Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.

Human papillomavirus and World Health Organization type III nasopharyngeal carcinoma: Multicenter study from an endemic area in Southern China.

BACKGROUND: The current study was conducted to study the incidence of human papillomavirus (HPV)-associated nasopharyngeal carcinoma (NPC) in Southern China and the corresponding treatment outcome. METHODS: A retrospective chart review with a level of evidence of 4 was performed. RESULTS: Between 2000 and 2015, a total of 1328 patients with NPC were treated in 3 study institutes in Hong Kong and Foshan City in Guangdong Province, China. All tumors were undifferentiated, nonkeratinizing carcinoma, of which 91.9% were positive for the Epstein-Barr virus (EBV+) and 7.7% were positive for HPV/p16 (HPV+). Although coinfection with both viruses occurred only in 8 patients (0.6%), 94 patients had tumors that were EBV negative (EBV-) and HPV+. All patients were treated with intensity-modulated radiotherapy alone for American Joint Committee on Cancer stage I and II disease, and concurrent chemoradiotherapy for stage III and IV disease. With a median follow-up of 72.8 months, the authors found that the local recurrence rate was significantly lower for patients with tumors that were EBV-/HPV+ compared with patients with tumors that were EBV+/HPV- (6.4% vs 13.8%; P = .03). Similar trends were observed for the 5-year disease-free survival rate (89.8% vs 70.8%; P =.03) and 5-year overall survival rate (86% vs 72%; P =.03). CONCLUSIONS: In regions that are endemic for NPC, the prevalence of EBV and HPV coinfection in patients with NPC is extremely low. Conversely, patients with EBV-/HPV+ NPC demonstrate significantly better local tumor control and survival after radiotherapy. Cancer 2018;124:530-6. © 2017 American Cancer Society.

Predictors for Frey Syndrome Development After Parotidectomy.

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.

Application of Palpebral Spring in Asian Patients With Paralytic Lagophthalmos.

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.

Clinical Patterns of Melanoma in Asians: 11-Year Experience in a Tertiary Referral Center.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

IL-1ß promotes malignant transformation and tumor aggressiveness in oral cancer.

Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1ß) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1ß expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1ß was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1ß secretion in an inflammasome-dependent manner. IL-1ß treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-α following IL-1ß stimulation. The conditioned medium of IL-1ß-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1ß increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1ß can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC.

The role of Epstein-Barr virus-encoded microRNA BART7 status of resection margins in the prediction of local recurrence after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma.

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 (<5 mm) and clear (≥5 mm) margins was 31.6% and 12.5%, respectively. In patients with clear histologic margins, those with margins that were positive for EBV microRNA BART7 has a significantly higher chance of developing local tumor recurrence (P = .016) than those with negative molecular margins. The difference was not significant when the histologic clearance at the resection margins was <5 mm. CONCLUSIONS: Tissue EBV microRNA BART7 is useful for identifying a subgroup of patients with histologically clear margins who are at increased risk of subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted for these patients.

Surgical salvage of recurrent nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a unique tumour which is endemic in southern China including Hong Kong. Whilst the treatment results for the primary cancer has been encouraging, management of recurrent tumours has been challenging. Compared to other surgical approaches, the maxillary swing operation provides wide access to the bilateral nasopharynx and the ipsilateral parapharyngeal space, allowing resection of tumours with adequate margins. Among the 312 patients who had received salvage nasopharyngectomy via the maxillary swing approach, the chance of achieving microscopically clear resection margins was 79.5 %. The overall local recurrence rate after surgery was 13.1 %. Multivariate analysis showed that resection margin status, synchronous nodal recurrence and cavernous sinus invasion were independent prognostic factors for overall survival. For small tumours located in the posterior wall, endoscopic resection, or more recently, the transoral robotic (TORS)-assisted approach, can be performed. 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.

Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis.

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-ß) 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.

Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma by inhibiting the expression of miR-125a-5p.

