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This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated.In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge.To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog.The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Background Pulmonary embolism (PE) is a common and potentially life-threatening condition. Since it is considered a ‘do not miss’ diagnosis, PE tends to be over-investigated beyond the evidence-based clinical decision support systems (CDSS), which in turn subjects patients to unnecessary radiation and contrast agent exposure with no apparent benefits in terms of outcome. The purpose of this study was to evaluate the yield of ‘clinical hunch’ (gestalt) and four CDSS: the PERC Rule, Wells score, revised Geneva score, and Years criteria. Methods A review was conducted on the Electronic Medical Records (EMR) of 1566 patients from the Emergency Department at a tertiary teaching hospital who underwent CTPA from the 1st of January 2018 to the 31st of December 2019. The scores for the four CDSS were calculated retrospectively from the EMR data. We considered that a CTPA had been ordered on a clinical hunch when there was no mention of CDSS in the EMR, and no D-dimer test. A bypass of CDSS was confirmed when any step of the diagnostic algorithms was not followed. Results Of the total 1566 patients who underwent CTPA, 265 (17%) were positive for PE. The diagnosis yield from the five decision groups (clinical hunch and four CDSS) was as follows—clinical hunch, 15%; PERC rule, 18% (6% when bypassed); Wells score, 19% (11% when bypassed); revised Geneva score, 26% (13% when bypassed); and YEARS criteria, 18% (6% when bypassed). Conclusion Clinicians should trust the evidence-based clinical decision support systems in line with the international guidelines to diagnose PE.

OBJECTIVE/HYPOTHESIS To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer-related carotid blowout syndrome (CBS). STUDY DESIGN Retrospective case series. METHODS Retrospective analysis of clinical data of patients with head and neck cancer-related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results. RESULTS Thrity-seven patients were included. Twenty-five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA-related CBS, the median survival was 6 months, and the 90-day, 1-year, and 2-year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1-month, 6-month, and 2-year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA-related CBS, the median survival was 22.5 months, and the 90-day, 1-year, and 2-year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA-related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment. CONCLUSIONS For patients with ICA/CCA-related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred. LEVEL OF EVIDENCE 4 Laryngoscope, 131:1548-1556, 2021.

This study describes a novel approach in the reduction of SARS-CoV-2 transmission during trans-oral robotic surgery (TORS). Eight patients underwent TORS between 01 February 2020 and 07 September 2020. A sterile plastic sheet draped over sterile supports with water-tight seal around each cannula was used to create a sterile working space within which the robotic arms could freely move during operation. This set-up acts as an additional physical barrier against droplet and aerosol transmission. Operative diagnosis; droplet count and distribution on plastic sheet and face shields of console and assistant surgeons, and scrub nurse were documented. TORS tumour excision was performed for patients with suspected tonsillar tumour (n = 3) and tongue base tumour (n = 2). TORS tonsillectomy and tongue base mucosectomy was performed for cervical nodal metastatic carcinoma of unknown origin (n = 3). Droplet contamination was noted on all plastic drapes (n = 8). Droplet contamination was most severe over the central surface at 97.2% (91.7–100.0%), with the highest droplet count along the centre-most column where it overlies the site of operation in the oral cavity 33.3% (n = 31). Droplet count decreased towards the periphery. Contamination rate was 2.8% (0.0–8.3%) over the right lateral surface. There was no droplet contamination over the vertex and left lateral surface of plastic drapes. No droplet contamination was noted on face shields of all parties. The use of sterile plastic drapes with water-tight seal around each robotic cannula can help reduce viral transmission to healthcare providers during TORS.

In aquatic environments, microplastics (MPs) are pervasive which could have a considerable negative impact on the environment, organisms and pose a risk to human health. However, knowledge about the exposure and ecological risk of MPs in the coastal ecosystems of developing countries is limited. In this study, we analyzed salt samples from five commonly consumed processed and unprocessed sea salts of different commercial brands originated from 15 salt pans in Bangladesh to assess the abundance, characteristics and potential risks of MPs. The quantities of MPs in unprocessed salts (average 195 ± 56 item/kg) were higher than those in the processed salts (average 157 ± 34 item/kg). One-way analysis of variance (ANOVA) showed significant (p 0.05) differences among the average numbers of MPs in both processed and unprocessed salts. MP levels in this study were 2-3 times higher than those reported from some other countries. Fiber-shaped and transparent MPs were dominant in both cases. MPs less than 0.5 mm in size were the most abundant in both unprocessed (58.2%) and processed (62.2%) salts. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed five types of polymers, including polyethylene terephthalate (PET-35%), polypropylene (PP-27.5%), polyethylene (PE-25%), polystyrene (PS-10%), and Nylon (2.5%) in the studied salts. The sea salts were classified as potential hazard index (PHI) levels IV to V, indicating serious MP contamination, whereas potential ecological risk factor (E

