in Chinese patients undergoing laryngectomy, to identify the clinicopathologic factors for favorable outcome, and to evaluate the factors that determine prosthesis lifetime. DESIGN: Retrospective review. SETTING: Tertiary care institution. PATIENTS: Sixty consecutive patients with total laryngectomy were included. All had indwelling tracheoesophageal speaking valves for voice restoration. INTERVENTION: Anterograde replacement of voice prosthesis in case of failure of functional speech production or leakage of saliva. MAIN OUTCOME MEASURES: Incidence of successful tracheoesophageal speech rehabilitation for daily communication, influence of different clinicopathologic factors on the outcome, and prosthesis lifetime and its relationship to different clinicopathologic factors. RESULTS: The success rate of speech rehabilitation was 78%. Age younger than 60 years was the only clinicopathologic factor associated with successful speech rehabilitation (P = .04, Fisher exact test). The median device lifetime was 8.2 months. Both age of 60 years or older and the use of subsequent prosthetic valves were identified as risk factors for valve failure on univariate analysis (n = 192; log-rank test; P = .02 and P = .03, respectively), with age of 60 years or older as the only risk factor that reduced the device lifetime in the Cox proportional hazards model (P = .03; relative hazard ratio, 1.5; 95% confidence interval, 1.1-2.4). CONCLUSIONS: Our success rate in using indwelling tracheoesophageal speaking valves was comparable to that reported in the Western literature. The median device lifetime of 8.2 months was satisfactory. Patient age was found to be a significant predictor of successful tracheoesophageal speech rehabilitation, with age of 60 years or more adversely affecting device lifetime.

Early results of robotic assisted nasopharyngectomy for recurrent nasopharyngeal carcinoma.

BACKGROUND: Minimally invasive nasopharyngectomy with the da Vinci surgical robot has been shown to be a feasible operation for salvage of recurrent nasopharyngeal carcinoma. The current case series presents the early results of robotic nasopharyngectomy. METHODS: We conducted a prospective series of patients who underwent robotic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a single institution. RESULTS: Twelve patients underwent robotic nasopharyngectomy. The median operating time was 225 minutes. Median follow-up time was 23.8 months. Nine patients had clear resection margins, 2 patients had close margins, and 1 patient had positive margin. Two patients developed local recurrence and 1 patient had distant metastasis. Two patients in the cohort died of unrelated causes. The 2-year local control rate was 86%. The 2-year overall survival and disease-free survival was 83% and 61%, respectively. CONCLUSION: Early results of robotic nasopharyngectomy showed a high local control rate. The operating time was comparable to open surgery and morbidities were low.

A prospective controlled double-blind trial of great auricular nerve preservation at parotidectomy.

BACKGROUND: Earlier reports of the advantages of preservating the posterior branches of the great auricular nerve (GAN) at parotidectomy were conflicting. This prospective study was aimed at clarifying the controversy. METHODS: Eighty-one patients in a university otolaryngology department were recruited. The posterior branches were preserved whenever initial dissection showed that tumor clearance would not be compromised. Touch-pressure sensation was monitored in predefined territories supplied by the GAN using a Semmes-Weinstein aesthesiometer, preoperatively and postoperatively. Minimal pressure thresholds obtained were compared between the two groups. RESULTS: Preservation of the GAN was achievable in 69% of patients; sensory deficit was transient. With the GAN divided, measurable sensory depression occurred up to 2 years after surgery. The difference is statistically significant. Patients' subjective assessment of numbness also conformed to these trends. Additional time taken for preservation of the GAN was about 10 minutes. CONCLUSIONS: The posterior branches should always be preserved if tumor clearance is not compromised.

Outcome of patients with positive Epstein-Barr virus serologic status in the absence of nasopharyngeal carcinoma in Hong Kong.

