A single-arm open-label pilot study of brief mindfulness meditation to control impulsivity in Parkinson's disease.

BACKGROUND: Impulse control disorders are detrimental neuropsychiatric symptoms of Parkinson's disease. Increased impulsivity is a predisposing factor for impulse control disorders and should therefore be controlled. Recently, mindfulness meditation as a non-drug therapy has been reported to be useful in improving neuropsychiatric symptoms, such as impulsivity. METHODS: We performed a prospective single-arm, open-label pilot trial to investigate the effectiveness of mindfulness meditation to control impulsivity in patients with Parkinson's disease (UMIN clinical trials registry: UMIN000037779). RESULTS: Twenty patients with Parkinson's disease were enrolled in an 8-week mindfulness meditation program. As a primary outcome, we investigated whether the score of the Barratt Impulsiveness Scale (BIS-11) was significantly reduced after the intervention. As an exploratory examination, functional connectivity changes were also assessed by resting-state functional magnetic resonance imaging. After the intervention, the BIS-11 score was decreased from 59.5 [55.6, 63.3] (mean [95% confidence interval]) to 55.2 [50.3, 60.1] (ΔBIS-11: -4.2, [-7.5, -0.9]). Functional connectivity was increased in the default mode network (DMN) at a cluster including the precuneus, posterior cingulate gyrus, and left posterior lobe (false discovery rate-adjusted p [FDR-p] = 0.046) and in the right frontoparietal network (FPN) at the medial frontal lobe (FDR-p = 0.039). CONCLUSIONS: This open-label, single-arm pilot study provided preliminary data for mindfulness meditation to control the impulsivity of patients with PD. A brief mindfulness meditation program may be effective in controlling impulsivity in PD and may change the functional connectivity of the DMN and right FPN.

Technical Background for 4D Flow MR Imaging.

Recently, the hemodynamic assessments with 3D cine phase-contrast (PC) MRI (4D flow MRI) have attracted considerable attention from clinicians. Unlike 2D cine PC MRI, the technique allows for cardiac phase-resolved data acquisitions of flow velocity vectors within the entire FOV during a clinically viable period. Thus, the method has enabled retrospective flowmetry in the spatial and temporal axes, which are essential to derive hemodynamic parameters related to vascular homeostasis and those to the progression of the pathologies. Accelerations in imaging are critical for this technology to be clinically viable; however, a high SNR or velocity-to-noise ratio (VNR) is also vital for accurate flow measurements. In this chapter, the technologies enabling this difficult balance are discussed.

Cognitive functions relating to aberrant interactions between task-positive and task-negative networks: Resting fMRI study of patients with schizophrenia.

Brain functional connectivity in the resting-state represents intrinsic functional states and correlates with cognitive performance. In patients with schizophrenia, reports on the relationships between forms of functional disconnectivity in local areas and cognitive disability have used resting-state functional magnetic resonance imaging data. Meanwhile, cognitive deficits in relation to inter-network forms of functional connectivity on a large scale are not well understood. This study examines cognitive functions in relation to the number of resting-state inter-network forms of functional connectivity focusing on task-positive networks (fronto-parietal network [FPN] and cingulo-opercular network [CON]) and task-negative network (default mode network [DMN]). We compare patients with schizophrenia (SCH group) and healthy controls (HC group). We conducted a functional network analysis by applying graph theory and evaluated cognitive functions using the Brief Assessment of Cognition in Schizophrenia. The number of forms of functional connectivity between FPN and DMN and between CON and DMN were significantly higher in SCH group than in HC group, and those in SCH group were also weakly correlated with their attention scores. It is suggested that fewer than typical functional segregations between task-positive and task-negative networks in SCH group relate to inefficient distribution of cognitive resources and low attentional abilities.

The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events.

OBJECTIVES: Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs. METHODS: We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors. RESULTS: Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4-NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4-NE); p = 0.031]. CONCLUSION: The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

Subsequent systemic therapy for non-small cell lung cancer patients with immune checkpoint inhibitor-related interstitial lung disease.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD. METHODS: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017. RESULTS: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]. CONCLUSIONS: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.

