Managing complications of endoscopic transsphenoidal surgery in pituitary adenomas.

INTRODUCTION: Over the last two decades there has been a gradual shift from the traditional microscopic approach toward the use of endoscopic endonasal approach for resection of pituitary adenomas. Multiple medical and surgical complications can occur following endoscopic transsphenoidal resection of adenomas. AREAS COVERED: We discuss the evolution of the surgical practice from the use of the 'microscope' to the 'endoscope' in the resection of pituitary adenomas. We present a comprehensive review of the medical and surgical complications following surgery with particular emphasis on both the prevention and management of electrolyte disturbance, cerebrospinal fluid leak and the rare but dreaded complication of internal carotid injury (ICA). We also searched the PubMed database to identify relevant literature between 1984 and 2019. EXPERT OPINION: Use of endoscope compared with microscope may be associated with better preservation of pituitary gland function with similar extent of resection. Overall medical and surgical complications can be safely managed in high volume centers in association with endocrinologists and skull base trained otolaryngologists. Understanding of anatomico-technical nuances and meticulous surgical technique are important toward preventing ICA injury. Ongoing surgical and technical developments coupled with imaging advances will likely lead to better future outcomes for patients with functioning and nonfunctioning adenomas.

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

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

Squamous cell carcinoma of the nasal cavity: A descriptive analysis of cases from the head and neck 5000 study.

OBJECTIVES: This paper aims to provide contemporary epidemiological data on squamous cell carcinoma (SCC) of the nasal cavity, which represents a rare type of head and neck cancer. DESIGN, SETTING & PARTICIPANTS: A descriptive analysis of people with nasal cavity SCC treated with curative intent from the Head and Neck 5000 study; a multicentre clinical cohort study of people from the UK with head and neck cancer. People with tumours of the nasopharynx, paranasal sinuses and other sub-sites of the head and neck were excluded. MAIN OUTCOME MEASURES: Demographic data and treatment details are presented for all participants. The main outcomes were overall survival and survival according to categories of characteristics (eg, smoker vs non-smoker); these were explored using Kaplan-Meier plots. RESULTS: Thirty people with nasal cavity SCC were included in the study, of which most were male (67%) and current or ex-smokers (70%). The majority (70%) presented with early-stage (T1/2, N0) tumours. Cervical lymph node metastases at presentation were rare, occurring in only one person. Nine people died during the follow-up period (30%). Worse survival outcomes were seen in people with moderate or severe co-morbidities. CONCLUSIONS: This paper provides epidemiological data on nasal cavity SCC in the UK. Patterns of disease and survival outcomes are described, identifying high-risk groups. Further studies should explore whether primary treatment modality alters survival.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

Quality of physical health care among patients with personality disorder.

OBJECTIVE: To investigate the assessment and treatment of physical health in patients with personality disorder and compare this to the care received in schizophrenia. METHOD: We collected data from a random sample of 246 patients with personality disorder on monitoring and intervention for seven key aspects of physical health. We compared the results with those from a random sample with schizophrenia. RESULTS: In our sample, 160 (65%) people had the diagnosis of emotionally unstable personality disorder. In total, 104 (42.3%) people with personality disorder were being prescribed antipsychotic medication; 23 (9.3%) participants had all seven aspects of physical health recorded. Alcohol was most frequently recorded (76%); BMI (38.6%), blood glucose (25.2%) and blood cholesterol (20.7%) were less likely to be recorded. Interventions were not given to all those requiring them. Compared to people with schizophrenia, a lower proportion had evidence of assessment of smoking, illicit drug use, blood glucose and blood lipid levels. Smoking cessation advice was more likely to be offered to people with schizophrenia (difference = 29.4%, 95% CI = 12.5 to 44.7). CONCLUSION: Physical health is under-assessed and under-treated in patients with personality disorder. Medical staff must do more to help tackle increased morbidity among this group.

IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer.

