Outcome of elderly patients undergoing awake-craniotomy for tumor resection.

BACKGROUND: Awake-craniotomy allows maximal tumor resection, which has been associated with extended survival. The feasibility and safety of awake-craniotomy and the effect of extent of resection on survival in the elderly population has not been established. The aim of this study was to compare surgical outcome of elderly patients undergoing awake-craniotomy to that of younger patients. METHODS: Outcomes of consecutive patients younger and older than 65 years who underwent awake-craniotomy at a single institution between 2003 and 2010 were retrospectively reviewed. The groups were compared for clinical variables and surgical outcome parameters, as well as overall survival. RESULTS: A total of 334 young (45.4 ± 13.2 years, mean ± SD) and 90 elderly (71.7 ± 5.1 years) patients were studied. Distribution of gender, mannitol treatment, hemodynamic stability, and extent of tumor resection were similar. Significantly more younger patients had a better preoperative Karnofsky Performance Scale score (>70) than elderly patients (P = 0.0012). Older patients harbored significantly more high-grade gliomas (HGG) and brain metastases, and fewer low-grade gliomas (P < 0.0001). No significantly higher rate of mortality, or complications were observed in the elderly group. Age was associated with increased length of stay (4.9 ± 6.3 vs. 6.6 ± 7.5 days, P = 0.01). Maximal extent of tumor resection in patients with HGG was associated with prolonged survival in the elderly patients. CONCLUSIONS: Awake-craniotomy is a well-tolerated and safe procedure, even in elderly patients. Gross total tumor resection in elderly patients with HGG was associated with prolonged survival. The data suggest that favorable prognostic factors for patients with malignant brain tumors are also valid in elderly patients.

Evaluation of a multimodality MR/US coregistration system for investigation of hepatic metastases from colorectal cancer.

PURPOSE: To evaluate a magnetic resonance (MR)/ultrasound (US) coregistration system with US used in follow-up diagnostic studies of lesions originally identified by MR imaging. MATERIALS AND METHODS: A single-center prospective study enrolled 21 consecutive patients (age, 64.0 y±7.5; eight men [age, 63.0 y±7.1] and 13 women [age, 65.0 y±7.3]) evaluated for potential surgical resection of liver metastases. Each patient underwent same-day MR examination and two US examinations: one regular and one with the MR/US coregistration system. Target lesions were identified on MR imaging, and US was used in follow-up diagnostic studies of lesions originally identified by MR imaging. During US, two outcome measures (target localization success and target localization time) were collected. Ratios of lesions found per patient were compared with a paired Wilcoxon test, and a Student t test was used to compare target localization time. RESULTS: Ratios of lesions found per patient with the coregistered system (93.7%) and conventional US (73.3%) were statistically different (P =.003). Lesions found by the coregistration system but not conventional US were statistically smaller than those found by both systems (6.1 mm±4.0 vs 15.6 mm±9.8; P<.0006). There was no statistical difference in target localization time for detection of lesions found by coregistered (100 s±89) and conventional US (108 s±86; P = .78). CONCLUSIONS: The MR/US coregistration system increases the number of lesions detected with US versus standard US alone. This may prove beneficial in surgical and nonsurgical management of patients with focal liver lesions.

The Multicellular Effects of VDAC1 N-Terminal-Derived Peptide.

The mitochondrial voltage-dependent anion channel-1 (VDAC1) protein functions in a variety of mitochondria-linked physiological and pathological processes, including metabolism and cell signaling, as well as in mitochondria-mediated apoptosis. VDAC1 interacts with about 150 proteins to regulate the integration of mitochondrial functions with other cellular activities. Recently, we developed VDAC1-based peptides that have multiple effects on cancer cells and tumors including apoptosis induction. Here, we designed several cell-penetrating VDAC1 N-terminal-derived peptides with the goal of identifying the shortest peptide with improved cellular stability and activity. We identified the D-Δ(1-18)N-Ter-Antp comprising the VDAC1 N-terminal region (19-26 amino acids) fused to the Antp, a cell-penetrating peptide. We demonstrated that this peptide induced apoptosis, autophagy, senescence, cell volume enlargement, and the refusion of divided daughter cells into a single cell, it was responsible for reorganization of actin and tubulin filaments, and increased cell adhesion. In addition, the peptide induced alterations in the expression of proteins associated with cell metabolism, signaling, and division, such as enhancing the expression of nuclear factor kappa B and decreasing the expression of the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha. These cellular effects may result from the peptide interfering with VDAC1 interaction with its interacting proteins, thereby blocking multiple mitochondrial/VDAC1 pathways associated with cell functions. The results of this study further support the role of VDAC1 as a mitochondrial gatekeeper protein in controlling a variety of cell functions via interaction with associated proteins.

