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Background: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. Objective: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. Materials and methods: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow‐up closure date was September 1, 2021. Curative‐intent surgery, curative‐intent radiotherapy, or palliative care was undertaken. Endpoints included five‐year overall, disease‐specific, and disease‐free survival from the date of treatment. Results: Five‐year Kaplan–Meier overall survival was 61.9% (95% CI 46.2%–74.3%), with disease‐specific survival of 74.6% (95% CI 58.8%–85.3%), and disease‐free survival 62.1% (95% CI 46.5%–74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease‐specific survival of 94.1% at 5 years with 82.5% disease‐free survival. Discussion: Five‐year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative‐intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. Conclusion: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1. [ABSTRACT FROM AUTHOR]

Background: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. Patients and methods: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. Results: The median age was 56 years (IQR 44–67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow‐up of 7.1 years, the 5‐year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. Conclusion: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports. [ABSTRACT FROM AUTHOR]

Introduction: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population‐based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV‐associated disease. Methods: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age‐standardised rates (ASR) (3‐year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2‐ and 5‐year overall survival. Results: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy‐seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2‐ and 5‐ year overall survival of 89% and 79%, respectively. Conclusion: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV‐associated (p16+), presenting with early‐stage disease with a favourable prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Perineural spread (PNS) is a rare but potentially fatal consequence of cutaneous squamous cell carcinoma (cSCC) of the head and neck. We aimed to evaluate the accuracy of 3T MR neurography in detecting and defining the extent of facial nerve (VII) PNS from cSCC, and highlight characteristic radiological features in peripheral branches to improve early diagnosis. Methods: Single‐institution retrospective review of 38 patients with clinical, radiological, and/or histopathological findings consistent with VII PNS from cSCC who underwent pre‐operative 3T MR neurography. Results: Compared to histopathology (gold standard), 3T MR neurography had a sensitivity of 89% and positive predictive value of 97%. In true‐positive cases (n = 33), zonal extent was correctly identified in 100%. Seventy‐nine% had simultaneous trigeminal nerve (V) PNS, mostly involving the auriculotemporal branch of the mandibular nerve (64%). When the causative lesion was absent (n = 23), the extra‐temporal VII demonstrated asymmetrical enhancement alone (n = 6), bulky expansion (n = 8), or extra‐neural spread (n = 9). Peripheral VII branch involvement, particularly the buccal and zygomatic, was readily identified using known anatomical landmarks. Conclusion: 3T MR neurography is highly accurate in evaluating VII PNS from cSCC, and thus should be specifically requested by physicians if suspicious for disease. Coexistent V PNS was common, highlighting the need to examine V branches to allow complete treatment planning. The unique radiological patterns identified showcases disease progression. As early detection improves patient outcomes, the radiologist must look for peripheral VII involvement in specific anatomical areas, which is within the capabilities of 3T MR neurography. [ABSTRACT FROM AUTHOR]

"Epiphanies: An Ethics of Experience" by Sophie Grace Chappell challenges the constraints of traditional philosophical practice and argues for the importance of personal and experiential perspectives in philosophy. Chappell explores the concept of epiphanies, defined as peak experiences or "aha moments," and argues that they reveal important truths about value, motivation, and the nature of our lives. The book aims to construct an ethics based on epiphanies and addresses meta-ethical questions about justification and subjectivity. Chappell's writing style is personal and engaging, inviting readers to reflect on their own experiences. The book draws on literary works and engages with the tradition of Anglo-Saxon philosophy in search of alternative approaches to ethics. Overall, "Epiphanies: An Ethics of Experience" offers a refreshing and spacious conversation about philosophy. [Extracted from the article]

Duchenne muscular dystrophy (DMD) is a fatal X‐linked disease characterised by severe muscle wasting. The mechanisms underlying the DMD pathology likely involve the interaction between inflammation, oxidative stress and impaired Ca2+ signalling. Hypochlorous acid (HOCl) is a highly reactive oxidant produced endogenously via myeloperoxidase; an enzyme secreted by neutrophils that is significantly elevated in dystrophic muscle. Oxidation of Ca2+‐handling proteins by HOCl may impair Ca2+ signalling. This study aimed to determine the effects of HOCl on skeletal muscle function and its potential contribution to the dystrophic pathology. Extensor digitorum longus (EDL), soleus and interosseous muscles were surgically isolated from anaesthetised C57 (wild‐type) and mdx (dystrophic) mice for measurement of ex vivo force production and intracellular Ca2+ concentration. In whole EDL muscle, HOCl (200 μM) significantly decreased maximal force and increased resting muscle tension which was only partially reversible by dithiothreitol. The effects of HOCl (200 μM) on maximal force in slow‐twitch soleus were lower than found in the fast‐twitch EDL muscle. In single interosseous myofibres, HOCl (10 μM) significantly increased resting intracellular Ca2+ concentration and decreased Ca2+ transient amplitude. These effects of HOCl were reduced by the application of tetracaine, Gd3+ or streptomycin, implicating involvement of ryanodine receptors and transient receptor potential channels. These results demonstrate the potent effects of HOCl on skeletal muscle function potentially mediated by HOCl‐induced oxidation to Ca2+ signalling proteins. Hence, HOCl may provide a link between chronic inflammation, oxidative stress and impaired Ca2+ handling that is characteristic of DMD and presents a potential therapeutic target for DMD. Key points: Duchenne muscular dystrophy is a fatal genetic disease with pathological mechanisms which involve the complex interaction of chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca2+ concentrations.Hypochlorous acid can be endogenously produced by neutrophils via the enzyme myeloperoxidase. Both neutrophil and myeloperoxidase activity are increased in dystrophic mice.This study found that hypochlorous acid decreased muscle force production and increased cytosolic Ca2+ concentrations in isolated muscles from wild‐type and dystrophic mice at relatively low concentrations of hypochlorous acid.These results indicate that hypochlorous acid may be key in the Duchenne muscular dystrophy disease pathology and may provide a unifying link between the chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca2+ concentrations observed in Duchenne muscular dystrophy.Hypochlorous acid production may be a potential target for therapeutic treatments of Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

