Prognostic value of plasma circulating tumor DNA fraction across four common cancer types: a real-world outcomes study.

BACKGROUND: Genomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable calculation of circulating tumor fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are tumor type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool. PATIENTS AND METHODS: This study utilized a cohort of patients in a nationwide de-identified clinico-genomic database with metastatic castration-resistant prostate cancer (mCRPC), metastatic breast cancer (mBC), advanced non-small-cell lung cancer (aNSCLC), or metastatic colorectal cancer (mCRC) undergoing liquid biopsy testing as part of routine care. TF was calculated based on single-nucleotide polymorphism aneuploidy across the genome. Clinical, disease, laboratory, and treatment data were captured from the electronic health record. Overall survival (OS) was evaluated by TF level while controlling for relevant covariables. RESULTS: A total of 1725 patients were included: 198 mCRPC, 402 mBC, 902 aNSCLC, and 223 mCRC. TF ≥10% was highly correlated with OS in univariable analyses for all cancer types: mCRPC [hazard ratio (HR) 3.3, 95% confidence interval (CI) 2.04-5.34, P < 0.001], mBC (HR 2.4, 95% CI 1.71-3.37, P < 0.001), aNSCLC (HR 1.68, 95% CI 1.34-2.1, P < 0.001), and mCRC (HR 2.11, 95% CI 1.39-3.2, P < 0.001). Multivariable assessments of TF had similar point estimates and CIs, suggesting a consistent and independent association with survival. Exploratory analysis showed that TF remained consistently prognostic across a wide range of cutpoints. CONCLUSIONS: Plasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical conversations around expected treatment outcomes. With further prospective validation, ctDNA TF could be incorporated into care paradigms to enable precision escalation and de-escalation of cancer therapy based on patient-level tumor biology.

I22: SAXS/WAXS beamline at Diamond Light Source - an overview of 10 years operation.

Beamline I22 at Diamond Light Source is dedicated to the study of soft-matter systems from both biological and materials science. The beamline can operate in the range 3.7 keV to 22 keV for transmission SAXS and 14 keV to 20 keV for microfocus SAXS with beam sizes of 240 µm × 60 µm [full width half-maximum (FWHM) horizontal (H) × vertical (V)] at the sample for the main beamline, and approximately 10 µm × 10 µm for the dedicated microfocusing platform. There is a versatile sample platform for accommodating a range of facilities and user-developed sample environments. The high brilliance of the insertion device source on I22 allows structural investigation of materials under extreme environments (for example, fluid flow at high pressures and temperatures). I22 provides reliable access to millisecond data acquisition timescales, essential to understanding kinetic processes such as protein folding or structural evolution in polymers and colloids.

Ultra-low oxygen, liquid sample cell for in situ synchrotron-based small-wide angle scattering (SAXS-WAXS).

Here, we report the design and successful implementation of an ultra-low oxygen sample cell for use on the SAXS-WAXS (small-wide angle x-ray scattering) beamline I22 at DIAMOND. The rigorous exclusion of oxygen is found to require double jacketing with purge gas throughout the entire system, pipework, pumps, and the sample cell itself. This particularly includes a "double-window" arrangement at the sample location to accommodate the very tight geometrical restrictions of the sample position. The in situ cell design also requires the additional complexity of heating the sample/solution and real-time electrochemical measurements. We demonstrate the successful implementation of this arrangement with real-time in situ characterization of an iron foil corrosion evolving under the "sweet-scale environment," very anoxic conditions common, in particular, commercial situations. The formation of iron carbonate, siderite, rather than iron oxide, indicates that our system is oxygen free down very low levels (<35 ppb at 80 °C).

The interstellar carbon budget and the role of carbon in dust and large molecules.

Published data on stellar composition show that carbon in the sun is substantially more abundant than in other stars. A carbon abundance of 225 carbon atoms per 10(6) hydrogen atoms is representative of galactic stars, whereas published values for the sun range from 350 to 470 carbon atoms per 10(6) hydrogen atoms. Other elements are also present in enhanced quantities in the solar system, consistent with suggestions that a supernova event was closely associated with the formation of the solar system. The overabundance of carbon in the solar system has many important implications, including new constraints on nucleosynthesis models for supernovae and substantial modification of the so-called "cosmic" composition normally adopted in discussions of galactic and interstellar abundances. A reduction in the galactic carbon budget, as suggested by the stellar composition data, strongly constrains the quantity of carbon that is available for the formation of interstellar dust, and some dust models now appear implausible because they require more carbon than is available.