Curcumin suppresses proliferation, migration, invasion, metastasis and angiogenesis and induces apoptosis by regulating multiple signalling pathways and miRNAs in a wide variety of human malignancies. miRNAs play crucial roles in various steps of carcinogenesis in nasopharyngeal carcinoma (NPC); thus, they could serve as critical therapeutic targets for NPC treatment. Curcumin could provide a novel strategy to block or induce specific miRNAs for miRNA-based gene therapies. Nevertheless, there are no reports to date on the miRNAs regulated by curcumin in NPC. In the present study, we have carried out an miRNA microarray to identify the miRNAs regulated by curcumin in NPC. Curcumin treatment down-regulated the expression of hsa-miR-125a-5p, hsa-miR-574-3p and hsa-miR-210 as determined by miRNA microarray analysis and qPCR (real-time quantitative reverse transcription-PCR). Forced expression of miR-125a-5p enhanced proliferation, migration and invasion of HONE1 cells. Primary NPC exhibited a significantly higher expression level of miR-125a-5p than healthy controls. miR-125a-5p inhibited the expression of tumour protein 53 (TP53), and curcumin treatment up-regulated the expression of TP53. Taken together, these results indicate that curcumin exerted inhibitory effects on NPC by inhibiting the expression of miR-125a-5p and, subsequently, enhancing the expression of TP53. Curcumin could provide a novel strategy to block miR-125a-5p for miRNA-based gene therapies in NPC.

Epigenetic regulation of the X-linked tumour suppressors BEX1 and LDOC1 in oral squamous cell carcinoma.

The strong associations between oral squamous cell carcinoma (OSCC) and dietary habits such as alcohol consumption (A), betel quid chewing (B) and cigarette smoking (C) and its predominance in men have been well documented; however, systemic analysis of OSCC is limited. Our study applied high-throughput screening methods to identify causative epigenetic targets in a cohort of men with ABC-associated OSCC. We identified BEX1 and LDOC1 as two epigenetically silenced X-linked tumour suppressors and demonstrated a functional link between the transcription of BEX1 and LDOC1 and promoter hypermethylation. Methylation of the BEX1 and LDOC1 promoters was associated significantly (p < 0.0001) with OSCC and were detected in 75% (42/56) and 89% (50/56) of the samples, respectively. We observed concordant increases in the methylation of both genes in 71% (40/56) of the tumours, and potent in vitro and in vivo growth inhibitory effects in OSCC cells ectopically expressing BEX1 and/or LDOC1. Restored expression of BEX1 and LDOC1 suppressed the nuclear factor-κB (NF-κB) signalling pathway, which is the most frequently hyperactivated signalling pathway in OSCC. This suppression might result from decreased p50 and p65 expression. These findings suggest that silencing of BEX1 and LDOC1 by promoter hypermethylation might represent a critical event in the molecular pathogenesis of OSCC and account for the oncogenic effects of ABC exposure and the male predominance of OSCC occurrence. Microarray data are available in the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/)

Efficacy of neck dissection in the management of isolated nodal recurrence after head and neck cancer treatment.

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.

Quality of dying in head and neck cancer patients: the role of surgical palliation.

To study the role of surgery for symptom palliation in patients with advanced head and neck malignancy. Between 2000 and 2011, patients with locoregionally advanced cancer in the head and neck region, who chose surgical palliation for symptom control, were studied retrospectively. During the study period, 52 patients were included. The index tumour included carcinoma of the maxilla (23.1 %), tongue (19.2 %), larynx/hypopharynx (15.4 %), post-radiation sarcoma (11.5 %), primary sarcoma (11.5 %), carcinoma of the lower alveolus (11.5 %), nasal mucosal melanoma (3.9 %) and metastatic tumour in the head and neck region (3.9 %). The major symptoms included bleeding (53.9 %), tumour pain (19.2 %), dysphagia (11.5 %), non-healing ulcerations (7.7 %), airway obstruction (5.8 %) and pathological fracture of the mandible (1.9 %). Ligation of the carotid artery was performed in 10 patients, complete resection of tumour in 35, and surgical debulking of the tumour in 7 patients. Mean survival of the patients was 5.6 months. The majority of the patients achieved satisfactory and persistent control of symptoms. One patient died from pneumonia during the hospital stay, and the rest were discharged after a mean duration of 16.4 days. In selected patients, surgery is effective in palliating symptoms which are otherwise difficult to manage. Detailed planning and good communication is the key to success in improving the quality of dying.

Safety of intra-operative vasopressor in free jejunal flap reconstruction.

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.

Detection of CSF1 gene derangement in 'sclerosing mucoepidermoid carcinoma with eosinophilia' of the parotid gland masquerading as Langerhans cell histiocytosis.