Background: Improvements can be made in the management and staging of advanced pre‐auricular cutaneous squamous cell carcinoma (cSCC). We aimed to analyze radiological patterns of spread and clinico‐anatomical prognostic factors. Methods: Retrospective review of 54 patients with pre‐auricular cSCC (cutaneous/nodal) who underwent temporal bone resection with curative intent. Results: Involvement of the cartilaginous external auditory canal (EAC) (79.6%) and retromandibular space (63.0%) was common. Styloid process/anterior carotid sheath (ACS) (11.1%) and bony EAC (7.4%) involvement were rare. ACS involvement resulted in high rates of involved surgical margins (100%) and poor outcomes on univariable analysis. Negative prognostic factors on multivariable analysis included salvage surgery and invasion of the bony EAC, mandible, pterygoid muscle(s), and dura. Conclusion: The bony EAC and ACS can form temporary barriers to tumor spread, with the latter representing a potential limit of resectability. Prognostic factors revealed can lead to the development of a more appropriate staging tool. [ABSTRACT FROM AUTHOR]

Minimising the unintended capture of fish, marine mammals, reptiles, seabirds and other marine organisms is an important component of responsible fisheries management and for stabilising declines and rebuilding populations of threatened species. The analyses presented were designed to establish the first quantitative baseline of historical catches, catch rates and species composition for the dominant tuna fisheries operating in the western and central Pacific, the world's largest in terms of tuna catch. Using records from 612,148 fishing events collected by independent 'at sea' observers, estimates for finfish, billfish, elasmobranchs, marine mammals and sea turtles show that the composition and magnitude of catches varied considerably by fishery type and practice for the period 2003–2019. Simulations indicated that precision in longline estimates would be improved by monitoring a proportion of fishing sets from all fishing trips rather than full coverage from a proportion of all fishing trips. While attributing reasons for temporal trends in estimated bycatch was difficult due to the confounding impacts of changing abundances and fishing practices, the trends identified the nature of potential relationships for species that are not accurately quantified, or not covered, by fishing vessel logbooks. The trends in catch estimates, and the catch rate models, have utility in identifying species which may require targeted additional analyses and management interventions, including species of conservation interest (either due to their threatened status or vulnerability to fishing) such as elasmobranchs and sea turtles. Moreover, the estimates should support future evaluations of the impact of these industrial‐scale fisheries on bycatch species. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck lymphedema can occur in the internal or external structures of the head and neck region. Little is known about the development of this condition over the course of treatment for head and neck cancer. This study aimed to observe the development of internal and external lymphedema from diagnosis to 12 weeks postacute treatment. Methods: A single center, prospective observational cohort study assessed participants for external lymphedema, internal lymphedema, quality of life, and symptom burden. Assessments were conducted prior to starting radiotherapy (RT), at the end of RT, 6 and 12 weeks after RT. Results: Forty‐six participants were recruited. External lymphedema as measured by percentage water content, increased from 41.9 at baseline (95% CI: 39.3–44.4) to 50.4 (95% CI: 46.0–54.8) at 12 weeks following RT (p‐value <.001). After adjusting for changes in weight and participant age at baseline, a general increase in tape measurements was observed over time with significant increases from baseline to 12 weeks post‐RT for all measurement points. By 12 weeks post‐RT, all participants had lymphedema present in eight of 13 internal sites assessed. Conclusions: Internal and external head and neck lymphedema was observed to increase from baseline to 12 weeks after completion of RT without abatement. People with head and neck cancer should be educated about the potentially extended duration of this treatment side effect. Further research is required to determine the point at which swelling symptoms recede. [ABSTRACT FROM AUTHOR]

The aim of this work was to quantitatively analyse the magnitude of the migration of Rhipicephalus microplus ticks among cattle under field conditions, in groups of bovines with different stocking rates. The role of this phenomenon in the epidemiology of Anaplasma marginale has been discussed. Cattle naturally infested with R. microplus (donors) and cattle non‐infested with R. microplus (recipients) were clustered for 13 days into two groups with low and high stocking rates (G1 and G2 respectively). The initial prevalence of infestation (infested cattle / total cattle) was 20% in both groups. Adult migratory ticks from donor to recipient cattle were recorded by examination of the recipient cattle on days 2, 6, 9, and 13. The tick infestation rate, calculated using the Kaplan–Meier survival test, was higher in G2 (p = 0.05). The cumulative incidence on day 13 was 25% in G1 and 65% in G2, with no significant differences. The results demonstrate that migration of adults of R. microplus under field conditions occurs, in accordance with previous studies, and that its magnitude is associated with the stocking rate. These results highlight the relevance of R. microplus in the epidemiology of A. marginale through its role as a vector in the intrastadial transmission of this pathogen of cattle. [ABSTRACT FROM AUTHOR]

