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It is not uncommon for patients with hypopharyngeal cancer to present at an advanced stage of disease. Surgical treatment provides a cure for the tumour with immediate relief from obstruction to the airway and the swallowing passage. Careful planning of surgery is important to ensure good outcome of treatment and prevent complications, some of which may be fatal. The shape of the hypopharynx resembles that of a funnel, with a wide circumference above in continuity with the oropharynx, and a small circumference below where it joins with the cervical oesophagus. As a result, while small tumours require the partial removal of the hypopharynx, large tumours, especially those involving the post-cricoid region, warrant a complete, circumferential pharyngectomy. For tumours that invade the cervical esophagus, transcervical approach is still feasible, and this is facilitated by the removal of the manubrium, allowing access to the tumour and resection with clear margins. In the presence of synchronous tumours lower down in the esophagus, pharyngo-laryngo-esophagectomy is indicated. Successful reconstruction of defects after tumour extirpation allows proper wound healing and early delivery of adjuvant radiotherapy. It is also important to ensure quick recovery of the long-term swallowing function. It ranges from the use of the soft tissue flap with skin island that is sutured as a patch to the remnants of the pharyngeal mucosa, to the use of a visceral flap, such as the free jejunal flap, to repair the circumferential pharyngectomy defects. The treatment protocol is personalized according to the extent of the tumour and the characteristics of the patients.

Background The purpose of this study was to investigate the oncologic outcome and quality of life after surgical treatment of locally advanced (rT3–rT4) recurrent nasopharyngeal carcinoma (NPC) using the staged extracranial/intracranial vascular bypass and combined craniofacial approach. Methods We conducted a prospective study. Results Between 1998 and 2013, 28 patients with rT3 to rT4 tumors were treated with the proposed surgical protocol. Clear resection margin was achieved in 46.4%. The median follow-up was 42.6 months. The rate of local recurrence was 17.8%. The 5-year overall survival was 52%. There was no change in the mean global health system score after the extensive surgery, although the physical functioning scores deteriorated significantly. The most common symptoms experienced by patients were speech and swallowing problems. Conclusion The proposed surgical treatment for locally advanced recurrent NPC was associated with satisfactory local tumor control and survival. Quality of life after surgery was reasonable, although multidisciplinary training was required to maximize the postoperative speech and swallowing function. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

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

Background The purpose of this study was to present the feasibility of indocyanine green (ICG) mapping of sentinel lymph node in recurrent nasopharyngeal carcinoma (NPC). M1ethods Peritumoral injection of 5-mg ICG solution and real-time mapping of the sentinel lymph nodes in the neck was performed during surgery. The sentinel lymph node identified was excised and sent separately for laboratory analysis. Selective neck dissection was then performed. The number and level of the sentinel lymph nodes, their signal-to-background ratio, and the histopathology of the sentinel lymph nodes and the neck dissection specimens were studied. Results A total of 5 patients were recruited into this study, of which 9 sentinel lymph nodes were identified. The majority of them were located in level II. The mean detection time after ICG injection was 288 seconds. The sentinel lymph nodes in 3 patients tested positive for malignancy. None of the selective neck dissection specimens harbored microscopic tumor deposits. Conclusion ICG mapping of sentinel lymph nodes in locally recurrent NPC is potentially feasible. It offers a better nodal staging in patients with clinically N0 disease status © 2015 Wiley Periodicals, Inc. Head Neck 37: E169–E173, 2015

Background The purpose of this study was to present the postoperative local tumor control and survival with regard to the different resection margin statuses during salvage nasopharyngectomy. Methods We conducted a whole-organ study of nasopharyngectomy specimens. Results Between 2005 and 2010, 126 patients underwent maxillary swing nasopharyngectomy. The T classification of the recurrent tumor was: T1, 23.8%; T2, 41.3%; T3, 28.6%; and T4, 6.3%. The chance of clear, close, and involved resection margins at nasopharyngectomy was 44.4%, 31.0%, and 24.6%, respectively. At follow-up, the corresponding risk of local tumor recurrence after surgery was 10.7%, 38.5%, and 67.7%, respectively. The local tumor control was significantly worse in patients with involved margins compared with those with close margins (p = .01), which was, in turn, significantly worse than those with clear margins (p = .04). Conclusion The primary objective of salvage nasopharyngectomy is to achieve clear resection margins. Close and involved margins result in significantly inferior local tumor control and overall survival. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

BACKGROUND Local recurrence is the major cause of treatment failure in patients who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. The authors investigated the role of Epstein-Barr virus (EBV)-encoded Bam HI-A rightward transcript 7 microRNA (BART7) status in resection margins in the identification of a subgroup of patients who may benefit from adjuvant reradiation after surgery. METHODS One hundred two consecutive patients who had histologically clear resection margins after undergoing nasopharyngectomy for recurrent NPC were studied. The status of EBV microRNA BART7 in resection margins was investigated and correlated with the pattern of subsequent disease recurrence. RESULTS After a median follow-up of 64 months, 20 patients (19.6%) developed local recurrence after surgery despite histologically uninvolved margins. The risk of local recurrence in patients with histologically close (

