Brain tumor craniotomy outcomes for dual-eligible medicare and medicaid patients: a 10-year nationwide analysis.

INTRODUCTION: Dual-eligible (DE) patients, simultaneous Medicare and Medicaid beneficiaries, have been shown to have poorer clinical outcomes while incurring higher resource utilization. However, neurosurgical oncology outcomes for DE patients are poorly characterized. Accordingly, we examined the impact of DE status on perioperative outcomes following glioma, meningioma, or metastasis resection. METHODS: We identified all admissions undergoing a craniotomy for glioma, meningioma, or metastasis resection in the National Inpatient Sample from 2002 to 2011. Assessed outcomes included inpatient mortality, complications, discharge disposition, length of stay (LOS), and hospital costs. Multivariable regression adjusting for 13 patient, severity, and hospital characteristics assessed the association between DE status and outcomes, relative to four reference insurance groups (Medicare-only, Medicaid-only, private insurance, self-pay). RESULTS: Of 195,725 total admissions analyzed, 3.0% were dual-eligible beneficiaries (n = 5933). DEs were younger than Medicare admissions (P < 0.001) but older than Medicaid, private, and self-pay admissions (P < 0.001). Relative to other insurance groups, DEs also exhibited higher severity of illness, risk of mortality, and Charlson Comorbidity Index scores as well as treatment at low-volume hospitals (all P < 0.001). DEs had lower mortality than self-pay admissions (odds ratio [OR] 0.47, P = 0.017). Compared to Medicare, Medicaid, private, and self-pay admissions, DEs had lower rates of discharge disposition (OR 0.53, 0.50, 0.34, and 0.27, respectively, all P < 0.001). DEs also had higher complications (OR 1.23 and 1.20, respectively, both P < 0.05) and LOS (ß = 1.06 and 1.13, respectively, both P < 0.01) than Medicare and private insurance beneficiaries. Differences in discharge disposition remained significant for all three tumor subtypes, but only glioma DE admissions continued to exhibit higher complications and LOS. CONCLUSIONS: DEs undergoing definitive craniotomy for brain tumor had higher rates of unfavorable discharge disposition compared to all other insurance groups and, especially for glioma surgery, had higher inpatient complication rates and LOS. Practice and policy reforms to improve outcomes for this vulnerable clinical population are warranted.

Cranial Irradiation for Childhood Cancers and Adult Risk of Meningioma.

INTRODUCTION: Following cranial irradiation, there is an increased risk of developing secondary neoplasms, especially meningiomas. Despite childhood cancer survivors who have undergone cranial irradiation having an increased risk of acquiring radiation-induced meningioma (RIM), there is no widely used standard guideline for meningioma screening. METHODS: At a single institution, we reviewed three adult survivors of childhood cancer who were treated for RIM between 2010 and 2020. We recorded age at diagnosis for the primary lesion, the radiation dose, age at RIM diagnosis, and tumor characteristics including treatment, pathology, and outcome. Two had had T-cell acute lymphocytic leukemia and one a rhabdomyosarcoma. The age of diagnosis of the RIM ranged from 20 to 40 years, with latencies ranging from 18 to 33 years. All lesions were classified as WHO Grade I meningiomas, and only 1 patient had a subsequent recurrence. A literature search identified articles that address RIM: a total of 684 cases were identified in 36 publications. RESULTS: Mean radiation doses ranged from 1.4 gray to 70 gray. Mean age of diagnosis for secondary meningioma ranged from 8 to 53.4 years old, with latency periods ranging from 2.8 to 44 years. Given variability in the way that investigators have published their results, it is difficult to make a single recommendation for RIM screening. Using our experience and the literature, we devised two different screening protocols and calculated their expense. CONCLUSIONS: We recommend that data be standardized in a registry to provide greater insight into the clinical and resource allocation questions, especially as long-term survival of children with pediatric cancer into full adulthood becomes more commonplace worldwide.

Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity.

