The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows.

Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked ap2s1 gene which supports acoustically evoked habituation learning. ap2s1 encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, ap2s1 biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for ap2s1's role in human conditions including autism spectrum disorder.

Elective management of regional nodal basins in cutaneous squamous cell carcinoma of the head and neck: Controversies and contemporary perspectives.

Non-melanoma skin cancer (NMSC) is among the most common cancers worldwide, with an incidence that continues to rise. Although cutaneous squamous cell carcinoma (cSCC) constitutes only approximately 20% of such cases, it represents the most common cause of NMSC mortality, owing largely to the propensity for development of regional lymph node metastases (LNM), which, when present, carry a dismal prognosis. Whilst overall rates of LNM are low, there are a number of patient and tumour factors that likely confer considerably higher risks, which has led several investigators to propose more proactive elective management of regional nodal basins in selected high-risk cases. Current international guidelines, however, do not recommend any elective treatment or sampling of regional nodal basins in the absence of clinically apparent disease. The purpose of this review is to explore in detail the fundamental issues underlying this controversy, focusing specifically on cSCC of the head and neck (cSCCHN). In particular the rationale for more a proactive elective approach to regional nodal basins, including the evidence-base underlying identification of potentially high-risk factors for development of LNM is discussed, along with oncological outcomes for those patients that do go onto suffer LNM. We also provide contemporary perspectives and evidence for approaches to electively managing regional nodal basins, and offer insight into how these may develop both in the clinical and research arenas.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: main results of a cluster preference randomised controlled trial.

PURPOSE: The patient concerns inventory (PCI) is a prompt list allowing head and neck cancer (HNC) patients to discuss issues that otherwise might be overlooked. This trial evaluated the effectiveness of using the PCI at routine outpatient clinics for one year after treatment on health-related QOL (HRQOL). METHODS: A pragmatic cluster preference randomised control trial with 15 consultants, 8 'using' and 7 'not using' the PCI intervention. Patients treated with curative intent (all sites, disease stages, treatments) were eligible. RESULTS: Consultants saw a median (inter-quartile range) 16 (13-26) patients, with 140 PCI and 148 control patients. Of the pre-specified outcomes, the 12-month results for the mean University of Washington Quality of Life (UW-QOLv4) social-emotional subscale score suggested a small clinical effect of intervention of 4.6 units (95% CI 0.2, 9.0), p = 0.04 after full adjustment for pre-stated case-mix. Results for UW-QOLv4 overall quality of life being less than good at 12 months (primary outcome) also favoured the PCI with a risk ratio of 0.83 (95% CI 0.66, 1.06) and absolute risk 4.8% (- 2.9%, 12.9%) but without achieving statistical significance. Other non-a-priori analyses, including all 12 UWQOL domains and at consultant level also suggested better HRQOL with PCI. Consultation times were unaffected and the number of items selected decreased over time. CONCLUSION: This novel trial supports the integration of the PCI approach into routine consultations as a simple low-cost means of benefiting HNC patients. It adds to a growing body of evidence supporting the use of patient prompt lists more generally.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.

Outcomes and prognosticators in regionally recurrent cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: Data regarding regionally metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is limited and derived almost exclusively from Australian and United States (US) institutions. We report the first United Kingdom perspective, with the aims of benchmarking survival outcomes and identifying clinically relevant prognosticators. MATERIALS AND METHODS: Ninety-one patients with regionally recurrent cSCCHN treated with curative intent over a ten-year period (2009-2018) were studied retrospectively. Time-to-event analyses were used to estimate oncological outcomes, and log-rank statistics and Cox proportional hazards models used to examine potential prognosticators. Receiver operating characteristics were also used to analyse the influence of nodal disease burden. RESULTS: Parotid involvement (with or without neck involvement) was most common (79.2%), and time to recurrence in those with parotid disease alone significantly shorter than for any other disease distribution (p = 0.034). Respective five-year overall, disease-specific, and disease-free survival estimates were 43.8%, 63.8%, and 36.2%. Extracapsular spread (ECS) portended reduced DFS and DSS (p = 0.012 and p = 0.005 respectively). Increasing nodal burden (≥4 involved nodes) also reduced DSS (p = 0.020), while parotid disease alone predicted more favourable DSS (p = 0.008). ECS and isolated parotid involvement remained significant on multi-variate analysis (p = 0.014 and p = 0.028 respectively). CONCLUSIONS: Oncological outcomes were unfavourable but broadly consistent with previous reports, notionally lending support to a more proactive approach in managing the clinically node negative neck/parotid in selected high-risk cases. Our data also support distinct parotid classification and consideration of involved lymph node number in future staging systems.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: baseline results in a cluster preference randomised controlled trial.