Background: In our experience, the anterior carotid sheath forms an important plane of dissection when excising temporal bone region cancers. However, its anatomical composition, relationships, and radiological appearance remains unclear. Methods: Eight sides of cadaveric heads were dissected. Anatomical findings were correlated with a high‐resolution baseline T1 MRI. Results: The anterior carotid sheath was formed by the tensor‐vascular‐styloid fascia, stylopharyngeal fascia, buccopharyngeal fascia (BPF), and longus capitis fascia (LCF), and appeared as a hypointense line on MRI. Not previously described, the glossopharyngeal nerve pierced the sheath 9.0 mm (SD 2.1 mm) below the skull base and traveled through its LCF and BPF layers to exit near the pharynx. Conclusion: Multiple fascial layers formed the anterior carotid sheath at the skull base, and this was radiologically identifiable. Further studies are required to validate findings and investigate the role this fascial plane has in forming an effective barrier to spread of malignancy. [ABSTRACT FROM AUTHOR]

Background: Ileostomy formation may be permanent or intended as temporary to defunction a high‐risk pelvic anastomosis to reduce the risk of septic consequences of anastomotic leak. However, these procedures have a high rate of readmission, most commonly due to dehydration and associated with acute kidney injury (AKI). Methods: A single centre retrospective cohort study of patients who underwent ileostomy formation from 2015 to 2020 and analysed in two groups: those who needed readmission within 60 days and those who did not. Data collected included demographics and renal function and electrolytes at baseline (ileostomy formation) and at elective ileostomy closure. Results: A total of 171 patients were included in the analysis, with a readmission rate 38% within 60 days of discharge. There was a significant increase in creatinine from baseline blood tests compared to date of elective ileostomy closure in both the readmission and no readmission arms. There was a significant decrease in eGFR from baseline blood tests compared with date of ileostomy closure in both readmission and no readmission arms. There was no significant difference in creatinine or eGFR between readmission and no readmission arms at date of ileostomy closure. Baseline serum sodium levels were lower in the readmission arm compared to no readmission arm. Conclusion: Ileostomy formation is associated with a deterioration in renal function, which occurs independent of whether the patient requires readmission to hospital. Low serum sodium may be used as a predictor for patients with an increased risk of readmission. A single centre retrospective cohort study of ileostomy patients comparing those readmitted versus those who weren't. Ileostomy formation was associated with a deterioration in renal function, which occurs independent of whether the patient requires readmission to hospital. [ABSTRACT FROM AUTHOR]

Background: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. Methods: Retrospective analysis of 167 Australian patients with primary and peri‐temporal bone cSCC. Results: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post‐operative radiotherapy (n = 146, 87.4%), 5‐year disease‐free survival, locoregional recurrence‐free survival, disease‐specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre‐auricular tumors, salvage surgery, tumor size (≥40 mm medial‐lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. Conclusion: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre‐auricular cancers is required given poorer associated survival outcomes. [ABSTRACT FROM AUTHOR]

Oropharyngeal cancer is increasingly caused by human papillomavirus (HPV), and this increase is believed to be caused by changing sexual behaviour. It has been hypothesised that an immune response to HPV through sexual intercourse is much stronger than an immune response elicited from oral sex. Therefore, people who have their debut of oral sex before or at the same time as sexual intercourse would have a weaker immune response to HPV and hence be more likely to develop a persistent oral HPV infection and oropharyngeal cancer. Drake et al (Cancer. 2021;127[7]:1029‐1038) found some evidence that supported this hypothesis. We have reanalysed two of our Australian cohorts with similar data in order to provide a perspective of Drake and colleagues' publication, as sexual behaviour varies depending on culture and geographical location. We found that engaging in oral sex (OR 4.46, 95% CI [1.88‐10.62]) and being younger than 20 years at oral sex debut (OR 9.46, 95% CI [3.53‐25.31]) were both very strong risk factors for oropharyngeal cancer. Participants in the general population cohort who had their sexual intercourse debut before the age of 18 were more likely to be oral HPV positive (OR 2.69, 95% CI [1.50‐4.83]). Oral sex debut before sexual intercourse debut was quite uncommon in our two Australian cohorts. However, timing of or sexual debuts may further add to risks of oropharyngeal cancer, and future studies should be designed to investigate timing and order of sexual debuts to help clarify the roles of these potential causal factors. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. Methods: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. Results: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post‐operative radiotherapy. In these patients, 5‐year disease‐free survival, disease‐specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. Conclusion: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post‐operative radiotherapy remains the mainstay treatment. Outcomes are improved in early‐stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. Methods: Retrospective review of 13 patients with PNS receiving anti‐PD‐1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi‐Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). Results: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8–2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3–4 treatment related adverse events. Conclusions: This case series supports developing evidence for anti‐PD‐1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population. [ABSTRACT FROM AUTHOR]

Front Cover: The cover image is based on the article Skull base surgery for malignant tumors: The 2nd international collaborative study (1995–2015) by Jatin P. Shah MD et al., https://doi.org/10.1002/hed.27746. [ABSTRACT FROM AUTHOR]

Background: Previous microbiome studies of oropharyngeal cancer have shown that there are differences in the oral microbiota between human papillomavirus (HPV)‐positive and HPV‐negative patients. Methods: We collected saliva, normal tissue, and tumor biopsies from 13 patients with oropharyngeal cancer (eight HPV‐positive, five HPV‐negative). We obtained basic clinical data from each patient. Extracted DNA was 16S rRNA gene sequenced. Analysis was based on HPV status and sample site using univariate, multivariate, and mixed effect regression methods. Results: Multivariate analysis methods separated samples based on HPV status (Adonis, p < 0.001). Comparison of patients showed that there were significant changes in microbial richness across all sites based on HPV status (linear mixed effects regression, p = 0.0002). Conclusions: We found significant differences in overall microbial community and bacterial richness between oropharyngeal patients based on HPV status. Our results suggest that there are significant differences in the microbiome in patients with oropharyngeal cancer based on HPV status. [ABSTRACT FROM AUTHOR]

