Validation of the TNM-8 AJCC classification for HPV-positive oropharyngeal cancers in patients undergoing trans-oral robotic surgery.

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC). HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is based on ICON-S data with 98% of patients treated with primary chemoradiation. To validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57 years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T-stage cancer in 72.8%. Primary treatment was surgery & adjuvant therapy (70%) while primary chemoradiation (30%). Survival analyses were performed for the 7th and 8th AJCC systems. The reclassification to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is, therefore, validated in a cohort treated, predominantly, with primary surgery and adjuvant therapy.

Normal, dust-obscured galaxies in the epoch of reionization.

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1-3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4-7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare population of extreme starburst galaxies8-12 and companions of rare quasars13,14. These studies conclude that the contribution of dust-obscured galaxies to the cosmic star formation rate density at z > 6 is sub-dominant. Recent ALMA and Spitzer observations have identified a more abundant, less extreme population of obscured galaxies at z = 3-6 (refs. 15,16). However, this population has not been confirmed in the reionization epoch so far. Here, we report the discovery of two dust-obscured star-forming galaxies at z = 6.6813 ± 0.0005 and z = 7.3521 ± 0.0005. These objects are not detected in existing rest-frame UV data and were discovered only through their far-infrared [C II] lines and dust continuum emission as companions to typical UV-luminous galaxies at the same redshift. The two galaxies exhibit lower infrared luminosities and star-formation rates than extreme starbursts, in line with typical star-forming galaxies at z ≈ 7. This population of heavily dust-obscured galaxies appears to contribute 10-25% to the z > 6 cosmic star formation rate density.

Constraints on the Ecomorphological Convergence of Zooplanktivorous Butterflyfishes.

Whether distantly related organisms evolve similar strategies to meet the demands of a shared ecological niche depends on their evolutionary history and the nature of form-function relationships. In fishes, the visual identification and consumption of microscopic zooplankters, selective zooplanktivory, is a distinct type of foraging often associated with a suite of morphological specializations. Previous work has identified inconsistencies in the trajectory and magnitude of morphological change following transitions to selective zooplanktivory, alluding to the diversity and importance of ancestral effects. Here we investigate whether transitions to selective zooplanktivory have influenced the morphological evolution of marine butterflyfishes (family Chaetodontidae), a group of small-prey specialists well known for several types of high-precision benthivory. Using Bayesian ancestral state estimation, we inferred the recent evolution of zooplanktivory among benthivorous ancestors that hunted small invertebrates and browsed by picking or scraping coral polyps. Traits related to the capture of prey appear to be functionally versatile, with little morphological distinction between species with benthivorous and planktivorous foraging modes. In contrast, multiple traits related to prey detection or swimming performance are evolving toward novel, zooplanktivore-specific optima. Despite a relatively short evolutionary history, general morphological indistinctiveness, and evidence of constraint on the evolution of body size, convergent evolution has closed a near significant amount of the morphological distance between zooplanktivorous species. Overall, our findings describe the extent to which the functional demands associated with selective zooplanktivory have led to generalizable morphological features among butterflyfishes and highlight the importance of ancestral effects in shaping patterns of morphological convergence.

A evolução de estratégias similares para suprir as demandas de nichos ecológicos compartilhados em organismos pouco relacionados, depende da sua história evolutiva e da natureza das relações entre forma e função. Em peixes, a identificação visual e o consumo de zooplanctôn microscópico, a zooplanctivoria seletiva, é um tipo distinto de forrageamento frequentemente associado a um conjunto de especializações morfológicas. Estudos anteriores identificaram inconsistências na trajetória e magnitude das mudanças morfológicas que surgem a partir das transições para a zooplanctivoria seletiva, fazendo alusão à diversidade e importância dos efeitos ancestrais. Aqui investigamos se transições para a zooplanctivoria seletiva influenciaram a evolução morfológica dos peixes-borboleta marinhos (família Chaetodontidae), um grupo especialista em presas pequenas conhecido pelos muitos tipos de bentivoria de alta precisão. Utilizando uma estimativa ancestral bayesiana, inferimos a evolução recente da zooplanctivoria dentre os ancestrais bentívoros que caçavam pequenos invertebrados e alimentavam-se de pólipos de coral. Características relacionadas a captura de presa parecem ser funcionalmente versáteis com pouca distinção entre as espécies com modo de forrageamento bentívoro e planctívoro. Em contraste, várias características relacionadas a detecção da presa ou capacidade natatória estão evoluindo em direção a um novo ótimo, específico para a zooplanctivoria. Apesar da história evolutiva relativamente recente, uma morfologia geral comum, e evidência de uma restrição na evolução do tamanho corporal, a evolução convergente reduziu significativamente a distância morfológica entre as espécies zooplanctívoras. No geral, nossos resultados descrevem até que ponto as demandas funcionais associadas à zooplanctivoria seletiva levaram a características morfológicas generalizadas nos peixes-borboleta e destacam a importância dos efeitos ancestrais em moldar os padrões de convergência morfológica.