The Impact of Colloid Cyst Treatment on Neurocognition.

BACKGROUND: Colloid cysts (CC) have been associated with neurocognitive function (NCF) decline, both preoperatively and after resection. Factors such as local pressure on the fornix and hydrocephalus are thought to contribute to preoperative NCF decline. The potential cause of postoperative decline is thought to be forniceal injury during surgery. In the current series, we describe NCF outcomes amongst patients with CC, both nonoperated and operated. METHODS: A total of 36 patients (23 operated, 13 nonoperated) were included in this retrospective study. All patients underwent at least 1 NCF evaluation battery. Of the 13 nonoperated cases, 5 had follow-up tests too. Of the 23 operated, 14 had both pre- and postoperative tests, and 8 had early and late postoperative tests. RESULTS: There was no significant difference in baseline NCF between nonoperated and operated cases (as evaluated preoperatively). Nonoperated patients had a stable NCF test over time. Patients who were operated showed a significant improvement after surgery in several NCF variables. There was no significant change in NCF between early and late postoperative evaluation. None of the operated patients had a postoperative NCF decline. CONCLUSIONS: Patients with CC should undergo routine NCF testing with a standardized protocol, whether they are operated or followed. Surgery has a positive impact on NCF; however, it remains to be determined if the improvement is solely secondary to treatment of hydrocephalus, or to a reduction of local pressure on the fornices. It remains to be determined whether the surgical technique, that is, endoscopic, interhemispheric, or transcortical, has an impact on NCF outcome.

Improvement in cognitive function after surgery for low-grade glioma.

OBJECTIVECognition is a key component in health-related quality of life (HRQoL) and is currently incorporated as a major parameter of outcome assessment in patients treated for brain tumors. The effect of surgery on cognition and HRQoL remains debatable. The authors investigated the impact of resection of low-grade gliomas (LGGs) on cognition and the correlation with various histopathological markers.METHODSA retrospective analysis of patients with LGG who underwent craniotomy for tumor resection at a single institution between 2010 and 2014 was conducted. Of 192 who underwent resective surgery for LGG during this period, 49 had complete pre- and postoperative neurocognitive evaluations and were included in the analysis. These patients completed a full battery of neurocognitive tests (memory, language, attention and working memory, visuomotor organization, and executive functions) pre- and postoperatively. Tumor and surgical characteristics were analyzed, including volumetric measurements and histopathological markers (IDH, p53, GFAP).RESULTSPostoperatively, significant improvement was found in memory and executive functions. A subgroup analysis of patients with dominant-side tumors, most of whom underwent intraoperative awake mapping, revealed significant improvement in the same domains. Patients whose tumors were on the nondominant side displayed significant improvement only in memory functions. Positive staining for p53 testing was associated with improved language function and greater extent of resection in dominant-side tumors. GFAP positivity was associated with improved memory in patients whose tumors were on the nondominant side. No correlation was found between cognitive outcome and preoperative tumor volume, residual volume, extent of resection, or IDH1 status.CONCLUSIONSResection of LGG significantly improves memory and executive function and thus is likely to improve functional outcome in addition to providing oncological benefit. GFAP and pP53 positivity could possibly be associated with improved cognitive outcome. These data support early, aggressive, surgical treatment of LGG.

Surgery-Independent Language Function Decline in Patients Undergoing Awake Craniotomy.