Background: Malignancies in and around the temporal bone are aggressive and difficult to manage. In Queensland (Australia), where skin cancer rates are exceedingly high, tumours extending to the temporal bone from surrounding structures occur more commonly than primary cancers. Yet, a paucity of evidence exists as to their management and outcomes. This study aimed to review an Australian centre's experience of managing temporal and peritemporal bone malignancies, reporting on patient and tumour characteristics, treatment, and survival outcomes. Methods: Retrospective analysis of patients with primary temporal bone cancer and cancers extending to the temporal bone managed by the Queensland Skull Base Unit (Princess Alexandra Hospital) between 2000 and 2019. Results: A total of 222 patients were identified, of which 203 (91.4%) had cutaneous primaries, with 167 (75.2%) being squamous cell carcinoma (SCC). 73.9% presented with locoregionally recurrent or residual disease. Secondary tumours (92.8%) were 12 times more frequent than primary malignancies (7.2%), with the preauricular subsite the most common (45.5%). In the 201 patients (90.5%) who underwent curative intent surgery, 5‐year overall survival, disease‐free survival (DFS), and disease‐specific survival was 46.6%, 52.2%, and 65.9%, respectively. The preauricular subsite (p = 0.004), melanoma (vs. SCC, p = 0.027), involved margins (p < 0.001), and pathologically involved nodes (p < 0.001) were associated with significantly worse DFS. Conclusion: This is one of the largest studies of temporal bone malignancy in the literature, comprised primarily of secondary cutaneous malignancies. Although clear differences in epidemiological characteristics exist around the world, survival remains poor. Treatment should focus on achieving a clear margin of resection to optimize outcomes. [ABSTRACT FROM AUTHOR]

Background: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)‐associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. Methods: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer‐specific survival (CSS) and progression‐free survival (PFS). Results: Median follow‐up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26–4.45, p < 0.01) and 2.58 (95% CI 1.40–4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00–3.35, p = 0.04)]. Smoking status did not predict for CSS. Conclusion: Detailed smoking behavior should be considered in refining risk groups in HPV‐associated OPC treated with radiotherapy and in future trial design eligibility and stratification. [ABSTRACT FROM AUTHOR]

Background: Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death‐1 (PD‐1), programmed death‐ligand 1 (PD‐L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease. Patients and methods: Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto‐staining platform for EGFR, PD‐1, PD‐L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD‐L1 positive cases and log‐rank testing was performed to examine the relationship between PD‐L1 expression status and disease‐free survival (DFS) and overall survival (OS). Results: CPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P =.021), advanced pathological N status (P =.006), high histological tumor grade (P =.045), and positive histological margin (P =.023). Patients with PD‐L1 positivity in tumor cells did not have an inferior 3‐year OS (P =.93). Conclusion: The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma, and in particular hypopharyngeal squamous cell carcinoma, has long been associated with disfiguring treatment options, significant morbidity and limited long‐term survival outcomes. Total pharyngolaryngectomy (TPL) with free flap reconstruction followed by post‐operative radiation therapy or chemoradiotherapy is a widely accepted treatment of choice for advanced disease of the hypopharynx. Methods: Our unit undertook a 11‐year review of all primary TPL patients aiming to provide an update on survival outcomes, morbidity, post‐operative complications and evolving management strategies. We report one of the largest single‐centre series to date with 89 patients undergoing primary TPL between 2003 and 2013, and compare these outcomes to 180 patients undergoing TPL at the same facility in the previous 23 years. Results: Between study periods, we saw a shift in patient population towards higher stage disease (T‐stage 3 or 4 97% 2003–2013; 68% 1979–2002) and increased nodal involvement (node positive 88% 2003–2013; 70% 1979–2002) without a subsequent reduction in 5‐year disease‐specific survival (52% 2003–2013; 52% 1979–2002) or 5‐year overall survival (32% 2003–2013; 33% 1979–2002). [ABSTRACT FROM AUTHOR]

Background/Objectives: Perineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols. Methods: We retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post‐definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion. Results: There was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves <0.1 mm were more commonly treated with surgery alone, compared to lesions with nerves ≥0.1 mm which were offered adjuvant radiotherapy. Of the total BCC lesions with incidental perineural invasion, those with perineural margins ≥5 mm and peripheral tumour margins ≥3 mm were predominantly treated with surgery alone. Eighty‐nine per cent of cSCC lesions with incidental perineural invasion were treated with surgery and adjuvant radiotherapy. Conclusion: Surgery alone is suitable for BCC lesions with incidental perineural invasion. The majority of BCC lesions achieved ≥5 mm perineural and ≥3 mm peripheral tumour margins. Future research can guide if adjuvant radiation is required for BCC with perineural invasion. The treatment of cSCC with incidental perineural invasion with surgery alone remains undetermined. [ABSTRACT FROM AUTHOR]

Background/Objectives: Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair‐skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non‐representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients. Methods: We retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population‐based cohort of 43 794 Queensland residents recruited 2010–2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high‐risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012–2014.) We estimated the prevalence of perineural invasion (and 95% confidence interval) in BCC and SCC, respectively, and identified clinical factors associated with perineural invasion. Results: In QSkin, we observed 35 instances of perineural invasion in 9850 histopathologically confirmed BCCs (0.36%) and 9 instances of perineural invasion in 3982 confirmed SCC (0.23%) lesions. In the STAR cohort, we identified 4 lesions with perineural invasion in 692 BCCs (0.58%) and 16 reports of perineural invasion in 875 SCC lesions (1.9%). Conclusions: These data suggest that the overall prevalence of perineural invasion in keratinocyte cancer is low, although perineural invasion prevalence may be slightly higher among organ transplant recipients when compared to the general population. [ABSTRACT FROM AUTHOR]

