Second surgery for progressive glioblastoma: a multi-centre questionnaire and cohort-based review of clinical decision-making and patient outcomes in current practice.

PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well.

Obstructive Sleep Apnea in Obese Patients: a UK Population Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is an increasingly common disorder associated with increased cardiovascular disease, mortality, reduced productivity, and an increased risk of road traffic accidents. A significant proportion of patients with OSA in the UK are undiagnosed. This study aims to identify risk factors for OSA in an obese cohort. METHOD: A population-based study was conducted of obese patients (BMI ≥ 30 kg/m2) from the Clinical Practice Research Datalink (CPRD). A logistic regression model was used to calculate odds ratios (ORs) for developing OSA according to other clinicopathological characteristics. Multivariate analysis was conducted of individual factors that affect the propensity to develop OSA. Statistical significance was defined as p < 0.050. RESULTS: From 276,600 obese patients identified during a data extraction of the CPRD in July 2017, the prevalence of OSA was 5.4%. The following risk factors were found to be independently associated with increased likelihood of OSA: male sex (OR = 3.273; p < 0.001), BMI class II (OR = 1.640; p < 0.001), BMI class III (OR = 3.768; p < 0.001), smoking (OR = 1.179; p < 0.001), COPD (OR = 1.722; p < 0.001), GERD (OR = 1.557; p < 0.001), hypothyroidism (OR = 1.311; p < 0.001), acromegaly (OR = 3.543; p < 0.001), and benzodiazepine use (OR = 1.492; p < 0.001). Bariatric surgery was associated with reduced risk of OSA amongst this obese population (OR = 0.260; p < 0.001). CONCLUSIONS: In obese patients, there are numerous comorbidities that are associated with increased likelihood of OSA. These factors can help prompt clinicians to identify undiagnosed OSA. Bariatric surgery appears to be protective against developing OSA.

Comparison of gaze behaviour of trainee and experienced surgeons during laparoscopic gastric bypass.

BACKGROUND: Eye tracking presents a novel tool that could be used to profile skill levels in surgery objectively. The primary aim of this study was to identify differences in gaze behaviour between expert and junior surgeons performing a laparoscopic Roux-en-Y gastric bypass (LRYGB) for obesity. METHODS: This prospective observational study used a lightweight eye-tracking apparatus to determine the difference in gaze behaviours between expert (more than 75 procedures) and junior (75 or fewer procedures) surgeons at defined stages of LRYGB. Primary endpoints were normalized dwell time and fixation frequency. Secondary endpoints were blink rate, maximum pupil size and rate of pupil change. RESULTS: A total of 20 procedures (12 junior, 8 expert) were analysed. Compared with juniors, experts showed a prolonged dwell time on the screen during angle of His dissection (median (range) 91·20 (83·40-94·40) versus 68·95 (59·80-87·60) per cent; P = 0·001), formation of the retrogastric tunnel (91·50 (85·80-95·50) versus 73·60 (34·60-90·50) per cent; P = 0·001) and gastric pouch formation (86·95 (83·60-90·20) versus 67·60 (37·10-80·00) per cent P < 0·001). Juniors had a greater blink frequency throughout all recorded segments (P < 0·010) and had a larger maximum pupil size during all recorded operative segments (P < 0·010). Rate of pupil change was greater in juniors in all analysed segments (P < 0·010). CONCLUSION: These results suggest that experts display more focused attention on significant stimuli, alongside experiencing a reduced mental workload and having increased concentration. This has the potential for future use in validation of surgical skill in high-stakes assessment.

Meta-analysis of determinants of survival following treatment of recurrent hepatocellular carcinoma.