The processes of anaerobic digestion and co-digestion are complicated and the development of computational models that are capable of simulation and prediction of anaerobic digester performances can assist in the operation of the anaerobic digestion processes and the optimization for methane production. The artificial neural network approach is considered to be an appropriate and uncomplicated modelling approach for anaerobic digestion applications. This study developed neural network models to predict the outcomes of anaerobic co-digestion of leachate with pineapple peel using experimental data. The multilayered feed forward neural network model proposed was capable of predicting the outcomes of biogas production from the anaerobic co-digestion processes with a mean squared error for validation of 2.67 x 10-2 and a R value for validation of 0.9942. The approach was found to be effective, flexible and versatile in coping with the non-linear relationships using available information.

Health risk characterization of exposure to benzene in service stations and petroleum refineries has been carried out in previous studies using guideline values set by various agencies. In this work, health risk was characterized with the exposure data as cumulative probability distribution (CPD) plots but using human epidemiological data. This was achieved by using lowest observable adverse effects levels (LOAEL) data plotted as cumulative probability lowest effects distribution (CPLED). The health risk due to benzene was characterized by using probabilistic methods of hazard quotient (HQ50/50 and HQ95/5), Monte-Carlo simulation (MCS) and overall risk probability (ORP). CPD relationships of adverse health effects relationships and exposure data were in terms of average daily dose (ADD) and lifetime average daily dose (LADD) for benzene. For service station environments HQ50/50 and HQ95/5 were in a range of 0.000071–0.055 and 0.0049–21, respectively. On the other hand, the risk estimated for petroleum refinery environments suggests higher risk with HQ50/50 and HQ95/5 values ranging from 0.0012 to 77 and 0.17 to 560, respectively. The results of Monte-Carlo risk probability (MRP) and ORP indicated that workers in petroleum refineries (MRP of 2.9–56% and ORP of 4.6–52% of the affected population) were at a higher risk of adverse health effects from exposure to benzene as compared to exposure to benzene in service station environments (MRP of 0.051 –3.4% and ORP of 0.35–2.7% affected population). The adverse effect risk probabilities estimated by using the Monte-Carlo simulation technique and the ORP method were found to be generally consistent.

The aquatic environments of the Pearl River Delta (PRD) in China have been contaminated by various industrial chemicals from local industries. In this study, the spatial–temporal distribution of six priority phthalate esters (PAEs) in surface water and sediments from the PRD was investigated. The PAEs were detected with total concentrations (Σ6PAEs) ranging from 0.35 to 20.70 μg L−1 in surface water and dry weight ranging from 0.88 to 5.69 μg g−1 in sediments. The Σ6PAEs concentrations in surface water were higher in the wet season than those in the dry season, while the opposite pattern was observed in sediments. Di(2-ethylhexyl) phthalate (DEHP) was the most abundant congener, which was higher than those reported in the literature. Risk quotients for relevant aquatic organisms were obtained and showed that most of these PAEs, in particular, butyl benzyl phthalate, DEHP and di-n-octyl phthalate, have significant potential health and ecological risks for the aquatic environment studied.

Evasion from natural killer (NK) cell surveillance enables cancer to proliferate and spread at the early stages. NK cells mediate specific cytolysis by activation of the triggering receptors on their cell surface, of which the communication between natural killer group 2, member D (NKG2D) and major histocompatibility complex class I chain-related peptide A (MICA) is a key regulatory axis. It has been indicated that cancer cells can reduce the surface expression of MICA, which thereby reduces the cytotoxicity of NK cells. In nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains unclear. The present study indicated that MICA expression in NPC was regulated by TGFβ1. Furthermore, the human MICA gene was demonstrated to contain the c-Myc binding site in the promoter region. Notably, the results suggested that TGFβ1 upregulated MICA expression by promoting c-Myc expression. Additionally, the findings demosntrated that TGFβ1 expression in NPC was negatively controlled by Epstein-Barr virus-encoded microRNA BART7 (ebv-miR-BART7). In ebv-miR-BART7-expressing NPC, the TGFβ1/c-Myc/MICA regulatory axis was significantly inhibited. Notably, functional analysis indicated that NPC cells expressing ebv-miR-BART7 were less sensitive to the cytolysis mediated by NK cells. In conclusion, the present results revealed that ebv-miR-BART7-expressing NPC may impair NK cells recognition and activity, which suggests that targeting ebv-miR-BART7 may be a useful therapeutic strategy in NPC immunotherapy.

