The latest medical research on Neurosurgery

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Robotic versus laparoendoscopic single-site hysterectomy: a systematic review and meta-analysis.

Journal of Robotic Surgery

Single-site hysterectomy (SSH) laparoscopic or robotic presented distinct advantages with regards to postoperative cosmetic outcome, wound-related ...

Germline cancer predisposition variants and pediatric glioma: a population-based study in California.

Neuro-Oncology

Pediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level.

DNA samples were extracted from neonatal dried bloodspots from 280 pediatric astrocytoma patients (predominantly high grade) born and diagnosed in California and were subjected to whole-exome sequencing. Sequencing data were analyzed using agnostic exome-wide gene-burden testing and variant identification for putatively pathogenic variants in 175 a priori candidate cancer-predisposition genes.

We identified thirty-three putatively pathogenic germline variants among 31 patients (11.1%) which located in 24 genes largely involved in DNA repair and cell cycle control. Patients with pediatric glioblastoma were most likely to harbor putatively pathogenic germline variants (14.3%, N=9/63). Five variants were located in TP53, of which four were identified among patients with glioblastoma (6.3%, N=4/63). The next most frequently mutated gene was NF1, in which putatively pathogenic variants were identified in four astrocytoma NOS patients. Gene-burden testing also revealed that putatively pathogenic variants in TP53 were significantly associated with pediatric glioblastoma on an exome-wide level (OR:32.8, p=8.04×10-7).

A considerable fraction of pediatric glioma patients, especially those of higher grade, harbor a putatively pathogenic variant in a cancer predisposition gene. Some of these variants may be clinically actionable or may warrant genetic counseling.

Subtype switching in breast cancer brain metastases: a multicenter analysis.

Neuro-Oncology

Breast cancer brain metastases (BCBM) can have discordant hormonal (HR) or human epidermal growth factor receptor 2 (HER2) expression compared to corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in the brain metastasis (BM).

BCBM patients seen at four tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed.

In brain metastases from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen (ER), 25.2% for progesterone (PR), and 10.4% for HER2. Because ER and PR were considered together for hormonal status, fifty (22.8%) patients switched subtype as a result; 20 of these switches were HER2-based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by ER loss (hazard ratio=1.80, p=0.03). Patients gaining HER2 status (n=8) showed a nonsignificant tendency towards improved survival (hazard ratio=0.64, p=0.17).

In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.

Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients.

Neuro-Oncology

Building on an initiative to enhance clinical trial participation involving the Society for Neuro-Oncology (SNO), the Response Assessment in Neuro-...

Effect of Multimodal Prehabilitation vs Postoperative Rehabilitation on 30-Day Postoperative Complications for Frail Patients Undergoing Resection of Colorectal Cancer: A Randomized Clinical Trial.

JAMA Surgery

Research supports use of prehabilitation to optimize physical status before and after colorectal cancer resection, but its effect on postoperative complications remains unclear. Frail patients are a target for prehabilitation interventions owing to increased risk for poor postoperative outcomes.

To assess the extent to which a prehabilitation program affects 30-day postoperative complications in frail patients undergoing colorectal cancer resection compared with postoperative rehabilitation.

This single-blind, parallel-arm, superiority randomized clinical trial recruited patients undergoing colorectal cancer resection from September 7, 2015, through June 19, 2019. Patients were followed up for 4 weeks before surgery and 4 weeks after surgery at 2 university-affiliated tertiary hospitals. A total of 418 patients 65 years or older were assessed for eligibility. Of these, 298 patients were excluded (not frail [n = 290], unable to exercise [n = 3], and planned neoadjuvant treatment [n = 5]), and 120 frail patients (Fried Frailty Index,≥2) were randomized. Ten patients were excluded after randomization because they refused surgery (n = 3), died before surgery (n = 3), had no cancer (n = 1), had surgery without bowel resection (n = 1), or were switched to palliative care (n = 2). Hence, 110 patients were included in the intention-to-treat analysis (55 in the prehabilitation [Prehab] and 55 in the rehabilitation [Rehab] groups). Data were analyzed from July 25 through August 21, 2019.

Multimodal program involving exercise, nutritional, and psychological interventions initiated before (Prehab group) or after (Rehab group) surgery. All patients were treated within a standardized enhanced recovery pathway.

The primary outcome included the Comprehensive Complications Index measured at 30 days after surgery. Secondary outcomes were 30-day overall and severe complications, primary and total length of hospital stay, 30-day emergency department visits and hospital readmissions, recovery of walking capacity, and patient-reported outcome measures.

