Sarah Olson

Evidence for label-retaining tumour-initiating cells in human glioblastoma

Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.

Microvascular decompression for trigeminal neuralgia: recurrences and complications

BACKGROUND The purpose of this study was to review the complications and pain recurrences after microvascular decompression (MVD) for trigeminal neuralgia. METHODS This is a retrospective review of 156 patients undergoing MVD in the last 25 years at Princess Alexandra Hospital, Brisbane, Australia. Patients were contacted by telephone and a questionnaire was used for the interview. RESULTS The probability of becoming pain free after MVD in our study was 0.93. There were no deaths and the incidence of serious complication was 2%. Our complication profile is similar to other authors. Pain recurrences occurred in 18% of patients over a 25 year period. This was most likely within two years of surgery and thereafter occurred at a rate of 2-3.5% a year. Seventy-four percent of patients were still pain free at 10 years. In half of the patients the recurrence was not as severe as the initial occurrence of pain. Thirty percent of recurrences occurred on the opposite side. Eighteen percent of patients were not pain free despite any intervention. CONCLUSIONS Microvascular decompression in experienced hands has an excellent pain outcome in the majority of patients. Major complications are uncommon.

The Problematic Slit Ventricle Syndrome

This review discusses the clinical difficulties with the so-called slit ventricle syndrome. It discusses why this terminology makes it difficult to formulate treatment algorithms. Slit ventricle syndrome should probably be known as the non-compliant ventricle syndrome to avoid confusion of radiological ‘slit ventricles’ with the syndrome. Therapeutic measures should ideally focus on the underlying pathology related to the syndrome. For those patients with iatrogenic small calvaria and synostosis, subtemporal decompression would appear a low-risk and quick procedure. Calvarial expansion would be a second-line treatment. For those patients with a normal-sized calvarium and non-compliant ventricle syndrome, valve upgrade, adding an antisiphon device or programmable valve would appear a good first step. For patients in whom the diagnosis is unclear, a potential management plan is discussed.

Post-operative complications with titanium mesh

Titanium mesh is a commonly used material for cranioplasty. While it is a safe and highly biocompatable material, it can modify the presentation of post-operative complications. This case report details 3 patients (2 recurrent meningiomas and an extradural haematoma) in whom post-operative complications, although not caused by the titanium mesh, were modified in their presentation by the permeability of the material. The permeable nature of the mesh allows intracranial pathological processes to extend extracranially and vice versa.

Hippocampal-sparing radiotherapy: The new standard of care for World Health Organization grade II and III gliomas?

The neurocognitive effects of cranial radiotherapy in patients with gliomas are well-recognised and may be related to the dose delivered to the hippocampi. Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be used to selectively spare the hippocampi without compromising the dose delivered to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is achievable in patients with World Health Organization (WHO) grade II and III gliomas. A retrospective review of consecutive patients with WHO grade II and III gliomas treated with IMRT at our institution between January 2009 and August 2012 was performed. Hippocampal-sparing was defined as a mean dose to at least one hippocampus of less than 30 Gy. The dose delivered to the tumour was never compromised to achieve the hippocampal dose constraint. Logistic regression analyses were performed to identify predictive factors for achieving hippocampal-sparing treatment. Eighteen patients were identified and hippocampal-sparing was achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and 11 patients had WHO grade III gliomas. The mean dose to the contralateral hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm3 were more likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7, p=0.03) and there was a trend with oligodendrogliomas and anaplastic oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed prospectively. The relationship between hippocampal dose and neurocognitive function in adults is currently under investigation.

Radiation-induced primary cerebral atypical teratoid/rhabdoid tumour in an adult.

Atypical teratoid/rhabdoid tumours (ATRT) of the central nervous system are uncommon embryonal carcinomas that predominantly affect infants and young children, and less commonly adults. We report a 58 year old woman who presented with ATRT involving the right parietal lobe which was treated with surgery and adjuvant radiotherapy. Her history was significant for soft tissue sarcoma of the right ear treated with surgery and adjuvant radiotherapy at age 3, thus raising the possibility of radiation-induced aetiology.

Review of the role of anticonvulsant prophylaxis following brain injury.

Anticonvulsants were once routinely used as prophyllaxis for all head injuries. There has been a decline in their recent use. The evidence for use of prophylaxis is reviewed. Questions postulated will be answered with the best available evidence.

Rapid growth of cervical cancer metastasis in the brain

Cervical cancer rarely metastasises to the brain, with occurrences of approximately 0.77%. Our patient was referred for treatment of a brain lesion on the background of known metastatic cervical cancer to the lungs and new onset seizure activity. The lesion grew in size from 18 mm to 29 mm in a period of 14 days. The lesion was debulked and the patient returned to the care of her oncology team. The brain is an increasingly common site for metastases of cervical cancer and must be considered when staging these patients.

Lymph node metastasis of medulloblastoma in a young adult

Medulloblastoma is the commonest primary central nervous system malignancy in childhood, but is rare in adults. Rarer still is metastasis of such a tumour to a lymph node. This report describes such a case, and briefly discusses relevant pathophysiology and epidemiology.

Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors

Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state. In other patient lines hyperdiploid cells display genetic drift in vitro and in vivo, suggesting that in these patients hyperdiploidy is a transient cell state that generates novel phenotypes, potentially facilitating rapid tumor evolution. We show that the hyperdiploid cells are resistant to conventional therapy, in part due to infrequent cell division due to a delay in the G₀/G₁ phase of the cell cycle. Hyperdiploid tumor cells are significantly larger and more metabolically active than euploid cancer cells, and this correlates to an increased sensitivity to the effects of glycolysis inhibition. Together these data identify GB hyperdiploid tumor cells as a potentially important subpopulation of cells that are well positioned to contribute to tumor evolution and disease recurrence in adult brain cancer patients, and suggest tumor metabolism as a promising point of therapeutic intervention against this subpopulation.