Background To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of drainage after neck dissection. Methods Patients with oral cavity squamous cell carcinoma were randomized into Group A (study group) and Group B (control). In the study group, upon the completion of neck dissection, a total of 2.5 mg of ICG was injected submucosally at the four quadrants around the tumour. Another 2.5 mg of ICG was injected subdermally in the groin bilaterally. The neck was screened using Near Infrared fluorescence. The presence of lymphatic leakage was noted and plicated with silk stitches. The total drainage volume of post-operative day 1, day 2 and the total accumulated volume until drain removal was measured. Results Twenty-two patients (Group A, n = 12; Group B, n = 10) were recruited. All patients in Group A had at least one site of lymphatic leakage identified. One patient in Group B developed chylous fistula and was excluded from analysis. The mean total drain output for day 1 and 2 after surgery, as well as the mean total output before drain removal, were significantly lower in Group A (22.4 ml vs. 86.2 ml [p = .02]; 14.2 ml vs. 72.8 ml [p = .02]; and 58.4 ml vs. 392 ml [p = .01], respectively), allowing earlier drain removal (2.2 days vs. 7.2 days, p = .02). Conclusions Intra-operative ICG lymphangiography is useful in the reduction of drainage volume after neck dissection for caners in the head and neck region.

Background Frey syndrome is a common complication after parotidectomy. The aim of this study is to investigate potential predictors for development of Frey syndrome and explore their implications in additional prophylactic procedures. To the best of our knowledge, this is the first study to address these issues. Methods A computer search was performed to identify all patients who received parotidectomy from January 2009 to December 2011 in Queen Mary Hospital, Hong Kong. Individual case notes were reviewed to retrieve details for analysis. Results A total of 155 parotidectomies were identified. Tumor size was the only statistically significant clinical predictor (Frey group: 43.5 ± 38.4 mm vs No Frey group: 33.1 ± 27.5 mm; P = 0.018). Disease pathology, type of resection, and previous treatments such as radiotherapy or parotidectomy did not appear to be associated with development of Frey syndrome.Post hoc analysis of our data showed that Frey incidence nearly doubled in patients with tumor size of 4 cm or greater (33%) compared to those with tumors that sized less than 4 cm (18%). Conclusions Frey syndrome is common after parotidectomy. Tumor size is the only statistically significant predictor of its development. Routine preventive interventions, for example, use of acellular dermal matrix, dermofat graft or muscle flaps to prevent Frey syndrome, should be considered for high risk patients.

Head and neck cancer is a major cause of morbidity and mortality in Hong Kong. HNC is well-known for its heterogeneity in epidemiology, clinical behavior, clinic-pathological features and patient characteristics. Treatment strategies for this heterogeneous disease vary greatly in different parts of the world, depending on availability of resources, local expertise and experience. Extensive research in head and neck cancer, particularly nasopharyngeal carcinoma, has been conducted in Hong Kong in the past few decades. In this article, we will review the available local evidence and summarize common practice in management of head and neck cancer in Hong Kong.

Background Nasopharyngeal carcinoma (NPC) latently infected by Epstein-Barr virus (EBV) expresses 40 EBV BART microRNAs (miRNAs). Difference in diagnostic efficacy of these miRNAs on NPC detection was observed. Here, we performed a comprehensive evaluation on the efficacy of these miRNAs. Methods Quantitative polymerase chain reaction was performed on plasma nucleic acid isolated from patients with NPC and noncancer donors. Results For primary NPC, BART2-5P, BART6-3P, BART7-3P, BART7-5P, BART9-5P, BART11-3P, BART17-5P, and BART19-5P were significantly elevated. For recurrent NPC, plasma levels of BART2-3P, BART2-5P, BART5-3P, BART5-5P, BART6-3P, BART8-3P, BART9-5P, BART17-5P, BART19-3P, and BART20-3P were significantly increased. Area under curve (AUC) analysis showed that BART19-5P had the best performance to identify NPC which was serologically EBV DNA undetectable. For recurrent NPC, BART8-3P and BART10-3P had highest AUC value for identifying cancer in EBV DNA undetectable plasma. Conclusion Our data supported the use of circulating EBV miRNAs in NPC and recurrent NPC detection.

Background This report presents an immunocompetent lady suffering from Candida parapsilosis associated with polybacterial cervical necrotizing fasciitis and descending mediastinitis. A literature review and management of invasive candidiasis is discussed. Methods A 57-year-old healthy lady presented with cervical necrotizing fasciitis and descending mediastinitis. She was promptly managed with emergency debridement. Both blood and tissue culture yielded multiple microorganisms including C. parapsilosis. Results The patient recovered progressively. She was discharged 2 months later. Conclusions Fungal infection is emerging in this medical era. Vigilance in patient management and as well as considering atypical microorganisms in aetiology may improve patient outcome.