Of 110 patients randomized, mean (SD) age was 78 (7) years; 52 (47.3%) were men and 58 (52.7%) were women; 31 (28.2%) had rectal cancer; and 87 (79.1%) underwent minimally invasive surgery. There was no between-group difference in the primary outcome measure, 30-day Comprehensive Complications Index (adjusted mean difference, -3.2; 95% CI, -11.8 to 5.3; P = .45). Secondary outcome measures were also not different between groups.

In frail patients undergoing colorectal cancer resection (predominantly minimally invasive) within an enhanced recovery pathway, a multimodal prehabilitation program did not affect postoperative outcomes. Alternative strategies should be considered to optimize treatment of frail patients preoperatively.

ClinicalTrials.gov identifier: NCT02502760.

Association of Early Postdonation Renal Function With Subsequent Risk of End-Stage Renal Disease in Living Kidney Donors.

JAMA Surgery

Living kidney donation is associated with increased long-term risk of end-stage renal disease (ESRD). An early postdonation marker of ESRD risk could improve postdonation risk assessment and counseling for kidney donors and allow early intervention for donors at increased risk.

To determine the association between renal function in the first 6 months postdonation and subsequent risk of ESRD in kidney donors.

This secondary analysis of a prospective national cohort uses a population-based registry of all living kidney donors in the United States between October 26, 1999, and January 1, 2018, with follow-up through December 31, 2018. All kidney donors who had donated in the date range and had serum creatinine measured at 6 months (±3 months) postdonation were included.

Renal function as measured by estimated glomerular filtration rate 6 months after donation (eGFR6).

End-stage renal disease, ascertained via linkage to Centers for Medicare & Medicaid Services data.

A total of 71 468 living kidney donors were included (of 109 065 total donors over this period). Their median (interquartile range) eGFR6 was 63 (54-74) mL/min/1.73 m2. Cumulative incidence of ESRD at 15 years postdonation ranged from 11.7 donors per 10 000 donors with eGFR6 values greater than 70 mL/min/1.73 m2 to 33.1 donors per 10 000 donors with eGFR6 values of 50 mL/min/1.73 m2 or less. Adjusting for age, race, sex, body mass index, and biological relationship, every 10 mL/min/1.73 m2 reduction in eGFR6 was associated with a 28% increased risk of ESRD (adjusted hazard ratio, 1.28 [95% CI, 1.06-1.54]; P = .009). The association between predonation eGFR and ESRD was not significant and was fully mediated by eGFR6 (adjusted hazard ratio, 1.00 [95% CI, 0.86-1.17]; P = .97). The postdonation eGFR value was a better marker of ESRD than eGFR decline after donation or the ratio of eGFR6 to predonation eGFR, as determined by the Akaike information criterion (in which a lower value indicates a better model fit; eGFR6, 1495.61; predonation eGFR - eGFR6, 1503.58; eGFR6 / predonation eGFR, 1502.30).

In this study, there was an independent association of eGFR6 with subsequent ESRD risk in living kidney donors, even after adjusting for predonation characteristics. The findings support measurement of early postdonation serum creatinine monitoring in living kidney donors, and the use of these data to help identify donors who might need more careful surveillance and early intervention.

Use of Radiomics for the Prediction of Local Control of Brain Metastases After Stereotactic Radiosurgery.

Neuro-Oncology

Local response prediction for brain metastases (BM) after stereotactic radiosurgery (SRS) is challenging, particularly for smaller BM, as existing criteria are based solely on unidimensional measurements. This investigation sought to determine whether radiomic features provide additional value to routinely available clinical and dosimetric variables to predict local recurrence following SRS.

408 BM in 87 patients treated with SRS were analyzed. A total of 440 radiomic features were extracted from the tumor core, and the peritumoral regions, using the baseline pre-treatment volumetric post-contrast T1 (T1c) and volumetric T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences. Local tumor progression was determined based on RANO-BM criteria, with a maximum axial diameter growth of >20% on the follow-up T1c indicating local failure. The top radiomic features were determined based on resampled Random Forest (RF) feature importance. An RF classifier was trained using each set of features and evaluated using the area under the receiver operating characteristic curve (AUC).

The addition of any one of the top ten radiomic features to the set of clinical features resulted in a statistically significant (p<0.001) increase in the AUC. An optimized combination of radiomic and clinical features resulted in a 19% higher resampled AUC (mean = 0.793, 95% C.I. = 0.792-0.795) than clinical features alone (0.669, 0.668-0.671).