Growth factor-mediated proliferation and self-renewal maintain tissue-specific stem cells and are frequently dysregulated in cancers. Platelet-derived growth factor (PDGF) ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors, as proven in genetically engineered models. While PDGFRα alterations inform intertumoral heterogeneity toward a proneural glioblastoma (GBM) subtype, we interrogated the role of PDGFRs in intratumoral GBM heterogeneity. We found that PDGFRα is expressed only in a subset of GBMs, while PDGFRß is more commonly expressed in tumors but is preferentially expressed by self-renewing tumorigenic GBM stem cells (GSCs). Genetic or pharmacological targeting of PDGFRß (but not PDGFRα) attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFRß inhibition decreased activation of the cancer stem cell signaling node STAT3, while constitutively active STAT3 rescued the loss of GSC self-renewal caused by PDGFRß targeting. In silico survival analysis demonstrated that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor. Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies.

Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.

BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer. METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining. RESULTS: LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta+ tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival. CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma.

The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p = 0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients.

Surgical outcomes in patients with Cushing's disease: the Cleveland clinic experience.

CONTEXT: Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging. OBJECTIVE: To report surgical outcomes and predictors of remission in a specialist center for patients with CD. PATIENTS AND METHODS: Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated. RESULTS: One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%). CONCLUSIONS: A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

Risk associated with perioperative red blood cell transfusion in cranial surgery.

We assessed the impact of intra- and postoperative RBC transfusion on postoperative morbidity and mortality in cranial surgery. A total of 8924 adult patients who underwent cranial surgery were identified in the 2006-2011 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Patients undergoing a biopsy, radiosurgery, or outpatient surgery were excluded. Propensity scores were calculated according to demographic variables, comorbidities, and preoperative laboratory values. Patients who had received RBC transfusion were matched to those who did not, by propensity score, preoperative hematocrit level, and by length of surgery, as an indirect measure of potential intraoperative blood loss. Logistic regression was used to predict adverse postoperative outcomes. A total of 625 (7%) patients were transfused with one or more units of packed RBCs. Upon matching, preoperative hematocrit, length of surgery, and emergency status were no longer different between transfused and non-transfused patients. RBC transfusion was associated with prolonged length of hospitalization (OR 1.6, 95% CI 1.2-2.2), postoperative complications (OR 2.8, 95% CI 2.0-3.8), 30-day return to operation room (OR 2.0, 95% CI 1.3-3.2), and 30-day mortality (OR 4.3, 95% CI 2.4-7.6). RBC transfusion is associated with substantive postoperative morbidity and mortality in patients undergoing both elective and emergency cranial surgery. These results suggest judicious use of transfusion in cranial surgery, consideration of alternative means of blood conservation, or pre-operative restorative strategies in patients undergoing elective surgery, when possible.

Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1-3 newly diagnosed brain metastases.

Patients with 1-3 brain metastases (BM) often receive sterotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT). SRS without WBRT carries a high rate of relapse in the central nervous system (CNS). This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Eligible patients with 1-3 newly diagnosed BM, RTOG RPA class 1-2, received sunitinib after SRS. Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/days 1-28 every 42 days until CNS progression. Neuropsychological testing and MRIs were obtained every two cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Fourteen patients with a median age of 59 years were enrolled. Primary cancers included lung 43 %, breast 21 %, melanoma 14 %. Toxicity included grade 3 or higher fatigue in five patients and neutropenia in two patients. The CNS PFS6 and PFS12 were 43 ± 14 and 34 ± 14 %, respectively. Of the ten patients who completed >1 neurocognitive assessment, none showed cognitive decline. Sunitinib after SRS for 1-3 BM was well tolerated with a PFS6 of 43 %. The prevention of progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient's primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of BM after definitive local therapy.

Multi-modal management of acromegaly: a value perspective.