A stand-alone down-flow hanging sponge (DHS) system with a two-stage configuration was operated for 700 days to treat synthetic soft drink wastewater at 3000 mg/L chemical oxygen demand (COD). Throughout the operation,90% COD and total organic carbon (TOC) removal efficiency was obtained by the first stage, and a final effluent of COD60 mg/L (TOC20 mg/L) was consistently maintained with the second stage. Lower organic removal efficiency was observed to closely correlate with lower pH, higher volatile fatty acid (VFA) concentration, and higher suspended solid (SS) in the effluent. Occasionally, biomass sloughing was observed as a cause to unstable reactor performance in the first stage. The microbial community of the retained biomass on the sponges differed significantly based on spatial locations of sponges, sampling time points, and loading shocks. In general, Proteobacteria were found to be more abundant in the reactor at an organic removal efficiency80% than that at50%. Specifically, operational taxonomic units closely related to Tolumonas auensis and Rivicola pingtungensis were identified as important populations that were responsible for degrading the major substrate in the soft drink wastewater toward to the end of the reactor operation. In addition, high abundance of Bacteroidetes in the reactor was speculated to be responsible for the VFA accumulation in the effluent. This study demonstrated that stand-alone DHS reactor could be used in treating high-strength wastewater efficiently.

Summary Objectives: Nasopharyngeal carcinoma is a unique tumour which is endemic in Southern China including Hong Kong. While the treatment results for primary cancer has been encouraging, management of persistent or recurrent tumours has been challenging. Compared to other surgical approaches, the maxillary swing operation provides spacious access to the bilateral nasopharynx and the ipsilateral parapharyngeal space, allowing resection of tumours with wide margins. In this article, we will present our results in the surgical management of recurrent nasopharyngeal carcinoma. Materials and Methods: Retrospective review. Results: Over the years, we have performed salvage maxillary swing nasopharyngectomy for 312 patients. Microscopic negative resection margins were achieved in the majority (79.5%) of the patients. The overall local recurrence rate after surgery was 13.1%, the risk of which was significantly higher in patients with previous positive resection margins. The overall 5-year actuarial local tumour control and overall survival was 74% and 62%, respectively, which was significantly higher in patients with clear resection. For small tumours located in the posterior wall, minimally invasive approach can be used, which included the endoscopic resection, or more recently, the transoral robotic (TORS) assisted approach. Conclusion: The result of surgical salvage of recurrent nasopharyngeal carcinoma is promising. Every effort should be made to ensure microscopic clearance of disease as well as to minimize the potential complications of surgery that may adversely affect the subsequent quality of life.

We noticed that a significant proportion of our patients with head and neck mucoepidermoid carcinoma (HNMEC) had second primary malignancies. To our knowledge, such an association has never been described. The aim of our study is to elucidate the association between second primary malignancies and HNMEC.Case series with chart review.Tertiary referral center.We included all patients with histologically proven HNMEC managed in the Department of Surgery, Queen Mary Hospital, from January 2003 through December 2013. Medical records were retrospectively reviewed and analyzed.Fifty-seven patients with HNMEC were identified. Fourteen (24.6%) had second primary malignancies. The commonest second primary malignancy was nasopharyngeal carcinoma, followed by carcinoma of the thyroid. Second primary malignancies developed before HNMEC in 7 patients, with a mean interval of 196 months. Five patients had second primary malignancies after development of HNMEC, with a mean interval of 65 months. Two patients had synchronous second primary malignancies. Clinical patterns of patients with HNMEC with and without second primary malignancies were compared. Major salivary glands were more frequently affected among patients with second primary malignancies, while minor salivary glands were more frequently affected among those without secondary primary malignancies (P = .032). Development of second primary malignancy was not found to affect the survival.About one-fourth of patients with HNMEC had a second primary malignancy. Major salivary glands were more frequently affected among patients with second primary malignancies. Development of second primary malignancy did not affect survival.

Background Management of cervical esophageal tumor postesophagectomy is mainly palliative because of inadequate exposure of tumor in the cervicothoracic region. In this study, we propose a means of cure for these patients. Methods Between January 2003 and June 2013, 6 patients underwent curative pharyngolaryngectomy and completion cervical esophagectomy via manubrial resection. Operative outcomes were analyzed and compared with a historical cohort who received palliative therapy. Results One patient required prolonged hospital stay for pneumonia, resulting in a median hospital stay of 30 days (range, 21–55 days). All patients resumed oral feeding at a mean of 15.2 days (range, 14–19 days). Tracheostoma stenosis was noted in 2 patients. One patient developed nodal recurrence, another with distant metastasis, resulting in a median disease-free survival of 13 months (range, 4–20 months). Median overall survival was significantly longer than the cohort group (19.0 vs 3.0 months; p = .013). Conclusion Salvage surgery in patients with carcinoma of the cervical esophagus postesophagectomy is feasible with significantly prolonged survival. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1170–1175, 2015

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. © 2014 Wiley Periodicals, Inc. Head Neck 37: 788–793, 2015

Background The purpose of this study was to report on the treatment outcomes of patients with postradiation second head and neck malignancies. Methods Fifty-seven consecutive patients with postradiation second malignancy were reviewed. Progression-free survival (PFS), overall survival (OS), and prognostic factors were analyzed. Results Mean time interval between first course of radiation therapy to the development of postradiation second malignancy was 13.2 years. Median PFS and OS for the whole group were 12.0 and 67.0 months, respectively. Postradiation sarcoma conferred a worse PFS (p = .003) and OS (p = .001) as compared to postradiation carcinoma. Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (p = .034), postradiation sarcoma (p = .007), and lack of radical surgery (p = .044) are prognostic of PFS, whereas postradiation sarcoma (p = .002), lack of postprogression surgery (p < .001), and lack of postprogression systemic therapy (p = .011) were prognostic factors of OS. Conclusion Treatment outcomes of postradiation second malignancy seemed promising under a multidisciplinary management. © 2014 Wiley Periodicals, Inc. Head Neck 37: 815–822, 2015

