Current Treatment Approaches and Global Consensus Guidelines for Brain Metastases in Melanoma.

Background: Up to 60% of melanoma patients develop melanoma brain metastases (MBM), which traditionally have a poor diagnosis. Current treatment strategies include immunotherapies (IO), targeted therapies (TT), and stereotactic radiosurgery (SRS), but there is considerable heterogeneity across worldwide consensus guidelines. Objective: To summarize current treatments and compare worldwide guidelines for the treatment of MBM. Methods: Review of global consensus treatment guidelines for MBM patients. Results: Substantial evidence supported that concurrent IO or TT plus SRS improves progression-free survival (PFS) and overall survival (OS). Guidelines are inconsistent with regards to recommendations for surgical resection of MBM, since surgical resection of symptomatic lesions alleviates neurological symptoms but does not improve OS. Whole-brain radiation therapy is not recommended by all guidelines due to negative effects on neurocognition but can be offered in rare palliative scenarios. Conclusion: Worldwide consensus guidelines consistently recommend up-front combination IO or TT with or without SRS for the treatment of MBM.

Cross-sectional associations between domain-specific sitting time and other lifestyle health behaviours: the Stormont study.

BACKGROUND: There is a dearth of literature on how different domains of sitting time relate to other health behaviours. Therefore, this study aimed to explore these associations in a sample of office workers. METHODS: 7170 Northern Irish Civil Servants completed an online survey which included information on workday and non-workday sitting time in five domains (travel, work, TV, computer-use, leisure-time), physical activity, fruit and vegetable intake, alcohol consumption and cigarette smoking. An unhealthy behaviour score was calculated by summing the number of health behaviours which did not meet the current guidelines. Multinomial regressions examined associations between unhealthy behaviour score and each domain of sitting time. RESULTS: ≥7 hours sitting at work and ≥2 hours TV viewing on a workday both more than doubled the odds of partaking in ≥3 unhealthy behaviours [Odds ratio, OR = 2.03, 95% CI, (1.59-2.61); OR = 2.19 (1.71-2.80)] and ≥3 hours of TV viewing on a non-workday nearly tripled the odds [OR = 2.96 (2.32-3.77)]. CONCLUSIONS: High sitting time at work and TV viewing on a workday and non-workday are associated with increased odds of partaking in multiple unhealthy behaviours. Interventions need to focus on these domains and public health policy should consider sitting time as an important health behaviour.

The Safety and Feasibility of Image-Guided BrainPath-Mediated Transsulcul Hematoma Evacuation: A Multicenter Study.

BACKGROUND: Subcortical injury resulting from conventional surgical management of intracranial hemorrhage may counteract the potential benefits of hematoma evacuation. OBJECTIVE: To evaluate the safety and potential benefits of a novel, minimally invasive approach for clot evacuation in a multicenter study. METHODS: The integrated approach incorporates 5 competencies: (1) image interpretation and trajectory planning, (2) dynamic navigation, (3) atraumatic access system (BrainPath, NICO Corp, Indianapolis, Indiana), (4) extracorporeal optics, and (5) automated atraumatic resection. Twelve neurosurgeons from 11 centers were trained to use this approach through a continuing medical education-accredited course. Demographical, clinical, and radiological data of patients treated over 2 years were analyzed retrospectively. RESULTS: Thirty-nine consecutive patients were identified. The median Glasgow Coma Scale (GCS) score at presentation was 10 (range, 5-15). The thalamus/basal ganglion regions were involved in 46% of the cases. The median hematoma volume and depth were 36 mL (interquartile range [IQR], 27-65 mL) and 1.4 cm (IQR, 0.3-2.9 cm), respectively. The median time from ictus to surgery was 24.5 hours (IQR, 16-66 hours). The degree of hematoma evacuation was ≥90%, 75% to 89%, and 50% to 74% in 72%, 23%, and 5.0% of the patients, respectively. The median GCS score at discharge was 14 (range, 8-15). The improvement in GCS score was statistically significant ( P < .001). Modified Rankin Scale data were available for 35 patients. Fifty-two percent of those patients had a modified Rankin Scale score of ≤2. There were no mortalities. CONCLUSION: The approach was safely performed in all patients with a relatively high rate of clot evacuation and functional independence.