Computed tomography findings for predicting the future occurrence of pancreatic cancer: value of pancreatic volumetry.

BACKGROUND: The features of pancreatic parenchyma that tend to progress towards pancreatic cancer (PC) are unknown. We performed volumetry of the pancreas in PC patients using computed tomography (CT) scans acquired before detection of PC, and investigated whether CT findings of pancreatic parenchyma could predict the future occurrence of PC. METHODS: Between April 2009 and March 2017, a total of 3769 patients underwent abdominal contrast-enhanced CT, the scans of which were archived as digital images. Among them, 15 PC patients underwent abdominal CT 6-120 months before diagnosis of PC. This retrospective study compared the 15 PC patients (PC group) with 15 propensity score-matched subjects without PC (non-PC group). Pancreatic volumetry and radiological findings were compared between the two groups. RESULTS: There were significant differences between the PC and non-PC groups in the volume of the main pancreatic duct (MPD) plus any cystic lesion (P = 0.007), volume of the MPD plus any cystic lesion/body surface area (BSA; P = 0.009), MPD diameter (P = 0.011), and MPD diameter/BSA (P = 0.013). Univariate analysis revealed volume of MPD plus any cystic lesion/BSA ≥ 0.53 mL/m2 (odds ratio [OR] 38.50, P = 0.002), volume of pancreatic parenchyma/BSA < 27.0 mL/m2 (OR 12.25, P = 0.030), and MPD diameter/BSA ≥ 1.0 mm/m2 (OR 13.00, P = 0.006) as significant risk factors for PC. CONCLUSIONS: Quantification of the volume of MPD plus any cystic lesion/BSA, volume of pancreatic parenchyma/BSA, and MPD diameter/BSA on pre-diagnosis CT were useful for predicting the future occurrence of PC.

Regional abnormality of functional connectivity is associated with clinical manifestations in individuals with intractable focal epilepsy.

We explored regional functional connectivity alterations in intractable focal epilepsy brains using resting-state functional MRI. Distributions of the network parameters (corresponding to degree and eigenvector centrality) measured at each brain region for all 25 patients were significantly different from age- and sex-matched control data that were estimated by a healthy control dataset (n = 582, 18-84 years old). The number of abnormal regions whose parameters exceeded the mean + 2 SD of age- and sex-matched data for each patient were associated with various clinical parameters such as the duration of illness and seizure severity. Furthermore, abnormal regions for each patient tended to have functional connections with each other (mean ± SD = 58.6 ± 20.2%), the magnitude of which was negatively related to the quality of life. The abnormal regions distributed within the default mode network with significantly higher probability (p < 0.05) in 7 of 25 patients. We consider that the detection of abnormal regions by functional connectivity analysis using a large number of control datasets is useful for the numerical assessment of each patient's clinical conditions, although further study is necessary to elucidate etiology-specific abnormalities.

Haemodynamics in a patient-specific intracranial aneurysm according to experimental and numerical approaches: A comparison of PIV, CFD and PC-MRI.

BACKGROUND: The haemodynamics determined by different approaches for studying fluid dynamics - i.e. computational fluid dynamics (CFD), particle image velocimetry (PIV), and phase-contrast magnetic resonance imaging (PC-MRI) - have rarely been thoroughly compared; nor have the factors that affect accuracy and precision in each method. As each method has its own advantages and limitations, this knowledge is important for future studies to be able to achieve valid analyses of fluid flows. OBJECTIVE: To gauge the capacity of these methods for analysing aneurysmal flows, we compared the haemodynamic behaviours determined by each method within a patient-specific aneurysm model. METHODS: An in vitro silicone aneurysm model was fabricated for PIV and PC-MRI, and an in silico aneurysm model with the same geometry was reconstructed for CFD. With the same fluid model prepared numerically and physically, CFD, PIV and PC-MRI were performed to study aneurysmal haemodynamics. RESULTS: 2D velocity vectors and magnitudes show good agreement between PIV and CFD, and 3D flow patterns show good similarity between PC-MRI and CFD. CONCLUSIONS: These findings give confidence to future haemodynamic studies using CFD technology. For the first time, the morphological inconsistency between the PCMRI model and others is found to affect the measurement of local flow patterns.