PURPOSE: The Acromegaly Consensus Group recently released updated guidelines for medical management of acromegaly patients. We subjected these guidelines to a cost analysis. METHODS: We conducted a cost analysis of the recommendations based on published efficacy rates as well as publicly available cost data. The results were compared to findings from a previously reported comparative effectiveness analysis of acromegaly treatments. Using decision tree software, two models were created based on the Acromegaly Consensus Group's recommendations and the comparative effectiveness analysis. The decision tree for the Consensus Group's recommendations was subjected to multi-way tornado analysis to identify variables that most impacted the value analysis of the decision tree. RESULTS: The value analysis confirmed the Consensus Group's recommendations of somatostatin analogs as first line therapy for medical management. Our model also demonstrated significant value in using dopamine agonist agents as upfront therapy as well. Sensitivity analysis identified the cost of somatostatin analogs and growth hormone receptor antagonists as having the most significant impact on the cost effectiveness of medical therapies. CONCLUSION: Our analysis confirmed the value of surgery as first-line therapy for patients with surgically accessible lesions. Surgery provides the greatest value for management of patients with acromegaly. However, in accordance with the Acromegaly Consensus Group's recent recommendations, somatostatin analogs provide the greatest value and should be used as first-line therapy for patients who cannot be managed surgically. At present, the substantial cost is the most significant negative factor in the value of medical therapies for acromegaly.

PITUITARY MRI FINDINGS IN PATIENTS WITH PITUITARY AND ECTOPIC ACTH-DEPENDENT CUSHING SYNDROME: DOES A 6-MM PITUITARY TUMOR SIZE CUT-OFF VALUE EXCLUDE ECTOPIC ACTH SYNDROME?

OBJECTIVE: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS). METHODS: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS. RESULTS: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3-14) and 8 mm (2-31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN) Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.

Evidence-based interventions to reduce shunt infections: a systematic review.

PURPOSE: Cerebrospinal fluid shunt infection is associated with patient morbidity and high cost. We conducted a systematic review of the current evidence of comprehensive surgical protocols or individual interventions designed to reduce shunt infection incidence. METHODS: A systematic review using PubMed and SCOPUS identified studies evaluating the effect of a particular intervention on shunt infection risk. Systemic prophylactic antibiotic or antibiotic-impregnated shunt efficacy studies were excluded. A total of 7429 articles were screened and 23 articles were included. RESULTS: Eight studies evaluated the effect of comprehensive surgical protocols. Shunt infection was reduced in all studies (absolute risk reduction 2.2-12.3 %). Level of evidence was low (level 4 in seven studies) due to the use of historical controls. Compliance ranged from 24.6 to 74.5 %. Surgical scrub with antiseptic foam and omission of a 5 % chlorhexidine gluconate preoperative hair wash were both associated with increased shunt infection. Twelve studies evaluated the effect of a single intervention. Only antibiotic-impregnated suture, a no-shave policy, and double gloving with glove change prior to shunt handling, were associated with a significant reduction in shunt infection. In a hospital with high methicillin-resistant staphylococcus aureus (MRSA) prevalence, a randomized controlled trial found that perioperative vancomycin rather than cefazolin significantly reduced shunt infection rates. CONCLUSION: Despite wide variation in compliance rates, the implementation of comprehensive surgical protocols reduced shunt infection in all published studies. Antibiotic-impregnated suture, a no-shave policy, double gloving with glove change prior to device manipulation, and 5 % chlorhexidine hair wash were associated with significant reductions in shunt infection.

ß-Catenin signaling initiates the activation of astrocytes and its dysregulation contributes to the pathogenesis of astrocytomas.

Astrocytes are the most abundant cell of the CNS and demonstrate contact inhibition in which a nonproliferative, nonmotile cellular state is achieved once stable intercellular contacts are formed between mature cells. Cellular injury disrupts these intercellular contacts, causing a loss of contact inhibition and the rapid initiation of healing. Dysregulation of the molecular pathways involved in this process is thought to lead to an aggressive cellular state associated with neoplasia. We investigated whether a comparable correlation exists between the response of astrocytes to injury and the malignant phenotype of astrocytomas. We discovered that the loss of contact inhibition plays a critical role in the initiation and regulation of reactive astrocytes in the healing of wounds. In particular, injury of the astrocytes interrupts and destabilizes the cadherin-catenin complexes at the cell membrane leading to nuclear translocation of ß-catenin and characteristic changes associated with the activation of astrocytes. Similar signaling pathways are found to be active--but dysregulated--in astrocytomas. Inhibition of ß-catenin signaling diminished both the response of astrocytes to injury and induction of the malignant phenotype of astrocytomas. The findings shed light on a unique mechanism associated with the pathogenesis of astrocytomas and provide a model for the loss of contact inhibition that may broadly apply to understanding the mechanisms of tissue repair and tumorigenesis in the brain.