The increase in AUC of the RF classifier, after incorporating radiomic features, suggests that quantitative characterization of tumor appearance on pretreatment T1c and FLAIR adds value to known clinical and dosimetric variables for predicting local failure.

The association of robotic lobectomy volume and nodal upstaging in non-small cell lung cancer.

Journal of Robotic Surgery

Robotic lung resection for lung cancer has gained popularity over the last 10 years. As with many surgical techniques, there are improvements in ou...

Neurologic and oncologic features of Erdheim-Chester disease: a 30-patient series.

Neuro-Oncology

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm characterized by recurrent alterations in the mitogen-activating protein kinase (MAPK) pathway. The existing literature about the neuro-oncological spectrum of ECD is limited.

We present retrospective clinical, radiographic, pathologic, molecular, and treatment data from 30 patients with ECD neurohistiocytic involvement treated at a tertiary center.

Median age was 52 (range: 7-77) years and 20 (67%) patients were male. Presenting symptoms included ataxia in 19 (63%), dysarthria in 14 (47%), diabetes insipidus in 12 (40%), cognitive impairment in 10 (33%), and bulbar affect in 9 (30%) patients. Neurosurgical biopsy specimens in 8 patients demonstrated varied morphologic findings often uncharacteristic of typical ECD lesions. Molecular analysis revealed mutations in BRAF (18 patients), MAP2K1 (5), RAS isoforms (2), and two fusions involving BRAF and ALK. Conventional therapies (corticosteroids, immunosuppresants, interferon-alpha [IFN-α], cytotoxic chemotherapy) led to partial radiographic response in 8/40 (20%) by MRI with no complete responses, partial metabolic response in 4/16 (25%) and complete metabolic response in 1/16 (6%) by FDG-PET scan. In comparison, targeted (kinase inhibitor) therapies yielded partial radiographic response in 10/27 (37%) and complete radiographic response in 14/27 (52%) by MRI, and partial metabolic response in 6/25 (24%) and complete metabolic response in 17/25 (68%) by FDG-PET scan.

These data highlight underrecognized symptomatology, heterogenous neuropathology, and robust responses to targeted therapies across the mutational spectrum in ECD patients with neurological involvement, particularly when conventional therapies have failed.

FYN tyrosine kinase, a downstream target of receptor tyrosine kinases, modulates anti-glioma immune responses.

Neuro-Oncology

High grade gliomas are aggressive and immunosuppressive brain tumors. Molecular mechanisms that regulate the inhibitory immune tumor microenvironment (TME) and glioma progression remain poorly understood. FYN tyrosine kinase is a downstream target of the oncogenic receptor tyrosine kinases pathway and is overexpressed in human gliomas. FYN's role in vivo in glioma growth remains unknown. We investigated whether FYN regulates glioma initiation, growth and invasion.

We evaluated the role of FYN using genetically engineered mouse glioma models (GEMM). We also generated FYN knockdown stem cells to induce gliomas in immune-competent and immune-deficient mice (NSG, CD8-/-, CD4-/-). We analyzed molecular mechanism by RNA-Seq and bioinformatics analysis. Flow cytometry was used to characterize immune cellular infiltrates in the FYN knockdown glioma TME.

We demonstrate that FYN knockdown in diverse immune-competent GEMMs of glioma reduced tumor progression and significantly increased survival. Gene ontologies (GOs) analysis of differentially expressed genes in wild type vs. FYN knockdown gliomas showed enrichment of GOs related to immune reactivity. However, in NSG, CD8-/- and CD4-/- immune-deficient mice, FYN knockdown gliomas failed to show differences in survival. These data suggest that the expression of FYN in glioma cells reduces anti-glioma immune activation. Examination of glioma immune infiltrates by flow-cytometry displayed reduction in the amount and activity of immune suppressive myeloid derived cells (MDSCs) in the FYN glioma TME.

Gliomas employ FYN mediated mechanisms to enhance immune-suppression and promote tumor progression. We propose that FYN inhibition within glioma cells could improve the efficacy of anti-glioma immunotherapies.

Association of Low-Dose Whole-Body Computed Tomography With Missed Injury Diagnoses and Radiation Exposure in Patients With Blunt Multiple Trauma.

JAMA Surgery

Initial whole-body computed tomography (WBCT) for screening patients with suspected blunt multiple trauma remains controversial and a source of excess radiation exposure.

To determine whether low-dose WBCT scanning using an iterative reconstruction algorithm does not increase the rate of missed injury diagnoses at the point of care compared with standard-dose WBCT with the benefit of less radiation exposure.