Detection of gastric slow oscillatory contraction using parasagittal cine MR images: Comparison with simultaneously measured electrogastrogram.

PURPOSE: To determine if parasagittal gastric cine magnetic resonance imaging (MRI) is able to measure gastric oscillatory contractions around 0.05 Hz and to determine its relationship with electrical activity as measured by electrogastrography (EGG). METHODS: Assessment of the gastric motility is important for the research of the enteric nervous system and for the diagnosis of functional gastric disorders. Electrogastrography is a non-invasive method that can measure gastric oscillatory electrical activity around 0.05 Hz (slow wave) using electrodes on the abdominal skin, but its sensitivity and specificity of the slow wave detection is limited. We used parasagittal gastric cine MRI around the angular incisure to measure gastric oscillatory contraction around 0.05 Hz in 24 healthy volunteers. Cine MRI was acquired with time resolution of 1 s for 10 min while freely breathing participants were lying on the bed. The gastric area of the cross section was measured for each MR image and assessed its change over time. The results were compared with those for simultaneously recorded EGG. RESULTS: The main frequency of the gastric area change for each participant ranged from 0.041 to 0.059 Hz (mean ± S.D. = 0.049 ± 0.004), which corresponds to the gastric slow wave frequency (mean ± S.D. = 0.049 ± 0.004) as measured by EGG (p = 7.9585 × 10 -8, Kendall 's tau test). Cross correlation analysis showed that 22 of 24 participants' gastric area changes were significantly (p < 0.05) related to the EGG waveforms. Displacement of the stomach due to respiration did not affect gastric area measurements. CONCLUSIONS: Parasagittal cine MRI is correlated with EGG recordings and able to detect and quantifying gastric motility abnormalities.

Evaluation of magnetic resonance angiography as a possible alternative to rotational angiography or computed tomography angiography for assessing cerebrovascular computational fluid dynamics.

The aim of this study was to conduct a flow experiment using a cerebrovascular phantom and investigate whether magnetic resonance angiography (MRA) could replace three-dimensional rotational angiography (RA) and computed tomography angiography (CTA) to construct vascular models for computational fluid dynamics (CFD). We performed MRA and 3D cine phase-contrast (PC) MR imaging with a silicone cerebrovascular phantom of an internal carotid artery-posterior communicating artery aneurysm with blood-mimicking fluid, and controlled flow with a flowmeter. We also obtained RA and CTA data for the phantom. Four analysts constructed vascular models based on the three different modalities. These 12 constructed models used flow information based on 3D cine PC MR imaging for CFD. We compared RA-, CTA-, MRA-based CFD results using the micro-CT-based CFD result as the criterion standard to investigate whether MRA-based CFD was not inferior to RA- or CTA-based CFD. We also analyzed the inter-analyst variability. Wall shear stress (WSS) distributions and streamlines of RA- or MRA-based CFD and those of micro-CT-based CFD were similar, but the vascular models and WSS values were different. Accuracy in measurements of blood vessel diameter, cross-sectional maximum velocity, and spatially averaged WSS was the highest for RA-based CFD, followed by MRA-based and CTA-based CFD using micro-CT-based CFD result as the reference. Except maximum velocity from CTA, all other parameters had good inter-analyst agreement using different modalities. The results demonstrated that non-invasive MRA can be used for cerebrovascular CFD models with good inter-analyst agreements.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography in patients with small hepatocellular carcinoma treated by radiofrequency ablation.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) uptake in hepatocellular carcinoma (HCC) is significantly associated with early recurrence and survival after curative surgical resection. However, there are no reports regarding the relationship between 18F-FDG uptake and outcomes after radiofrequency ablation (RFA). A prospective cohort study was conducted to evaluate the prognostic value of 18F-FDG positron emission tomography (PET) in HCC patients after RFA. METHODS: A total of 121 consecutive patients with primary HCC (≤3 tumors, of diameter ≤ 3 cm) without vascular invasion on imaging were examined by 18F-FDG-PET computed tomography prior to RFA. An HCC with a component of 18F-FDG uptake visibly stronger than that of surrounding liver was defined as 18F-FDG-PET positive. RESULTS: The median follow-up period was 1267 days. There were 110 18F-FDG-PET negative and 11 positive tumors. The cumulative 1-year recurrence rates in the 18F-FDG negative and positive groups were 30 and 64% (P = 0.017), respectively, and cumulative 1-year metastatic recurrence rates were 6 and 36% (P < 0.001), respectively. The cumulative 5-year survival rates were 88 and 22% (P < 0.001), respectively. Multivariate analysis revealed 18F-FDG-PET positivity and tumor size as independent factors related to metastatic recurrence and survival after RFA. CONCLUSIONS: 18F-FDG-PET positivity was significantly associated with outcomes after RFA. RFA should not be readily selected as the first-line treatment for small HCC that includes a component of visually strong 18F-FDG uptake.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Increased large-scale inter-network connectivity in relation to impulsivity in Parkinson's disease.