BACKGROUND: Intrahepatic recurrence of hepatocellular carcinoma (HCC) following resection is common. However, no current consensus guidelines exist to inform management decisions in these patients. Systematic review and meta-analysis of survival following different treatment modalities may allow improved treatment selection. This review aimed to identify the optimum treatment strategies for HCC recurrence. METHODS: A systematic review, up to September 2016, was conducted in accordance with MOOSE guidelines. The primary outcome was the hazard ratio for overall survival of different treatment modalities. Meta-analysis of different treatment modalities was carried out using a random-effects model, with further assessment of additional prognostic factors for survival. RESULTS: Nineteen cohort studies (2764 patients) were included in final data analysis. The median 5-year survival rates after repeat hepatectomy (525 patients), ablation (658) and transarterial chemoembolization (TACE) (855) were 35·2, 48·3 and 15·5 per cent respectively. Pooled analysis of ten studies demonstrated no significant difference between overall survival after ablation versus repeat hepatectomy (hazard ratio 1·03, 95 per cent c.i. 0·68 to 1·55; P = 0·897). Pooled analysis of seven studies comparing TACE with repeat hepatectomy showed no statistically significant difference in survival (hazard ratio 1·61, 0·99 to 2·63; P = 0·056). CONCLUSION: Based on these limited data, there does not appear to be a significant difference in survival between patients undergoing repeat hepatectomy or ablation for recurrent HCC. The results also identify important negative prognostic factors (short disease-free interval, multiple hepatic metastases and large hepatic metastases), which may influence choice of treatment.

Management of central nervous system tumours in the elderly.

Brain tumours in the elderly show differences from the general population in their spectrum of incidence, their molecular profile and their response to treatment. Furthermore, this population also finds it more difficult to tolerate the treatments applied to younger patients. For these reasons it is justified to investigate older patients separately and to devise treatments applicable specifically to this population. In recent years important information has come from the research literature that allows us to make specific recommendations for the management of elderly patients with brain tumours. Here we review the important publications and document these recommendations.

Recognition of mental incapacity when consenting patients with intracranial tumours for surgery: how well are we doing?

INTRODUCTION: Many patients with intracranial tumours have cognitive deficits that might affect their mental capacity to give valid consent to neurosurgical treatment. The aim of this study was to determine the incidence of mental incapacity, as assessed by neurosurgeons, in patients with intracranial tumours undergoing neurosurgery. METHODS: The case notes of successive patients undergoing brain tumour surgery between 16 October 2008 and 16 October 2010 were reviewed. The frequency of use of standard consent forms and Certificates of Incapacity was recorded. In addition, the frequency and scores of pre-operative cognitive assessments were recorded. RESULTS: Case notes of 247 of 262 patients undergoing surgery for intracranial tumours were reviewed since there was no record of either a standard consent form or a Certificate of Incapacity in the case notes for 15 patients. Nine of 247 brain tumour patients were issued with a Certificate of Incapacity (3.6%, 95% CI 1.6-6.8%), while 238 (96.4%) signed a standard consent form. Seven of these nine had high-grade gliomas, for an incidence of incapacity of 5.9% (95% CI 2.8-11.8%), while the remaining two Certificates of Incapacity were issued for patients with meningiomas (incidence 3%; 95% CI 0.04-10.4%). Fifty of the 262 patients (19%) had some form of pre-operative cognitive assessment documented, but only three of these were issued with a Certificate of Incapacity. All three patients issued with a Certificate of Incapacity had Mini-Mental State Examination scores suggestive of cognitive impairment. CONCLUSIONS: Incapacity to consent to brain tumour surgery, as assessed by neurosurgeons, is uncommon. The incidence of incapacity is less than might be expected given the level of cognitive impairment known in this population. Decisions about capacity by neurosurgeons are often made in the absence of any documented assessment of cognition or other objective evidence that could support their decision in the event of dispute.

Trends in classification, referral and treatment and the effect on outcome of patients with glioma: a 20 year cohort.

This retrospective audit was conducted to examine the changes in patient characteristics, referral, treatment and outcome over a 20-year period in a large regional neuro-oncology centre, focusing on the impact of the changes in pathological classification of gliomas. Using the Edinburgh Cancer Centre (ECC) database all cases of glioma were identified and patient, tumour and treatment characteristics noted. Survival was calculated from date of surgery or, if no operation was performed, the date of referral. Comparison was made between four periods 1988-1992 (c1), 1993-1997(c2), 1998-2002(c3) and 2003-2007 (c4). During the 20 years, 1175 patients with a glioma were referred to ECC. The median age increased from 53 years to 57 years (p < 0.001) but the proportion without pathology remained unchanged (10%). The distribution of pathological grades changed over time Grade I-II: 24, 6, 6, and 6%, Grade III: 42, 27, 17, and 13% and Grade IV: 24, 61, 68, and 68% in c1, c2, c3 and c4, respectively (p < 0.001). Immediate RT was given to 68% (c1), 70% (c2), 78% (c3) and 79% (c4). Median interval from resection to RT reduced from 43 days (c1) to 36 days (c4) (p < 0.001). 5-year overall survival for patients with Grade III lesions increased: 21% (c1), 35% (c2), 37% (c3), 33% (c4) as did 1-year overall survival for Grade IV lesions: 18% (c1), 26% (c2), 29% (c3), 27% (c4)). This improvement probably reflects the change in pathological classification rather than a change in management. Proportional hazards analysis of grade IV 1993-2007 only (to reduce pathological variation) showed that younger age, frontal lesions, excision, higher RT dose had reduced hazard of death. Interval from surgery to RT had no impact on survival in this series.