Refining the Indications for the Addition of Orbital Osteotomy during Anterior Cranial Base Approaches: Morphometric and Radiologic Study of the Anterior Cranial Base Osteology.

Objectives In anatomic and radiologic morphometric studies, we examine a predictive method, based on preoperative imaging of the anterior cranial base, to define when addition of orbital osteotomy is warranted. Design Anatomic and radiographic study. Setting In 100 dry skulls, measurements in the anterior cranial fossa included three lines and two angles based on computerized tomography (CT) scans taken in situ and validated using frameless stereotactic navigation. The medial angle (coronal plane) was the intersection between the highest point of both orbits and the midpoint between the two frontoethmoidal sutures to each orbital roof high point. The oblique angle (sagittal plane) was the intersection at the midpoint of the limbus sphenoidale. Results No identifiable morphometric patterns were found for our classification of anterior fossae; the two-tailed distribution pattern was similar for all skulls, disproving the hypothetical correlation between visual appearance and morphometry. Orbital heights (range: 6.6-18.7 mm) showed a linear relationship with medial and oblique angles, and they had a linear distribution relative to angular increments. Orbital heights > 11 mm were associated with angles ≥ 20 degrees and more likely to benefit from orbitotomy. Conclusion Preoperative CT measurement of orbital height appears feasible for predicting when orbitotomy is needed, and it warrants further testing.

Anatomic variation of the optic strut: classification schema, radiologic evaluation, and surgical relevance.

Objective Anatomic variability of the optic strut in location, orientation, and dimensions is relevant in approaching ophthalmic artery aneurysms and tumors of the anterior cavernous sinus, medial sphenoid wing, and optic canal. Methods In 84 dry human skulls, imaging studies were performed (64-slice computed tomography [CT] scanner, axial view, aligned with the zygomatic arch). Optic strut location related to the prechiasmatic sulcus was classified as presulcal, sulcal, postsulcal, and asymmetric. Morphometric analysis was performed. Results The optic strut was presulcal in 11.9% specimens (posteromedial margin bilaterally anterior to limbus sphenoidale), sulcal in 44% (posteromedial part adjacent to the sulcus's anterior two thirds bilaterally), postsulcal in 29.8% (posteromedial margin posterior to the sulcus's anterior two thirds), and asymmetric (left/right) in 14.3%. Optic strut length, width, and thickness measured 6.54 ± 1.69 mm, 4.23 ± 0.69 mm, and 3.01 ± 0.79 mm, respectively. Optic canal diameter was 5.14 ± 0.47 mm anteriorly and 4.79 ± 0.64 mm posteriorly. Angulation was flat (>45 degrees) in 13% or acute (<45 degrees) in 87% specimens. Conclusions Anatomical variations in the optic strut are significant in planning for anterior clinoidectomy and optic-canal decompression. Our optic strut classification considers these variations relative to the prechiasmatic sulcus on preoperative imaging.

Phase II clinical trial of paclitaxel loaded polymeric micelle in patients with advanced pancreatic cancer.

PURPOSE: To determine in patients, with locally advanced or metastatic pancreatic cancer (APC), efficacy and safety of treatment with intravenous paclitaxel loaded polymeric micelle (GPM). PATIENTS AND METHODS: This was a multicenter, open-label Phase II study. Patients with APC, ECOG performance status < or = 2, no prior chemotherapy and adequate organ function were treated with 3-hour GPM infusions every 3 weeks. Initial patients were treated with 435 mg/m(2) (n = 11). The dose was reduced for subsequent patients to 350 or 300 mg/m(2) (n = 45). Primary endpoint was time to tumor progression (TTP). RESULTS: 56 patients were enrolled. Median TTP for patients treated with 300 or 350 mg/m(2) doses was 3.2 months (95% CI, 2.6-4.2). Median progression free survival (PFS) was 2.8 months (95% CI, 1.4-4.0). Median overall survival (OS) was 6.5 months (95% CI, 5.1-7.9). Among patients treated with above doses of GPM, there was 1 complete remission (CR) and 2 partial remissions (PR) with an overall response rate (ORR) of 6.7%. Disease control rate (CR + PR + stable disease) was 60.0%. Most common grade 3 toxicities were: neutropenia (40.0%), fatigue (17.8%), infection, dehydration, neuropathy (each 13.3%), and abdominal pain (11.1%). CONCLUSIONS: Treatment of APC with GPM at a dose of 300 mg/m(2) q 3 weeks was well tolerated and common toxicities were qualitatively similar to Cremophor-based paclitaxel. GPM monotherapy resulted in OS and other efficacy parameters preferable to that seen historically with gemcitabine. Future studies of GPM in combination with other agents for treatment of APC are warranted.

Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging?

OBJECT: Endoscopic approaches to pituitary tumors have become an effective alternative to traditional microscopic transsphenoidal approaches. Despite a proven potential to decrease unexpected residual tumor, intraoperative MR (iMR) imaging is infrequently used even in the few operating environments in which such technology is available. Its use is prohibitive because of its cost, increased complexity, and longer operative times. The authors assessed the potential of intrasellar endoscopy to replace the need for iMR imaging without sacrificing the maximum extent of resection. METHODS: In this retrospective study, 27 consecutive patients underwent fully endoscopic resection of pituitary macroadenomas. Intrasellar endoscopy was used to determine the presence of residual tumor within the sella turcica and tumor cavity. Intraoperative MR imaging was used to identify rates of unexpected residual tumor and the need for further tumor resection. RESULTS: Intraoperative estimates of the extent of tumor resection were correct in 23 patients (85%). Of 4 patients with unacceptable tumor residuals, 3 underwent further tumor resection. After iMR imaging, the rate of successful completion of the planned extent of resection increased to 26 patients (96%). Rates of both endocrinopathy reversal and postoperative complications were consistent with previously published results for microscopic and endoscopic resection techniques. CONCLUSIONS: The findings in this study provided quantitative evidence that intrasellar endoscopy has significant promise for maximizing the extent of tumor resection and is a useful adjunct to surgical approaches to pituitary tumors, particularly when iMR imaging is unavailable. A larger prospective study on the extent of resection following endoscopic transsphenoidal surgery would strengthen these findings.

High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses.

PURPOSE: Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial is a multicenter study of imatinib 400 mg twice a day as initial therapy in 115 patients (70% Sokal low risk) with newly diagnosed CML in chronic phase who were observed for both molecular and cytogenetic responses for up to 18 months. Eighty-three patients (72%) completed the study, 10 patients (9%) discontinued the study because of adverse events, and six patients (5%) discontinued because of unsatisfactory therapeutic effect. RESULTS: Polymerase chain reaction analysis demonstrated rapid kinetics of major molecular response (MMR), with 48% of patients achieving MMR by 6 months, 54% by 12 months, and 63% by 18 months. Corresponding complete molecular response rates were 39%, 44%, and 55%, respectively. Median dose-intensity was 98%. Overall, 79% of patients who received at least 90% dose-intensity achieved MMR. The most frequent adverse events included myelosuppression, rash, fatigue, and musculoskeletal symptoms. CONCLUSION: This study suggests that imatinib 400 mg twice a day results in more rapid reduction in tumor burden than imatinib 400 mg/d with minimal added toxicity.

Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib.

This clinical trial was conducted to determine the safety and efficacy of bortezomib retreatment in patients with multiple myeloma (MM) who had previously responded to bortezomib. Patients with progressive MM who had previously tolerated bortezomib as a single agent or in combination with other drugs, with a minimum of partial response (PR; >or=50% M-protein reduction) for >or=4 months, who had not received intervening MM therapy, were retreated with bortezomib (days 1, 4, 8, and 11 of a 21-day cycle) with a starting dose being the dose at which the patient ended the initial treatment. Patients were allowed to receive bortezomib on retreatment in combination with dexamethasone, thalidomide, or doxorubicin. Thirty-two patients received bortezomib retreatment (most with added dexamethasone). The median treatment-free interval (last dose of initial bortezomib treatment to first dose of retreatment) was 9.9 (range 2.5-34.0) months. The median duration of retreatment was 2.8 (<1-7.9) months; median total duration of bortezomib treatment was 6.7 (2.5-19.8) months. Based on the investigators' assessment of best response, the overall response rate (complete plus PR) was 50%. The median time from start of retreatment to progressive disease (PD) was 6.6 (95% confidence interval: 5.1-9.6) months. Thirteen patients (41%) experienced PN; bortezomib-related SAEs were reported in four patients. Retreatment with bortezomib alone or in combination is effective and well tolerated in patients with MM who have responded to their initial bortezomib treatment.