Impulsivity is a neuropsychiatric feature of Parkinson's disease (PD). We investigated the pathophysiology of impulsivity in PD using resting-state functional magnetic resonance imaging (rs-fMRI). We investigated 45 patients with idiopathic PD and 21 healthy controls. Based on Barratt Impulsiveness Scale (BIS-11) score, PD patients were classified as higher (PD-HI) or lower impulsivity (PD-LI). Functional connectivity (FC) between various large-scale brain networks were analysed using the CONN toolbox. FC between the right frontoparietal network (FPN) and medial visual network (MVN) was significantly higher in PD-HI patients than PD-LI patients (false discovery rate [FDR]-adjusted p = 0.0315). FC between the right FPN and MVN had a significant positive correlation with total BIS-11 score (FDR-adjusted p = 0.010) and the attentional impulsivity (FDR-adjusted p = 0.046) and non-planning impulsivity subscale scores (FDR-adjusted p = 0.018). On the other hand, motor impulsivity subscale score had a significant negative correlation with the FC between the default-mode and salience networks (right supramarginal gyrus, FDR-adjusted p = 0.018; anterior cingulate cortex, FDR-adjusted p = 0.027); this trend was observed in healthy controls. The attentional and non-planning impulsivity, regarded as 'cognitive' impulsivity, may be associated with dysfunction in integration of perceptual information and flexible cognitive control in PD.

Prognostic significance of the radiologic features of pneumonitis induced by anti-PD-1 therapy.

BACKGROUND: Interstitial lung disease (ILD) induced by anti-programmed-cell death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) is potentially life-threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune-related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti-PD-1/PD-L1 therapies, the association between radiologic features and clinical outcomes remains unclear. METHODS: Patients with advanced non-small-cell lung cancer who were treated with 1st to 3rd line anti-PD-1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD. RESULTS: A total of 231 patients who received anti-PD-1 therapy were enrolled. Thirty-one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2-NE) versus not reached (95% CI: 13.2-NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival. CONCLUSIONS: This study demonstrated that patients who developed GGO exhibited worse outcomes among non-small-cell lung cancer patients receiving anti-PD-1 therapies.

Optimal Plane Selection for Measuring Post-prandial Blood Flow Increase within the Superior Mesenteric Artery: Analysis Using 4D Flow and Computational Fluid Dynamics.