An infrared spectral match between GEMS and interstellar grains.

Infrared spectral properties of silicate grains in interplanetary dust particles (IDPs) were compared with those of astronomical silicates. The approximately 10-micrometer silicon-oxygen stretch bands of IDPs containing enstatite (MgSiO3), forsterite (Mg2SiO4), and glass with embedded metal and sulfides (GEMS) exhibit fine structure and bandwidths similar to those of solar system comets and some pre-main sequence Herbig Ae/Be stars. Some GEMS exhibit a broad, featureless silicon-oxygen stretch band similar to those observed in interstellar molecular clouds and young stellar objects. These GEMS provide a spectral match to astronomical "amorphous" silicates, one of the fundamental building blocks from which the solar system is presumed to have formed.

Cytomegalic interneurons: a new abnormal cell type in severe pediatric cortical dysplasia.

A defining histopathologic feature of Taylor-type cortical dysplasia (CD) is the presence of cytomegalic neurons and balloon cells. Most cytomegalic neurons appear to be pyramidal-shaped and glutamatergic. The present study demonstrates the presence of cytomegalic GABAergic interneurons in a subset of pediatric patients with severe CD. Cortical tissue samples from children with mild, severe, and non-CD pathologies were examined using morphologic and electrophysiologic techniques. By using in vitro slices, cytomegalic cells with characteristics consistent with interneurons were found in 6 of 10 patients with severe CD. Biocytin labeling demonstrated that cytomegalic interneurons had more dendrites than normal-appearing interneurons. Whole-cell patch clamp recordings showed that cytomegalic interneurons had increased membrane capacitance and time constant compared with normal-appearing interneurons. They also displayed signs of cellular hyperexcitability, evidenced by increased firing rates, decreased action potential inactivation, and the occurrence of spontaneous membrane depolarizations. Single-cell reverse transcription-polymerase chain reaction and immunohistochemistry for GABAergic markers provided further evidence that these cells were probably cytomegalic interneurons. The pathophysiologic significance of GABAergic cytomegalic interneurons in severe CD tissue is unknown, but they could inhibit glutamatergic cytomegalic pyramidal neurons, or contribute to the synchronization of neuronal networks and the propagation of ictal activity in a subset of pediatric patients with severe CD.

Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly.

In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23), this study compared clinical, neuroimaging and pathologic features to discern potential mechanisms for suboptimal post-hemispherectomy developmental outcomes and structural pathogenesis. MRI measured affected and non-affected cerebral hemisphere volumes for HME and non-HME cases, including monozygotic twins where one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and white matter cell densities and sizes in HME and autopsy cases, including the non-affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was larger and the non-affected side smaller in HME compared with non-HME children. The affected HME side showed enlarged abnormal deep grey and white matter structures and/or T2-weighted hypointensity in the subcortical white matter in 75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias. Histopathological examination of the affected HME side revealed immature-appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of cases. Compared with autopsy cases, in HME children NeuN cell densities on the affected side were increased in the molecular layer and upper cortex (+244 to +18%), decreased in lower cortical layers (-35%) and increased in the white matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted white matter hypointensity correlated with the presence of immature-appearing neurons and PMG on histopathology, decreased NeuN cell densities in lower cortical layers and a positive history of infantile spasms. Post-surgery seizure control was associated with decreased NeuN densities in the molecular layer. In young children with HME and epilepsy, these findings indicate that there are bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly is a likely explanation for poorer post-surgery seizure control and cognitive outcomes. In addition, our findings support the hypothesis that HME pathogenesis probably involves somatic mutations that affect each developing cerebral hemisphere differently with more neurons than expected on the HME side.

The modular small-angle X-ray scattering data correction sequence.

