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Background Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4–5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. Methods We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. Results The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. Conclusions These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Transnasal endoscopic cranial base surgery is a novel minimal-access method for reaching the midline cranial base. Postoperative cerebrospinal fluid leak remains a persistent challenge. A new method for watertight closure of the anterior cranial base is presented. To achieve watertight closure of the anterior cranial base, autologous fascia lata was used to create a \"gasket seal\" around a bone buttress, followed by application of a tissue sealant such as DuraSeal (Confluent Surgical, Inc., Waltham, MA). The gasket-seal closure was used to seal the anterior cranial base in a series of 10 patients with intradural surgery for suprasellar craniopharyngiomas (n = 5), planum meningiomas (n = 3), clival chordoma (n = 1), and recurrent iatrogenic cerebrospinal fluid leak (n = 1). Lumbar drains were placed intraoperatively in five patients and remained in place for 3 days postoperatively. After a mean follow-up period of 12 months, there were no cerebrospinal fluid leaks. The gasket-seal closure is an effective method for achieving watertight closure of the anterior cranial base after endoscopic intradural surgery.

The endoscopic, endonasal, extended transsphenoidal approach is a minimal-access technique for managing craniopharyngiomas. Outcome measures such as return to employment and body mass index (BMI) have not been reported and are necessary for comparison with open transcranial approaches. Most prior reports of the endoscopic, endonasal approach have reported unacceptably high cerebrospinal fluid (CSF) leak rates. To assess the outcome of endoscopic, endonasal surgery in a consecutive series of craniopharyngiomas with special attention to extent of resection, CSF leak, return to employment, and BMI. Twenty-six surgeries were performed on 24 patients at Weill Cornell Medical College-New York Presbyterian Hospital. Five patients had recurrent lesions. Gross-total resection (GTR) was attempted in 21 surgeries. Indications for intended subtotal resection were advanced age, medical comorbidities, preservation of pituitary function, and hypothalamic invasion. Mean tumor diameter was 2.9 cm. GTR (18 surgeries) or near-total (>95%) resection (2 surgeries) was achieved in 95% when GTR was the goal. Seven patients received postoperative radiation therapy. Mean follow-up was 35 months with no recurrences in GTR cases and stable disease in all patients at last follow-up. Vision improved in 77%. Diabetes insipidus and panhypopituitarism developed in 42% and 38%, respectively. A more than 9% increase in BMI occurred in 39%; 69% returned to their preoperative profession/schooling. The postoperative CSF leak rate was 3.8%. Minimal-access, endoscopic, endonasal surgery for craniopharyngioma can achieve high rates of GTR with low rates of CSF leak. Return to employment and obesity rates are comparable to microscope-assisted transcranial and transsphenoidal reports.

Background The balloon-assisted coil embolization (BACE) technique represents an effective tool for the treatment of complex wide-necked intracranial aneurysms; however, its safety is a matter of debate. This study presents the authors' institutional experience regarding the safety of the BACE technique. Methods 428 consecutive patients with 491 intracranial aneurysms (274 acutely ruptured and 217 unruptured) treated with conventional coil embolization (CCE) or with BACE were retrospectively reviewed. All procedure-related adverse events were reported, regardless of clinical outcome. Thromboembolic events, intraprocedural aneurysm ruptures, device-related complications, morbidity and mortality were compared between the CCE and BACE groups. Results The total rate of procedural and periprocedural adverse events was 9.6% (47/491 embolizations). Thromboembolic events, intraprocedural aneurysmal rupture and device-related complications occurred in 2.4%, 3.9% and 3.3% of procedures, respectively. The risk of thromboembolic events and device-related problems was similar between the CCE and BACE groups. A trend towards a higher risk of intraprocedural aneurysm rupture was observed in the BACE group (not statistically significant). The total cumulative morbidity and mortality for both groups was 2.6% (11/428 patients) and there was no statistically significant difference in the morbidity, mortality and cumulative morbidity and mortality rates between the two groups. Conclusion In this series of patients with acutely ruptured and unruptured aneurysms, the BACE technique allowed treatment of aneurysms with unfavorable anatomic characteristics without increasing the incidence of procedural complications.

Abstract BACKGROUND The endoscopic, endonasal, extended transsphenoidal approach is a minimal-access technique for managing craniopharyngiomas. Outcome measures such as return to employment and body mass index (BMI) have not been reported and are necessary for comparison with open transcranial approaches. Most prior reports of the endoscopic, endonasal approach have reported unacceptably high cerebrospinal fluid (CSF) leak rates. OBJECTIVE To assess the outcome of endoscopic, endonasal surgery in a consecutive series of craniopharyngiomas with special attention to extent of resection, CSF leak, return to employment, and BMI. METHODS Twenty-six surgeries were performed on 24 patients at Weill Cornell Medical College-New York Presbyterian Hospital. Five patients had recurrent lesions. Gross-total resection (GTR) was attempted in 21 surgeries. Indications for intended subtotal resection were advanced age, medical comorbidities, preservation of pituitary function, and hypothalamic invasion. RESULTS Mean tumor diameter was 2.9 cm. GTR (18 surgeries) or near-total (>95%) resection (2 surgeries) was achieved in 95% when GTR was the goal. Seven patients received postoperative radiation therapy. Mean follow-up was 35 months with no recurrences in GTR cases and stable disease in all patients at last follow-up. Vision improved in 77%. Diabetes insipidus and panhypopituitarism developed in 42% and 38%, respectively. A more than 9% increase in BMI occurred in 39%; 69% returned to their preoperative profession/schooling. The postoperative CSF leak rate was 3.8%. CONCLUSION Minimal-access, endoscopic, endonasal surgery for craniopharyngioma can achieve high rates of GTR with low rates of CSF leak. Return to employment and obesity rates are comparable to microscope-assisted transcranial and transsphenoidal reports.

The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms. We found that MYC directly controls IRE1 transcription by binding to its promoter and enhancer. Furthermore, MYC forms a transcriptional complex with XBP1, a target of IRE1, and enhances its transcriptional activity. Importantly, we demonstrate that XBP1 is a synthetic lethal partner of MYC. Silencing of XBP1 selectively blocked the growth of MYC-hyperactivated cells. Pharmacological inhibition of IRE1 RNase activity with small molecule inhibitor 8866 selectively restrained the MYC-overexpressing tumor growth in vivo in a cohort of preclinical patient-derived xenograft models and genetically engineered mouse models. Strikingly, 8866 substantially enhanced the efficacy of docetaxel chemotherapy, resulting in rapid regression of MYC-overexpressing tumors. Collectively, these data establish the synthetic lethal interaction of the IRE1/XBP1 pathway with MYC hyperactivation and provide a potential therapy for MYC-driven human breast cancers.