This study aims to assess the feasibility of using indocyanine green and robotic near infra-red fluorescent imaging (Firefly®) for sentinel lymph node biopsy in cN0 oral cavity cancer. Ten patients with early squamous cell carcinoma of the tongue (n = 8) and buccal mucosa (n = 2) were included. Peritumoral injection of 10 mg indocyanine green and real-time mapping of sentinel lymph nodes in the neck was performed using Firefly® via a retro-auricular trans-hairline incision. Sentinel lymph node was detected in all patients at 1.2 sentinel lymph node per person. Majority were situated in level II (91.7%). Mean time to detection of sentinel lymph node was 171.0 (68.0–312.0)s. Mean signal-to-background ratio was 5.62 (3.51–7.91). Frozen section of one sentinel lymph node was positive for malignancy, paraffin section of which confirmed the presence of metastatic disease. Modified radical neck dissection was performed for that particular patient, paraffin section of which did not show any tumor deposit. Frozen section and paraffin section of all other sentinel lymph nodes (n = 11) and neck dissection specimens yielded no malignancy. All resection margins were clear. Three patients completed adjuvant radiotherapy for pT2N0 (n = 2) and pT2N1 (n = 1) carcinoma of the tongue. Mean follow-up was 12.0 (4.0–18.0) months. All patients were alive at last follow-up with no disease recurrence. There were no adverse outcomes associated with the use of indocyanine green and robot-assisted neck dissection. Indocyanine green and Firefly® for sentinel lymph node biopsy in cN0 oral cavity cancer is feasible with no adverse effects.

This technique for setting guideline values differs from that currently used by regulatory agencies throughout the world. Data for benzene were evaluated from epidemiological studies on human populations (29 studies). Exposure durations were evaluated in terms of Long Term Exposure (LTE) and Lifetime Exposure. All data was reported as Lowest Observed Adverse Effect Levels (LOAEL) and converted into exposure doses using Average Daily Dose (ADD) and Lifetime Average Daily Dose (LADD). These values were plotted as a Toxicant Sensitivity Distribution (TSD) which was the cumulative probability of LOAEL-ADD and LOAEL-LADD. From the TSD plots, linear regression equations gave correlation coefficients (R2) ranging from 0.69 to 0.97 indicating normal distributions. Guideline Values (GVs) for LTE (8hr/day) and Lifetime (24hr/70yrs) exposure to benzene were calculated using data from human epidemiological studies as 5% level of cumulative probability (CP) of LOAEL–ADD and LOAEL–LADD from the cumulative probability distributions (CPD). The derived guideline values from the human epidemiological studies were 92 μg/kg/day for LTE and 3.4 μg/kg/day for lifetime exposure. GV for LTE is appropriate for occupational exposure and GV derived for lifetime exposure appropriate for the general population. The guideline value for occupational exposure limit was below all the guideline values developed by regulatory agencies. But the general population guideline is within the range of values formulated by European Union, ATSDR, EPAQS, USEPA and OEHHA for air quality for the general population. This is an alternative method which eliminates the application of safety factors and other sources of errors in deriving guideline values for benzene.

The maxillary swing approach was introduced three decades ago in the head and neck field providing optimal surgical exposure for tumors in the nasopharyngeal and/or the retromaxillary space.To report the clinical experience, patient surgical morbidity and survival outcomes following the introduction of the maxillary swing approach in Denmark.A retrospective study including patients who underwent the maxillary swing approach from January 2012 - January 2020. Baseline and perioperative data, pathology, postoperative morbidity and survival outcomes were registered.Sixteen patients were included of which 15 had a malignant tumor with different histology, while one patient had a benign tumor. Most commonly reported short-term morbidity were trismus, cheek hypoesthesia, nasopalatal fistula, lacrimation and nasal stenosis (3 months postoperatively) improving markedly at 12 months follow-up. For patients with malignant tumors, the 5-year overall survival and recurrence-free survival rates were 60% and 66.7%, respectively.The maxillary swing approach was safely implemented by a multidisciplinary team at a high-volume centralized head and neck cancer center in Denmark. The procedure may be considered for salvage surgery of recurrent nasopharyngeal carcinomas and selected malignant and benign tumors located in the nasopharynx and/or retromaxillary space inaccessible by other surgical modalities.