Data correction is probably the least favourite activity amongst users experimenting with small-angle X-ray scattering: if it is not done sufficiently well, this may become evident only during the data analysis stage, necessitating the repetition of the data corrections from scratch. A recommended comprehensive sequence of elementary data correction steps is presented here to alleviate the difficulties associated with data correction, both in the laboratory and at the synchrotron. When applied in the proposed order to the raw signals, the resulting absolute scattering cross section will provide a high degree of accuracy for a very wide range of samples, with its values accompanied by uncertainty estimates. The method can be applied without modification to any pinhole-collimated instruments with photon-counting direct-detection area detectors.

Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus.

Changes in the expression of ion channels, contributing to altered neuronal excitability, are emerging as possible mechanisms in the development of certain human epilepsies. In previous immature rodent studies of experimental prolonged febrile seizures, isoform-specific changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCNs) correlated with long-lasting hippocampal hyperexcitability and enhanced seizure susceptibility. Prolonged early-life seizures commonly precede human temporal lobe epilepsy (TLE), suggesting that transcriptional dysregulation of HCNs might contribute to the epileptogenic process. Therefore, we determined whether HCN isoform expression was modified in hippocampi of individuals with TLE. HCN1 and HCN2 expression were measured using in situ hybridization and immunocytochemistry in hippocampi from three groups: TLE with hippocampal sclerosis (HS; n = 17), epileptic hippocampi without HS, or non-HS (NHS; n = 10), and autopsy material (n = 10). The results obtained in chronic human epilepsy were validated by examining hippocampi from the pilocarpine model of chronic TLE. In autopsy and most NHS hippocampi, HCN1 mRNA expression was substantial in pyramidal cell layers and lower in dentate gyrus granule cells (GCs). In contrast, HCN1 mRNA expression over the GC layer and in individual GCs from epileptic hippocampus was markedly increased once GC neuronal density was reduced by >50%. HCN1 mRNA changes were accompanied by enhanced immunoreactivity in the GC dendritic fields and more modest changes in HCN2 mRNA expression. Furthermore, similar robust and isoform-selective augmentation of HCN1 mRNA expression was evident also in the pilocarpine animal model of TLE. These findings indicate that the expression of HCN isoforms is dynamically regulated in human as well as in experimental hippocampal epilepsy. After experimental febrile seizures (i.e., early in the epileptogenic process), the preserved and augmented inhibition onto principal cells may lead to reduced HCN1 expression. In contrast, in chronic epileptic HS hippocampus studied here, the profound loss of interneuronal and principal cell populations and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might provoke a "compensatory" enhancement of HCN1 mRNA and protein expression.

Failure of inositol 1,4,5-trisphosphate to elicit or potentiate Ca2+ release from isolated skeletal muscle sarcoplasmic reticulum.

This study was conducted to resolve the conflicting reports regarding the ability of inositol 1,4,5-trisphosphate (IP3) to elicit the release of Ca2+ from isolated sarcoplasmic reticulum derived from skeletal muscle. Three different conditions were employed, one of which has been reported to produce an IP3 induced release of Ca2+. Sarcoplasmic reticulum vesicles with and without intact feet structures failed to respond to added IP3. In addition, IP3 had no effect on the Ca2+-induced release of Ca2+. These results suggest that, unlike other tissue, IP3 does not mobilize the release of Ca2+ from skeletal muscle sarcoplasmic reticulum. IP3 is therefore unlikely to be the physiological signal linking transverse-tubule depolarization with Ca2+ release from the sarcoplasmic reticulum.

Characterization of the oxygen probe pyrenebutyric acid in rabbit heart mitochondria.

The fluorescence of pyrenebutyric acid is quenched by oxygen and the quenching is a linear function of the oxygen concentration. In addition, pyrenebutyric acid has been shown to be readily taken up by the cell with a partition coefficient of approx. 200. Results are presented on the effect of pyrenebutyric acid on oxidative metabolism in rabbit heart mitochondria. 1. Pyrenebutyric acid is readily taken up by heart mitochondria: 0.843 +/- 0.087 nmol pyrenebutyric acid taken up by Mr/mg dried weight. 2. Pyrenebutyric acid does not alter the steady-state redox levels (State 1, 2, 4 or 5) of any member of the respiratory chain. 3. Pyrenebutyric acid does not alter the response of cytochrome b, cytochrome c or NADH in the State 4-3-4 transition induced by the addition of ADP. Thus pyrenebutyric acid would appear to be non-toxic to oxidative metabolism.

