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.

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.

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.

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.

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.

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.

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.

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.

Secondary head and neck cancer in patients with history of hematological malignancy.

BACKGROUND: Head and neck cancer is a common second cancer in patients with a history of hematological malignancies. The purpose of this study was present the clinical characteristics and treatment outcomes of this group of patients. METHODS: A retrospective analysis was conducted of all patients who had a history of hematological malignancy and developed head and neck cancer in a 10-year period. RESULTS: The cohort had 10 patients; median age was 45.8 years. Most patients were nonsmokers and nondrinkers. Seven patients had chronic graft-versus-host disease. The median interval between the completion of treatment of hematological malignancy and the development of head and neck cancers was 8.79 years (range, 2.33-26.83 years). Six patients were alive and disease-free, 3 developed local recurrence, and 3 had metachronous head and neck cancers. CONCLUSION: The risk factors and etiology of head and neck cancers in patients with hematological malignancy may be different from the ordinary population.

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 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.

Overexpression of Epstein-Barr virus-encoded microRNA-BART7 in undifferentiated nasopharyngeal carcinoma.

AIM: To validate Epstein-Barr virus BamHI-A rightward transcript 7 microRNA (ebv-miR-BART7) expression in plasma from patients with nasopharyngeal carcinoma (NPC) and explore the oncogenic role of ebv-miR-BART7 in NPC cells. PATIENTS AND METHODS: Plasma ebv-miR-BART7 levels were measured using real-time quantitative RT-PCR. Effects on cell proliferation, invasion, migration, and resistance to cisplatin were studied on NPC cells using real-time cell analyzer. RESULTS: The plasma ebv-miR-BART7 level was significantly higher in patients with NPC in comparison with that from healthy individuals. The ebv-miR-BART7 was detectable in all the patient plasma samples and was independent of the EBV DNA level. In vitro expression of ebv-miR-BART7 enhanced proliferation, migration, and invasion of NPC cells. Furthermore, NPC cells expressing ebv-miR-BART7 were more resistant to cisplatin. High-throughput gene expression analysis suggested that ebv-miR-BART7 affects multiple cancer-related pathways. CONCLUSION: Our results indicate that plasma ebv-miR-BART7 could be used in NPC screening, especially in cases where EBV DNA is not detectable. The association of ebv-miR-BART7 with common oncogenic pathways suggests that ebv-miR-BART7 is a potential biomarker for undifferentiated NPC.

Epigenetic dysregulation in laryngeal squamous cell carcinoma.

Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.

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.

Combined transnasal endoscopic and transoral robotic resection of recurrent nasopharyngeal carcinoma.

BACKGROUND: We report a case of resecting a recurrent nasopharyngeal carcinoma using a combined technique of transoral robotic surgery and transnasal endoscopic surgery. METHOD: A small recurrent tumor was located in the roof of the nasopharynx. The inferior part of the resection was performed with a da Vinci surgical robot transorally after splitting the soft palate to expose the nasopharynx. The superior part of the resection, including removal of the anterior wall and floor of the sphenoid was performed transnasally under endoscopic vision. RESULTS: The tumor was removed enbloc with the sphenoid sinus wall with clear resection margin. Recovery was uneventful and the patient had minimal morbidity from the operation. CONCLUSION: For minimally invasive surgery to resect recurrent nasopharyngeal carcinoma, transnasal endoscopic surgery and transoral robotic surgery compliments each other, allowing improved resection.

Efficacy of neck dissection for locoregional failures versus isolated nodal failures in nasopharyngeal carcinoma.

BACKGROUND: Neck dissection has been shown to be effective in controlling nodal failures in nasopharyngeal carcinoma. Its efficacy in controlling the disease in patients with synchronous locoregional failure is, however, not documented. METHOD: A retrospective review of all patients who underwent neck dissection for nodal failures with or without treated local failure within 6 months was conducted for this study. The survivals of these 2 groups of patients were analyzed. RESULTS: The 5-year overall survival of the whole cohort was 58%. There was no difference in 5-year disease specific survival (68% vs 40%; p = .121) and 5-year progression free survival (44% vs 36%; p = .334) when comparing patients with isolated nodal failures and synchronous locoregional failures. Multivariate analysis showed that only the initial N classification affects survival. CONCLUSION: Neck dissection is efficacious in patients with nasopharyngeal carcinoma with nodal failure, with or without synchronous local failures.

Hypoxia in head and neck squamous cell carcinoma.

Hypoxia is a common feature in most of the solid tumors including head and neck squamous cell carcinoma (HNSCC). Hypoxia reflects the imbalance between oxygen consumption by the rapidly proliferating cancer cells and the insufficient oxygen delivery due to poor vascularization and blood supply. The hypoxic microenvironment in the HNSCC contributes to the development of aggressive carcinoma phenotype with high metastatic rate, resistance to therapeutic agents, and higher tumor recurrence rates, leading to low therapeutic efficiency and poor outcome. To overcome the therapeutic resistance due to hypoxia and improving the prognosis of the HNSCC patients, many approaches have been examined in laboratory studies and clinical trials. In this short paper, we discuss the mechanisms involved in the resistance of radiotherapy and chemotherapy in hypoxic condition. We also exploit the molecular mechanisms employed by the HNSCC cells to adapt the hypoxic condition and their tumorigenic role in head and neck, as well as the strategies to overcome hypoxia-induced therapeutic resistance.

mTOR Pathway and mTOR Inhibitors in Head and Neck Cancer.

Head and neck cancer is the sixth most common type of Cancer worldwide. Since conventional treatment regimens are nonselective and are associated with systemic toxicities, intense investigations focus on molecular targeted therapy with high selectivity and low adverse effects. mTOR signaling pathway has been found to be activated in head and neck cancer, making it attractive for targeted therapy. In addition, expression levels of mTOR and downstream targets eIF4E, 4EBP1, S6K1, and S6 are potential diagnostic and prognostic biomarkers for head and neck cancer. mTOR inhibitors, such as rapamycin and its derivatives temsirolimus and everolimus, exhibit inhibitory effects on head and neck cancer in both in vitro cell line model and in vivo xenograft model. A large number of clinical trials have been initiated to evaluate the therapeutic effects of mTOR inhibitors on patients with head and neck cancer. mTOR inhibitor has potential as a single therapeutic agent or in combination with radiation, chemotherapeutic agents, or other targeted therapeutic agents to obtain synergistic repression on head and neck cancer.