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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
P14.85 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery
Abstract BACKGROUND The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS). MATERIAL AND METHODS A sequential audit was conducted of all patients receiving intracranial SRS at our local institution for the first 22 months of a new SRS service. Lesions were contoured first by clinical oncologist then reviewed/edited by the MDT. The initial contour was compared with final contour using Jaccard conformity and geographical miss indices. The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contour. The impact of the contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up (24–46 months). RESULTS 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32–1.00) and 38% needed significant editing (JCI<0.95). Mean GMI was 0.03 (0.0–0.65) and 17% showed significant miss (GMI>0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p<0.05). There was no significant improvement on JCI or GMI shown over time. Dosimetric analysis indicated a strong association of conformity metrics with PTV dose metrics; a 0.1 change in GTV conformity metric association with 6–17% change in dose to 95% of resulting PTV. Greater association was seen in resection cavity suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate in the treated areas of 0.89 (0.8–0.94) at 40 months, and 0.9 (0.83–0.95) radio-necrosis free rate at 40 months with a median 17 months to developing radio-necrosis for those that did. CONCLUSION This work highlights that a MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at our local institution compared with previously published data. Radio-necrosis rates are below 10%. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist. MDT input is recommended in particular in contouring of resection cavities.
Cerebral vascular anatomy and physiology
Knowledge of normal cerebral vascular anatomy and physiology is critical for both recognizing and safely managing a range of neurosurgical conditions through either open or endovascular techniques. In this article we summarize the key features of the arterial supply and venous drainage of the brain along with their main clinical significance.
Endoscopic Endonasal Surgery for Resection of a Pterygopalatine Fossa Malignant Peripheral Nerve Sheath Tumor: 2-Dimensional Operative Video.
The pterygopalatine fossa (PPF) is an inverted, pyramid-shaped space immediately behind the posterior wall of the maxillary sinus, and lesions arising here include juvenile angiofibromas, schwannomas, and, in exceptionally rare cases, malignant peripheral nerve sheath tumors.1,2 Surgical access to the PPF is challenging and has been historically achieved via an open transmaxillary approach associated with facial scaring/deformity as well as potential injury to facial and infraorbital nerve branches.3 We present the case of a 67-year-old woman with facial numbness secondary to a presumed trigeminal schwannoma in the right PPF on magnetic resonance imaging. This surgical video highlights the key stages in performing an endoscopic endonasal excision of a PPF tumor. We start with a wide medial maxillary antrostomy, mobilization of the inferior turbinate, ethmoidectomy, and sphenoidotomy. The posterior wall of the maxillary sinus is then lifted off the anterior aspect of the tumor. The soft tissue attachment medial to the tumor containing the sphenopalatine artery is then cauterized and divided. This is followed by circumferential blunt dissection of the tumor until it is sufficiently mobile to remove in a piecemeal fashion. The PPF is then examined for any residual tumor and any bleeding from the maxillary artery within the fat pad. Hemostasis and reattachment of the inferior turbinate into the lateral nasal wall is demonstrated. The patient did not have any new deficits postoperatively, but histology indicated a malignant peripheral nerve sheath tumor and she underwent postoperative proton beam therapy. Postoperative surveillance magnetic resonance imaging at 14 months showed no tumor recurrence. The patient consented to the procedure in a standard fashion (Video 1).
Reduced decision bias and more rational decision making following ventromedial prefrontal cortex damage.
Human decisions are susceptible to biases, but establishing causal roles of brain areas has proved to be difficult. Here we studied decision biases in 17 people with unilateral medial prefrontal cortex damage and a rare patient with bilateral ventromedial prefrontal cortex (vmPFC) lesions. Participants learned to choose which of two options was most likely to win, and then bet money on the outcome. Thus, good performance required not only selecting the best option, but also the amount to bet. Healthy people were biased by their previous bet, as well as by the unchosen option's value. Unilateral medial prefrontal lesions reduced these biases, leading to more rational decisions. Bilateral vmPFC lesions resulted in more strategic betting, again with less bias from the previous trial, paradoxically improving performance overall. Together, the results suggest that vmPFC normally imposes contextual biases, which in healthy people may actually be suboptimal in some situations.