Key Clinical Message: When faced with a slowly enlarging firm mass in the parotid gland accompanied by a histological picture of unusual sclerosis with abundant Langerhans cells and eosinophilic infiltrates, sclerosing mucoepidermoid carcinoma with eosinophilia should be considered as one of the differential diagnoses. Further studies are warranted for accurate diagnosis and appropriate treatment. Abstract: Sclerosing mucoepidermoid carcinoma of the salivary gland with eosinophilia is a rare tumor mostly negative for the MAML2 rearrangement commonly seen in salivary mucoepidermoid carcinoma. It was not listed as an entity in the 2022 WHO Classification of Head and Neck Tumors. We presented one case initially diagnosed as Langerhans cell histiocytosis and recurred as a frankly invasive carcinoma. Molecular studies showed CSF1 gene derangement and provided new understanding concerning the Langerhans cell and eosinophilic reaction. Further molecular studies on this entity would throw light on its oncogenesis and refine its nomenclature.

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

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

Oncological outcome after free jejunal flap reconstruction for carcinoma of the hypopharynx.

It has been a common practice among the oncologist to reduce the dosage of adjuvant radiotherapy for patients after free jejunal flap reconstruction. The current aims to study potential risk of radiation to the visceral flap and the subsequent oncological outcome. Between 1996 and 2010, consecutive patients with carcinoma of the hypopharynx requiring laryngectomy, circumferential pharyngectomy and post-operative irradiation were recruited. Ninety-six patients were recruited. TNM tumor staging at presentation was: stage II (40.6%), stage III (34.4%) and stage IV (25.0%). Median follow-up period after surgery was 68 months. After tumor ablation, reconstruction was performed using free jejunal flap (60.4%), pectoralis major myocutaneous (PM) flap (31.3%) and free anterolateral thigh (ALT) flap (8.3%). All patients underwent adjuvant radiotherapy within 6.4 weeks after surgery. The mean total dose of radiation given to those receiving cutaneous and jejunal flap reconstruction was 62.2 Gy and 54.8 Gy, respectively. There was no secondary ischaemia or necrosis of the flaps after radiotherapy. The 5-year actuarial loco-regional tumor control for the cutaneous flap and jejunal flap group was: stage II (61 vs. 69%, p = 0.9), stage III (36 vs. 46%, p = 0.2) and stage IV (32 vs. 14%, p = 0.04), respectively. Reduction of radiation dosage in free jejunal group adversely affects the oncological control in stage IV hypopharyngeal carcinoma. In such circumstances, tubed cutaneous flaps are the preferred reconstructive option, so that full-dose radiotherapy can be given.

Mitochondrial DHODH regulates hypoxia-inducible factor 1 expression in OTSCC.

Oral tongue squamous cell carcinoma (OTSCC) was one of the most hypoxic tumors with unfavorable outcomes. Hypoxia-inducible factor-1 (HIF-1) signaling was associated with cancer proliferation, lymph node metastasis, angiogenesis and poor prognosis of OTSCC. Dihydroorotate dehydrogenase (DHODH) catalyzed the rate-limiting step in the de novo pyrimidine biosynthesis. The aim of the study was to explore the biological function of DHODH and investigate whether DHODH regulated HIF-1 signaling in OTSCC. Proliferation, migration and anoikis resistance were used to determine the function of DHODH. Western blot and luciferase activity assays were used to determine the regulatory role of DHODH on HIF-1. We found that increased DHODH expression was associated with advanced tumor stage and poorly differentiated tumor in head and neck cancer patients in The Cancer Genome Atlas (TCGA). DHODH enhanced the proliferation and aggressiveness of OTSCC. Moreover, DHODH prompted tumor growth and metastasis in vivo. DHODH promoted transcription, protein stability, and transactivation activity of HIF1A. DHODH-induced HIF1A upregulation in OTSCC can be reversed by reactive oxygen species (ROS) scavenger, indicating that DHODH enhanced HIF1A expression via ROS production. DHODH inhibitor suppressed DHODH-mediated ROS generation and HIF1A upregulation. Targeting DHODH using clinically available inhibitor, atovaquone, might provide a new strategy to treat OTSCC.

Novel approach to reduce SARS-CoV-2 transmission during trans-oral robotic surgery.

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.