Cervical esophageal smooth muscle tumors are traditionally resected via lateral transcervical with or without video-assisted thoracoscopic approaches. Exposure is frequently limited, however, with risks of recurrent laryngeal nerve and posterior tracheal wall injury and jeopardization of cervical tracheal and cervical esophageal blood supply. We herein describe an anterior transcervical transtracheal approach to counter some of the aforementioned problems and avoid morbidities associated with thoracoscopic surgery when resecting smooth muscle tumors arising from the cervical esophagus.

Background This study describes a novel approach in reducing SARS‐CoV‐2 transmission during tracheostomy. Methods Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented. Results Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%‐100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%‐10.0%) and 3.3% (6.7%‐10.0%), respectively. No droplet contamination was noted on all face shields. Conclusion Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.

Background COVID‐19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery. Methods Fifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented. Results Forty‐five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery. Conclusion Face shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.

Objectives Free jejunal flap for circumferential pharyngeal reconstruction is associated with late-onset dysphagia, regurgitation and prolonged transit time. This study aims to assess the feasibility and efficacy of Botulinum toxin A (Botox) in alleviating such swallowing dysfunction. Materials and methods Twenty-six consecutive patients underwent free jejunal flap for circumferential pharyngeal reconstruction between January 2012 and December 2018. Outcomes were compared at 6, 12 and 24 months. Results In the non-Botox group (n = 13), video-fluoroscopic and manometry studies demonstrated asynchronous contractions and retrograde propulsion. All patients complained of nasal regurgitation on thin fluids at 6, 12 and 24 months. Bolus residue accumulation along jejunal mucosal folds resulted in prolonged transit time. In the Botox group (n = 13), amplitude of asynchronous contractions were lower: 25.4 mmHg vs. 52.1 mmHg (p = 0.037) for thin fluids at 12 months. Three patients complained of nasal regurgitation on thin fluids at 6 months. All 3 were asymptomatic at 12 months. Transit time was shortened overall. Functional Oral Intake Scale was higher. MD Anderson Dysphagia Inventory global (72.5% vs 45.7%, p = 0.003) and functional (62.0% vs 40.6%, p = 0.012) subscales were significantly improved at 24 months. Conclusion Botox safely and effectively alleviates swallowing dysfunction associated with free jejunal flap for circumferential pharyngeal reconstruction.

Background Prospective, observational study to assess the efficacy of salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma (NPC) via the endoscopic endonasal approach using a three-dimensional (3D) high-definition endoscopic system. Methods Between 2016 and 2017, 30 patients with recurrent NPC were recruited. Patient demographics, tumor characteristics, and perioperative data were recorded. Instrument ergonomics and perceived advantages were assessed by the operating, assisting, and observing surgeons. Results The majority (70%) of patients received radiotherapy alone as the initial treatment for NPC, and tumor recurred after a mean interval of 16.8 months. The tumor (T) classifications of the recurrent (R) tumors were: RT1: 46.7%; RT2: 33.3%; and RT3: 20.0%. The mean operative time was 293.3 minutes, and no conversion to open approach was necessary. Internal carotid artery dissection was required in nine patients, and the resection and repair of dura was required in six patients. The most common method of reconstruction was free vastus lateralis flap (46.7%). Microscopically clear resection margins were achieved in 73.3% of patients. The mean hospital stay was 6.8 days. There was no hospital mortality. One patient developed minor secondary hemorrhage, whereas the other developed transient contralateral vocal cord paralysis. On quantitative assessment, surgeons noticed a significant advantage of the 3D system with regard to depth and size perception, anatomy identification, and hand-eye coordination, whereas there was no significant difference in terms of strain sensation and dizziness. Conclusion The 3D high-definition endoscopic system improves the precision of endoscopic nasopharyngectomy, particularly when dissection of the internal carotid artery and dura is required. Level of evidence 4. Laryngoscope, 128:1386-1391, 2018.