PURPOSE: The main aim of this paper is to present baseline demographic and clinical characteristics and HRQOL in the two groups of the Patient Concerns Inventory (PCI) trial. The baseline PCI data will also be described. METHODS: This is a pragmatic cluster preference randomised control trial with 15 consultant clusters from two sites either 'using' (n = 8) or 'not using' (n = 7) the PCI at a clinic for all of their trial patients. The PCI is a 56-item prompt list that helps patients raise concerns that otherwise might be missed. Eligibility was head and neck cancer patients treated with curative intent (all sites, stage of disease, treatments). RESULTS: From 511 patients first identified as eligible when screening for the multi-disciplinary tumour board meetings, 288 attended a first routine outpatient baseline study clinic after completion of their treatment, median (IQR) of 103 (71-162) days. At baseline, the two trial groups were similar in demographic and clinical characteristics as well as in HRQOL measures apart from differences in tumour location, tumour staging and mode of treatment. These exceptions were cluster (consultant) related to Maxillofacial and ENT consultants seeing different types of cases. Consultation times were similar, with PCI group times taking about 1 min longer on average (95% CL for the difference between means was from - 0.7 to + 2.2 min). CONCLUSION: Using the PCI in routine post-treatment head and neck cancer clinics do not elongate consultations. Recruitment has finished but 12-month follow-up is still ongoing.

Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach.

BACKGROUND: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). METHODS: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics. RESULTS: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. CONCLUSION: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016.

The role of surgery in the palliation of head and neck cancer.

PURPOSE OF REVIEW: The public demands that 'all modes of treatment' should be offered to patients who present with head and neck cancer. Up to 40% of patients present with advanced stage disease, of whom some 10% have metastatic disease and are currently deemed incurable. This review summarizes the current role and philosophy of surgical interventions in the palliation of head and neck cancer. RECENT FINDINGS: Patients who present with advanced or recurrent head and neck cancers over the past decade have been offered nonsurgical palliative treatments of radiotherapy with or without chemotherapy, with variable responses. The aims are to achieve tumour shrinkage and gain effective relief of symptoms, such as pain, breathing and swallowing. The use of surgery in the palliation of disease and its symptoms has declined significantly since the 1980s. Within the concept of multidisciplinary clinical working as the 'gold standard' for the provision of optimum care for the head and neck patient, the place for surgery should be discussed within the many options available currently. SUMMARY: Patients who present with advanced, incurable or recurrent head and neck cancer should be made aware of their prognosis and the potential need and benefits of palliative care. The active involvement of patients and their carers, their desires and wishes should be the prime consideration for any interventions. Careful selection of suitable patients can achieve prolonged symptom relief safely and result in an improvement in their quality of living. The ultimate goal should incorporate not only quality of life but quality of dying.

Trichilemmal carcinoma: an unusual presentation of a rare cutaneous lesion.

Trichilemmal carcinoma (TC) is a rare cutaneous neoplasm which is derived from adnexal keratinocytes, is histologically invasive, contains cytologically atypical clear cell neoplasm and is in continuity with the epidermis and/or follicular epithelium. However, the diagnostic criteria and even the existence of TC have been contentious. We report the case of a 92-year-old woman with TC of the head and neck region who presented with an unusually long history. She was treated successfully with wide local excision. Important aspects in presentation, differential diagnosis, including histopathological features and management are discussed.

