In December of 2016, phase 2 of the Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation (MISTIE) study demonstrated that this form of stereotactic thrombolysis safely reduces clot burden and may improve functional outcome 6 months after injury. A smaller arm of this study, the Intraoperative Stereotactic Computer Tomography-Guided Endoscopic Surgery (ICES) study, also demonstrated feasibility and good functional outcome for endoscopic minimally invasive evacuation. Early-phase clinical studies evaluating various forms of minimally invasive surgery for intracerebral hemorrhage evacuation have shown safety and feasibility with a preliminary signal towards improved functional long-term outcome. Results from phase 3 studies addressing various minimally invasive techniques are imminent and will shape how intracerebral hemorrhage is treated.
Introduction The term Tolosa-Hunt Syndrome was first used more than half a century ago to describe painful ophthalmoplegia accompanied by cranial nerve palsies. In the decades since, its diagnostic criteria have evolved considerably. The beta version of the 3rd Edition of the International Classification of Headache Disorders narrows these criteria to require the demonstration of granulomatous inflammation on MRI or biopsy. We believe this may introduce challenges to accurate diagnosis. Discussion Requiring the demonstration of granulomatous inflammation for a diagnosis of Tolosa-Hunt Syndrome may introduce the potential for false negative and false positive diagnoses. Although the disorder presents secondary to granulomatous inflammation, MRI technology may not be able to identify it reliably, and biopsy is not always indicated for its symptomatology. Additionally, several cases have been reported of Tolosa-Hunt Syndrome diagnosed with MRI-confirmed granulomatous inflammation that later prove to be attributable to other pathologies. The emphasis on neuroimaging may therefore exclude some true Tolosa-Hunt Syndrome cases and include others resulting from other latent pathologies that are not visible on MRI. Conclusion We wish to offer several potential modifications to the International Classification of Headache Disorders guidelines for Tolosa-Hunt Syndrome, including making the demonstration of granulomatous inflammation on MRI or biopsy non-mandatory and lengthening patient follow-up to two years for cases in which MRI is unrevealing.
The role of axillary surgery has evolved over the last three decades from routine axillary lymph node dissection (ALND) to sentinel lymph node biopsy to omission of axillary surgery altogether in select patients. This evolution has been achieved through the design and conduct of multiple clinical trials demonstrating that ALND does not impact survival and is not necessary for local control in patients with early-stage breast cancer and limited nodal involvement. Importantly, this practice-changing shift mirrored the trend towards earlier stage at diagnosis and the recognition of the interplay between local and systemic therapies in maintaining local control. There are numerous clinical scenarios today in which axillary staging can be safely avoided, including (1) DCIS treated with lumpectomy, (2) at the time of contralateral prophylactic mastectomy, and (3) in elderly patients with early-stage, HRþ/HER2-clinically node-negative (cN0) disease. Ongoing clinical trials seek to expand the cohorts in which surgical nodal staging can be omitted. These populations include a broader range of early-stage, cN0 patients undergoing upfront surgery, as seen in the SOUND, INSEMA, BOOG 2013e08, SOAPET and NAUTILUS trials. Omission of axillary surgery in cN0 patients with HER2þ or triple-negative disease treated with neoadjuvant chemotherapy is also being tested in the ASICS and EUBREAST-01 trials. Continued advances in imaging and the growing role of genomic assays in selecting patients for systemic therapy are likely to further minimize the need for axillary surgery; thereby further reducing the morbidity of local therapy for women with breast cancer.
OBJECTIVE Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population. METHODS SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion. RESULTS Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months). CONCLUSIONS SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors’ results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical. Clinical trial registration no.: NCT01884740 (clinicaltrials.gov)
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