Background The purpose of this study was to review the efficacy of surgery for patients with osteoradionecrosis (ORN) after radiotherapy for nasopharyngeal carcinoma (NPC). Methods Between 2000 and 2016, we identified 162 patients with skull base ORN, among which 58 patients required surgery. A retrospective medical chart review was performed and the indications and results of surgical interventions were recorded. Results All surgeries were performed for the treatment of secondary complications of ORN, including central nervous system (CNS) infection (48.4%), blowout bleeding (24.1%), and severe pain (17.2%). Endoscopic debridement was done in 12 patients, whereas the rest required either maxillary swing or mandibulotomy, depending on the location of the necrosis. The majority of the patients required free vastus lateralis flap (72.5%) for reconstruction. Surgery was effective in the control of infection, bleeding, and pain. Multivariate analysis identified reirradiation and bone exposure on MRI as the significant independent risk factors predicting the future need of surgery. Conclusion Surgery is effective in the treatment of secondary complications of skull base ORN after previous radiotherapy for NPC.

Purpose Literature on palpebral springs is scarce, and even more so for the Asian population. In this study, the authors evaluated their experience with palpebral spring placement for paralytic lagophthalmos in an Asian population. The authors report the unique challenges encountered due to the distinctive features in Asian eyelids and how they overcome them. To the best of our knowledge, this is the first report on the application of palpebral springs in Asians. Methods All patients treated for paralytic lagophthalmos in the Department of Surgery, Queen Mary Hospital, from November 2013 to December 2015, were included in this study. The authors retrieved and analyzed the demographic data, preoperative assessment details, and treatment outcomes. Results A total of 17 patients were recruited. The median interval between facial palsy occurrence and surgery was 66 months. Preoperatively, vertical palpebral fissure was 12.3 ± 1.7 mm with margin reflex distance 1 of 3.7 ± 0.3 mm and margin reflex distance 2 of 8.6 ± 1.6 mm. Lagophthalmos before surgery was 9.6 ± 2.3 mm. After the palpebral spring surgeries, vertical palpebral fissure was reduced to 9.1 ± 1.4 mm. margin reflex distance 1 is slightly reduced (3.3 ± 0.8 mm) and margin reflex distance 2 improved to 5.8 ± 1.0 mm. Lagophthalmos reduced significantly to 0.8 ± 1.3 mm. Seven patients required revision procedures. Conclusions Palpebral spring is a safe and effective treatment for Asian patients with paralytic lagophthalmos. However, surgeons should be aware of the unique challenges associated with the anatomy of Asian eyelids. Special adaptation of the procedure is required to optimize the outcome.

// Wei Gao 1, 2 , Zeng-Hong Li 3 , Siqi Chen 1, 2 , Jimmy Yu-Wai Chan 1, 2 , Min Yin 4 , Min-Juan Zhang 1, 2 , Thian-Sze Wong 1, 2 1 Department of Surgery, The University of Hong Kong, Hong Kong SAR 2 Shenzhen Institute of Research and Innovation, The University of Hong Kong, Guangdong Province, China 3 Department of Otolaryngology, The First People's Hospital of Foshan, Guangdong Province, China 4 Department of Otorhinolaryngology Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China Correspondence to: Thian-Sze Wong, email: thiansze@gmail.com Keywords: nasopharyngeal carcinoma, EBV, radiation sensitivity, MicroRNA BART7 Received: April 18, 2016 Accepted: January 10, 2017 Published: February 20, 2017 ABSTRACT Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very sensitive to radiotherapy. To date, the underlying mechanism remains poorly understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7 (ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by targeting GFPT1/TGFβ1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGFβ1 production. TGFβ1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells. TGFβ1 can protect zebrafish embryo from the lethal effects of radiation treatment. In silico analysis showed that ebv-miR-BART7 could target GFPT1 transcript. Correlation analysis on primary NPC tissues suggested that ebv-miR-BART7 and GFPT1 have negative expression correlation. Expression of GFPT1 and TGFβ1 were inducible by radiation in NPC cell with ebv-miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited TGFβ1 which subsequently increased the responsiveness of NPC to radiation treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls TGFβ1 production by targeting GFPT1. Detection of ebv-miR-BART7 may provide useful indicator for monitoring NPC progression and predict therapeutic outcomes.

