Has the survival of patients with glioblastoma changed over the years?

BACKGROUND: Over the last decade, the approach to the management of brain tumours and the understanding of glioblastoma tumour biology has advanced and a number of therapeutic interventions have evolved, some of which have shown statistically significant effects on overall survival (OS) and progression-free survival in glioblastoma. The aim of this study is to compare survival in glioblastoma patients over a 10-year period (1999-2000 and 2009-2010). METHODS: A retrospective cohort study was performed. Identification of all histologically confirmed glioblastoma in a single centre in years 1999, 2000, 2009 and 2010, and production of survival analysis comparing 1999-2000 and 2009-2010 were achieved. RESULTS: A total of 317 patients were included in the analysis (133 in year 1999-2000, and 184 in year 2009-2010). Cox regression analysis showed that the survival was significantly longer in patients in years 2009-2010 than those in 1999-2000 at P<0.001 with HR=0.56, confidence interval (CI) (0.45-0.71). The 1- and 3-year survival rates were 20.7% and 4.4%, respectively, for patients in 1999-2000, improving to 40.0% and 10.3%, respectively, for patients in 2009-2010. The comparisons between the two groups in survival at 1, 2 and 3 years are all statistically significant at P<0.001, respectively. The median OS was 0.36 and 0.74 in 1999-2000 and 2009-2010 groups, respectively. CONCLUSIONS: Over this period, OS from glioblastoma has increased significantly in our unit. We believe this is due to the institution of evidence-based surgical and oncological strategies practised in a multidisciplinary setting.

Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Neurobehavioural changes in patients following brain tumour: patients and relatives perspective.

PURPOSE: Patients and relatives experiences of behavioural and personality changes following brain tumour were assessed to determine whether these changes are more prominent in the experience of patients with frontal tumours and their relatives as a first step to evaluate the need to develop appropriate support and management of such changes, which have a substantial impact on social functioning, and ultimately to improve quality of life. METHODS: Patients and relatives rated the patients' current levels of apathy, disinhibition and executive dysfunction on the Frontal Systems Behaviour Scale. Patients also completed the Hospital Anxiety and Depression Scale. The data from 28 patients with frontal tumours and 24 of their relatives, and 27 patients with nonfrontal tumours and 25 of their relatives, were analysed. RESULTS: Patients with frontal tumours rated themselves significantly higher than patients with nonfrontal tumours on all frontal systems-related behaviours. The number of patients reporting clinical levels of difficulty was significantly greater in patients with frontal tumours for disinhibition. The ratings of relatives of patients with frontal tumours were significantly higher than those of relatives of patients with nonfrontal tumours for apathy. Clinically significant levels of apathy and executive dysfunction were however reported by at least 40 % of patients and relatives regardless of tumour location. Clinical levels of anxiety were reported by significantly more patients with frontal tumours than those with nonfrontal tumours. CONCLUSION: Support and management of behavioural and personality change for patients with brain tumours and their relatives, regardless of tumour location, would be most appropriate.

Identifying functional cortical plasticity after spinal tumour resection using navigated transcranial magnetic stimulation.

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

Papillary glioneuronal tumour: a review of the literature with two illustrative cases.

We report two cases of papillary glioneuronal tumour (PGNT). One was located in the supratentorial parenchyma and the other was intraventricular. Both patients underwent gross total resection of their tumour and have returned to normal lifestyle. Papillary glioneuronal tumor is a recently described rare cerebral neoplasm. Recently classified by the World Health Organization in 2007 as a Grade I neuronal-glial tumour, these tumours are infrequent lesions that can be challenging to the practising pathologist. Patients commonly present with headaches or seizures, but may be asymptomatic with the mass discovered incidentally. The characteristic radiological, histological and immunohistochemical features are discussed. Surgical excision has been curative in most of the cases with only a handful of cases of recurrence reported. The increasing number of reports in the literature shows how PGNT forms a good example of a newly diagnosed tumour category in evolution. New classifications and re-classifications of broad categories of brain tumours will hopefully lead to a narrower diagnostic, prognostic and therapeutic profile. The even rarer presence of atypia calls for longer follow-up to help elucidate further its biological behaviour.

Good outcome following emergency decompressive craniectomy in a case of malignant middle cerebral artery infarction in a 14-month-old infant.