Effect of a randomized controlled trial on the surgical treatment of spinal metastasis, 2000 through 2010: a population-based cohort study.

BACKGROUND: The effect of randomized controlled trials (RCT) on clinical practice patterns and patient outcomes is understudied. A 2005 RCT by Patchell et al demonstrated benefit for surgical decompression in patients with spinal metastasis (SpM). We examined trends in spinal surgery for patients with SpM before and after publication of the Patchell RCT. METHODS: The Nationwide Inpatient Sample (NIS) was used to identify a 20% stratified sample of surgical SpM admissions to nonfederal United States hospitals from 2000 to 2004 and 2006 to 2010, excluding 2005 when the RCT was published. Propensity scores were generated and logistic regression analysis was performed to compare outcomes in pre- and post-RCT time periods. RESULTS: A total of 7404 surgical admissions were identified. The rate of spine surgery increased post-RCT from an average of 3.8% to 4.9% surgeries per metastatic admission per year (P = .03). Admissions in the post-RCT group were more likely to be non-Caucasian, lower income, Medicaid recipients, and have more medical comorbidities and a greater metastatic burden (P < .001). Logistic regression of the propensity-matched sample showed increased odds post-RCT for expensive hospital stay (2.9; 95% confidence interval [CI] = 2.6-3.4) and some complications, including neurologic (1.7; 95% CI = 1.1-2.8), venous thromboembolism (2.8; 95% CI = 1.9-4.2), and decubitis ulcers (15.4; 95% CI = 6.7-34.5). However, odds for in-hospital mortality decreased (0.6; 95% CI = 0.5-0.8). CONCLUSIONS: Surgery for SpM increased after publication of a positive RCT. A significantly greater proportion of patients with lower socioeconomic status, more comorbidities, and greater metastatic burden underwent surgery post-RCT. These patients experienced more postoperative complications and higher in-hospital charges but less in-hospital mortality.

Absence of immunostaining for growth hormone in a subset of patients with acromegaly.

The presence of growth hormone (GH) immunostaining in patients who lack the biochemical and clinical features of acromegaly has been described. In contrast, there is little information on the absence of GH immunostaining in patients with acromegaly. We describe five patients with acromegaly with no intratumoral immunostaining for GH. We reviewed all patients undergoing surgery for acromegaly. Out of 136 patients treated surgically in a 10 year period, five (3.7%) were found to have no GH immunostaining on repetitive testing at pathological examination. Their pathology slides were re-examined by an experienced neuropathologist, along with twenty nonfunctional pituitary tumors and ten GH-positive adenomas as negative and positive controls, respectively. All patients had clinical features consistent with acromegaly and elevated baseline insulin-like growth factor-1 (IGF-1) and GH. All patients had no immunostaining for GH on multiple inspections. Of twenty patients with nonfunctional tumors, two had ≤25% staining for GH in a scattered and non-coherent pattern and the rest were negative. In all ten positive control patients >25% of the tumor cells stained diffusely for GH. All five patients achieved biochemical remission at 1.4-8 years post-op using a combination of primary surgery alone (n = 1), repeat surgery (n = 1), radiotherapy (n = 3) and/or medical therapy (n = 2). GH immunostaining of an adenoma may not be sufficient to confirm the diagnosis of acromegaly. All patients in our small series achieved remission by multimodality therapies. Further studies are needed to evaluate the significance of our observation and whether this subset of patients follows a distinct long term clinical course.

Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

Significant hypercortisolism during fractionated radiotherapy in a patient with a large corticotroph adenoma: a case report and literature review.

OBJECTIVE: We describe a patient with a large, invasive corticotroph adenoma who developed severe hypercortisolism shortly after starting fractionated radiotherapy. METHODS: We reviewed the patient's clinical course, along with relevant literature for similar reported cases. RESULTS: A 29-year-old man was referred for radiotherapy for a residual and recurrent, invasive corticotroph adenoma. Prior to radiotherapy, he had a normal urine free cortisol (UFC) level of 44.7 µg/24 hours, with minimal symptoms. Within 2 weeks of radiotherapy, he developed hypertension, ankle edema, and hypokalemia (potassium level, 2.8 mEq/L), with a markedly elevated UFC level of 9,203 µg/24 hours. His UFC gradually decreased and normalized by the end of radiotherapy. One month later, the patient became adrenal insufficient, with a nondetectable 24-hour UFC. His adrenal function slowly recovered in 3 months. We are aware of only one previous case report of clinically significant hypercortisolism following radiotherapy in Cushing disease. CONCLUSION: Radiotherapy may result in acute severe hypercortisolism in patients with a large corticotroph adenoma. This uncommon, but clinically significant, acute adverse effect of radiotherapy suggests that clinical observation and biochemical monitoring during or soon after radiotherapy may be indicated.

Lumbar Decompression With and Without Fusion for Lumbar Stenosis With Spondylolisthesis: A Cost Utility Analysis.

STUDY DESIGN: Markov model. OBJECTIVE: To compare the cost-effectiveness of lumbar decompression alone (DA) with lumbar decompression with fusion (DF) for the management of adults undergoing surgery for lumbar stenosis with associated degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Rates of lumbar fusion have increased for all indications in the United States over the last 20 years. Recent randomized controlled trial data, however, have suggested comparable functional outcomes and lower reoperation rates for lumbar decompression and fusion as compared with DA in the treatment of lumbar stenosis with degenerative spondylolisthesis. MATERIALS AND METHODS: A multistate Markov model was constructed from the US payer perspective of a hypothetical cohort of patients with lumbar stenosis with associated spondylolisthesis requiring surgery. Data regarding clinical improvement, costs, and reoperation were generated from contemporary randomized trial evidence, meta-analyses of recent prospective studies, and large retrospective cohorts. Base case, one-way sensitivity analysis, and probabilistic sensitivity analyses were conducted, and the results were compared with a WTP threshold of $100,000 (in 2022 USD) over a two-year time horizon. A discount rate of 3% was utilized. RESULTS: The incremental cost and utility of DF relative to DA were $12,778 and 0.00529 aggregated quality adjusted life years. The corresponding incremental cost-effectiveness ratio of $2,416,281 far exceeded the willingness to pay threshold of $100,000. In sensitivity analysis, the results varied the most with respect to rate of improvement after DA, rate of improvement after lumbar decompression and fusion, and odds ratio of reoperation between the two groups. Zero percent of one-way and probabilistic sensitivity analyses achieved cost-effectiveness at the willingness-to-pay threshold. CONCLUSIONS: Within the context of contemporary surgical data, DF is not cost-effective compared with DA in the surgical management of lumbar stenosis with associated spondylolisthesis over a two-year time horizon.

Natural language processing augments comorbidity documentation in neurosurgical inpatient admissions.

