Frailty, a state of decreased physiological reserve, has been shown to significantly impact outcomes of surgery. The authors sought to examine the impact of frailty on the short-term outcomes of ...patients undergoing transsphenoidal pituitary surgery.
Weighted data from the 2000-2014 National (Nationwide) Inpatient Sample were studied. Patients diagnosed with pituitary tumors or disorders who had undergone transsphenoidal pituitary surgery were identified. Frailty was determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. Standard descriptive techniques and matched propensity score analyses were used to explore the odds ratios of postoperative complications, discharge dispositions, and costs.
A total of 115,317 cases were included in the analysis. Frailty was present in 1.48% of cases. The mean age of frail versus non-frail patients was 57.14 ± 16.96 years (mean ± standard deviation) versus 51.91 ± 15.88 years, respectively (p < 0.001). A greater proportion of frail compared to non-frail patients had an age ≥ 65 years (37.08% vs 24.08%, respectively, p < 0.001). Frail patients were more likely to be black or Hispanic (p < 0.001), possess Medicare or Medicaid insurance (p < 0.001), belong to lower-median-income groups (p < 0.001), and have greater comorbidity (p < 0.001). Results of propensity score-matched multivariate analysis revealed that frail patients were more likely to develop fluid and electrolyte disorders (OR 1.61, 95% CI 1.07-2.43, p = 0.02), intracranial vascular complications (OR 2.73, 95% CI 1.01-7.49, p = 0.04), mental status changes (OR 3.60, 95% CI 1.65-7.82, p < 0.001), and medical complications including pulmonary insufficiency (OR 2.01, 95% CI 1.13-4.05, p = 0.02) and acute kidney failure (OR 4.70, 95% CI 1.88-11.74, p = 0.01). The mortality rate was higher among frail patients (1.46% vs 0.37%, p < 0.001). Frail patients also demonstrated a greater likelihood for nonroutine discharges (p < 0.001), higher mean total charges ($109,614.33 95% CI $92,756.09-$126,472.50 vs $56,370.35 95% CI $55,595.72-$57,144.98, p < 0.001), and longer hospitalizations (9.27 days 95% CI 7.79-10.75 vs 4.46 days 95% CI 4.39-4.53, p < 0.001).
Frailty in patients undergoing transsphenoidal pituitary surgery is associated with worse postoperative outcomes and higher costs, indicating that state's potential role in routine preoperative risk stratification.
Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the ...blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% 95% confidence interval (95% CI) = 57−88% of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88−100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P< 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.
Functional endoscopic sinus surgery (FESS) is one of the most common outpatient surgical procedures performed in the head and neck region. It is used to treat chronic sinusitis, a disease ...characterized by inflammation in the nose and surrounding paranasal sinuses, affecting about 15% of the adult population. During FESS, the nasal cavity is visualized using an endoscope, and instruments are used to remove tissues that are often within a millimeter of critical anatomical structures, such as the optic nerve, carotid arteries, and nasolacrimal ducts. To maintain orientation and to minimize the risk of damage to these structures, surgeons use surgical navigation systems to visualize the 3-D position of their tools on patients' preoperative Computed Tomographies (CTs). This paper presents an image-based method for enhanced endoscopic navigation. The main contributions are: (1) a system that enables a surgeon to asynchronously register a sequence of endoscopic images to a CT scan with higher accuracy than other reported solutions using no additional hardware; (2) the ability to report the robustness of the registration; and (3) evaluation on in vivo human data. The system also enables the overlay of anatomical structures, visible, or occluded, on top of video images. The methods are validated on four different data sets using multiple evaluation metrics. First, for experiments on synthetic data, we observe a mean absolute position error of 0.21mm and a mean absolute orientation error of 2.8° compared with ground truth. Second, for phantom data, we observe a mean absolute position error of 0.97mm and a mean absolute orientation error of 3.6° compared with the same motion tracked by an electromagnetic tracker. Third, for cadaver data, we use fiducial landmarks and observe an average reprojection distance error of 0.82mm. Finally, for in vivo clinical data, we report an average ICP residual error of 0.88mm in areas that are not composed of erectile tissue and an average ICP residual error of 1.09mm in areas that are composed of erectile tissue.
Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). ...To better understand the genetic basis for MPNSTs, we performed genome-wide or targeted sequencing on 50 cases. Sixteen MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation.
Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of ...this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers.
EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs).
Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma.
Abstract
BACKGROUND: Microsurgical and endoscopic techniques are commonly utilized surgical approaches to pituitary pathologies. There are limited data comparing these 2 procedures.
OBJECTIVE: To ...evaluate postoperative complications, associated costs, and national and regional trends of microscopic and endoscopic techniques in the United States employing a nationwide database.
METHODS: The Truven MarketScan database 2010 to 2014 was queried and Current Procedural Terminology codes identified patients that underwent microscopic and/or endoscopic transsphenoidal pituitary surgery. International Classification of Diseases codes identified postoperative complications. Adjusted logistic regression and matched propensity analysis evaluated independent odds for complications.
RESULTS: Among 5886 cases studied, 54.49% were microscopic and 45.51% endoscopic. The commonest surgical indications were benign pituitary tumors. Annual trends showed increasing utilization of endoscopic techniques vs microscopic procedures. Postoperative complications occurred in 40.04% of cases, including diabetes insipidus (DI; 16.90%), syndrome of inappropriate antidiuretic hormone (SIADH; 2.02%), iatrogenic hypopituitarism (1.36%), fluid/electrolyte abnormalities (hypoosmolality/hyponatraemia 5.03% and hyperosmolality/hypernatraemia 2.48%), and cerebrospinal fluid (CSF) leaks (CSF rhinorrhoea 4.42% and other CSF leak 6.52%). In our propensity-based model, patients that underwent endoscopic surgery were more likely to develop DI (odds ratio OR = 1.48; 95% confidence interval CI = 1.28-1.72), SIADH (OR = 1.53; 95% CI = 1.04-2.24), hypoosmolality/hyponatraemia (OR = 1.17; 95% CI = 1.01-1.34), CSF rhinorrhoea (OR = 2.48; 95% CI = 1.88-3.28), other CSF leak (OR = 1.59; 95% CI = 1.28-1.98), altered mental status (OR = 1.46; 95% CI = 1.01-2.60), and postoperative fever (OR = 4.31; 95% CI = 1.14-16.23). There were no differences in hemorrhagic complications, ophthalmological complications, or bacterial meningitis. Postoperative complications resulted in longer hospitalization and increased healthcare costs.
CONCLUSION: Endoscopic approaches are increasingly being utilized to manage sellar pathologies relative to microsurgery. Postoperative complications occur in both techniques with higher incidences observed following endoscopic procedures.
Targeting the AKT pathway in glioblastoma McDowell, Kelli A; Riggins, Gregory J; Gallia, Gary L
Current pharmaceutical design,
08/2011, Letnik:
17, Številka:
23
Journal Article
Recenzirano
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The treatment options for patients diagnosed with GBM are limited and the current median survival is 14-16 months ...following diagnosis. Genetic mutations have been identified that act as drivers of GBM growth and these should be considered as a basis for identifying novel therapeutic strategies. AKT is a downstream serine/threonine kinase in the RTK/PTEN/PI3K pathway and large scale genomic analysis of GBM has demonstrated that this pathway is mutated in the majority of GBMs. This RTK/PTEN/PI3K pathway leads to activated AKT and phospho-AKT levels are elevated in the majority of GBM tumor samples and cell lines, which studies show help glioma cells grow uncontrolled, evade apoptosis, and enhance tumor invasion. AKT represents a nodal point in this pathway which allows for amplification of growth signals, thereby making inhibition of AKT an attractive target for GBM therapy. Many different classes of AKT inhibitors exist, however, few have been tested sufficiently to demonstrate in vivo efficacy. This article will summarize the key components of the Akt pathway with special attention to gliomas, the genetic alterations driving this pathway in gliomas, and the studies evaluating inhibitors of this pathway. Inhibitors of the Akt pathway represent a potential treatment option against GBM and additional research efforts are required to fully explore and develop this possible treatment strategy.