BACKGROUND: Despite selection process before awake-craniotomy, some patients experience an unexpected decline in language functions in the operating room (OR), compared with their baseline evaluation, which may impair their functional monitoring. To investigate this phenomenon we prospectively compared language function the day before surgery and on entrance to the OR. METHODS: Data were collected prospectively from consecutive patients undergoing awake-craniotomy with intraoperative cortical mapping for resection of gliomas affecting language areas. Language functions of 79 patients were evaluated and compared 1-2 days before surgery and after entering the OR. Changes in functional linguistic performance were analyzed with respect to demographic, clinical, and pathologic characteristics. RESULTS: There was a significant decline in language function, beyond sedation effect, after entering the OR, (from median/interquartile range: 0.94/0.72-0.98 to median/interquartile range: 0.86/0.51-0.94; Z = -7.19, P < 0.001). Univariate analyses revealed that this decline was related to age, preoperative Karnofsky Performance Scale, tumor location, tumor pathology, and preexisting language deficits. Multivariate stepwise regression identified tumor pathology and the presence of preoperative language deficit as significant independent predictors for this functional decline. CONCLUSIONS: Patients undergoing awake-craniotomy may experience a substantial decline in language functioning after entering the OR. Tumor grade and the presence of preoperative language deficits were significant risk factors for this phenomenon, suggesting a possible relation between cognitive reserve, psychobehavioral coping abilities and histologic features of a tumor involving language areas. Capturing and identifying this unique population of patients who are prone to experience such language decline may improve our ability in the future to select patients eligible for awake-craniotomy.

Utility of simultaneous brain, CSF and hyperintensity quantification in dementia.

Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.

Real-Time Measurement of Functional Tumor Volume by MRI to Assess Treatment Response in Breast Cancer Neoadjuvant Clinical Trials: Validation of the Aegis SER Software Platform.

PURPOSE: To evaluate the Aegis software implementation for real-time calculation of functional tumor volume (FTV) in the neoadjuvant breast cancer treatment trial setting. METHODS: The validation data set consisted of 689 contrast-enhanced magnetic resonance imaging (MRI) examinations from the multicenter American College of Radiology Imaging Network 6657 study. Subjects had stage III tumors ≥3 cm in diameter and underwent MRI before, during, and after receiving anthracycline-cyclophosphamide chemotherapy. Studies were previously analyzed by the University of California San Francisco core laboratory using the three-timepoint signal enhancement ratio (SER) FTV algorithm; FTV measurement was subsequently implemented on the Hologic (formerly Sentinelle Medical Inc) Aegis platform. All cases were processed using predefined volumes of interest with no user interaction. Spearman rank correlation was evaluated for all study sites and visits. Cox proportional hazards analysis was used to compare predictive performance of the platforms for recurrence-free survival (RFS) time. RESULTS: Overall agreement between platforms was good; ρ varied from 0.96 to 0.98 for different study visits. Site-by-site analysis showed considerable variation, from ρ = 0.54 to near perfect agreement (ρ = 1.000) for several sites. Mean absolute difference between platforms ranged from 1.67 cm(3) pretreatment to 0.2 cm(3) posttreatment. The two platforms showed essentially identical performance for predicting RFS using pretreatment or posttreatment FTV. CONCLUSION: Implementation of the SER FTV algorithm on a commercial platform for real-time MRI volume assessments showed very good agreement with the reference core laboratory system, but variations by site and outlier analysis point out sensitivities to implementation-specific differences.

Failed awake craniotomy: a retrospective analysis in 424 patients undergoing craniotomy for brain tumor.