Radiation therapy is the standard treatment for primary nasopharyngeal carcinoma (NPC). MicroRNA regulates cancer responsiveness to radiation therapy by controlling the genes involved in radiation responses. Recent studies suggested that downregulation of microRNA-138-5p was clinically significant in NPC. Here, we evaluated the effect of miR-138-5p on radiosensitivity of NPC cells and explored the underlying mechanisms by identifying its target gene that impacted sensitivity to radiation. Our results revealed that overexpression of miR-138-5p reduced the ability to form colonies, inhibited proliferation, and enhanced radiation-induced DNA damage and autophagy in NPC cells upon radiation treatment. By integrating predicted targets with the transcripts downregulated by miR-138-5p, EIF4EBP1 was identified to be a target gene of miR-138-5p. Results from luciferase reporter assay demonstrated that miR-138-5p downregulated the expression of EIF4EBP1 by binding to the 3'-UTR. Silence of EIF4EBP1 enhanced radiosensitivity of NPC cells as evidenced by reduced ability to form colonies after radiation exposure. In summary, our results indicated that miR-138-5p enhanced radiosensitivity of NPC cells by targeting EIF4EBP1. Further studies are warranted to investigate the potential use of miR-138-5p in the clinical management and treatment prediction of NPC patients.

Background Definitive chemoradiotherapy is offered for most patients with isolated cervical esophageal tumor. Surgery is reserved for locally advanced diseases and salvage for failed chemoradiotherapy. Traditionally, surgery comprises total pharyngolaryngeal esophagectomy and gastric pull-up, which is associated with high morbidity and mortality rates. We hereby propose pharyngo-laryngo-cervico-esophagectomy by a transcervical approach, allowing preservation of the esophagus and stomach below, reducing operative morbidity and mortality. Methods A retrospective review of 31 patients who underwent curative pharyngo-laryngo-cervico-esophagectomy for isolated cervical esophageal tumor at the Department of Surgery, The University of Hong Kong, Queen Mary Hospital, between January 1, 2005, and June 30, 2018, was performed. Results There were 26 male and 5 female patients. Median age was 64.8 years. Seventeen patients underwent definitive surgery. Fourteen patients underwent salvage surgery for failed chemoradiotherapy. Most patients presented with stage III and IV diseases (90.3%). Median length of pharyngoesophageal defect was 14.0 cm (range, 8.0-21.0 cm). Free jejunal flap was used for pharyngoesophageal reconstruction in 77.4%. Eight complications developed in 7 patients (22.6%). There was no in-hospital mortality. Clear radial and longitudinal resection margins were achieved in 96.8%. Median follow-up was 21.5 months. Locoregional recurrence rate was 32.3%. Nine patients died of disease progression (29.0%). Seven died of other causes (22.6%). Median survival was 21.5 months. Overall 2-year survival rate was 36.7%. Conclusions Transcervical pharyngo-laryngo-cervico-esophagectomy should be considered in patients with isolated cervical esophageal tumors. Pharyngo-laryngo-cervico-esophagectomy allows adequate tumor resection while preserving the esophagus and stomach below. Operative morbidity and mortality outcomes were improved without compromising oncologic control.

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.

The levels of nitrate in 52 drinking water wells in rural Central Java, Indonesia were evaluated in April 2014, and the results were used for a health risk assessment for the local populations by using probabilistic techniques. The concentrations of nitrate in drinking water had a range of 0.01-84 mg/L, a mean of 20 mg/L and a medium of 14 mg/L. Only two of the 52 samples exceeded the WHO guideline values of 50 mg/L for infant methaemoglobinaemia. The hazard quotient values as evaluated against the WHO guideline value at the 50 and 95 percentile points were HQ50 at 0.42 and HQ95 at 1.2, respectively. These indicated a low risk of infant methaemoglobinaemia for the whole population, but some risk for the sensitive portion of the population. The HQ50 and HQ95 values based on WHO acceptable daily intake dose for adult male and female were 0.35 and 1.0, respectively, indicating a generally a low level of risk. A risk characterisation linking birth defects to nitrate levels in water consumed during the first three months of pregnancy resulted in a HQ50/50 values of 1.5 and a HQ95/5 value of 65. These HQ values indicated an elevated risk for birth defects, in particular for the more sensitive population. A sanitation improvement program in the study area had a positive effect in reducing nitrate levels in wells and the corresponding risk for public health. For example, the birth defect HQ50/50 values for a subset of wells surveyed in both 2014 and 2015 was reduced from 1.1 to 0.71.