The enigmatic trigeminal caroticodural fold: an anatomic description and surgical relevance to anterior petrosectomy.

OBJECTIVES/HYPOTHESIS: We describe our cadaveric dissections and clinical findings that address anterior and ventral limitations imposed by the trigeminal nerve. Particularly, we identify the trigeminal caroticodural fold, the vestment of dura that traverses the space between the nerve and the internal carotid artery. We address the effect of mobilization of this fold to optimize access in Kawase's space when approaching the clivus and posterior fossa. METHODS: Histological study and cadaveric dissections were performed to examine this regional anatomy. Our clinical series (2002 to 2007) includes 30 patients who underwent anterior petrosectomy as part of more complex approaches for lesions of the skull base. RESULTS: Histological and dissection specimens showed a dense fibrous confluence lateral to the trigeminal ganglion and portions of the trigeminal nerve that we called the trigeminal caroticodural fold. This fold was prominent in 18 patients, ill-defined in six, and absent in six patients. Incision of the trigeminal caroticodural fold permitted between 1 mm and 3 mm of additional exposure for drilling in Kawase's space without direct trauma to V(3). CONCLUSIONS: Our study highlights the existence of a dural tethering of the trigeminal nerve and ganglion relevant to surgical exposure of Kawase's space. The regional dural anatomy that contributes to the trigeminal caroticodural fold is complex with subtle variances. We suggest that identification of this fold and its sharp dissection allows mobilization of the trigeminal ganglion and nerve without violation of V(3), and ultimately can improve the transpetrosal access to the upper clivus and posterior fossa via this corridor. Laryngoscope, 2009.

Delayed extrusion of hydroxyapatite cement after transpetrosal reconstruction.

OBJECTIVE: Use of hydroxyapatite cement has been advocated for closure of transpetrosal defects to decrease the incidence of cerebrospinal fluid leaks. We previously identified delayed extrusion of this cement as a significant complication associated with this closure technique and now update our long-term experience. METHODS: In our retrospective review, we identified 1231 patients who underwent transpetrosal procedures by our multidisciplinary cranial base team between 1984 and 2005. Of the subgroup of 177 patients who had hydroxyapatite cement used during the closure of the procedure, 13 patients (7.3%) experienced delayed extrusion of hydroxyapatite cement. RESULTS: Extrusion occurred in 3 patients within 12 months and in 10 patients within 68 to 140 months. Twelve patients presented with draining fistulae and concomitant Staphylococcus aureus infection; 1 patient presented asymptomatically with a large temporal lobe abscess identified on surveillance magnetic resonance imaging. All 13 patients underwent reoperation, including 1 who underwent a second procedure. CONCLUSION: Delayed extrusion of hydroxyapatite cement resulted in significant morbidity to our patients and often presented in an indolent manner. We recommend serial examination and imaging studies in patients who have had transpetrosal closures with hydroxyapatite cement. Because of the complication rates associated with hydroxyapatite cement, we have discontinued its use.

Dye-sensitized nickel(II)oxide photocathodes for tandem solar cell applications.

To date, nickel(II) oxide (NiO) is one of the few p-type semiconductors that has successfully been used for the construction of dye-sensitized photocathodes as well as tandem dye-sensitized solar cells. In this study we present a novel fabrication method for the preparation of mesoporous NiO films based on preformed NiO nanopowders. Critical properties such as pore-size distribution, crystallinity, and internal surface area of the resulting NiO films were controlled through the sintering process and optimized for their application as dye-sensitized photocathodes, resulting in a significantly increased photovoltaic performance, compared to earlier studies. A series of different sensitizers and electrolytes was scrutinized for their application in dye-sensitized NiO photocathodes. Despite its limited absorption range the dye coumarin 343 clearly outperforms other sensitizers used in this study. Values for short-circuit current densities of 2.13 mA cm(-2) and overall energy conversion efficiencies of 0.033% under simulated sunlight (AM1.5, 1000 W m(-2)) are the highest values reported in literature so far.