A comprehensive evaluation of the adverse health effects of human exposures to BTX from service station emissions was carried out using BTX exposure data from the scientific literature. The data was grouped into different scenarios based on activity, location and occupation and plotted as Cumulative Probability Distributions (CPD) plots. Health risk was evaluated for each scenario using the Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. HQ50 and HQ95 > 1 were obtained with benzene in the scenario for service station attendants and mechanics repairing petrol dispensing pumps indicating a possible health risk. The risk was minimized for service stations using vapour recovery systems which greatly reduced the benzene exposure levels. HQ50 and HQ95 < 1 were obtained for all other scenarios with benzene suggesting minimal risk for most of the exposed population. However, HQ50 and HQ95 < 1 was also found with toluene and xylene for all scenarios, suggesting minimal health risk. The lifetime excess Cancer Risk (CR) and Overall Risk Probability for cancer on exposure to benzene was calculated for all Scenarios and this was higher amongst service station attendants than any other scenario.

Background The purpose of this study was to investigate the complications after maxillary swing nasopharyngectomy. Methods Salvage nasopharyngectomy was performed for 338 patients during 1990 to 2012. Patient and tumor characteristics, perioperative and intraoperative information, and long-term morbidities were analyzed. Results There were significantly more patients with locally advanced tumors (rT3 and rT4) operated during the recent study period (2002–2012). However, the mean operative time and blood loss was significantly lower than in the earlier period (1990–2001). There was no hospital mortality. There was a significant reduction in the postoperative trismus and palatal fistula formation. Patients with locally advanced tumor, particularly those who required adjuvant chemoradiation, had a higher chance of facial numbness, nasal blockage, and swallowing problems after surgery. Conclusion Salvage nasopharyngectomy via the maxillary swing approach is safe with acceptable long-term morbidities. Prevention of complications associated with surgery, particularly for patients with locally advanced tumors, is crucial to ensure the best outcome of surgery. © 2014 Wiley Periodicals, Inc. Head Neck 37: 487–492, 2015

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. Level of Evidence 4 Laryngoscope 124:2292–2296, 2014

Background The purpose of this study was to investigate the prognostic factors for salvage nasopharyngectomy. Methods A retrospective review was conducted on maxillary swing nasopharyngectomy performed between 1998 and 2010. Univariate and multivariate analyses identified prognostic factors affecting actuarial local tumor control and overall survival. Results The median follow-up duration was 52 months. Among the 268 patients, 79.1% had clear resection margins. The 5-year actuarial local tumor control and overall survival was 74% and 62.1%, respectively. On multivariate analysis, tumor size, resection margin status, and gross tumor in the sphenoid sinus were independent prognostic factors for local tumor control. For overall survival, resection margin status, synchronous cervical nodal recurrence, and cavernous sinus invasion had a negative influence on overall survival after surgery. Conclusion Extent of nasopharyngectomy should be tailored to the individual tumor to achieve clear resection margins. Cavernous sinus invasion is associated with poor survival outcome, and detailed counseling and meticulous surgical planning is crucial in such circumstances. © 2014 Wiley Periodicals, Inc. Head Neck 36: 1013–1017, 2014

Background The purpose of this study was to investigate the treatment outcome of radiation-induced squamous cell carcinoma (SCC) of the nasopharynx after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Methods We conducted a retrospective review of patients who underwent radiation therapy for NPC, which resulted in radiation-induced SCC of the nasopharynx. Results Between 1998 and 2011, 24 patients had radiation-induced SCC of the nasopharynx. The median age of diagnosis was 68.2 years. The majority of patients (66.7%) presented with early-stage NPC initially, and they were treated with RT alone (n = 18) or concurrent chemoradiation (n = 6). The mean latency period for the second malignancy was 10.5 years. All the patients were treated with maxillary-swing nasopharyngectomy. Clear resection margin was achieved in 66.7%, and 75% of those with involved margin received adjuvant RT. The mean follow-up duration was 48.2 months. The overall 5-year actuarial local tumor control was 56% and the overall 5-year disease-free survival was 38%. Conclusion Radiation-induced SCC of the nasopharynx is rare after RT for NPC. The prognosis remained poor despite aggressive surgery and adjuvant RT. © 2013 Wiley Periodicals, Inc. Head Neck 36: 772–775, 2014