Comparison of body composition and bone mineral measurements from two DXA instruments in young men.

The purpose of this study was to compare body-composition and whole-body, lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle (WT) bone mineral measurements by using the Hologic QDR 1000W (DXAH) and the Lunar DPX-L (DXAL) dual-energy X-ray absorptiometry instruments. In addition, the ability of conversion equations to predict DXAH data from DXAL data were tested. Thirteen healthy young adult males (aged 22.2 +/- 3.6 y, 177.4 +/- 5.3 cm in height, and 72.7 +/- 9.6 kg in weight) were scanned on the same day by using DXAH and DXAL. Whereas measured body mass was not different (P > 0.05) between machines, whole-body fat mass [DXAH-DXAL (DXAdiff) = 1152 +/- 1395 g], percentage fat (DXAdiff = 1.5 +/- 1.7% of body mass), bone mineral density (BMD; DXAdiff = 0.016 +/- 0.023 g/cm2), and bone mineral content (BMC; DXAdiff = 316 +/- 50 g) were lower and whole-body fat-free soft tissue (FFST; DXAdiff = 1781 +/- 1859 g) was higher with DXAH than with DXAL. Lower fat mass (DXAdiff = 2145 +/- 855 g) and BMC (DXAdiff = 216 +/- 36 g) and higher FFST (DXAdiff = 1966 +/- 943 g) in the trunk were primarily responsible for the whole-body differences. Lower BMD and BMC values were found for LS (DXAdiff = 0.145 +/- 0.038 g/cm2 and 3 +/- 2 g, respectively), trochanter (DXAdiff = 0.100 +/- 0.044 g/cm2 and 1.7 +/- 1.0 g), and WT (DXAdiff = 0.195 +/- 0.061 g/cm2 and 1.93 +/- 0.51 g) with DXAH compared with DXAL. DXAH BMD of FN was also lower (DXAdiff = 0.141 +/- 0.032 g/cm2) than with DXAL. Only DXAH whole-body BMC and LS BMD were accurately predicted from DXAL with conversion equations. Predicted DXAH FN BMD was significantly lower than the actual DXAH value (P < or = 0.05), whereas the discrepancy between DXAH and DXAL actually increased for whole-body percentage fat and BMD (DXAdiff = 6.6 +/- 1.3% body mass and 0.020 +/- 0.025 g/cm2). In conclusion, lower whole-body fat mass, percentage fat, and BMC, and higher whole-body FFST with DXAH were due primarily to measurement differences in the trunk. Whereas conversion equations accurately predicted DXAH whole-body BMC and LS BMD from DXAL measurements in young adult males, they did not accurately predict DXAH, percentage fat, and BMD of the whole body and FN BMD.

Beneficial effect of initial warm crystalloid reperfusion in 6-hour lung preservation.

BACKGROUND: To achieve successful lung transplantation, it is essential to minimize reperfusion injury occurring as a result of metabolite accumulation during the preservation period or at the time of initial interaction of blood with constricted pulmonary vasculature. Initial reperfusion with warm crystalloid solution may be advantageous in preventing this injury. METHODS: This study was designed to evaluate the effect of low-potassium (4 mmol/L) dextran (1%) solution as the initial warming solution after 6 hours of hypothermic storage. In 23 New Zealand White rabbits the lungs were flushed with low-potassium dextran solution (10 degrees C, 40 ml/kg, 600 cm H2O), excised, inflated with room air, and stored in a low-potassium dextran solution (10 degrees C) for 6 hours. After storage, the lungs were divided into two groups. Group 1 (n = 8) was reperfused with warm low potassium dextran for 4 minutes, at 37 degrees C followed by blood reperfusion for 30 minutes at 37 degrees C. Group II (n = 15) was reperfused only with blood for 30 minutes at 37 C. The mean pulmonary vascular resistance measured during cold flush and prior to storage was similar in both groups (group I = 20.0 +/- 5.9 mm Hg.sec/ml, group II = 19.3 +/- 1.9 mm Hg.sec/ml). RESULTS: During reperfusion, only 4 of the 15 lungs in group II maintained an acceptable (< 80 mm Hg) mean pulmonary artery pressure; six failed immediately. All eight lungs in group I completed the 30-minute reperfusion (p < 0.005). The mean pulmonary artery pressure was significantly less, and effluent oxygen tension was significantly greater in group I during reperfusion. CONCLUSIONS: In this experimental model, initial warm reperfusion with low-potassium dextran ameliorated the deleterious effects of reperfusion, thus providing an environment to improve lung preservation.