A Systematic Review on Outcomes of Anterior Skull Base Reconstruction.
INTRODUCTION: Anterior skull base resection often results in large defects that need to be reconstructed. This can be done using loco-regional, free flaps or both. OBJECTIVE: The aim of this systematic review is to evaluate the surgical outcomes (mortality, complication rates and functional outcomes) for patients undergoing anterior skull base reconstruction. METHODS: Electronic databases (MEDLINE, EMBASE and Scopus) were systematically searched for relevant articles from 1974 to March 2018. A total of 41 studies were included in this systematic review. No randomized controlled trials were identified; therefore, a meta-analysis was not performed. RESULTS: Mortality from anterior skull base reconstruction were about 0-4% for loco-regional flaps while free flaps were around 0-7%. Overall complications ranged from 0% to 43% in loco-regional flaps, while rate of complications for free flaps ranged from 25% to 66.7%. Flap complications ranged from 0% to 14% for free flaps and 0% to 35% for local flaps. Quality-of-life measures did not differ significantly depending on surgical approach but were worse for patients with malignancies. CONCLUSION: Due to varying standards of reporting of outcomes, lack of a standardized classification system for anterior skull base defects and absence of clinical trials, we were unable to perform a meta-analysis in this systematic review. Recommendations to guide future studies are proposed.
Mixed Olfactory Neuroblastoma and Adenocarcinoma with In Situ Neuroendocrine Hyperplasia.
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising from the superior aspect of the nasal vault. Cases are characterised by insidious clinical presentation and high rates of recurrence despite surgical resection and adjuvant radiotherapy. There are a small number of reports showing ONB with divergent epithelial or ganglionic differentiation, and ONB has also been found to coincide with adenocarcinoma. We present a case of mixed ONB with adenocarcinoma. The clinical presentation was unusual, with a tonic-clonic seizure preceded by chronic headache and anosmia. Imaging revealed a mass extending from the olfactory recess of the left nasal cavity through the cribriform plate to the anterior cranial fossa. The pathology demonstrated intraepithelial neuroendocrine cell hyperplasia in the left olfactory groove. This finding provides a unique insight into the cellular origin of this rare tumour, and appears to confirm the theory that ONB arises from neural stem cells in the olfactory neuroepithelium. Despite radical treatment, the patient suffered a distant recurrence within 1 year of treatment, which underlines the aggressive nature of this tumour.
Primary Gliosarcoma of the Cerebellum in a Young Pregnant Woman: Management Challenges and Immunohistochemical Features.
BACKGROUND: Gliosarcoma (GS) represents a rare, high-grade (WHO Grade IV), central nervous system neoplasm, characterized by a very poor prognosis. Similar to other high-grade gliomas, GS affects mainly adults in the 5th-7th decade of life and presents a higher incidence in males. The most reported locations of GS are the temporal lobe and the frontal lobe, while only eight cases of GS originating from the posterior cranial fossa are reported in the literature. CASE DESCRIPTION: We report the first case occurring during pregnancy in a 33-year-old patient. Diagnosis was obtained on the 15th week of gestation when patient presented with signs and symptoms of life-threatening raised intracranial pressure. Surgical excision was followed by early recurrence and eventually disease progression because the patient refused adjuvant treatment to save her fetus. CONCLUSIONS: GS should be considered in the differential diagnosis of posterior cranial fossa tumors with radiological features of meningioma or glioblastoma, even in young patients. To this regard, sarcomas, solitary fibrous tumors, and even metastases should be considered, especially in light of the tendency of GS to give rise to extracranial localizations. Whenever an aggressive management with radical excision and adjuvant treatment is not safely achievable, disease progression is likely to be unavoidable.
Sir Hugh Cairns: a pioneering collaborator.