OBJECTIVE: To evaluate the current clinical practice of follow-up and the outcomes of patients with raised Epstein-Barr virus (EBV) antibody levels but without pathological evidence of nasopharyngeal carcinoma (NPC) for a possible risk of developing NPC in the future. DESIGN: Retrospective review of prospectively collected database. SETTING: Tertiary referral otorhinolaryngology center. PATIENTS: The study population comprised 66 patients (27 male and 39 female; median age, 43.5 [range, 9-78] years) who presented in 1997 with a positive EBV IgA viral capsid antigen titer but a negative nasopharyngeal biopsy result. MAIN OUTCOME MEASURES: The detection of NPC and EBV seroconversion rate. RESULTS: Of the 66 patients studied, 14 had a positive family history of NPC. Fourteen patients (27%) were excluded because of loss of contact or refusal of follow-up. The median follow-up period of the remaining 52 patients was 54.5 months (range, 12-64 months). Of these 52 patients, 39 (75%) had initial nasendoscopic finding described as completely normal. During the follow-up period, NPC was diagnosed in 1 patient (2%) 18 months after first biopsy. The initial nasendoscopy and histological findings in this patient were normal despite the patient having a raised EBV IgA VCA titer of 1:640. Overall, the EBV serologic status of 36 patients (69%) reverted to normal within the studied period (median interval of 54.5 [range, 12-64] months). CONCLUSIONS: In the median follow-up period of 54.5 months, only 1 patient (2%) developed NPC. A significant proportion of the patients seroconverted back to normal, none of whom developed NPC.

Managing disturbing snoring with palatal implants: a pilot study.

OBJECTIVE: To evaluate the safety and efficacy of polyethylene terephthalate implants in the soft palate to modify disturbing snoring. DESIGN: Interventional study, before-after trial. SETTING: Referral center, institutional practice, hospitalized care. PATIENTS: Twelve consecutive patients with disturbing snoring and an apnea-hypopnea index less than 15 per hour and a body mass index of 30 or less were recruited. One patient with no adverse effects was lost to follow-up. Extrusion of implants occurred in 2 patients. Complete data in 9 patients were available for analysis. INTERVENTION: Polyethylene terephthalate implants were inserted in the soft palate. MAIN OUTCOME MEASURES: Safety of the procedure and evaluation of the loudness of snoring by bed partners using a visual analog scale. RESULTS: There were no complications of infection or bleeding. Extrusion of implants occurred in 2 patients with no clinical sequelae. The mean (SD) loudness of snoring at baseline, as assessed by bed partners using a visual analog scale of 0 to 100, was 79 (17.2). This significantly decreased to 48 (20.4) at 3 months (Wilcoxon signed rank test, P =.008). Daytime sleepiness as measured with the Epworth Sleepiness Scale also decreased from an average score of 8.9 at baseline to 5.7 at 3 months (P =.007). There were no significant changes in the apnea-hypopnea index and body mass index from baseline to 3 months' follow-up. CONCLUSIONS: Polyethylene terephthalate implants in the soft palate are safe. Snoring decreased significantly at 3 months after surgery. Polyethylene terephthalate implants in the soft palate should be further explored as a treatment for snoring.

Time course in the relief of nasal blockage after septal and turbinate surgery: a prospective study.

OBJECTIVE: To evaluate prospectively the time course of the change in efficacy of septal and turbinate surgery in relieving nasal obstruction. DESIGN: Interventional study, before-after trial. SETTING: Referral center, institutional practice, hospitalized care. PATIENTS: Thirty-four consecutive patients undergoing septal and turbinate surgery were recruited. Seven patients were unwilling to complete the follow-up after surgery. No patient withdrawal was because of adverse effects. Twenty-five normal subjects with no nasal obstruction were included as control subjects. INTERVENTION: Functional nasal septal and turbinate surgery was performed to relieve nasal obstruction. MAIN OUTCOME MEASURE: Patient assessment of severity of nasal blockage on a 0-mm (no blockage) to 100-mm (maximum blockage) visual analog scale before surgery and at fixed intervals after surgery. RESULTS: The mean nasal blockage scores significantly decreased from the preoperative values at all intervals of follow-up. For the whole group, the nasal blockage score was on average 52% of the preoperative value at the last follow-up. The probability of having at least a 50% reduction in blockage decreased from 73%, to 60%, to 41%, and then to 27% at 3 months, 6 months, 1 year, and 2(1/2) years, respectively. CONCLUSIONS: Improvement in nasal blockage was found in patients after functional septal and turbinate surgery. However, the probability of substantial relief gradually decreased with time. Patients should be followed up after septal and turbinate surgery for possible recurring symptoms.

Stenting of the eustachian tube to prevent otitis media with effusion after maxillary swing approach nasopharyngectomy.