Preservation of competent rabbit lung function after 30 hours of storage with a low-potassium dextran solution.

BACKGROUND: The goal of organ preservation is maintenance of physiologic functions during extended extracorporeal storage. METHODS: This study was designed to evaluate the efficacy of using low-potassium (4 mmol/L) dextran (1%) solution on lung function after 30 hours hypothermic (10 degrees C) storage and to compare this with lung function after no storage. With low-potassium dextran solution rabbit lungs were flushed (10 degrees C, 40 ml/kg, 60 cm H2O), excised, inflated (with room air), and either not stored (control; no preservation; n = 9) or stored in low-potassium dextran solution (10 degrees C) 30 hours (experimental group; n = 9). RESULTS: During the flush the infusion pressure and pulmonary vascular resistance for the two groups did not differ (17.56 +/- 1.3 versus 16.74 +/- 1.5 mm Hg/ml/sec). After either no preservation or after 30 hours of storage, the lungs were first reperfused with low-potassium dextran solution (37 degrees C) for 4 minutes and then with blood (37 degrees C) for 30 minutes at 100 ml/min. During the reperfusion period the mean pulmonary artery pressure and end-inspiratory airway pressure for the control and experimental groups did not differ. After reperfusion the wet and dry weights of the left lung were determined. The wet/dry ratio for the two groups did not differ (5.32 +/- 2.20 versus 4.70 +/- 2.70, respectively). CONCLUSIONS: These data suggest that cold flush, cold storage, and initial warm perfusion with low-potassium dextran solution crystalloid preserve lung function after 30 hours of storage.

Effects of allopurinol pretreatment with pulmonary flush on lung preservation.

This study was designed to test whether use of allopurinol could improve lung preservation after 6 hours of cold storage. Thirty-two rabbits were divided into four groups (n = 8 each group): (1) the control group received no flush or storage, (2) the EC group received Euro-Collins (EC) solution for both flush and storage, (3) the Allo-F group received Euro-Collins solution with allopurinol (1 mmol/L) for both flush and storage, and (4) the Allo-R group received Euro-Collins solution to which allopurinol (1 mmol/L) was added only to the reperfused blood. For groups 2 through 4, the lungs were flushed (40 ml/kg) in situ, excised, and then stored at 4 degrees C. After storage, the lungs were reperfused for 1 hour with an in vitro blood-perfused ventilated model. Lung function was measured during reperfusion with mean pulmonary arterial pressure, end-inspiratory airway pressure, and blood gas data. The lung wet/dry weight ratio was used to measure lung edema. The lungs in the EC group had a significant increase in mean pulmonary arterial pressure, airway pressure, and wet/dry weight ratio when compared with the control group. The mean pulmonary arterial pressure in either of the groups receiving allopurinol was consistently lower than that in the EC group. The airway pressure in the Allo-R group also significantly decreased compared with the EC group.(ABSTRACT TRUNCATED AT 250 WORDS)

Donor-heart evaluation by monitoring the left ventricular pressure-volume relationship: clinical observations.