Background The purpose of this study was to investigate if nodal ratio has a prognostic role in the survival of patients with recurrent nasopharyngeal carcinoma (NPC) in the neck. Methods Patients with recurrent NPC in the neck who were treated in Queen Mary Hospital from 2000 to 2011 were identified. Clinical data, pathological results, and survival outcome were analyzed. Results Only nodal ratio remained as a statistically significant predictor in multivariate analysis for nodal recurrence (p = .045) and nodal recurrence-free survival (p = .010). All other predictors lost significance when compared with each other and with nodal ratio. Nodal ratio was also a significant predictor for overall survival (OS) in univariate analysis (p = .001) but lost its significance in multivariate analysis. The cutoff points 10% and 15% effectively stratified the patients into 3 risk groups (p = .02). Conclusion In patients with NPC with neck recurrence, nodal ratio (the ratio of positive nodes to the total number of nodes examined) is a strong predictor of further nodal recurrence and nodal recurrence-free survival. Nodal ratio also impacts the OS but loses its significance in multivariate analysis, including concurrent local recurrence. Stratification of patients into low, medium, and high-risk groups according to nodal ratio may have a potential role in guiding therapeutic decision-making. Therefore, further exploration in this area is warranted. © 2014 Wiley Periodicals, Inc. Head Neck 37: 12–17, 2015

Background. The deregulated tumorigenic long non-coding RNA (lncRNA) has been reported in several malignancies. However, there is still no comprehensive study on tongue squamous cell carcinoma (SCC). Methods. Functional reannotation for the human lncRNA was carried out by ncFANs. Real-time quantitative PCR was used to validate the identified lncRNAs. Results. Using the functional annotation algorithm from ncFANs, 8 differentially expressed lncRNAs were identified. Lnc-PPP2R4-5, lnc-SPRR2D-1, lnc-MAN1A2-1, lnc-FAM46A-1, lnc-MBL2-4:1, and lnc-MBL2-4:3 were upregulated in the microdissected tongue SCC tissues. In comparison, lnc-AL355149.1-1 and lnc-STXBP5-1 showed significant downregulation. High level of lnc-MBL2-4:3 was significantly associated with the node positive tongue SCC patients. Further, patients with advanced T-stage demonstrated a further reduction of lnc-AL355149.1-1 in the tumor tissues. Treatment of tongue SCC cells with 5-fluorouracil and paclitaxel can reserve the expression patterns observed in the tongue SCC tissues. Further, changes of lnc-MBL2-4:3 and lnc-AL355149.1-1 expression levels were noticed in the cisplatin-resistant tongue SCC cells. Conclusions. Our results demonstrated that functional reannotation allows us to identify novel lncRNAs using the existing gene expression array dataset. The association of lncRNA with the T-stage and nodal status of tongue SCC patients suggested that lncRNA deregulation was involved in the pathogenesis of tongue SCC., published_or_final_version

Keloid is a cutaneous dermal outgrowth resulting from uncontrolled deposition of collagen and glycosaminoglycan around the wound. The uncontrolled and persistent growth of keloids scar will result in cosmetic disfigurement, functional impairment and affect the quality of life. Triamcinolone acetonide (TAC) is traditionally employed in treating keloid scars. In the present study, we aim to evaluate the effectiveness of TAC and compare it with other common therapy employed in keloid treatment. Only randomized controlled trial (RCT) and controlled trial (CT) were included. Inverse variance risk ratio (RR), weighted mean difference (WMD) and corresponding 95% confidence intervals (CI) were calculated to evaluate the effect of intervention. Meta-analysis indicated that TAC treatment significantly reduced the size of keloid compared to untreated control. Reduction in size was statistically different in favor of TAC compared to silicone gel sheet. Significant difference in favor of TAC was observed compared with verapamil in term of vascularity and scar pliability. TAC treatment was more effective in reducing scar thickness in comparison with cryotherapy. However, the current meta-analysis has several limitations. Only a limited number of trials with the same comparison are available. Most trials recruited a small number of patients and used inconsistent outcome assessment. Most trials did not provide detail information on allocation concealment and blinding. Therefore, further evaluation in multi-center randomized controlled trials with consistent comparisons and outcome measurements are warrant to reach a consensus on the selection between TAC and different treatment modalities.