We report the case of a 14-month-old infant presenting with unresponsiveness and seizure following thoracic surgery. Imaging showed full territory left middle cerebral artery infarct and signs of raised intracranial pressure (ICP) that required emergency decompressive craniectomy (DC). The child made a good functional recovery. We discuss the case.

Relationship between guideline adherence and outcomes in severe traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and morbidity worldwide. Evidence-based guidelines for managing severe TBI have been available for over 25 years. However, adherence to guidelines remains variable despite evidence highlighting improvement in outcomes with individual recommendations. There is limited evidence to support a superior outcome with compliance to whole sets of recommendations. The aim of this review was to determine whether adherence to TBI guidelines as a package improves outcomes in adults and paediatric patients with severe TBI. METHODS: A structured literature search was conducted using the MEDLINE®, Embase™, PubMed and CINAHL® (Cumulative Index to Nursing and Allied Health Literature) databases. Studies were considered eligible for inclusion in this review if they were quantitative studies investigating the use of TBI guidelines in relation to one or more of the following outcomes: mortality, functional outcome and length of hospital stay. RESULTS: Nine cohort studies were identified that fulfilled the inclusion criteria and answered the clinical question. A review of these papers was conducted. CONCLUSIONS: Mortality after severe TBI improves with increasing adherence to evidence-based guidelines in both adults and children. The evidence also suggests that compliance with guideline recommendations results in improved functional outcomes and reduced length of hospital stay.

Patient-reported outcomes version of the common terminology criteria for adverse events and quality-of-life linear analogue self-assessment in breast cancer patients receiving radiation therapy: single-institution prospective registry.

PURPOSE/OBJECTIVES: We sought to investigate the impact of patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) on overall quality-of-life (QOL) employing linear analogue self-assessment (LASA) in breast cancer (BC) patients undergoing radiation therapy (RT). MATERIALS/METHODS: All patients treated with RT for BC with curative intent from 2015 to 2019 at our institution were included. Breast specific PRO-CTCAE and overall QOL LASA questionnaires were administered at baseline, end-of-treatment, 3, 6, 12 months, and then annually. Minimal clinically important difference in overall QOL was a 10-point change in LASA. Hypofractionation was any treatment > 2 Gy per fraction. Mixed models for repeated measures were used to determine the association of PRO-CTCAE and overall QOL LASA. RESULTS: Three hundred thirty-one (331) patients with a median follow-up of 3.1 years (range 0.4-4.9) were included. Average overall QOL LASA scores were 78.5 at baseline, 79.8 at end-of-treatment, 79.8 at 3 months, 77.1 at 6 months, 79.4 at 12 months, and 79.7 at 24 months. On univariate analysis, patients reporting a grade ≥ 3 PRO-CTCAE had, on average, a 10.4-point reduction in overall LASA QOL (p < 0.0001). On multivariate analysis, not being treated with hypofractionation and higher BMI were predictive for worse overall LASA QOL with a 10-point reduction in LASA for patients reporting a grade ≥ 3 PRO-CTCAE (p < 0.0001). CONCLUSIONS: Patients reporting a grade ≥ 3 PRO-CTCAE experienced statistically significant and clinically meaningful deterioration in overall QOL LASA. Hypofractionation improved QOL while higher BMI predicted for worse QOL. PRO-CTCAE should be integrated into future clinical trials.

Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Delayed presentation of iatrogenic ventriculoperitoneal shunt transection following laparoscopic weight loss surgery in a patient with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension is strongly associated with central obesity and consequential raised intra-abdominal pressure. If left untreated it poses significant risk to vision and can eventually cause blindness. Owing to its pathophysiology, this condition is managed by both medical and surgical specialities. When medical management fails neurosurgeons commonly treat idiopathic intracranial hypertension by permanent cerebrospinal fluid peritoneal shunting. Weight reduction surgery provides patients who are obese with a multitude of benefits and it is not uncommon for the general surgeon to be presented with a patient with idiopathic intracranial hypertension and a cerebrospinal fluid peritoneal shunt in place. This provides a potential challenging situation in weight-loss surgical procedures. We describe an interesting case where laparoscopic bariatric surgery resulted in transection of the abdominal catheter with a delayed presentation of recurrent symptoms and an abdominal cerebrospinal fluid collection in a patient with idiopathic intracranial hypertension. We discuss how this could be avoided and its management.

Differentiating childhood-onset schizophrenia from psychotic mood disorders.