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules. What's new?: Given limited recent advances in chemotherapeutic regimens, there is an urgent need to develop targeted therapies for metastatic nasopharyngeal carcinoma (NPC) that reduce toxicity and improve survival benefit. This review of clinical trials with monoclonal antibodies against checkpoint inhibitors shows that anti‐PD1 is a potential treatment option for patients with recurrent/metastatic NPC. Camrelizumab combination therapy achieved the best clinical outcome, but was associated with a high rate of serious adverse events. As immunotherapy gets incorporated into standard treatments, issues of optimal combinations with targeting agents and immune adjuvants and sequence with chemotherapy and radiation therapy will need to be addressed. [ABSTRACT FROM AUTHOR]

Solution conductivity plays a fundamental role for the employment of electrochemical advanced oxidation processes (EAOPs) and in the determination of their energy consumption. In this paper, a conventional flow cell based on a boron-doped diamond (BDD) anode that requires the addition of supporting electrolyte, is compared with a cell setup based on solid polymer electrolyte (SPE). The new cell configuration avoids the addition of salt to increase solution conductivity. The performances of the two systems are compared for the treatment of different solutions containing methylparaben, ethylparaben and propylparaben. Both systems are able to remove all the three parabens, but the SPE-system provided a better performance, with a maximum COD removal of 91% and energy consumption of 16.25 kWhm-3, whereas the conventional system can remove a maximum of 81% consuming 10.92 kWhm-3. The influences of parameters such as current density, flow conditions and supporting electrolyte concentration were analyzed, and results confirm that the SPE system is a promising system to treat low-conductive solutions polluted by parabens. [ABSTRACT FROM AUTHOR]

The ion pump Na+, K+-ATPase (NKA) is a receptor for the cardiotonic steroid ouabain. Subsaturating concentration of ouabain triggers intracellular calcium oscillations, stimulates cell proliferation and adhesion, and protects from apoptosis. However, it is controversial whether ouabain-bound NKA is considered a signal transducer. To address this question, we performed a global analysis of protein phosphorylation in COS-7 cells, identifying 2580 regulated phosphorylation events on 1242 proteins upon 10- and 20-min treatment with ouabain. Regulated phosphorylated proteins include the inositol triphosphate receptor and stromal interaction molecule, which are essential for initiating calcium oscillations. Hierarchical clustering revealed that ouabain triggers a structured phosphorylation response that occurs in a well-defined, time-dependent manner and affects specific cellular processes, including cell proliferation and cell-cell junctions. We additionally identify regulation of the phosphorylation of several calcium and calmodulin-dependent protein kinases (CAMKs), including 2 sites of CAMK type II-γ (CAMK2G), a protein known to regulate apoptosis. To verify the significance of this result, CAMK2G was knocked down in primary kidney cells. CAMK2G knockdown impaired ouabain-dependent protection from apoptosis upon treatment with high glucose or serum deprivation. In conclusion, we establish NKA as the coordinator of a broad, tightly regulated phosphorylation response in cells and define CAMK2G as a downstream effector of NKA. [ABSTRACT FROM AUTHOR]

Objective: To compare the neck and shoulder motor function of patients following neck dissection, including comparison with a group of healthy volunteers.Study Design: Cross-sectional study.Setting: Two tertiary hospitals in Brisbane, Australia.Subjects and Methods: Participants included patients 0.5 to 5 years after unilateral nerve-sparing neck dissection and healthy control subjects. Demographic and clinical information was collected with cervical and shoulder motor function measures (scapular resting position, active range of motion, and isometric muscle strength). Differences between groups were examined via regression analyses that included statistical adjustment for the potential effect of age, sex, body mass index, and other disease-related variables.Results: The 57 patients (68%, men; median age, 62 years) were typically older than the 34 healthy controls (47%, men; median age, 46 years). There were no differences between types of nerve-preserving neck dissection for any of the motor function measures. When adjusted for age, sex, and body mass index, healthy volunteers (vs patients) had significantly greater cervical range (eg, extension coefficient [95% CI]: 11.04° [4.41°-17.67°]), greater affected shoulder range (eg, abduction: 16.64° [1.19°-31.36°]), and greater isometric strength of the cervical flexors (eg, men: 4.24 kgf [1.56-6.93]) and shoulder flexors (eg, men: 8.00 kgf [1.62-14.38]).Conclusions: Strength and flexibility of the neck and shoulder are impaired following neck dissection in comparison with healthy controls. Clinicians and researchers are encouraged to consider the neck-and the neck dissection as a whole-as a source of motor impairment for these patients and not just the status of the accessory nerve. [ABSTRACT FROM AUTHOR]

The application of electrochemical technologies to wastewater treatment is limited by solution conductivity. In this paper, a solid polymer electrolyte Nafion® membrane has been used sandwiched between a boron doped diamond (BDD) anode and Ti/RuO2 cathode meshes to treat Bismarck Brown Y (BBY) solutions with very low conductivity. BBY has been chosen as model compound to the system, and the influence of several process parameters has been investigated. During the experiments the evolution of chemical oxygen demand (COD), color removal and nitrogen compounds have been monitored. The performances were strongly related with applied current and stirring rate, changed in a range of 0.5–2 A and 200 and 850 rpm, respectively. Their increment leads to a decrease of oxidation time required to remove BBY completely. The effect of the presence of Na2SO4 (2 and 7 mM) as supporting electrolyte has been also evaluated. Results were compared with a removal treatment carried out with a conventional batch system, using a flow cell containing liquid supporting electrolyte (Na2SO4). This comparison highlighted that the new cell setup is performing better in removing organic compounds, and thus, can be considered as effective process for the treatment of solutions with a low conductivity. Garbage in, clean water out: A solid polymer electrolyte Nafion® membrane is used sandwiched between a boron doped diamond (BDD) anode and Ti/RuO2 cathode meshes to treat solutions with very low conductivity containing Bismarck Brown Y (BBY) as model compound for waste water treatment. The new cell setup is performing good in removing organic compounds, and thus, can be considered as effective process for the treatment of solutions with a low conductivity. [ABSTRACT FROM AUTHOR]