Background: Head and neck squamous cell carcinoma (HNSCC) has an increased content of reactive oxygen species (ROS). However, clinical trials of antioxidant resulted in no benefit towards HNSCC anti-cancer treatment. NADPH oxidase (NOX) family is found to be the major generator of ROS which might contribute to the failure of antioxidant therapy. For the past 10 years, NOX family have been found with a range of functions in different cancers. Of which, NOX5 is the least well-understood one with limited details of signaling roles. Purpose of the study: To investigate the role of NOX5 in HNSCC. Experimental procedures: Online databases were used to analyze the expression of NOX5 in HNSCC patients. Immunohistochemistry was performed to detect the NOX5 expression level and its co-expression with hypoxia-inducible factors (HIFs) in paraffin-embedded tumor tissues surgically resected from HNSCC patients in Hong Kong. Subcutaneous xenograft model was established using NOX5-silenced HNSCC cells to evaluate the tumor growth potential in vivo. Sulforhodamine B assay and colony formation assay were used to measure the proliferation potential of NOX5-silenced HNSCC cells in vitro. Hypoxia chamber was applied to mimic the hypoxic condition of tumor tissue in vitro. Flow cytometry with Dihydroethidium staining was performed to measure the production of superoxide when silencing or overexpressing NOX5. Superoxide scavenger TEMPOL was applied to test the signaling role of superoxide generated by NOX5. Quantitative PCR and western blot were used to measure the mRNA and protein expression level of NOX5 and HIFs in HNSCC cell lines. Results: Relative mRNA expression of NOX5 was found significantly increased in HNSCC tumor tissues comparing to normal tissues both in Oncomine and TCGA datasets. Interestingly, NOX5 expression was found higher in central areas of tumor nests with the co-expression of HIF-1α and HIF-2α in our HNSCC patients’ samples. Further, NOX5 was upregulated in HNSCC cell lines under hypoxic condition (1% oxygen). Knocking-down of NOX5 impaired HNSCC cell growth both in vivo and in vitro, and this reduction was more significant under hypoxic condition in vitro. Loss of NOX5 resulted in superoxide reduction and HIF-2α impairment but not HIF-1α. Overexpressed NOX5 induced superoxide production and HIF-2α expression, and this induction was attenuated by TEMPOL. Conclusions: Hypoxia-induced NOX5 promotes HNSCC tumor growth by regulating HIF-2α via generating superoxide. NOX5 might serve as a novel therapeutic target for treatment of HNSCC. Citation Format: Siqi Chen, Wei Gao, Jimmy Yu-Wai Chan, Thian-Sze Wong. Hypoxia-induced NADPH oxidase 5 (NOX5) promotes tumor growth of head and neck squamous cell carcinoma through HIF-2á signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2648.

Background Frozen section analysis (FSA) is frequently used in salvage surgery for recurrent or residual nasopharyngeal carcinoma (rNPC) after radiotherapy to ensure adequate tumor removal. However, the diagnostic accuracy of FSA in rNPC has never been clearly established. We believe that this is the first study to specifically address these issues. Methods Patients with rNPC who underwent nasopharyngectomy in Queen Mary Hospital from 2006 to 2011 were identified. Clinical data, FSA results, and permanent histological results were analyzed. Results In the tissue-based analysis, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 70.6%, 100%, 100%, 95.2%, and 95.7%, respectively. Only 37% of inconclusive FSA turned out negative on permanent histology. Presence of inconclusive (p = .000) or positive (p = .000) FSA results in the same operation significantly lowered the NPV of FSA. Conclusion FSA is useful in ensuring clear resection margins for rNPC. Further resection is advisable in cases of inconclusive FSA results. © 2013 Wiley Periodicals, Inc. Head Neck 36: 638–642, 2014

Middle East respiratory syndrome coronavirus (MERS-CoV) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs 10%) than SARS coronavirus (SARS-CoV) infection. To understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in MERS-CoV–infected human monocyte–derived macrophages (MDMs) versus SARS-CoV–infected MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (interferon α [IFN-α] and IFN-β) but induced comparable levels of tumor necrosis factor α and interleukin 6. Notably, MERS-CoV induced significantly higher expression levels of interleukin 12, IFN-γ, and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, and interleukin 8) than SARS-CoV. The expression of major histocompatibility complex class I and costimulatory molecules were significantly higher in MERS-CoV–infected MDMs than in SARS-CoV–infected cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.

SUMMARY The thermal behaviour and kinetic analysis of biomass (cypress wood chips and macadamia nut shells) and Australian bituminous coal during combustion were studies using the thermogravimetric technique with four different heating rates under an air atmosphere. Each type of biomass was blended with coal at mass ratios (biomass:coal) of 95:5, 90:10, 85:15 and 80:20 to investigate the effect of coal as a supplementary fuel on thermal behaviour during the combustion process. Combustion of the individual samples and the blends took place in three steps comprising dehydration, devolatilisation and char oxidation. During co-combustion, the thermal decomposition behaviour of the blends followed that of the weighted average of the individual samples in the blends. In kinetic analysis, thermal decomposition of biomass and coal appeared to take place independently, and thus, the activation energy of the blends can be calculated from that of the two components. No evidence for any significant synergetic effects or thermal interaction was found between either type of biomass and the coal during co-combustion based on the lack of deviation from expected behaviour of the blends. Copyright © 2013 John Wiley & Sons, Ltd.

PURPOSE OF REVIEW To review the current practice of rehabilitation for laryngectomees in Hong Kong. RECENT FINDINGS Factors affecting the quality of life of laryngectomees include their performance in speech restoration, the presence of complications of treatment, as well as the availability of psycho-social support. In Hong Kong, more than 90% of laryngectomees have speech restoration by various means, the commonest of which being tracheo-oesophageal puncture and electrolaryngeal speech. However, they face special problems in communication using the current alaryngeal speech modalities, as it is difficult to produce variation in tones, which is important to express different meanings in Cantonese. The responsibility of surgeons to follow-up patients after surgery and the practice of management of common complications after laryngectomy are also discussed. The New Voice Club of Hong Kong promotes self-help and mutual help between laryngectomees, with the aim of helping new members to regain normal speech and to re-integrate into society. Quality-of-life study in Hong Kong shows that although the mean global health score is satisfactory, the social functioning domain is most severely affected after surgery. SUMMARY Cantonese-speaking laryngectomees in Hong Kong are facing unique challenges in speech restoration and re-integration into society after surgery. Surgeons should take the leading role in the multidisciplinary management of these patients.