Is POSSUM predictive of morbidity and mortality in laryngectomy patients?

OBJECTIVES: To test the validity of the comparative audit tool of POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity) against a cohort of 92 consecutive laryngectomies at a major tertiary referral centre for head and neck cancer. The major outcome measurements were 30-day mortality rates, formation of a pharyngo-cutaneous fistula, and length of hospital stay. METHODS: By means of a prospective and retrospective case note analysis. RESULTS: No significant difference between the mean POSSUM morbidity scores of those patients who did, or did not develop a fistula, was found (p=0.535, 95% C.I. -4.36 to 8.33). No significant correlation was observed between POSSUM predicted morbidity and bed occupancy [r=0.137 (95% C.I. -0.070 to 0.334)]. The Portsmouth POSSUM equation for mortality however did accurately predict the mortality rate (observed to expected ratio of 1.05). CONCLUSION: The authors propose that whilst there are many similar factors linked to mortality between cohorts of general surgical and head and neck patients, there are several highly specific risk factors in open surgery of the upper aero-digestive tract in the head and neck which are linked with wound breakdown and morbidity which are omitted from the POSSUM scoring system. The authors warn against the use of this comparative audit tool in its current state for such surgical procedures and recommend the creation of a specific POSSUM for head and neck cancer surgery.

A systematic review and Number Needed to Treat analysis to guide the management of the neck in patients with squamous cell carcinoma of the head and neck.

OBJECTIVES: To systematically review the literature to identify studies from which it is possible to perform a Number Needed to Treat (NNT) analysis to identify, in a more clinically intuitive manner, neck node levels for which treatment is essential in the N0 and N+ neck with respect to the primary site of tumour. METHODS: Systematic literature review using a defined search strategy; data extraction from studies meeting the inclusion criteria; calculation of NNT for individual neck node levels with respect to primary site. RESULTS: A total of 6169 articles were identified from searches of Embase, Medline, The Cochrane library of randomised control trials, conference proceedings and the bibliographies of retrieved papers. Titles and abstracts were screened; from these, 219 studies were retrieved for detailed review. One hundred and ninety six papers were excluded and 23 studies were included in the final analysis. Following review of the data from these studies, and accepting a NNT cut-off of 5 we confirmed that the following lymph node levels should be treated: CONCLUSIONS: NNT is a clinically intuitive parameter to guide appropriate lymph node level treatment in patients presenting with squamous cell carcinoma of the head and neck.

Laser safety in head and neck cancer surgery.

The use of trans-oral laser techniques for the resection of head and neck carcinomas has increased exponentially over the last four decades. Inadvertent laser damage to the patient or operating theatre staff is an acknowledged risk. However, no data exist to verify the safety margin of commonly employed precautions. The aims of this study was to assess the safety margins of protective strategies commonly adopted when using CO(2) lasers to resect tumours of the head and neck. A Sigmacon Acupulse Lumenis CO(2) laser was evaluated. The beam was focused to 2 mm diameter at 402 mm focal length. Gauze swabs, neurosurgical patties, surgical gloves, paper drapes and conventional endotracheal (ET) tubes were tested against the following laser variables: power, beam characteristics and angle of beam incidence (90 & 45°). Laser penetration time through the material under test was recorded in seconds (s). All the materials where tested dry and some, when appropriate, were tested wet. The mean of three recordings was calculated. The results demonstrated dry gauze swabs, neurosurgical patties and paper drapes provided 0 s protection at 2 W (lowest power). However, when wet, the laser failed to penetrate the swabs and neurosurgical patties, even after 180 s of continuous application. Gloves (single or double layer), and ET cuffs were penetrated in less than 1 s at 2 W. Time to penetrate a size 6.0 ET tube at 2 W continuous setting increased from <1 s at 90° to 42 s at 45°. These data are essential for anyone using CO(2) lasers for the resection of head and neck tumours. The importance of keeping laser consumables wet throughout the procedure is highlighted. The angle at which the laser hits the ET tube may impart some protection against airway fire but the data support the need to cover the ET tube with damp swabs or neuropatties when possible.