In recent years, frailty indices such as the 11- and 5-factor modified frailty indices (mFI-11 and mFI-5), American Society of Anesthesiologists (ASA) physical status classification, and Charlson ...Comorbidity Index (CCI) have been shown to be effective predictors of various postoperative outcomes in neurosurgical patients. The Hospital Frailty Risk Score (HFRS) is a well-validated tool for assessing frailty; however, its utility has not been evaluated in intracranial tumor surgery. In the present study, the authors investigated the accuracy of the HFRS in predicting outcomes following intracranial tumor resection and compared its utility to those of other validated frailty indices.
A retrospective analysis was conducted using an intracranial tumor patient database at a single institution. Patients eligible for study inclusion were those who had undergone resection for an intracranial tumor between January 1, 2017, and December 31, 2019. ICD-10 codes were used to identify HFRS components and subsequently calculate risk scores. In addition to several postoperative variables, ASA class, CCI, and mFI-11 and mFI-5 scores were determined for each patient. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC), and the DeLong test was used to assess for significant differences between AUROCs. Multivariate models for continuous outcomes were constructed using linear regression, whereas logistic regression models were used for categorical outcomes.
A total of 2518 intracranial tumor patients (mean age 55.3 ± 15.1 years, 53.4% female, 70.4% White) were included in this study. The HFRS had a statistically significant greater AUROC than ASA status, CCI, mFI-11, and mFI-5 for postoperative complications, high hospital charges, nonroutine discharge, and 90-day readmission. In the multivariate analysis, the HFRS was significantly and independently associated with postoperative complications (OR 1.14, p < 0.0001), hospital length of stay (coefficient = 0.50, p < 0.0001), high hospital charges (coefficient = 1917.49, p < 0.0001), nonroutine discharge (OR 1.14, p < 0.0001), and 90-day readmission (OR 1.06, p < 0.0001).
The study findings suggest that the HFRS is an effective predictor of postoperative outcomes in intracranial tumor patients and more effectively predicts adverse outcomes than other frailty indices. The HFRS may serve as an important tool for reducing patient morbidity and mortality in intracranial tumor surgery.
Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously ...observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 µM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.
Surgery is first-line therapy for glioblastoma, and there is evidence that gross total resection is associated with improved survival. Gross total resection, however, is not always possible, and ...relationships among extent (percent) of resection (EOR), residual volume (RV), and survival are unknown. The goals were to evaluate whether there is an association between EOR and RV with survival and recurrence and to establish minimum EOR and maximum RV thresholds.
Adult patients who underwent primary glioblastoma surgery from 2007 to 2011 were retrospectively reviewed. Three-dimensional volumetric tumor measurements were made. Multivariate proportional hazards regression analysis was used to evaluate the relationship between EOR and RV with survival and recurrence.
Of 259 patients, 203 (78%) died and 156 (60%) had tumor recurrence. The median survival and progression-free survival were 13.4 and 8.9 months, respectively. The median (interquartile range) pre- and postoperative tumor volumes were 32.2 (14.0-56.3) and 2.1 (0.0-7.9) cm(3), respectively. EOR was independently associated with survival (hazard ratio HR, 0.995; 95% confidence interval CI: 0.990-0.998; P = .008) and recurrence (HR 95% CI, 0.992 0.983-0.998, P = .005). The minimum EOR threshold for survival (P = .0006) and recurrence (P = .005) was 70%. RV was also associated with survival (HR 95% CI, 1.019 1.006-1.030, P = .004) and recurrence (HR 95% CI, 1.024 1.001-1.044, P = .03). The maximum RV threshold for survival (P = .01) and recurrence (P = .01) was 5 cm(3).
This study shows for the first time that both EOR and RV are significantly associated with survival and recurrence, where the thresholds are 70% and 5 cm(3), respectively. These findings may help guide surgical and adjuvant therapies aimed at optimizing outcomes for glioblastoma patients.
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