This article contributes to the study of the politics of patronage appointments by creating a typology of patronage roles based on the nature of trust between patrons and appointees and on the skills patrons seek in appointees. Our classification brings together the dispersed literature on patronage roles and can be applied to the study of modalities of patronage across and within countries. We offer preliminary evidence from our study of the politics of patronage appointments in Latin America suggesting that variations in patronage roles can be related to variations in the institutionalization of party systems and to the nature of the links between political actors and voters. Finally, we explore whether the categories identified in our empirical study can be found in other settings. We conclude that our typology can contribute to the study of the impact of modalities of patronage on the quality of public administration and on political governability. [ABSTRACT FROM AUTHOR]

This article reports the high performance of a solid polymer electrolyte cell, equipped with a Nafion® N117 membrane packed between a Nb/boron‐doped diamond (Nb/BDD) mesh anode and a Ti/RuO2 mesh cathode, to degrade the insecticide imidacloprid spiked at 1.2–59.2 mg L−1 into low conductivity groundwater by electrochemical oxidation. The natural water matrix was first softened using valorized industrial waste in the form of zeolite as reactive sorbent. Total removal of the insecticide, always obeying pseudo‐first‐order kinetics, and maximum mineralization degrees of 70 %–87 % were achieved, with energy consumption of 26.4±1.6 kWh m−3. Active chlorine in the bulk and.OH at the BDD surface were the main oxidants. Comparative studies using simulated water with analogous anions content revealed that the natural organic matter interfered in the groundwater treatment. Trials carried out in ultrapure water showed the primary conversion of the initial N and Cl atoms of imidacloprid to NO3− and Cl− ions, being the latter anion eventually transformed into ClO3− and ClO4− ions. 6‐Chloro‐nicotinonitrile, 6‐chloro‐pyridine‐3‐carbaldehyde, and tartaric acid were identified as oxidation products. Break new ground: a solid polymer electrolyte (SPE) cell with a Nb/boron doped diamond mesh anode, a Ti/RuO2 mesh cathode, and a Nafion® N117 membrane is used to effectively degrade and mineralize the drug imidacloprid spiked into softened groundwater with very low conductivity under galvanostatic conditions. [ABSTRACT FROM AUTHOR]

Objective To measure patient-perceived upper limb and neck function following neck dissection and to investigate potential associations between clinical factors, symptoms, and function. Study Design Cross-sectional. Setting Two tertiary hospitals in Brisbane, Australia. Subjects and Methods Inclusion criteria: patients treated with neck dissection (2009-2014).Exclusion Criteria: aged <18 years, accessory nerve or sternocleidomastoid sacrifice, previous neck dissection, preexisting shoulder/neck injury, and inability to provide informed consent (cognition, insufficient English). Primary outcomes were self-reported function of the upper limb (Quick Disabilities of the Arm, Shoulder, and Hand) and neck (Neck Disability Index). Secondary outcomes included demographics, oncological management, self-efficacy, and pain. Generalized linear models were prepared to examine relationships between explanatory variables and self-reported function. Results Eighty-nine participants (male n = 63, 71%; median age, 62 years; median 3 years since surgery) reported mild upper limb and neck dysfunction (median [quartile 1, quartile 3] scores of 11 [3, 32] and 12 [4, 28], respectively). Significant associations were found between worse upper limb function and longer time since surgery (coefficient, 1.76; 95% confidence interval [CI], 0.01-3.51), having disease within the thyroid (17.40; 2.37-32.44), postoperative radiation therapy (vs surgery only) (13.90; 6.67-21.14), and shoulder pain (0.65; 0.44-0.85). Worse neck function was associated with metastatic cervical lymph nodes (coefficient, 6.61; 95% CI, 1.14-12.08), shoulder pain (0.19; 0.04-0.34), neck pain (0.34; 0.21-0.47), and symptoms of neuropathic pain (0.61; 0.25-0.98). Conclusion Patients can experience upper limb and neck dysfunction following nerve-preserving neck dissection. The upper quadrant as a whole should be considered when assessing rehabilitation priorities after neck dissection. [ABSTRACT FROM AUTHOR]