In April 1988, Peter Schurr delivered the twelfth Sir Hugh Cairns Memorial Lecture to the Society of British Neurological Surgeons. In his lecture, The Cairns Tradition, Schurr extolled the personal virtues of Cairns. He encouraged his colleagues to draw inspiration from Cairns' renowned determination, organisation, drive for perfection, compassion, and commitment to the training of those around him. Indeed, Cairns' own personality has come to define the specialty which he established in Britain. Today's neurosurgeons are, whether knowingly or not, formed in his image. But there is a side to Hugh Cairns that has been lost in the telling of his remarkable story, and yet it played a central role in his greatest achievements. This is the side of himself which he turned towards others. Throughout his career, Cairns received an inordinate number of personal accolades. His tutelage under Cushing during a formative trip to America and the impact of his role in caring for T. E. Lawrence are well known to many. But, more than thirty years after Peter Schurr's memorial lecture, and following the eightieth anniversary of the department of neurosurgery founded by Cairns in Oxford, it is his work as a pioneering collaborator which defines his legacy today, and which calls us to learn yet another lesson from his remarkable life. In this legacy article, we review the origins of Cairns' collaborative spirit and uncover the achievements he shared with Charles Hallpike, Howard Florey, Derek Denny-Brown, William Ritchie Russell, Ludwig Guttman, and Peter Medawar, among many others.
More than meets the MRI: case report of a carcinoid tumour metastasis mimicking a meningioma.
Cerebral metastases from carcinoid tumours are rarely reported and confer a much poorer prognosis than carcinoid metastases elsewhere in the body. We describe a case of carcinoid brain metastasis closely resembling a meningioma on magnetic resonance imaging (MRI), and review current treatment options.
Cerebral vascular anatomy and physiology
Knowledge of normal cerebral vascular anatomy and physiology is critical for both recognizing and safely managing a range of neurosurgical conditions through either open or endovascular techniques. In this article we summarize the key features of the arterial supply and venous drainage of the brain along with their main clinical significance.
Surgical consent practice in the UK following the Montgomery ruling: A national cross-sectional questionnaire study.
BACKGROUND: The Supreme Court case of Montgomery vs Lanarkshire Health Board in 2015 was a landmark case for consent practice in the UK which shifted focus from a traditional paternalistic model of consent towards a more patient-centered approach. Widely recognised as the most significant legal judgment on informed consent in the last 30 years, the case was predicted to have a major impact on the everyday practice of surgeons working in the UK National Health Service (NHS). Two years after the legal definition of informed consent was redefined, we carried out an audit of surgical consent practice across the UK to establish the impact of the Montgomery ruling on clinical practice. MATERIALS & METHODS: Data was collected by distribution of an electronic questionnaire to NHS doctors working in surgical specialities with a total of 550 respondents. RESULTS: 81% of surgical doctors were aware of the recent change in consent law, yet only 35% reported a noticeable change in the local consent process. Important barriers to modernisation included limited consent training, a lack of protected time for discussions with patients and minimal uptake of technology to aid decision-making/documentation. CONCLUSIONS: On the basis of these findings, we identify a need to develop strategies to improve the consent process across the NHS and limit the predicted rise in litigation claims.
Perfused Three-dimensional Organotypic Culture of Human Cancer Cells for Therapeutic Evaluation.
Pharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in-vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion is a vital factor for engineered human tissues to recapitulate key aspects of the tumour microenvironment. Organotypic culture and human tumour explants were allowed to grow long-term (14-35 days) and phenotypic features of perfused microtumours compared with those in the static culture. Differentiation status and therapeutic responses were significantly different under perfusion, indicating a distinct biological response of cultures grown under static conditions. Furthermore, heterogeneous co-culture of tumour and endothelial cells demonstrated selective cell-killing under therapeutic perfusion versus episodic delivery. We present a perfused 3D microtumour culture platform that sustains a more physiological tissue state and increased viability for long-term analyses. This system has the potential to tackle the disadvantages inherit of conventional pharmaceutical models and is suitable for precision medicine screening of tumour explants, particularly in hard-to-treat cancer types such as brain cancer which suffer from a lack of clinical samples.
Head Injury in the Elderly: What Are the Outcomes of Neurosurgical Care?