Three years of erlotinib in routine practice for non-small cell lung cancer in South East Scotland.

We present a review of 111 patients who were treated over an initial 3-year period with erlotinib. The median treatment time was 68 days and 59% of patients had stopped treatment within the first 3 months. However, 20 patients were on erlotinib for more than 12 months. Performance status and smoking history were the significant prognostic factors. The overall 3-year survival in patients who had never smoked was 26%.

Non-small-cell lung cancer dimensions: CT-pathological correlation and interobserver variation.

The aim of the study was to identify the most accurate CT window level setting for the measurement of non-small-cell lung cancer to optimise CT planning for radiotherapy treatment. 27 patients who underwent resection for non-small-cell lung cancer in a single institution were studied. The maximal superior-inferior, anteroposterior and mediolateral dimensions of the resected tumours were measured by a consultant pathologist. Two radiologists made corresponding measurements using pre-operative CT scans independently of each other and of the pathologist's findings. The measurements were obtained using four different CT window settings. The mean pathological size of the superior-inferior tumours, the anteroposterior tumours and the mediolateral tumours was 32 mm, 28 mm and 25 mm, respectively. A total of 648 CT measurements were taken, of which 321 were within +/-5 mm of the pathological size (49.5%). There was significant interobserver variability between the two radiologists. There was poor correlation between the pathological and radiological measurements of tumour size. Significant interobserver variability was noted between the two radiologists and no window setting could be identified as being superior in accurately assessing the tumour size.

Fourth ventricle ependymoma in father and son.

A father and son presented ten years apart with a fourth ventricle ependymoma. The history, imaging and pathology are presented and the aetiology of familial ependymoma discussed.

General practitioner assessment of stage and performance status in lung cancer patients at a population level: implications for prognosis and radiotherapy needs analyses.

BACKGROUND: Stage, weight loss, and performance status (PS) are important prognostic factors and eligibility factors for curative intent therapy for lung cancer patients. Details of stage, weight loss, and PS are often not collected until referral to a cancer specialist, and since not all patients are referred to cancer specialists these important variables are not well defined at a population level. PATIENTS AND METHODS: Data on stage, weight loss, PS and referral pattern were requested from general practitioners (GPs) on all lung cancer patients diagnosed between May and June of 2002 in the province of British Columbia, Canada. Outcomes were analyzed in relation to survival and referral to a cancer centre. RESULTS: 395 patients were identified, and GP questionnaires were returned on 85% of the cases. Patients referred to a cancer centre shortly after diagnosis differed from those who were not referred. Patients who were not referred to a cancer centre consisted of two groups-patients with localized disease and good PS who tended to have a better survival than those who were referred, and patients with advanced disease and poor performance status who tended to have a worse survival than those who were referred. GP assessed stage and PS are prognostic factors for survival. CONCLUSIONS: GP assessed stage and PS are prognostic factors for survival in lung cancer patients. The case mix of patients who are not referred to a cancer centre shortly after their diagnosis differs from those that are referred.

Improving outcomes for limited stage small cell lung cancer patients in Scotland with concomitant chemoradiation.