Malignant melanoma is a relatively common malignancy in the West, but has a significantly lower incidence in Asians. Stark contrast in clinicopathological characteristics and prognosis has been observed between the 2 populations, yet data are limited. Here, we evaluate 106 Asian patients from a tertiary referral center in Hong Kong during an 11-year period. The purpose of this study was to collectively review all types of melanomas to analyze the clinicopathological characteristics of this poorly understood condition in an Asian population.A total of 106 patients diagnosed with malignant melanoma from 2002 to 2012 were retrospectively reviewed. Demographics, clinical presentations, pathological subtypes, treatments, and survival outcomes were evaluated.Cutaneous melanomas dominated with 46 (43.4%) cases, followed by mucosal (39.6%), ocular (9.4%), and melanomas of unknown primary (7.5%); 43.3% patients presented in stage I, 36.7% in stage II, 18.9% in stage III, and 1.1% in stage IV. Acral lentiginous melanoma was the commonest subtype of cutaneous melanomas (60.9%). When types of melanomas were reviewed collectively, the median overall survival, disease-specific survival, and recurrence-free survival were 37, 45, and 48 months, respectively. Cutaneous melanoma had the best median overall survival of 59 months, followed by ocular melanoma (58 months), mucosal melanoma (18 months), and melanoma of unknown primary (2 months). Similar patterns were observed for disease-specific survival and recurrence-free survival.Melanoma among Asians remains poorly understood. There is a clear distinction in the clinical patterns between Asians and whites and the difference is not solely accounted for by the lower incidence of cutaneous melanoma. Certain subtypes, such as mucosal melanoma and is acral lentiginous melanoma, seemed to have disproportionately high incidences. Further studies are warranted to elucidate these observations. The poor survival outcomes reflected the need for better awareness and understanding of the condition by both the general public and the physicians.

Background To report on the feasibility of total laryngopharyngectomy and free jejunal flap transfer for patient with hypopharyngeal cancer via the transoral robotic surgery (TORS) approach. Material and methods A patient with hypopharyngeal cancer involving the post-cricoid region is used for demonstration of the TORS total laryngopharyngectomy and free jejunal flap reconstruction. Results The procedure starts with a cruciate incision for terminal tracheostomy. The trachea and cervical esophagus is exposed and transected, making sure that the resection margins are adequate. This is followed by the transoral dissection using the robotic surgical system. The laryngopharyngectomy specimen is delivered and the free jejunal flap is replaced transorally. Jejuno-oesophageal suturing and the microvascular anastomosis are performed through the tracheostomy wound. The remaining pharyngo-jejunal anastomosis is performed transorally via the TORS approach. Conclusion TORS total laryngopharyngectomy and free jejunal flap reconstruction is feasible and provides and alternative option to the traditional transcervical approach.

The lack of representative nasopharyngeal carcinoma (NPC) models has seriously hampered research on EBV carcinogenesis and preclinical studies in NPC. Here we report the successful growth of five NPC patient-derived xenografts (PDXs) from fifty-eight attempts of transplantation of NPC specimens into NOD/SCID mice. The take rates for primary and recurrent NPC are 4.9% and 17.6%, respectively. Successful establishment of a new EBV-positive NPC cell line, NPC43, is achieved directly from patient NPC tissues by including Rho-associated coiled-coil containing kinases inhibitor (Y-27632) in culture medium. Spontaneous lytic reactivation of EBV can be observed in NPC43 upon withdrawal of Y-27632. Whole-exome sequencing (WES) reveals a close similarity in mutational profiles of these NPC PDXs with their corresponding patient NPC. Whole-genome sequencing (WGS) further delineates the genomic landscape and sequences of EBV genomes in these newly established NPC models, which supports their potential use in future studies of NPC., The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.

Background To study the efficacy of surgery for recurrent T3 nasopharyngeal carcinoma (NPC) and to determine the prognostic significance of various skull base bone invasion. Method Retrospective view of the surgical outcome for recurrent T3 NPC. Kaplan Meier and log rank tests were used to determine the 5-year overall and disease specific survival. Multivariate analysis was used to identify significant independent prognostic factors that affect the surgical outcome. Results Between 1990 and 2017, 208 patients with recurrent T3 NPC were recruited. Salvage surgery was performed via the endoscopic endonasal approach (n = 22, 10.6%), endoscopic transpterygoid approach (n = 63, 30.3%) and the maxillary swing approach (n = 123, 59.1%). Thirty-eight (18.3%) patients required vascular bypass. The skull base bone involved by the tumours included: maxillary sinus (n = 13), clivus (n = 36), pterygoid process (n = 61), sphenoid sinus (n = 30), petrous part of the temporal bone (n = 42) and a combination of the above (n = 26). The mean follow-up duration was 41.7 months. Multivariate analysis identified tumours involving with both cortexes of the clivus and the lateral wall of the sphenoid sinus, as well as positive bone resection margins as the significant independent prognostic factors for surgical outcome. Conclusion Outcome of surgical salvage is significantly worse for tumours that involve multiple bones at the skull base, particularly when both cortexes of the clivus and the lateral wall of the sphenoid sinus are invaded. Indication of aggressive surgery in such circumstances is controversial.