El hecho de que organismos con parentesco lejano evolucionen estrategias similares para satisfacer las demandas de un nicho ecológico compartido depende de su historia evolutiva y de la naturaleza de la relación forma-función. En peces, la identificación visual y el consumo de plancton microscópico, la zooplanctivoría selectiva, es un tipo específico de alimentación usualmente asociado a un conjunto de especializaciones morfológicas. Estudios previos han identificado inconsistencias en la trayectoria y magnitud de cambios morfológicos tras transiciones hacia zooplanctivoría selectiva, aludiendo a la diversidad e importancia de efectos ancestrales. Aquí investigamos si las transiciones a zooplanctivoría selectiva han influido en la evolución morfológica de los peces mariposa marinos (familia Chaetodontidae), un grupo especializado en presas pequeñas conocido por varios tipos de alimentación de alta precisión en el bentos. Usando una estimación de estado ancestral Bayesiana, inferimos la evolución reciente de la zooplanctivoría entre ancestros bentívoros que cazaron pequeños invertebrados y se alimentaron de pólipos de coral. Los rasgos relacionados con la captura de presas parecen ser versátiles funcionalmente con escasa distinción morfológica entre especies con modos de alimentación bentívoros y planctívoros. En cambio, múltiples rasgos relacionados con la detección de presas o con la capacidad natatoria están evolucionando hacia un nuevo óptimo específico para zooplanctivoría. A pesar de una historia evolutiva relativamente corta, una morfología general común, y evidencia de restricción en la evolución del tamaño de los peces, una evolución convergente ha reducido la distancia morfológica entre especies zooplanctívoras de forma casi significativa. En conclusión, nuestros hallazgos describen hasta qué punto las demandas funcionales asociadas con la zooplanctivoría selectiva han desembocado en rasgos morfológicos generalizados en peces mariposa y destacan la importancia de los efectos ancestrales en la creación de patrones de morfología convergente.

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations.

BACKGROUND: Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. OBJECTIVE: To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. METHODS: A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. RESULTS: Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8-18.0). Populations included typical development (n = 118), perinatal stroke/cerebral palsy (n = 101), mild traumatic brain injury (n = 121) neuropsychiatric disorders (n = 37), and other (n = 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. CONCLUSIONS: Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.

Colour dimorphism in labrid fishes as an adaptation to life on coral reefs.

Conspicuous coloration displayed by animals that express sexual colour dimorphism is generally explained as an adaptation to sexual selection, yet the interactions and relative effects of selective forces influencing colour dimorphism are largely unknown. Qualitatively, colour dimorphism appears more pronounced in marine fishes that live on coral reefs where traits associated with strong sexual selection are purportedly more common. Using phylogenetic comparative analysis, we show that wrasses and parrotfishes exclusive to coral reefs are the most colour dimorphic, but surprisingly, the effect of habitat is not influenced by traits associated with strong sexual selection. Rather, habitat-specific selective forces, including clear water and structural refuge, promote the evolution of pronounced colour dimorphism that manifests colours less likely to be displayed in other habitats. Our results demonstrate that environmental context ultimately determines the evolution of conspicuous coloration in colour-dimorphic labrid fishes, despite other influential selective forces.

Transoral robotic narrow field oropharyngectomy for tumours of the parapharyngeal space.

The advent of transoral robotic surgery (TORS) has allowed transoral approaches for parapharyngeal space (PPS) tumours to be re-evaluated. It provides enhanced visualisation and instrument access for appropriate tumours. We describe a specific technique, TORS narrow-field oropharyngectomy, that is ideal for benign PPS tumours which have been violated by intra-oral biopsy or incision and drainage. This allows the contaminated, overlying oropharyngeal mucosa to be resected en-bloc with the PPS tumour, reducing the risk of local recurrence. This technique provides a window into the PPS, improving visualisation of underlying neurovascular structures as well as the tumour. This reduces the risk of tumour spillage and leads to superior vascular access and haemorrhage control. This technique is only applicable to PPS tumours that are appropriate for transoral approaches and is specifically designed for those selected patients that have been placed at risk of seeding or local scarring by intra-oral procedures prior to definitive resection. We present two such cases: a 38-year-old male with a PPS inflammatory cyst and a 66-year-old female with a PSS pre-styloid Schwannoma.

High-redshift star formation in the Atacama large millimetre/submillimetre array era.