Background While human papillomavirus ( HPV) is an accepted risk factor for oropharyngeal squamous cell carcinoma ( SCC), its aetiological role in oral cavity SCC remains unclear. This study aimed to determine the HPV prevalence in an Australian population. Methods DNA was extracted from 63 formalin-fixed paraffin-embedded tumour specimens histologically confirmed as SCC of the oral cavity, diagnosed during 2006-2012. Clinical data were extracted from medical records. HPV presence was determined by polymerase chain reaction. Positive samples were typed by sequencing. Immunohistochemistry was used to assess p16INK4A , p53, pRB, Ki67, Cyclin D1 and p21WAF1 expression. Results Five of the 63 tumours (8%) were positive for HPV DNA (three HPV-16 positive and two HPV-18 positive). Two tumours overexpressed p16INK4A (3%) and one of these was also HPV positive. Overexpression of Cyclin D1 correlated significantly with tumour recurrence ( P = 0.029) and death ( P = 0.002). Conclusions This study has identified a low prevalence of high-risk HPV in Queensland, Australia. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To investigate balance, community mobility, gaze instability, and dizziness handicap and assess falls risk in people who are conservatively managed with small vestibular schwannoma (VS).Study Design: Cross-sectional study with controls.Methods: The study involved 18 people (mean age 58.7 ± 12.2 years) diagnosed with VS (<12 mm) and 22 age-matched controls (mean age 56.9 ± 8.0 years). Measures included standing on firm and foam surfaces with feet apart, then together with eyes open and closed, Timed Up and Go (TUG) test and dual TUG test, Dynamic Gait Index, 6-Minute Walk Test, Halmagyi Impulse Test, Dynamic Visual Acuity Test, and the Dizziness Handicap Inventory.Results: The clinical group failed more trials standing feet together on foam with eyes closed (P < .05); had inferior mobility and walked more slowly with divided attention (P < .05); had more difficulty walking with head movement, negotiating obstacles, and using stairs (P < .01); and walked shorter distances (P < .001) than controls. Reduced gaze stability (P < .01) and higher total (P = .007) and subcategory dizziness handicap scores (P < .05) were revealed compared to age-matched controls.Conclusions: Although outcomes for the clinical group are inferior to the control group across all measures and the dizziness impact is higher, the results fall in the low-risk category for falls. Preliminary data (level 4 evidence) support using a suite of clinical measures to monitor people with VS during conservative management.Level Of Evidence: 4 Laryngoscope, 127:1147-1152, 2017. [ABSTRACT FROM AUTHOR]

The incidence of oropharyngeal squamous cell carcinomas (SCCs) is increasing and is believed to reflect changing sexual practices in recent decades. For this case-case comparative study, we collected medical and life-style information and data on sexual behavior from 478 patients treated at the head and neck clinic of a tertiary hospital in Brisbane, Australia. Patients were grouped as ( i) oropharyngeal SCC ( n = 96), ( ii) oral cavity, larynx and hypopharynx SCC ('other HNSCCs,' n = 96), ( iii) other SCCs ( n = 141), and ( iv) other diagnoses ( n = 145). We fitted multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with lifestyle factors and sexual behaviors. Compared to the other three patient groups, the oropharyngeal SCC patients had overall more sexual lifetime partners (kissing, oral sex and sexual intercourse). Oropharyngeal SCC patients were significantly more likely to have ever given oral sex compared to the other three patient groups-93% of oropharyngeal SCC patients, 64% of other HNSCC patients, and 58% of patients with other SCC or other diagnoses. Oropharyngeal SCC patients were significantly more likely to have given oral sex to four or more partners when compared to patients with other HNSCC (odds ratio [OR] 11.9; 95% CI 3.5-40.1), other SCC (OR 16.6; 95% CI 5.3-52.0) or patients with other diagnoses (OR 25.2; 95% CI 7.8-81.7). The very strong associations reported here between oral sex practices and risks of oropharyngeal SCC support the hypothesis that sexually transmitted HPV infections cause some of these cancers. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Perineural spread (PNS) of cutaneous squamous cell carcinoma of the head and neck (SCCHN) can be associated with poor outcomes. Disease understanding and awareness is limited leading to delayed diagnosis and treatment. The purpose of this study was to identify epidemiological features of patients with PNS of cutaneous SCCHN. Methods Tumor characteristics and demographics of patients with PNS of cutaneous SCCHN managed through a single institution were collected between 1998 and 2013. Results One hundred twenty patients were included in this study. The majority had a history of skin cancer (85.8%). The median time from primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months). A total of 34.2% had no perineural invasion (PNI) detected in the primary, and 22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement at presentation. Conclusion Patients can present with PNS from cutaneous SCCHN with no known primary tumor or with primary tumors without PNI. The majority of patients presented without regional nodal involvement. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1416-1420, 2016 [ABSTRACT FROM AUTHOR]

Background Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. Methods A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Results Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. Conclusion This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT. © 2015 Wiley Periodicals, Inc. Head Neck 38: 824-831, 2016 [ABSTRACT FROM AUTHOR]

This Research Note presents a new dataset of party patronage in 22 countries from five regions. The data was collected using the same methodology to compare patterns of patronage within countries, across countries and across world regions that are usually studied separately. The Note addresses three research questions that are at the centre of debates on party patronage, which is understood as the power of political parties to make appointments to the public and semi-public sector: the scope of patronage, the underlying motivations and the criteria on the basis of which appointees are selected. The exploration of the dataset shows that party patronage is, to a different degree, widespread across all regions. The data further shows differences between policy areas, types of institutions such as government ministries, agencies and state-owned enterprises, and higher, middle and lower ranks of the bureaucracy. It is demonstrated that the political control of policy making and implementation is the most common motivation for making political appointments. However, in countries with a large scope of patronage, appointments serve the purpose of both political control and rewarding supporters in exchange for votes and services. Finally, the data shows that parties prefer to select appointees who are characterised by political and personal loyalty as well as professional competence. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To determine the feasibility of using a mouse tumor model as a microsurgical training tool for otolaryngology-head and neck surgery (OHNS) trainees.Study Design: Animal study.Methods: We injected athymic nude mice with human cutaneous squamous cell carcinoma (A431 cell line) deep to the parotid region overlying the masseter muscle. We sacrificed the animals 1 to 3 weeks postinjection, once a visible tumor growth was confirmed. We then asked 10 OHNS trainees to excise the tumor with preservation of the facial nerves under a high-magnification dissecting microscope. The trainees graded the tasks in several areas of specific measures using a visual analogue scale (VAS) including 1) tumor texture, 2) surgical realism, 3) usefulness, and 4) difficulty of the task.Results: Noticeable tumor growth occurred within 5 days following A431 cell injection and reached measureable size (0.5-1.5 cm) within 1 to 3 weeks. The tumor displaced the facial nerve laterally and medially, with few demonstrating infiltration of the nerve. VAS scores (± standard deviation) were 8.1 (± 1.7), 7.7 (± 2.5), 9.0 (± 0.9) and 6.6 (± 1.9) for tumor texture, surgical realism, usefulness, and the difficulty of the task, respectively.Conclusions: We demonstrate a novel, reliable and cost-effective mouse model for simulating tumor extirpation microsurgery with preservation of important neural structures. OHNS trainees have found this simulation model to be realistic, useful, and appropriately challenging. [ABSTRACT FROM AUTHOR]