BACKGROUND: Epidemiologic studies show that an increasing proportion of those presenting with head trauma are elderly. This study details the outcomes of elderly patients with head trauma admitted to a regional United Kingdom neurosurgical unit. METHODS: The notes and imaging were reviewed of all patients with head injury aged ≥75 years, admitted from 1 January 2007 to 31 December 2010, including mortality data up to at least 2 years after discharge. Outcomes comprised death as an inpatient, by 30 days and 1 year after discharge; Glasgow Outcome Score; discharge Glasgow Coma Scale (GCS) score; recurrence; readmission; reoperation; and complication. RESULTS: A total of 263 patients were admitted: 26 with acute subdural hematoma (ASDH); 175 with chronic subdural hematoma (CSDH); and 46 with mixed subdural collections (ACSDH). Sixteen patients had other head injury diagnoses. Patients with ASDH had a significantly lower survival rate than did those with CSDH or ACSDH: the odds of inpatient death for patients with ASDH was 15.38 (vs. those with CSDH). For all subdural hematomas (SDHs), low American Society of Anesthesiologists score was an independent predictor of early death. Death at 1 year was predicted by head injury severity measured by admission GCS score (P = 0.028), long anesthetic (P = 0.002), and the presence of bilateral SDH (P = 0.002). Unfavorable Glasgow Outcome Scale score (1-3) was predicted by age greater than 85 years (P = 0.029); larger depth of subdural (P < 0.001); and presence of any complication (P = 0.003). Those aged greater than 90 years with presentation GCS score lower than 10 all had poor outcomes. CONCLUSIONS: Most elderly patients admitted under neurosurgery after head injury have SDHs. Our results are better than many previously reported; however, the rate of death for those with ASDH is still high.
Neurosurgical Care in the Elderly: Increasing Demands Necessitate Future Healthcare Planning.
OBJECTIVES: The worldwide elderly population is steadily increasing. It has been recommended that age-appropriate information should be available for older patients, but little exists in neurosurgery. We aim to better understand the clinical characteristics, bed occupancy and outcomes of elderly patients admitted to a UK neurosurgical unit. METHODS: Retrospective review of medical records of all patients aged 75 years and older admitted for at least 1 night to the Southwest Neurosurgery Centre from 2007 to 2010. Mortality data up to 31 December 2012 were obtained from a national registry. RESULTS: Eight hundred and eighty-six elderly patients were admitted, for whom 877 records were available. Three hundred and eighty-nine patients were admitted electively; 488 were emergency or urgent; 48.8% had cranial pathology and 50.7% had spinal disease. Emergency cases were significantly older and more likely to be male than elective patients. The median length of stay for emergency patients was significantly longer than that of elective patients (P < 0.0001, 3 vs. 8 days). One elective patient died as an inpatient, compared with 46 emergency patients. Of emergency and elective patients, 25.6% and 3.6%, respectively, had died by 6 months after discharge. Age and length of stay were not associated with early death. CONCLUSIONS: The demographics and outcomes of the elderly admitted to a UK neurosurgical center are discussed. Differences between elective and emergency groups are attributable to both the pathologic processes and case selection. Neurosurgical treatment should not be denied based on age, however the high risks of emergency surgery in this age group should be acknowledged.
Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model.
Glioblastoma (World Health Organization grade IV) is an aggressive adult brain tumor that is inevitably fatal despite surgery, radiation, and chemotherapy. Treatment failures are attributed to combinations of cellular heterogeneity, including a subpopulation of often-resistant cancer stem cells, aberrant vasculature, and noteworthy immune suppression. Current preclinical models and treatment strategies do not incorporate or address all these features satisfactorily. Herein, we describe a murine glioblastoma stem cell (GSC) model that recapitulates tumor heterogeneity, invasiveness, vascularity, and immunosuppressive microenvironment in syngeneic immunocompetent mice and should prove useful for a range of therapeutic studies. Using this model, we tested a genetically engineered oncolytic herpes simplex virus that is armed with an immunomodulatory cytokine, interleukin 12 (G47-mIL12). G47Δ-mIL12 infects and replicates similarly to its unarmed oncolytic herpes simplex virus counterpart in mouse 005 GSCs in vitro, whereas in vivo, it significantly enhances survival in syngeneic mice bearing intracerebral 005 tumors. Mechanistically, G47-mIL12 targets not only GSCs but also increases IFN-γ release, inhibits angiogenesis, and reduces the number of regulatory T cells in the tumor. The increased efficacy is dependent upon T cells, but not natural killer cells. Taken together, our findings demonstrate that G47Δ-mIL12 provides a multifaceted approach to targeting GSCs, tumor microenvironment, and the immune system, with resultant therapeutic benefit in a stringent glioblastoma model.