The Atacama Large Millimetre/submillimetre Array (ALMA) is currently in the process of transforming our view of star-forming galaxies in the distant ( z ≳ 1 ) universe. Before ALMA, most of what we knew about dust-obscured star formation in distant galaxies was limited to the brightest submillimetre sources-the so-called submillimetre galaxies (SMGs)-and even the information on those sources was sparse, with resolved (i.e. sub-galactic) observations of the obscured star formation and gas reservoirs typically restricted to the most extreme and/or strongly lensed sources. Starting with the beginning of early science operations in 2011, the last 9 years of ALMA observations have ushered in a new era for studies of high-redshift star formation. With its long baselines, ALMA has allowed observations of distant dust-obscured star formation with angular resolutions comparable to-or even far surpassing-the best current optical telescopes. With its bandwidth and frequency coverage, it has provided an unprecedented look at the associated molecular and atomic gas in these distant galaxies through targeted follow-up and serendipitous detections/blind line scans. Finally, with its leap in sensitivity compared to previous (sub-)millimetre arrays, it has enabled the detection of these powerful dust/gas tracers much further down the luminosity function through both statistical studies of colour/mass-selected galaxy populations and dedicated deep fields. We review the main advances ALMA has helped bring about in our understanding of the dust and gas properties of high-redshift ( z ≳ 1 ) star-forming galaxies during these first 9 years of its science operations, and we highlight the interesting questions that may be answered by ALMA in the years to come.

How I do it: transnasal retraction during transoral robotic oropharyngeal resection.

Collapse of the resection plane presents a frustrating problem during transoral robotic resection, in a situation already typified by limited vision and access for instruments. We present a quick and cost-effective retraction technique to effectively mitigate this issue and increase the ease and reliability of robotic oropharyngeal resection. This technique utilises a simple transnasal apparatus to create greater exposure of the resection plane. A Y-suction catheter is inserted into the oropharynx via the nasal cavity. A silk suture is then used to attach it to the oropharyngeal resection specimen. When pulled from the nasal cavity, this apparatus adds a non-intrusive, tremor-free fixation point that pulls the resected specimen along a unique cephalo-posterior vector. This significantly improves access and vision of the desired dissection plane. The entire process takes approximately 1-2 min per side to properly execute. It can be adapted for various pathologies and subsites of the oropharynx. This transnasal technique is a simple, minimally invasive, and inexpensive method for improving wound tension during transoral oropharyngeal resection.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

Elective neck dissection for the node-negative neck during salvage laryngectomy: an analysis of survival outcomes and complication rates.

OBJECTIVES: This study aimed to evaluate the effect of neck dissection on survival and complication rates in patients with no clinical or radiological evidence of cervical nodal disease (N0) undergoing salvage laryngectomy. METHODS: A retrospective study was conducted of patients with squamous cell carcinoma of the larynx following primary radiotherapy that required salvage laryngectomy. Disease-free and overall survival rates were compared over three years using Kaplan-Meier analysis. Pharyngocutaneous fistula rate, hospitalisation length and the requirement for further surgical intervention were also compared across cohorts. RESULTS: Twenty-three cases met the inclusion criteria (17 neck dissections, 6 undissected). No significant differences in survival outcomes were identified. One patient who underwent neck dissection for advanced, recurrent transglottic squamous cell carcinoma showed evidence of occult lymph node metastases. Fistula rates did not differ significantly between dissected and non-dissected groups; however, two patients required surgical repair of post-operative pharyngocutaneous fistula following neck dissection. CONCLUSION: In this study, elective neck dissection did not appear to alter survival outcomes or complication rates during salvage laryngectomy. Given the small but significant risk of occult neck metastases, its true value remains unclear.

Sensory-motor network functional connectivity in children with unilateral cerebral palsy secondary to perinatal stroke.

BACKGROUND: Perinatal stroke is the most common cause of unilateral cerebral palsy. Mechanisms of post-stroke developmental plasticity in children are poorly understood. To better understand the relationship between functional connectivity and disability, we used resting-state fMRI to compare sensorimotor connectivity with clinical dysfunction. METHODS: School-aged children with periventricular venous infarction (PVI) and unilateral cerebral palsy were compared to controls. Resting-state BOLD signal was acquired on 3 T MRI and analyzed using CONN in SPM12. Functional connectivity was computed between S1, M1, supplementary motor area (SMA), and thalamus of the left/non-lesioned and right/lesioned hemisphere. Primary outcome was connectivity expressed as a Fisher-transformed correlation coefficient. Motor function was measured using the Assisting Hand Assessment (AHA), and Melbourne Assessment (MA). Proprioceptive function was measured using a robotic position matching task (VarXY). RESULTS: Participants included 15 PVI and 21 controls. AHA and MA in stroke patients were negatively correlated with connectivity (increased connectivity = poorer performance). Position sense was inversely correlated with connectivity (increased connectivity = improved performance) between the non-lesioned S1 and thalamus/SMA. In controls, VarXY was positively correlated with connectivity between the thalamus and bilateral sensorimotor regions. CONCLUSIONS: Resting state fMRI measures of sensorimotor connectivity are associated with clinical sensorimotor function in children with unilateral cerebral palsy secondary to PVI. Greater insight into understanding reorganization of brain networks following perinatal stroke may facilitate personalized rehabilitation.