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 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.

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.

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.

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 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

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.

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 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

The status of the regional cervical lymphatics is one of the most significant prognostic indicators in head and neck cancers. The traditional treatment for cancers with cervical nodal metastasis has been surgical. With the global trend towards organ-preserving therapy, chemoradiation has gained increasing popularity over primary surgical therapies for cancers in the head and neck region. The subsequent management of the neck for those with residual or recurrent nodal metastasis, however, has become one of the most debated topics in the field of head and neck oncology. This review addressed several important controversies, including the optimal assessment of the nodal response to chemoradiation, the potential role and the oncological results of planned and salvage neck dissection after chemoradiation, as well as the type and extent of neck dissection required in order to achieve the optimal balance between tumour control and surgical morbidities. Further clinical trials and on-going research will help us to define the best therapeutic option in such circumstances.

Background The purpose of this study was to assess the predictability of the American Joint Committee on Cancer (AJCC) staging system on patients with stage II recurrent nasopharyngeal carcinoma (NPC). Method We conducted a retrospective review of the surgical outcome for patients with recurrent NPC and retropharyngeal lymph node (RLN) metastasis (group I), recurrent NPC and parapharyngeal space (PPS) invasion (group II), and recurrent NPC and internal carotid artery (ICA) encasement (group III). Results Between 1990 and 2013, 145 patients received an operation for stage II recurrent NPC (group I, n = 62; group II, n = 65; and group III, n = 18). The rate of local tumor recurrence was significantly higher in groups II and III. The rate of systemic metastasis was significantly higher in group III (16.7%). Accordingly, the 5-year overall survival was significantly worse for patients in group III (group I: 81.2%; group II: 68.4%; and group III: 48.5%). Conclusion The significantly worse prognosis of recurrent NPC encasing the ICA warrants an upstage to the T3 classification in the current AJCC staging system.

Nasopharyngeal carcinoma (NPC) can develop cisplatin‐resistant phenotype. Research has revealed that enriched in cancer stem cell population is involved in developing cisplatin‐resistant phenotype. CD271 is a candidate stem cell maker in head and neck cancers. The CD receptor does not possess any enzymatic property. Signal transduction function of CD271 is mediated by the cellular receptor‐associated protein. Our data showed that Brain‐expressed X‐linked 3 (BEX3), a CD271 receptor‐associated protein, was overexpressed in NPC. BEX3 overexpression was a unique event in cancer developed in the head and neck regions, especially NPC. BEX3 expression was inducible by cisplatin in NPC. In cisplatin‐resistant NPC xenograft, treatment with nontoxic level of cisplatin led to a remarkable increase in BEX3 level. High BEX3 expression was accompanied with high octamer‐binding transcription factor 4 (OCT4) expression in cisplatin‐resistant NPC. To confirm the inducing role of BEX3 on OCT4 expression, we knockdown BEX3 using siRNA and compared the expression of OCT4 with mock transfectants. Suppressing BEX3 transcripts led to a significant reduction in OCT4. In addition, targeting BEX3 using shRNA could increase the sensitivity of NPC cells to cisplatin. In summary, our results indicated a unique functional role of BEX3 in mediating the sensitivity of NPC cells to cisplatin. Targeting or blocking BEX3 activity might be useful in reversing the cisplatin‐resistant phenotype in NPC.

Significance Host genetics, environmental factors, and EBV infection together contribute to nasopharyngeal carcinoma (NPC) development. A number of critical genetic and epigenetic events contributing to tumor development has been reported. However, the genomic alterations in NPC have not been completely deciphered. We used the whole-exome sequencing approach to study the somatic mutations in NPC, and an APOBEC-mediated mutagenesis signature was revealed. Importantly, multiple loss-of-function mutations in the NF-κB–negative regulators ( NFKBIA , CYLD , and TNFAIP3 ) were discovered in NPC tumors, and we functionally confirmed that the NFKBIA loss-of-function mutations induce damaging effects on the WT proteins. Detection of these mutations emphasizes the critical role of NF-κB signaling in NPC tumorigenesis and provides perspectives for targeting this pathway in NPC treatment.

MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC., published_or_final_version

Objectives/Hypothesis: Our purpose was to study the effect of previous radiotherapy (RT) on the efficacy of fine-needle aspiration (FNA) in diagnosing cervical nodal metastasis in nasopharyngeal carcinoma (NPC). Study Design: Case-control study. Methods: The diagnostic efficacy of FNA in a group of patients with residual or recurrent cervical lymphadenopathy after previous RT for NPC was compared with a cohort of patients with primary NPC before RT during the same period. Results: Between 2008 and 2010, 50 patients were included for each group in the study. The specificity (100% vs. 88%, P = .12) and positive predictive value (100% vs. 89%, P = .12) was comparable in the two groups. However, the sensitivity (82% vs. 40%, P = .04), negative predictive value (NPV; 74% vs. 36%, P = .03), and accuracy (88% vs. 54%, P = .05) were significantly worse after previous RT. Previous RT was the only factor that was significantly associated with worse diagnostic efficacy (P = .001). When used together with plasma Epstein–Barr virus (pEBV)-DNA level and magnetic resonance imaging (MRI) findings (triple assessment), the diagnostic efficacy was significantly improved, especially regarding sensitivity (40% vs. 98%, P = .01), NPV (36% vs. 96%, P = .02), and accuracy (54% vs. 97%, P = .03). Conclusions: Diagnostic efficacy of FNA for residual or recurrent cervical lymph node metastasis in NPC is significantly reduced after previous RT. To ensure that the proper diagnosis is made early, triple assessment using FNA, pEBV-DNA, and MRI should be adopted in this scenario. Laryngoscope, 2013

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. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

The aim of the current study was to report results of salvage nasopharyngectomy using the maxillary swing approach for persistent or recurrent nasopharyngeal carcinoma after primary treatment.Between 1989 and 2011, Nasopharyngectomies were performed in 312 patients. Data were composed of retrospective review of records of the first 72 patients followed by a prospective collection of data for the remaining patients.Among the patients, 41 (13.1%) had persistent tumours and 271 (86.9%) had recurrent disease. Curative resection was achieved in 248 (79.5%) patients. All patients survived the operations. The median follow up duration was 34 months. The overall 5-year actuarial local tumour control was 74% and the overall 5-year disease-free survival was 56%. Those with negative resection margins on frozen section and tumour size less than 1.5 cm in diameter had significantly better local tumour control in the nasopharynx as well as disease-free survival.Maxillary swing nasopharyngectomy is an effective salvage procedure for small, persistent or recurrent tumour in the nasopharynx after primary therapy.

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. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Background This study was carried out to determine the role of plasma Epstein-Barr virus (pEBV)-DNA and positron-emission tomography (PET)-CT scan in predicting the outcome of nasopharyngectomy and cervical lymphadenectomy for recurrent nasopharyngeal carcinoma (NPC). Methods Between 2007 and 2009, we recruited patients who had local or regional recurrent NPC after radiotherapy. The relationship between preoperative pEBV-DNA level, maximal standard uptake value (SUVmax), and surgical outcome was analyzed. Results Forty-two patients had local tumor recurrence. Their median pEBV-DNA level and SUVmax were 348 copies and 4.7, respectively. Both values were significantly lower than those with palliative nasopharyngectomy. Twenty-two patients had regional failure. Their mean pEBV-DNA level and tumor SUVmax were 626 copies and 7.6, respectively. The metastatic lymph nodes with extracapsular spread had a significantly higher mean SUVmax. Conclusions Preoperative pEBV-DNA and PET-CT predict the surgical outcome of nasopharyngectomy for recurrent NPC. Similarly, PET-CT scan predicts the presence of extracapsular spread of metastatic lymph nodes. These patients may warrant further postoperative adjuvant therapy.

Background The purpose of this study was to report on our experience on salvage nasopharyngectomy using the maxillary swing approach for persistent or recurrent nasopharyngeal carcinoma after primary treatment. Methods Over the past 2 decades, we have performed salvage nasopharyngectomies for 246 patients. Thirty-seven patients (15%) had persistent disease and 209 (85%) had recurrent tumors. Results All patients survived the operation with minimal morbidity. Negative resection margins were achieved in 191 patients (78%), and 55 patients (22%) had microscopic residual disease. The median follow-up was 38 months. The 5-year actuarial control of disease in the nasopharynx was 74%. The 5-year disease-free survival was 56%. Cox regression model identified the negative resection margin and the size of the tumor as 2 independent factors that affected local control of disease and survival. Conclusion Maxillary swing nasopharyngectomy is an effective salvage procedure for a small, persistent, or recurrent tumor in the nasopharynx after primary therapy. © 2010 Wiley Periodicals, Inc. Head Neck, 2011