Head and neck squamous cell carcinomas (HNSCC) are treated with surgery, radiotherapy and cisplatin-based chemotherapy, but survival from locally-advanced disease remains poor, particularly in patients whose tumors are negative for Human papillomavirus (HPV). Type 1 IGF receptor (IGF-1R) is known to promote tumorigenesis and resistance to cancer therapeutics. Here, we assessed IGF-1R immunohistochemistry on tissue microarrays containing 852 cores from 346 HNSCC patients with primary tumors in the oropharynx (n = 231), larynx (85), hypopharynx (28), oral cavity (2). Of these, 236 (68%) were HPV-negative, 110 (32%) positive. IGF-1R was detected in the cell membrane of 36% and cytoplasm of 92% of HNSCCs; in 64 cases with matched normal tonsillar epithelium, IGF-1R was overexpressed in the HNSCCs (P < 0.001). Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R [OS: hazard ratio (HR) = 1.63, P = 0.006; DSS: HR = 1.63, P = 0.016], cytoplasmic IGF-1R (OS: HR = 1.58, P = 0.009; DSS: HR = 1.58, P = 0.024) and total IGF-1R (OS: HR = 2.02, P < 0.001; DSS: HR = 2.2, P < 0.001). High tumor IGF-1R showed significant association with high-tumor T-stage (P < 0.001) and HPV-negativity (P < 0.001), and was associated with shorter OS when considering patients with HPV-positive (P = 0.01) and negative (P = 0.006) tumors separately. IGF-1R was independently associated with survival in multivariate analysis including HPV, but not when lymphovascular invasion, perineural spread and T-stage were included. Of these factors, only IGF-1R can be manipulated; the association of IGF-1R with aggressive disease supports experimental incorporation of anti-IGF-1R agents into multimodality treatment programs for HPV-negative and high IGF-1R HPV-positive HNSCC.

Long-term functional outcomes in surgically treated patients with oropharyngeal cancer.

OBJECTIVES/HYPOTHESIS: As survival rates in oropharyngeal cancer improve, long-term functional outcomes are increasingly important to understand. We report long-term functional outcomes in a cohort of surviving patients with oropharyngeal squamous cell carcinoma treated with primary surgery ± radiotherapy. STUDY DESIGN: Cross-sectional study. METHODS: Patients undergoing primary surgery for oropharyngeal cancer in Oxford, United Kingdom, between 2000 and 2010 were identified. The University of Washington Quality-of- Life and MD Anderson Dysphagia Inventory questionnaires were sent to all patients. Multivariate analysis was performed to determine the relationship between clinical factors and swallowing outcomes. RESULTS: Twenty percent of patients required gastrostomy-tube placement (mean feed duration, 114 days). On multivariate analysis, increased age, advanced T stage, and an open surgical approach were associated with significantly reduced quality-of-life scores. CONCLUSIONS: Mean functional scores were comparable to previously published series of patients treated with primary surgery. Gastrostomy insertion rate was lower than in many previously published studies. Furthermore, specific variables have been identified that are associated with adverse functional outcome.

Irrigation solutions in head and neck cancer surgery: a preclinical efficacy study.

INTRODUCTION: It is common practice to irrigate the operative site following tumor resection during major head and neck surgery. A variety of irrigation solutions are used, but there are few data on their relative efficacies in this context. METHODS: The effect of different irrigation solutions on cell survival was assessed by clonogenic survival assay in 5 head and neck squamous cell carcinoma cell lines at different time points. RESULTS: Saline had no effect on cell survival in any of the cell lines tested. Hydrogen peroxide, povidone-iodine, and a hydrogen peroxide/povidone-iodine mix caused complete cell death in all cell lines. Irrigation with distilled water caused a significant reduction in cell survival in 3 cell lines. Duration of exposure showed no effect on cell survival. CONCLUSION: These data suggest a significant difference in the cytocidal effect of commonly used irrigation solutions on head and neck cancer cells in an in vitro model.

Pharyngeal pouch surgery: a combined open and endoscopic approach.

Pharyngeal pouches are common, particularly in the elderly population, in whom they can cause significant morbidity. The advanced age of many patients and existing comorbidities mean that in some cases neither open nor endoscopic pouch stapling is possible. We present a technique of combined open and endoscopic pharyngeal pouch surgery, which may be used when other therapeutic options are limited.