OBJECTIVE: To establish whether or not a natural language processing technique could identify two common inpatient neurosurgical comorbidities using only text reports of inpatient head imaging. MATERIALS AND METHODS: A training and testing dataset of reports of 979 CT or MRI scans of the brain for patients admitted to the neurosurgery service of a single hospital in June 2021 or to the Emergency Department between July 1-8, 2021, was identified. A variety of machine learning and deep learning algorithms utilizing natural language processing were trained on the training set (84% of the total cohort) and tested on the remaining images. A subset comparison cohort (n = 76) was then assessed to compare output of the best algorithm against real-life inpatient documentation. RESULTS: For "brain compression", a random forest classifier outperformed other candidate algorithms with an accuracy of 0.81 and area under the curve of 0.90 in the testing dataset. For "brain edema", a random forest classifier again outperformed other candidate algorithms with an accuracy of 0.92 and AUC of 0.94 in the testing dataset. In the provider comparison dataset, for "brain compression," the random forest algorithm demonstrated better accuracy (0.76 vs 0.70) and sensitivity (0.73 vs 0.43) than provider documentation. For "brain edema," the algorithm again demonstrated better accuracy (0.92 vs 0.84) and AUC (0.45 vs 0.09) than provider documentation. DISCUSSION: A natural language processing-based machine learning algorithm can reliably and reproducibly identify selected common neurosurgical comorbidities from radiology reports. CONCLUSION: This result may justify the use of machine learning-based decision support to augment provider documentation.

Short-term outcomes of craniotomy for malignant brain tumors in the elderly.

BACKGROUND: Disparity in resection rates for malignant brain tumors in elderly patients is partially attributed to a belief that advanced age is associated with an increased risk of postoperative morbidity and mortality. The objective of this study was to investigate the effect of advanced age (≥75 years) on 30-day outcomes in patients with primary and metastatic brain tumors who underwent craniotomy for definitive resection of a malignant brain tumor. METHODS: The authors conducted prospective analyses of the American College of Surgeons' National Surgical Quality-Improvement Project (NSQIP) database from 2006 to 2010 of 970 patients aged ≥40 years who underwent craniotomy for definitive resection of neoplasm. Preoperative and intraoperative characteristics and 30-day outcomes were stratified by age. By using propensity scores, 134 patients (aged ≥75 years) were matched to 134 patients ages 40 to 74 years. Logistic regression was used to predict adverse postoperative outcomes. RESULTS: The median length of hospital stay was 5 days; the rate of minor and major complications were 5.9% and 13.1%, respectively; 5.7% of patients returned to the operating room; and 4.3% of patients died within 30 days. Advanced age did not increase the odds for poorer short-term outcomes. CONCLUSIONS: Advanced age did not increase the risk of poor outcomes after surgical resection of primary or metastatic intracranial tumors when analyses were controlled for other risk factors. These results suggest that age should not be used, in isolation, as an a priori factor to discourage pursuing craniotomy.

Bevacizumab for radiation necrosis following treatment of high grade glioma: a systematic review of the literature.

This review identifies the current literature on the use of bevacizumab for cerebral radiation necrosis in patients with high-grade gliomas, summarizes the clinical course and complications following bevacizumab, and discusses the relative costs and benefits of this therapeutic option. A Medline search was conducted of all clinical studies before September 2012 investigating outcomes following use of bevacizumab therapy for radiation necrosis in patients with high-grade gliomas. Clinical and radiographic outcomes are reviewed. Seven studies reported a total of 30 patients with high-grade gliomas treated with bevacizumab for radiation necrosis. All patients demonstrated decreased radiographic volume of edema on T1 and T2 MRI sequences. Clinical outcomes were reported for 23 patients: 16 (70 %) had improvement in neurologic signs or symptoms, 5 (22 %) had mixed results, and 2 (9 %) remained neurologically unchanged. Complications were documented in 5 of 7 studies (18 of 29 patients, 62 %) and included deep vein thrombosis, pulmonary embolism, visual field worsening, worsening hemiplegia, pneumonia, seizure, and fatigue. Only one study evaluated quality of life measures and none evaluated cost or cost effectiveness. Data regarding the use of bevacizumab to treat radiation necrosis in patients with high-grade gliomas is limited and primarily class III evidence. While bevacizumab improves neurological symptoms and reduces radiographic volume of necrosis-associated cerebral edema, it comes at the expense of a high rate of potentially serious complications. Definitive evidence for the utility, cost-effectiveness, and overall efficacy of this management strategy is currently lacking and additional investigation is warranted.