Introduction: Accurate definition of the presence and extent of large nerve perineural spread (PNS) is a vital component in planning appropriate surgery and radiotherapy for head and neck cancers. Our research aimed to define the sensitivity and specificity of 3T MRI in detecting the presence and extent of large nerve PNS, compared with histologic evaluation. Methods: Retrospective review of surgically proven cases of large nerve PNS in patients with preoperative 3T MRI performed as high resolution neurogram. Results: 3T MRI had a sensitivity of 95% and a specificity of 84%, detecting PNS in 36 of 38 nerves and correctly identifying uninvolved nerves in 16 of 19 cases. It correctly identified the zonal extent of spread in 32 of 36 cases (89%), underestimating the extent in three cases and overestimating the extent in one case. Conclusion: Targeted 3T MRI is highly accurate in defining the presence and extent of large nerve PNS in head and neck cancers. However, there is still a tendency to undercall the zonal extent due to microscopic, radiologically occult involvement. Superficial large nerve involvement also remains a difficult area of detection for radiologists and should be included as a 'check area' for review. Further research is required to define the role radiation-induced neuritis plays in the presence of false-positive PNS on MRI. [ABSTRACT FROM AUTHOR]

Purpose: To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy. Methods: The laterally integrated depth-dose-distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. FLUKA Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D-fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer-type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread-out-Bragg-peak, dose homogeneity in 2D-fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines. Results: The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy-dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ±1 mm over the whole 20×20 cm² scan field; homogeneity in a uniform squared field was within ±5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns. Conclusions: After successful dosimetric beam commissioning, quality assurance measurements performed during a 24-month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments. [ABSTRACT FROM AUTHOR]

Background Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. Methods The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. Results No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. Conclusion Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1611-1618, 2014 [ABSTRACT FROM AUTHOR]

ABSTRACT Background The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). Methods All patients with N3 (>6 cm) HNSCC treated with definitive chemoradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid residual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome. Results Median follow-up from diagnosis for 33 patients was 30 months (range, 6−76 months). INF occurred in 2 patients (6%) with neck dissections performed in 4 cases (12%). First failure was predominantly distant metastatic (10; 30%). Conclusion The rate of INF remains low when following a PET-directed neck management policy after definitive CRT for N3 (>6 cm) HNSCC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1200-1206, 2014 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Injury to the internal carotid artery is a feared complication of endoscopic endonasal surgery of the skull base. Such an event, although rare, is associated with high morbidity and mortality. Even if bleeding is controlled, permanent neurological defects frequently persist. Many techniques have been developed to manage internal carotid artery rupture with varying degrees of success. The purpose of this study was to explore endoscopic management of arterial damage with endovascular closure devices used for a femoral arteriotomy. The ability to remotely suture a damaged artery permits the possible adaptation of this technology in managing endoscopic arterial complications. Study Design Technical note. Methods After the creation of an endoscopic endonasal corridor in a cadaveric specimen, an arteriotomy was created at the cavernous portion of the internal carotid artery. The Angio-Seal, StarClose, and MynxGrip vascular closure devices were utilized under endoscopic guidance to repair the arteriotomy. Angiography was then done on a cadaver sutured with the StarClose. Results Both the Angio-Seal and StarClose were deployed quickly and appeared to provide sufficient closure of the arteriotomy. The Angio-Seal required the use of a guidewire and was longer to deploy when compared with the StarClose. The StarClose deployment was quick and facile. The MynxGrip also deployed without difficulty. Conclusions The Angio-Seal and StarClose systems were both successfully deployed utilizing an endoscopic endonasal approach. The MynxGrip was the easiest to deploy and has the greatest potential to be of benefit in this application. Further studies with hemodynamic models are required to properly assess the appropriateness in this setting. Level of Evidence NA Laryngoscope, 124:1318-1324, 2014 [ABSTRACT FROM AUTHOR]

Purpose: To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue.Materials and Methods: In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3–5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared.Results: In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8–17.5%; P < 0.0001), ultrasound (Δ18.3–20.0%; P < 0.0001), and mammography and/or ultrasound (Δ8.6–10.7%; P ≤ 0.0105) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0–5.5% vs. 11.1% at mammography; 6.3–8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2–97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2–84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2–96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7–88.5% on gadopentetate dimeglumine-enhanced MRI vs. 77.0–84.4% with conventional techniques). Overall diagnostic performance for the detection of cancer was superior on gadobenate dimeglumine-enhanced MRI than on conventional imaging or gadopentetate dimeglumine-enhanced MRI.Conclusion: Gadobenate dimeglumine-enhanced MRI significantly improves cancer detection compared to gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound in a selected group of patients undergoing breast MRI for preoperative staging or because of inconclusive findings at conventional imaging. [ABSTRACT FROM AUTHOR]