The acceptance and adoption of transoral robotic surgery in Australia and New Zealand.

Transoral robotic surgery (TORS) provides improved access to head and neck subsites resulting in well-validated functional and oncological outcomes, but access to and cost of robotic platforms can limit their use. Evidence suggests TORS is increasingly being adopted globally, but there is a paucity of data on the adoption and diffusion of TORS in Australia and New Zealand. A cross-sectional analysis was performed. An online survey was distributed to otolaryngologists and head and neck surgeons through three different Australian and New Zealand specialty membership databases. A 5-point Likert scale based on a Unified Theory of Acceptance and Use of Technology (UTAUT) model was incorporated to assess barriers and facilitators to adoption. 77 respondents completed the survey. 43.6% of head and neck surgeons had performed TORS. The most common cases were lateral oropharyngectomy (35.9%), base of tongue resection (33.3%), tongue base mucosectomy (28.2%), supraglottic laryngectomy (15.4%) and TORS for obstructive sleep apnoea (12.8%). Perceived barriers to adoption were high costs, access to and availability of the robotic platform and limited training opportunities. This study provides evidence of adoption of TORS in Australia and New Zealand; however, there is a perception that significant barriers to adoption persist. Results from this study may help guide decisions on how we train and license surgeons in the era of this technology.

Reviewing indications for panendoscopy in the investigation of head and neck squamous cell carcinoma.

BACKGROUND: The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer. METHOD: A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.

Robotic TMS mapping of motor cortex in the developing brain.

BACKGROUND: The human motor cortex can be mapped safely and painlessly with transcranial magnetic stimulation (TMS) to explore neurophysiology in health and disease. Human error likely contributes to heterogeneity of such TMS measures. Here, we aimed to use recently pioneered robotic TMS technology to develop an efficient, reproducible protocol to characterize cortical motor maps in a pediatric population. NEW METHOD: Magnetic resonance imaging was performed on 12 typically developing children and brain reconstructions were paired with the robotic TMS system. The system automatically aligned the TMS coil to target sites in 3 dimensions with near-perfect coil orientation and real-time head motion correction. Motor maps of 4 forelimb muscles were derived bilaterally by delivering single-pulse TMS at predefined, uniformly spaced trajectories across a 10 × 10 grid (7 mm spacing) customized to the participant's MRI. RESULTS: Procedures were well tolerated with no adverse events. Two male, eight-year-old participants had high resting motor thresholds that precluded mapping. The mean hotspot coordinate and centre of gravity coordinate were determined in each hemisphere for four forelimb muscles bilaterally. Average mapping time was 14.25 min per hemisphere. COMPARISON WITH EXISTING METHODS: Traditional manual TMS methods of motor mapping are time intensive, technically challenging, prone to human error, and arduous for use in pediatrics. This novel TMS robot approach facilitates improved efficiency, tolerability, and precision in derived, high-fidelity motor maps. CONCLUSIONS: Robotic TMS opens new avenues to explore motor map neurophysiology and its influence on developmental plasticity and therapeutic neuromodulation. Our findings provide evidence that TMS robotic motor mapping is feasible in young participants.

A comparison of oncological outcomes between transoral surgical and non-surgical treatment protocols in the management of oropharyngeal squamous cell carcinoma.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes. METHODS: This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated. RESULTS: Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group. CONCLUSION: This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Surgical anatomy of the spinal accessory nerve: review of the literature and case report of a rare anatomical variant.

OBJECTIVE: To evaluate the prevalence of variations in the anatomical route of the spinal accessory nerve from the base of the skull to the point where it enters the trapezius muscle. A case report is used to demonstrate an example of a rare but clinically important anatomical variant of this nerve. METHODS: An independent review of the literature using Medline, PubMed and Q Read databases was performed using combinations of terms including 'spinal accessory nerve', 'anatomy', 'surgical anatomy', 'anatomical variant', 'cranial nerve XI' and 'shoulder syndrome'. RESULTS: Our report demonstrates marked variation in spinal accessory nerve anatomy. At the point of crossing over the internal jugular vein, the spinal accessory nerve passes most commonly laterally (anterior) to the internal jugular vein. The reported incidence of this lateral relationship varies from 67 to 96 per cent. The nerve can also pierce the internal jugular vein, as demonstrated in our case study, with incidence ranging from 0.48 to 3.3 per cent. CONCLUSION: Anatomical variations of the spinal accessory nerve are not uncommon, and it is important for the surgeon to be aware of such variations when undertaking surgery in both the anterior and posterior triangles of the neck.

Citalopram and sertraline exposure compromises embryonic bone development.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.