OBJECTIVE: The authors systematically examined a sample of patients who were referred to an ongoing National Institute of Mental Health (NIMH) study of childhood-onset schizophrenia (COS), but who received diagnoses of mood disorders at the NIMH, to analyze the reliability of these research-setting diagnoses and to characterize the patients clinically. Pilot data regarding the clinical course of these patients over a 2- to 7-year follow-up period were also obtained. METHOD: Thirty-three cases were selected from the 215 pediatric patients who had been screened in person from 1991 to 1999 for admission to the COS study. These 33 patients had been excluded from the COS study on the basis of a day-long evaluation, including a structured diagnostic interview, which yielded a diagnosis of a mood disorder rather than schizophrenia. This subgroup, together with six COS subjects (for a total N= 39), were included in a diagnostic reliability study in which they were reevaluated by three psychiatrists who were blind to the initial research diagnosis. In addition, pilot follow-up data regarding current function and treatment status were obtained for 25 of the 33 patients with mood disorders. RESULTS: Overall, the interrater reliability of the three raters was excellent (kappa = 0.90). Global reliability between these raters and the NIMH research diagnoses was good (average kappa across diagnoses = 0.61), and agreement for those patients who had mood disorders was good (86% agreement; kappa = 0.60). Pilot follow-up data indicate that none of the subjects with a diagnosed mood disorder developed a clinical course resembling schizophrenia. CONCLUSIONS: Many of the patients referred to the NIMH COS study with clinical diagnoses of schizophrenia had psychotic mood disorders diagnosed on the basis of a comprehensive research evaluation including structured diagnostic interviews, and these research diagnoses were reliable. The diagnosis of COS is difficult and requires a time-consuming evaluation process.

Cavernous angiomas of the brain stem and spinal cord.

This article reviews the pathology, clinical course and management of cavernous angiomas in the brain stem and spinal cord. Both lesions have been diagnosed with increasing frequency as a result of magnetic resonance image scanning. Brain stem lesions tend to present dramatically; their treatment remains microsurgical excision despite some studies that have looked at the use of radiosurgery. Spinal lesions are either extra-, or more commonly, intramedullary. Intramedullary cavernomas present with a wide spectrum of symptoms ranging from acute haematomyelia to presentations that mimic demylelinating conditions; extramedullary cavernous angiomas tend to produce radicular symptoms or subarachnoid haemorrhage. Both are treated by microsurgical excision.

Cystic nodal metastasis in occult tonsil carcinoma--a case report.

A "branchial cyst" in a patient above 40 years old may turn out to be a malignant cystic nodal metastasis from a primary tumour in the tonsil. We present a case of a 45-year-old woman in whom an initial mistaken diagnosis of branchial cyst was made. The neck mass was discovered to be malignant and the left tonsil was subsequently implicated as the primary source. Older patients with cystic neck masses should be managed on the presumption that these may possibly be metastatic lesions from a primary oropharyngeal tumour.

Pathophysiology and treatment of secondary obsessive-compulsive behaviors and tics.

Advances in neurobiological research suggest that certain frontal-subcortical circuits play important roles in idiopathic obsessive-compulsive disorder and Tourette's syndrome. Tics and obsessive-compulsive behaviors secondary to neurologic insult appear to involve the same neural circuitry. There are few systematic studies of the treatment of obsessive-compulsive behaviors and tics associated with neurologic disorders. However knowledge of the circuitry and associated neurochemistry of these disorders can help to outline a rational approach to these behaviors.

Transmaxillary anterior decompressions in patients with severe basilar impression.

Severe basilar impression leads to an upward translocation of the upper cervical spine and clivus into the foramen magnum and is a diagnosis best made with computed tomography or magnetic resonance imaging scans. Basilar impression may be a primary condition or secondary to bone softening disorders. Symptoms relating to direct neuraxial compression, obstruction to cerebral spinal fluid outflow, and vascular compromise all have been described. Management depends on the exact nature of the abnormality seen, but it is now firmly accepted that those with anterior neuraxial compression should have an anterior decompression. The severe basilar impression and craniofacial abnormalities seen in osteogenesis imperfecta together with the progressive nature of the condition have led to the development of a specific surgical response, the open door maxillotomy combined with a contoured loop fixation of the cervical spine. Little is known of the long term outcome of severe basilar impression, and long term studies undertaken by centers familiar with the condition and its management are required if definitive care is to be delivered to these patients.