Objectives/Hypothesis To study the histopathological features of recurrent nasopharyngeal carcinoma and the accuracy of preoperative magnetic resonance imaging (MRI). Study Design Prospective. Methods Whole-organ study of nasopharyngectomy specimens. Results Between 2006 and 2009, 50 specimens were obtained after maxillary swing nasopharyngectomy and sent for whole-organ study. The tumors arose from the fossa of Rosenmuller (68%), posterior wall (18%), or roof of the nasopharynx (14%), and the majority (72%) took the form of an ulcerative tumor. The T-classifications of the recurrent tumors were: T1, 24%; T2, 48%; and T3, 28%. All the tumors appeared as islands of cancer cells separated by lymphoplasmacytic infiltrate and fibrosis. The tumor size measured by MRI correlated closely with that measured histologically, especially for the depth of invasion and parapharyngeal extension. For tumors with parapharyngeal extension, removal of the pharyngobasilar fascia was essential to ensure a clear margin on the surface of the petrosal internal carotid artery. None of the tumors showed invasion of the Eustachian tube. Conclusions Contrast MRI is accurate in assessing the local extent of recurrent nasopharyngeal carcinoma. During nasopharyngectomy, a radial resection margin of 15 mm should be taken with the underlying medial pterygoid muscle. For tumors with parapharyngeal extension, the pharyngobasilar fascia should be resected en bloc with the specimen. Level of Evidence N/A Laryngoscope, 124:446–450, 2014

Objectives/Hypothesis To study the role of plasma Epstein-Barr virus (EBV) DNA in patients with recurrent nasopharyngeal carcinoma (NPC) after previous chemoradiation. Study Design Prospective. Methods Sixty patients with recurrent NPC were recruited, and their plasma EBV DNA was checked preoperatively, 1 week postoperatively, and 6 months thereafter. In a pilot group of 30 patients, further testing was performed at 60 minutes after tumor resection. The plasma EBV DNA level was correlated with tumor T classification, resection margin status, and subsequent relapse. Results The mean preoperative plasma EBV DNA reflected the tumor load (T1: 48 copies/mL, T2: 316 copies/mL, T3: 890 copies/mL, P = .03). It was significantly higher in patients with positive margins at the time of surgery (722 vs. 126 copies/mL, P = .02) and in those with subsequent systemic metastasis (668 vs. 92 copies/mL, P = .01). However, it failed to predict local recurrence after surgery. Postoperative plasma EBV DNA was undetectable in all patients with positive resection margins. Serial measurements were able to identify 87.5% of local recurrences and 100% of distance metastases. Conclusions In patients with recurrent NPC requiring salvage nasopharyngectomy, preoperative plasma EBV DNA identifies patients at high-risk of subsequent distant failure after surgery. Serial measurements of plasma EBV DNA after surgery, especially for those with high preoperative levels, is crucial to allow early detection of local of distant failure. Laryngoscope, 124:126–130, 2014

Background Microvascular surgeons always hold strong belief against the use of vasopressors during free flap surgery. Our aim is to study the safety of intra-operative vasopressors on free jejunal flap reconstruction. Methods A retrospective chart review was performed on patients undergoing free jejunal flap reconstruction, aiming at investigating the intra-operative use of vasopressors and the potential complications associated. Results Between 1984 and 2012, 110 free jejunal flaps were performed for reconstruction of circumferential pharyngeal defects created after resection of cancers of the hypopharynx. Intra-operative vasopressor was given in 81 (73.6%) patients. The most common vasopressors used were ephedrine (42.7%), phenylephrine (14.5%) or both (42.8%). They were administered to the patients before the start of flap harvesting (n = 32, 29.1%), during the flap harvesting (n = 30, 27.3%), during microvascular anastomosis (n = 20, 18.2%), or they were given more than once during the whole operation (n = 28, 25.4%). The incidence of intra-operative re-anastomosis due to thrombosis was 4.5% and the post-operative flap failure rate was 5.4%. There was no significant relationship between the administration of vasopressor during surgery and the need for intra-operative re-anastomosis, post-operative flap failure and the timing of flap failure. Similarly, there was also no relationship between the timing of vasopressor administration and the above variables. The long-term stricture rate was 2.7%, the risk of which was not increased by the intra-operative use of vasopressors. Conclusion The intra-operative use of vasopressors is safe in free jejunal flap reconstruction. © 2013 Wiley Periodicals, Inc. Microsurgery 33:358–361, 2013.