OBJECT: Awake craniotomy for removal of intraaxial tumors within or adjacent to eloquent brain regions is a well-established procedure. However, awake craniotomy failures have not been well characterized. In the present study, the authors aimed to analyze and assess the incidence and causes for failed awake craniotomy. METHODS: The database of awake craniotomies performed at Tel Aviv Medical Center between 2003 and 2010 was reviewed. Awake craniotomy was considered a failure if conversion to general anesthesia was required, or if adequate mapping or monitoring could not have been achieved. RESULTS: Of 488 patients undergoing awake craniotomy, 424 were identified as having complete medical, operative, and anesthesiology records. The awake craniotomies performed in 27 (6.4%) of these 424 patients were considered failures. The main causes of failure were lack of intraoperative communication with the patient (n = 18 [4.2%]) and/or intraoperative seizures (n = 9 [2.1%]). Preoperative mixed dysphasia (p < 0.001) and treatment with phenytoin (p = 0.0019) were related to failure due to lack of communication. History of seizures (p = 0.03) and treatment with multiple antiepileptic drugs (p = 0.0012) were found to be related to failure due to intraoperative seizures. Compared with the successful awake craniotomy group, a significantly lower rate of gross-total resection was achieved (83% vs 54%, p = 0.008), there was a higher incidence of short-term speech deterioration postoperatively (6.1% vs 23.5%, p = 0.0017) as well as at 3 months postoperatively (2.3% vs 15.4%, p = 0.0002), and the hospitalization period was longer (4.9 ± 6.2 days vs 8.0 ± 10.1 days, p < 0.001). Significantly more major complications occurred in the failure group (4 [14.8%] of 27) than in the successful group (16 [4%] of 397) (p = 0.037). CONCLUSIONS: Failures of awake craniotomy were associated with a lower incidence of gross-total resection and increased postoperative morbidity. The majority of awake craniotomy failures were preventable by adequate patient selection and avoiding side effects of drugs administered during surgery.

Intraoperative seizures during awake craniotomy: incidence and consequences: analysis of 477 patients.

BACKGROUND: Awake craniotomy (AC) for removal of intra-axial brain tumors is a well-established procedure. However, the occurrence and consequences of intraoperative seizures during AC have not been well characterized. OBJECTIVE: To analyze the incidence, risk factors, and consequences of seizures during AC. METHODS: The database of AC at Tel Aviv Medical Center between 2003 to 2011 was reviewed. Occurrences of intraoperative seizures were analyzed with respect to medical history, medications, tumor characteristics, and postoperative outcome. RESULTS: Of the 549 ACs performed during the index period, 477 with complete records were identified. Sixty patients (12.6%) experienced intraoperative seizures. The AC procedure failed in 11 patients (2.3%) due to seizures. Patients with intraoperative seizures were significantly younger than nonseizing patients (45 ± 14 years vs 52 ± 16 years, P = .003), had a higher incidence of frontal lobe involvement (86% vs % 57%, P < .0001), and had higher prevalence of a history of seizures (P = .008). Short-term motor deterioration developed postoperatively in a higher percentage of patients with intraoperative seizures (20% vs 10.1%, P = .02) with a longer hospitalization period (4.0 ± 3.0 days vs 3.0 ± 3.0 days, P = .045). CONCLUSION: Although in most cases intraoperative seizures will not result in AC failure, the surgical team should be prepared to treat them promptly to avoid intractable seizures. Intraoperative seizures are more common in younger patients with a tumor in the frontal lobe and those with a history of seizures. Moreover, they are associated with a higher incidence of transient postoperative motor deterioration and protracted length of hospital stay.

Painful temporomandibular disorders and headaches in 359 dental and medical students.

OBJECTIVE: to assess the prevalence of headaches and painful tempormandibular disorders (TMDs) and examine these via demographic and specific lifestyle parameters, as well as examine the relationship among TMDs, headaches, and depression rates. METHOD AND MATERIALS: a group of 359 medical and dental students completed a detailed questionnaire regarding demographic features and the presence of headaches and facial pain. The survey included a section on lifestyle (nutrition, alcohol and tobacco consumption, physical activity) and a Zung depression assessment. RESULTS: about eleven percent of the subjects reported pain: 8.6% from the jaw joint, 1.7% from the muscles of mastication, and 0.8% had both (ie, painful TMD). Eighty-three percent reported a lifetime prevalence of any headache, most of which were episodic tension-type headaches (56.9%) or migraines (19.2%). There was no significant correlation between headache diagnosis and the presence of painful TMD. Patients with painful TMD had higher depression scores than patients without and smoked more tobacco. This was not observed in headache patients. Patients with headache complained of significantly more dizziness and fatigue, particularly in the migraine and frequent episodic tension-type headache groups. CONCLUSION: TMD patients should be carefully assessed for the presence of emotional problems and referred to a suitable care provider.