AIMS: To determine whether the introduction of early concomitant chemoradiotherapy for patients with limited stage small cell lung cancer (LS-SCLC) has resulted in acceptable outcomes and toxicity in a UK practice. MATERIALS AND METHODS: The case records of all patients with LS-SCLC treated with chemoradiotherapy from July 2001 to 2004 were reviewed, and subjected to descriptive statistics and proportional hazards analysis. RESULTS: Concomitant chemoradiotherapy was delivered to 30 patients and sequential chemoradiotherapy was delivered to 36 patients. The former patients tended to be younger (mean 58.9 vs 64.1 years, P=0.01); the latter patients tended to have bulkier disease. There was no difference in performance status, but cisplatin was given more often in the former group (90% vs 44%, P<0.0001). Grade 3 acute oesophagitis occurred in less than 10% of either group and there were no cases of grade 3 or greater pneumonitis. Two-year actuarial survival for the concomitant group was 53% (95% confidence interval 36-71%) and 36% (95% confidence interval 20-52%) for the sequential group (P=0.018). Proportional hazards analysis showed an increased hazard of death with increasing performance status and age, sequential therapy and the use of cisplatin with sequential therapy. CONCLUSION: Concomitant chemoradiotherapy can be safely given in a UK population with outcomes comparable with those reported in North American series.

The accuracy of meningioma grading: a 10-year retrospective audit.

Although descriptive classifications of meningioma subtypes are well established, there has been inconsistency in the categorization of meningiomas into benign, atypical and anaplastic groups. The aim of this study was to reassess the incidence of atypical (grade II) meningiomas over a 10-year period by applying the World Health Organization (WHO) 2000 classification system. A secondary aim was to determine if grade II and III tumours were becoming more common. Sections of 314 meningiomas resected between 1994 and 2003 were retrieved from the archives of the Western General Hospital's neuropathology unit in Edinburgh. They were reassessed and graded by using the WHO 2000 classification system. The reviewers were blind to the original classification and grading. There was a gradual increase in the numbers of meningiomas being resected annually over the 10-year period. On reclassification, 78% of the meningiomas were classified as grade I, 20.4% as grade II and 1.6% as grade III. With regard to grade II meningiomas classified by using the WHO 2000 classification system, 38.1% had originally been classified as grade I prior to 2000, whereas 13.6% had originally been classified as grade I after 2000. In most cases, reclassification was due to formal counts of mitotic figures. Atypical meningiomas are diagnosed more frequently under the current WHO classification system than they were under the previous classification systems. Although the current WHO (2000) classification is more prescriptive than its predecessors, interobserver variability is likely to remain because of the subjective nature of some of the criteria.

Symptom control and quality of life in people with lung cancer: a randomised trial of two palliative radiotherapy fractionation schedules.

AIMS: To determine whether palliation of chest symptoms from a 10 Gy single fraction (regimen 1) was equivalent to that from 30 Gy in 10 fractions (regimen 2). MATERIALS AND METHODS: Patients with cytologically proven, symptomatic lung cancer not amenable to curative therapy, with performance status 0-3, were randomised to receive either 30 Gy in 10 fractions or a 10 Gy single fraction. Local symptoms were scored on a physician-assessed, five-point categorical scale and summed to produce a total symptom score (TSS). This, performance status, Hospital Anxiety and Depression (HAD) score and Spitzer's quality-of-life index were noted before treatment, at 1 month after treatment and every 2 months thereafter. Palliation was defined as an improvement of one point or more in the categorical scale. Equivalence was defined as less than 20% difference in the number achieving an improvement in the TSS. RESULTS: We randomised 149 patients and analysed 74 in each arm. According to the design criteria, palliation was equivalent between the two arms. TSS improved in 49 patients (77%) on regimen 1, and in 57 (92%) patients on regimen 2, a difference of 15% (95% confidence interval [CI] 3-28) in the proportion improving between the two regimens. A complete resolution of all symptoms was achieved in three (5%) on regimen 1, and in 14 (23%) patients on regimen 2 (P < 0.001), a difference in the proportion between the two regimens of 21% (95% CI 10-33). A significantly higher proportion of patients experienced palliation and complete resolution of chest pain and dyspnoea with regimen 2. No differences were observed in toxicity. The median survival was 22.7 weeks for regimen 1 and 28.3 weeks for regimen 2 (P = 0.197). CONCLUSIONS: Although this trial met the pre-determined criteria for equivalence between the two palliative regimens, significantly more patients achieved complete resolution of symptoms and palliation of chest pain and dyspnoea with the fractionated regimen.

Myxopapillary ependymoma with intracranial metastases.

We report spontaneous seeding within the subarachnoid space from a myxopapillary ependymoma that progressed despite surgery and radiotherapy treatment.