Fourteen donor hearts were assessed by measurement of dopamine requirement, basic hemodynamic parameters (for example, systolic blood pressure), and the left ventricular pressure-volume relationship. The latter function was measured by a combination microtipped manometer/conductance catheter placed in the left ventricle through the ascending aorta. With an isoproterenol dose 24 hours after transplantation as the measure of cardiac performance, multiple linear regression analysis indicated that the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), ventriculoarterial coupling (Ea/Ees), and myocardial ischemic time were good predictors of posttransplantation cardiac performance. Dopamine requirement and basic hemodynamic data were not. Twelve implanted hearts showed an Ea/Ees of less than 1.0 and showed good early (less than 24 hours) and late function. Two hearts considered on clinical grounds to be unsuitable for transplantation showed an Ea/Ees of more than 1.0. The data suggest that measurement of the left ventricular pressure-volume relationship would appear to be a clinically useful predictor of donor-heart performance after transplantation.

Effect of race and resistance training status on the density of fat-free mass and percent fat estimates.

The impact of race and resistance training status on the assumed density of the fat-free mass (D(FFM)) and estimates of body fatness via hydrodensitometry (%Fat(D)) vs. a four-component model (density, water, mineral; %Fat(D,W,M)) were determined in 45 men: white controls (W; n = 15), black controls (B; n = 15), and resistance-trained blacks (B-RT; n = 15). Body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by dual-energy X-ray absorptiometry were used to estimate %Fat(D,W,M). D(FFM) was not different between B and W (or 1.1 g/ml); however, D(FFM) in B-RT was significantly lower (1.091 +/- 0.012 g/ml; P < 0.05). Therefore, %Fat(D) using the Siri equation was not different from %Fat(D,W,M) in W (17.5 +/- 5.0 vs. 18.3 +/- 5.4%) or B (14.9 +/- 5.6 vs. 15.7 +/- 5.7%) but significantly overestimated %Fat(D,W,M) in B-RT (14.0 +/- 5.9 vs. 10.4 +/- 6.0%; P < 0.05). The use of a race-specific equation (assuming D(FFM) = 1.113 g/ml) did not improve the agreement between %Fat(D) and %Fat(D,W,M), resulting in a significantly greater mean (+/-SD) discrepancy for B (1.7 +/- 1.8% fat) and B-RT (6.2 +/- 4.3% fat). Thus race per se does not affect D(FFM) or estimates of %Fat(D); however, B-RT have a D(FFM) lower than 1.1 g/ml, leading to an overestimation of %Fat(D).

Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients.

OBJECT: Cerebral hemispherectomy for intractable seizures has evolved over the past 50 years, and current operations focus less on brain resection and more on disconnection. In addition, cases involving cortical dysplasia and Rasmussen encephalitis are being identified and surgically treated in younger individuals. Few studies have been conducted to compare whether there are perioperative differences based on hemispherectomy technique and/or pathological substrate in pediatric patients with epilepsy. METHODS: In this study the authors compared, stratified by disease, anatomical (37 cases) and Rasmussen functional hemispherectomy (32 cases) with a new modified lateral hemispherotomy (46 cases). Pathological processes included cortical dysplasia (55 cases), Rasmussen encephalitis (21 cases), infarction/ischemia (27 cases), and other/miscellaneous (12 cases). The authors found differences in perioperative clinical factors based on operative technique and/or pathological substrate. In terms of technique, the lateral hemispherotomy was associated with the least intraoperative blood loss, shortest intensive care unit stay, and lowest complication rate. The anatomical hemispherectomy was associated with the longest hospital stay, delayed oral food intake, highest postsurgery fevers, and the highest incidence of shunt requirement. The functional hemispherectomy was associated with the highest reoperation rate for recurrent seizures (25%). In terms of pathology, patients with cortical dysplasia were the youngest at surgery, suffered the greatest amount of blood loss, and required the longest operative/anesthesia times compared with the other pathologically defined groups. Postoperative seizure control (range 0.5-2 years) was not statistically different according to technique or disease process and was similar to that in cases of pediatric temporal lobe epilepsy. CONCLUSIONS: The authors found differences in perioperative risks and hospital course but not postsurgery seizure control, which vary by hemispherectomy technique and/or disease process. The modified lateral hemispherotomy approach offers various advantages related to operative blood loss and reoperation compared with anatomical and functional hemispherectomies that are especially relevant in younger patients with cortical dysplasia and Rasmussen encephalitis with small and/or malformed ventricles.