This quasi-experimental, prospective time-series cohort study recruited 1074 consecutive patients admitted for suspected blunt multiple trauma to an academic metropolitan trauma center in Germany from September 3, 2014, through July 26, 2015, for the standard-dose protocol, and from August 7, 2015, through August 20, 2016, for the low-dose protocol. Five hundred sixty-five patients with suspected blunt multiple trauma prospectively received standard-dose WBCT, followed by 509 patients who underwent low-dose WBCT. Confounding was controlled by segmented regression analysis and a secondary multivariate logistic regression model. Data were analyzed from January 16, 2017, through October 14, 2019.

Standard- or low-dose WBCT.

The primary outcome was the incidence of missed injury diagnoses at the point of care, using a synopsis of clinical, surgical, and radiological findings as an independent reference test. The secondary outcome was radiation exposure with either imaging strategy.

Of 1074 eligible patients, 971 (mean [SD] age, 52.7 [19.5] years; 649 men [66.8%]) completed the study. A total of 114 patients (11.7%) had multiple trauma, as defined by an Injury Severity Score of 16 or greater. The proportion of patients with any missed injury diagnosis at the point of care was 109 of 468 (23.3%) in the standard-dose and 107 of 503 (21.3%) in the low-dose WBCT groups (risk difference, -2.0% [95% CI, -7.3% to 3.2%]; unadjusted odds ratio, 0.89 [95% CI, 0.66-1.20]; P = .45). Adjustments for autocorrelation and multiple confounding variables did not alter the results. Radiation exposure, measured by the volume computed tomography dose index, was lowered from a median of 11.7 (interquartile range, 11.7-17.6) mGy in the standard-dose WBCT group to 5.9 (interquartile range, 5.9-8.8) mGy in the low-dose WBCT group (P < .001).

Low-dose WBCT using iterative image reconstruction does not appear to increase the risk of missed injury diagnoses at the point of care compared with standard-dose protocols while almost halving the exposure to diagnostic radiation.

Interventions and Operations 5 Years After Bariatric Surgery in a Cohort From the US National Patient-Centered Clinical Research Network Bariatric Study.

JAMA Surgery

Additional data comparing longer-term problems associated with various bariatric surgical procedures are needed for shared decision-making.

To compare the risks of intervention, operation, endoscopy, hospitalization, and mortality up to 5 years after 2 bariatric surgical procedures.

Adults who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between January 1, 2005, and September 30, 2015, within the National Patient-Centered Clinical Research Network. Data from 33 560 adults at 10 centers within 4 clinical data research networks were included in this cohort study. Information was extracted from electronic health records using a common data model and linked to insurance claims and mortality indices. Analyses were conducted from January 2018 through October 2019.

Bariatric surgical procedures.

The primary outcome was time until operation or intervention. Secondary outcomes included endoscopy, hospitalization, and mortality rates.

Of 33 560 adults, 18 056 (54%) underwent RYGB, and 15 504 (46%) underwent SG. The median (interquartile range) follow-up for operation or intervention was 3.4 (1.6-5.0) years for RYGB and 2.2 (0.9-3.6) years for SG. The overall mean (SD) patient age was 45.0 (11.5) years, and the overall mean (SD) patient body mass index was 49.1 (7.9). The cohort was composed predominantly of women (80%) and white individuals (66%), with 26% of Hispanic ethnicity. Operation or intervention was less likely for SG than for RYGB (hazard ratio, 0.72; 95% CI, 0.65-0.79; P < .001). The estimated, adjusted cumulative incidence rates of operation or intervention at 5 years were 8.94% (95% CI, 8.23%-9.65%) for SG and 12.27% (95% CI, 11.49%-13.05%) for RYGB. Hospitalization was less likely for SG than for RYGB (hazard ratio, 0.82; 95% CI, 0.78-0.87; P < .001), and the 5-year adjusted cumulative incidence rates were 32.79% (95% CI, 31.62%-33.94%) for SG and 38.33% (95% CI, 37.17%-39.46%) for RYGB. Endoscopy was less likely for SG than for RYGB (hazard ratio, 0.47; 95% CI, 0.43-0.52; P < .001), and the adjusted cumulative incidence rates at 5 years were 7.80% (95% CI, 7.15%-8.43%) for SG and 15.83% (95% CI, 14.94%-16.71%) for RYGB. There were no differences in all-cause mortality between SG and RYGB.

Interventions, operations, and hospitalizations were relatively common after bariatric surgical procedures and were more often associated with RYGB than SG.

ClinicalTrials.gov identifier: NCT02741674.