Detection of synchronous lung tumors in patients presenting with squamous cell carcinoma of the head and neck.

BACKGROUND: Screening for synchronous pulmonary tumors in patients presenting with squamous cell carcinoma of the head and neck (SCCHN) is important, because detection may alter subsequent management. METHODS: We conducted a retrospective review, comparing effectiveness of pulmonary screening using thoracic CT or chest X-ray, in 1882 patients presenting with SCCHN. RESULTS: The overall rate of synchronous pulmonary tumors was 4.3%. The number needed to scan, ie, the number of thoracic CTs required to detect 1 pulmonary tumor, is reported for recurrent primary tumors, primary disease load (T and N classification), and individual primary sites. The incidence of pulmonary metastases is related to locoregional disease load while the incidence of bronchogenic carcinoma is sporadic. CONCLUSION: Although it is possible to propose a pragmatic screening protocol for pulmonary metastases, this is not possible for bronchogenic carcinomas. Therefore, we recommend that thoracic CT is used in all cases to screen for coexistent pulmonary pathology.

Comparison of two face masks used to deliver early ventilation to laryngectomized patients.

Emergency airway management of laryngectomized patients is inherently complicated by the altered contours of their necks, by the presence of awkwardly placed tracheostomas, and by stomal strictures. Effective ventilation can also be compromised by the presence of hypertrophic peristomal scar tissue and by tumor recurrence. One common method of airway management involves the use of a pediatric face mask attached to a standard ventilation bag. We conducted a study of 20 laryngectomized patients to determine if they could be adequately ventilated through two commonly used pediatric face masks--the Laerdal mask and the Ambu mask. Ten of these patients had had an end tracheostoma in place for at least 1 year, and the remaining 10 had undergone stoma placement only recently. We found that all 20 patients achieved an adequate peristomal seal when using the Laerdal mask, whereas only 11 adequate seals were achieved with the Ambu mask. Therefore, we recommend that the Laerdal pediatric mask be used for early ventilation in laryngectomized patients.

The local side effects of inhaled corticosteroids: current understanding and review of the literature.

The frequent use of inhaled corticosteroids (ICSs), especially at higher doses, has been accompanied by concern about both systemic and local side effects. The systemic complications of ICSs have been extensively studied and are well-documented in the literature. There are comparatively few studies reporting on the local complications of ICSs. Compared with systemic side effects, the local side effects of ICSs are considered to constitute infrequent and minor problems. However, while not usually serious, these local side effects are of clinical importance. They may hamper compliance with therapy and the symptoms produced may mimic more sinister pathology. This review considers the prevalence of local side effects, their clinical features, the potential causes, the role of inhaler devices, and current measures that have been suggested to avoid the problem.

Metastatic testicular seminoma--a case report.

We present the case of a 42-year-old male who presented with a hot, tender swelling in the left supraclavicular fossa. He was pyrexial on presentation with a mildly elevated leucocyte count of 12.4x10(9)/l. Clinical examination, including full ear, nose and throat assessment, proved unremarkable. The medical history revealed that 2 years earlier the patient had been diagnosed with a testicular seminoma for which he underwent a right inguinal orchidectomy and abdominal radiotherapy. CT scan highlighted a 6 cm para-laryngeal mass, of mixed attenuation, with an adjacent region of inflammation. Overall appearance was suggestive of an infective mass. Ultrasound-guided fine needle aspiration cytology revealed a metastatic seminomatous deposit. Imaging of the chest and abdomen revealed this as the only site of metastasis. He is currently undergoing chemotherapy, and is responding well. We review the pathology of testicular seminoma. This case highlights the myriad of pathologies that may present as a lump in the neck.