Understanding High Grade Glioma

Transcription

1 Ultrasound Guided Resection of High Grade Gliomas: A Pilot Study. MOHAMED ATEF ELZOGHBY L E C T U R E R O F N E U R O S U R G E R Y A I N S H A M S U N I V E R S I T Y S C H O O L O F M E D I C I N E N E U R O S U R G E R Y F E L L O W U N I V E R S I T Y O F V I R G I N I A H E A L T H C E N T E R Recent Trends in Neurosurgery March 2014 Understanding High Grade Glioma 1

2 Epidemiology * : Glioblastoma multiforme (GBM) or astrocytoma grade IV on WHO classification is the most aggressive and the most frequent (12-15%) of all primary brain tumors. The incidence of GBM is less than 10 / 100,000. The peak incidence is between 45 and 70 years, with a crest to 58 years; only 8.8% of children with CNS tumors had GBM. A male-to female ratio of 1.5:1 The association with an oncogenic virus remains controversial. * Journal of Medicine and Life Vol. 2, No.4, October-December 2009 Genetics * : Overexpression of several oncogenes and mutations leading to loss of function of key tumor suppressor genes concur to create one of the most aggressive cancers. Amplification of oncogenes such as the epidermal growth factor receptor (EGFR), as well as loss of tumor suppressors like PTEN on chromosome 10, p53 on chromosome 17, or p16/ink4a are some of the most common genetic alterations in GBM. The p53 dysfunction disrupts the downstream p14arf pathway, impedes the process of apoptosis and fosters further genomic instability. * Journal of Medicine and Life Vol. 2, No.4, October-December

3 Glioma Cancer Stem Cells * : Recent studies have demonstrated the existence of a small subpopulation of cells with stem like features known as Cancer Stem Cells (CSC). These GBM CSCs are selfrenewable and highly tumorigenic. They are not only chemo-radio-resistant, but also often contain multidrug resistance genes and drug transporter genes. These characteristics enable GBM CSCs to survive standard cytotoxic therapies. Understanding of CSC biology, glioma CSC specific immunotherapy combined with other therapeutic strategies may eventually provide new approaches to treat gliomas. * Neurosurg Clin N Am January ; 21(1): Brain cancer propagating cells (BCPCs) within primary central nervous system tumors (glioblastoma multiforme, medulloblastoma and ependymoma) are integral to tumor development. Accumulating evidence suggests that BCPCs might originate from the transformation of neural stem cells and their progenitors. Treatments that include specific targeting of BCPCs might potentially be more effective at treating the entire tumor. 3

4 Intraoperative Ultrasound (IOUS) in High Grade Glioma Technical Requirements: For burr hole access proceedures, a small end-fire transducer is used. A larger end-fire transducer provides a wider field of view during craniotomy. The transducer should be set at the highest possible frequency (7 15 MHz) and deepest penetration to identify anatomical landmarks. Transducers must have pulsed Doppler and color flow capability to delineate tumor vascularity and surrounding vasculature. Transducer ORIENTATION must be established before use. Use of degassed saline before application or insertion of the probe. The probe should be wrapped in a sterile sheath and applied directly to intact dura or exposed brain. Care must also be taken not to tear the sheath. 4

5 U/S Probes: High Grade Glioma: 5

6 Ultrasound Guided Resection of High Grade Gliomas: A Pilot Study in ASU. To Excise or Debulk, This is the Question!!! Value of total vs subtotal resection is still controversial.. Theoretically it decreases tumor burden, enhances response to adjuvant therapy & improves neurologic state. Still, no randomized prospective study was conducted. Most of data come from retrospective observational studies..biased distribution confounds results. Treatment bias comes from factors that influence the degree of resectability & concurrently influence survival: Tumor size, morphology & location Age & neurological status 6

7 IOUS Guided Glioma Resection in ASU: During the period from 1/1/2012 till 25/2/2012, 16 cases with a radiological diagnosis of High Grade Glioma were operated upon with U/S guidance. The surgical aim was to achieve Near Total Resection (96% of tumor volume). U/S initial acquisition was done after craniotomy to localize the lesion and determine if it has a well delineated tumor brain interface. Further U/S acquisitions were used to detect any tumor residual after resection and guide its removal. Postoperative MRI+C was done within 48 hrs. Localization & Extent of Resection: U/S assisted tumor localization was achieved in all cases (100%). Near total resection ( 96 %) was achieved in 10 patients (62%). Subtotal resection (>80%) was achieved in the remaining 6 patients (38%). 7

8 Clinical Outcome: Ten patients (62.5%) experienced detectable clinical improvement in the form of regain of motor power or speech. Four patients (25%) did not experience improvement or new neurological deficit. Only 2 patient (12.5%) experienced postoperative new neurological deficit in the form of dysphasia (resolved by the next day) and dense hemiparesis (improved in the lower limb but not yet on the upper). Case I: 8

9 Case I: Case I: 9

10 Case II: Case III: Preop Postop 10

11 Case IV: Case V: 11

12 Case V: Role of IOUS: Intraoperative accurate localization of the brain lesions. Delineating the surrounding anatomy. Guiding instrumentation (needle biopsy and ventricular shunt placement). Assisting tumor resection. Identifying residual tumors. Spinal cord lesions; tumors, cysts and syringomyelias. 12

13 Limitations of IOUS: Its poor signal-to-noise ratio (less details). Two dimentional. It covers limited brain volume, which may cause an orientation problem. Usually oblique orientation Difficulty in interpretation. It can not be used for localization of the lesion before craniotomy (Skull barrier). US does not have the potential of MRI to do functional imaging and tractographies. Could Ultrasound Guided Resection in HGG Be the Answer? There is no single answer for the HGG puzzle! U/S only helps to solve a part of the riddle, that is concerned with the extent of resection. It has an advantage over Neuronavigation; that is its Real Time image (yet it can t be performed until bone flap is removed). It is easier, faster and much cheaper than Intraoperative MRI (yet it provides less details and may not accurately detect small deep residuals). Further treatment is still required even after gross total resection (biological nature of the disease). 13