OBJECTIVES/HYPOTHESIS: Our previous report recommended that the management of ipsilateral otitis media with effusion (OME) after maxillary swing nasopharyngectomy was observation. The idea of introducing a stent into the eustachian tube (ET) at the nasopharyngeal side after nasopharyngectomy may prevent postoperative OME. The purpose of this study was to examine the feasibility of intraoperative ET stenting and the efficacy of preventing ipsilateral OME formation. STUDY DESIGN: Prospective cohort study. METHODS: From 2009 to 2011, 28 patients with nasopharyngectomy via the maxillary swing approach were recruited. Patients with curative resection were recruited (n = 21). ET stenting was performed intraoperatively using a 16-gauge Angiocath (BD Medical Systems, Franklin Lakes, NJ) with dimensions of 1.7 mm × 30 mm. The stent stays inplace indefinitely. The otologic status was evaluated using otoscopy, pure-tone audiogram, and tympanogram at 3 months, 6 months, and 1 year after the surgery. The outcomes were analyzed and compared with historical control. RESULTS: There were 9 (43%) patients with no OME at 6 months after surgery, and 15 (71%) patients had no OME at 1 year postoperatively. The results were statistically significant (P < .0001) when compared with our historical control of no ET stenting. There was no incidence of adverse effects of the stenting, such as acute otitis media, dislodgement of the stent, otalgia, and nasal pain. CONCLUSIONS: ET stenting was feasible after nasopharyngectomy. ET stenting prevented a significant number of patients from suffering from ipsilateral OME and alleviated the symptoms of unilateral aural fullness and unilateral conductive hearing impairment up to at least 1 year after the surgery. ET stenting is recommended in all patients after maxillary swing nasopharyngectomy.

Management of pseudoaneurysms of the internal carotid artery in postirradiated nasopharyngeal carcinoma patients.

OBJECTIVES/HYPOTHESIS: Massive epistaxis due to ruptured pseudoaneurysm of the internal carotid artery (ICA) is an often fatal complication of radiation treatment for patients with nasopharyngeal carcinoma. We review the clinical characteristics and predictors of survival in patients suffering from this serious complication after radiotherapy. STUDY DESIGN: Retrospective case series. METHODS: Clinical records and radiological investigations of postirradiated NPC patients with ICA pseudoaneurysm diagnosed with digital subtraction angiography in Queen Mary Hospital from January 2003 to December 2012 were reviewed. Risk factors analyzed for survival included gender, size of initial tumor, history of second course of radiotherapy, history of previous maxillary swing nasopharyngectomy, presence of persistent disease, successful initial hemostasis, successful airway control, and endovascular treatment. RESULTS: Twenty-six were included in the analysis. Twenty-three patients underwent endovascular treatment, and 20 (87%) had successful control of the bleeding. Eighteen (69%) patients survived. Univariate analysis showed that successful temporary control of bleeding and airway control were associated with survival. CONCLUSIONS: Prompt bleeding control and airway management is necessary to improve survival. Endovascular treatment is a good definitive treatment option with a high success rate.

The role of myringotomy and ventilation tube insertion in maxillary swing approach nasopharyngectomy: review of our 10-year experience.

OBJECTIVES/HYPOTHESIS: The use of myringotomy with ventilation tube insertion after maxillary swing nasopharyngectomy was originally described to prevent the occurrence of otitis media with effusion. The outcome of this otologic procedure has never been reviewed and discussed. The purpose of this study is to examine the role of myringotomy with ventilation tube insertion in this group of patients. STUDY DESIGN: Retrospective review. METHODS: One hundred forty-two patients with maxillary swing nasopharyngectomy were recruited from 1999 to 2008. The otologic status was evaluated using otoscopy, pure tone audiogram, and tympanogram at 3 months, 6 months, and then yearly after the operation. The results were reviewed periodically during that 10-year period. During this period, there were three groups; the first group had myringotomy with ventilation tube inserted, the second group had myringotomy alone, and the third group had no myringotomy performed. RESULTS: There were significantly (P < .0001) more patients in the myringotomy with ventilation tube insertion group who suffered from adverse otologic complications such as discharging grommet, discharging chronic suppurative otitis media, and perforated eardrum when compared with patients with myringotomy alone and patients without myringotomy at 3 months, 6 months, and 12 months. There were no differences in the incidence of acute otitis media among all three groups of patients. CONCLUSIONS: Patients who underwent maxillary swing nasopharyngectomy and myringotomy with ventilation tube insertions suffered from more otologic complications. The routine use of myringotomy with or without ventilation tube insertion for this group of patients is not recommended.