PURPOSE: 2D cine phase contrast (PC)-MRI is a standard velocimetry for the superior mesenteric artery (SMA); however, the optimal localization of the measurement plane has never been fully discussed previously. The purpose of this Institutional Review Board approved prospective and single arm study is to test whether flow velocimetry of the SMA with combined use of 2D cine PC-MRI and meal challenge is dependent on the localizations of the measurement planes and to seek optimal section for velocimetry. METHODS: Seven healthy volunteers underwent cardiac phase resolved ECG gated 2D cine PC-MRI pre- and 30 min post-meal challenge at three measurement planes: proximal, curved mid section and distal straight section of the SMA at 3T. 4D Flow using 3D cine PC-MRI with vastly undersampled isotropic projection imaging (PC VIPR) was also performed right after 2D cine PC-MRI to delineate the flow dynamics within the SMA using streamline analysis. Two radiologists measured flow velocities, and rated the appearances of the abnormal flow in the SMA on streamlines derived from the 4D Flow and the computational fluid dynamics (CFD). RESULTS: 2D cine PC-MRI measured increased temporally averaged flow velocity (mm/s) after the meal challenge only in the proximal (129.3 vs. 97.8, P = 0.0313) and distal section (166.9 vs. 96.2, P = 0.0313), not in the curved mid section (113.1 vs. 85.5, P = 0.0625). The average velocities were highest and their standard errors (8.5-26.5) were smallest at the distal straight section both before and after the meal challenge as compared with other sections. The streamline analysis depicted more frequent appearances of vertical or helical flow in the curved mid section both on 4D Flow and CFD (κ: 0.27-0.68). CONCLUSION: SMA velocimetry with 2D cine PC-MRI was dependent on the localization of the measurement planes. Distal straight section, not in the curved mid section is recommended for MR velocimetry.

Assessing the Risk of Intracranial Aneurysm Rupture Using Morphological and Hemodynamic Biomarkers Evaluated from Magnetic Resonance Fluid Dynamics and Computational Fluid Dynamics.

PURPOSE: Evaluate in vivo hemodynamic and morphological biomarkers of intracranial aneurysms, using magnetic resonance fluid dynamics (MRFD) and MR-based patient specific computational fluid dynamics (CFD) in order to assess the risk of rupture. METHODS: Forty-eight intracranial aneurysms (10 ruptured, 38 unruptured) were scrutinized for six morphological and 10 hemodynamic biomarkers. Morphological biomarkers were calculated based on 3D time-of-flight magnetic resonance angiography (3D TOF MRA) in MRFD analysis. Hemodynamic biomarkers were assessed using both MRFD and CFD analyses. MRFD was performed using 3D TOF MRA and 3D cine phase-contrast magnetic resonance imaging (3D cine PC MRI). CFD was performed utilizing patient specific inflow-outflow boundary conditions derived from 3D cine PC MRI. Univariate analysis was carried out to identify statistically significant biomarkers for aneurysm rupture and receiver operating characteristic (ROC) analysis was performed for the significant biomarkers. Binary logistic regression was performed to identify independent predictive biomarkers. RESULTS: Morphological biomarker analysis revealed that aneurysm size [P = 0.021], volume [P = 0.035] and size ratio [P = 0.039] were statistically significantly different between the two groups. In hemodynamic biomarker analysis, MRFD results indicated that ruptured aneurysms had higher oscillatory shear index (OSI) [OSI.max, P = 0.037] and higher relative residence time (RRT) [RRT.ave, P = 0.035] compared with unruptured aneurysms. Correspondingly CFD analysis demonstrated significant differences for both average and maximum OSI [OSI.ave, P = 0.008; OSI.max, P = 0.01] and maximum RRT [RRT.max, P = 0.045]. ROC analysis revealed AUC values greater than 0.7 for all significant biomarkers. Aneurysm volume [AUC, 0.718; 95% CI, 0.491-0.946] and average OSI obtained from CFD [AUC, 0.774; 95% CI, 0.586-0.961] were retained in the respective logistic regression models. CONCLUSION: Both morphological and hemodynamic biomarkers have significant influence on intracranial aneurysm rupture. Aneurysm size, volume, size ratio, OSI and RRT could be potential biomarkers to assess aneurysm rupture risk.

Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasonography for Early Diagnosis of Small Pancreatic Cancer.

This study aimed to assess whether contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), compared to multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI), is useful for early diagnosis of small pancreatic cancer (PC). Between March 2010 and June 2018, all three imaging modalities and surgery were performed for patients with a pancreatic solid lesion measuring ≤20 mm; diagnostic ability was compared among modalities. Fifty-one of 60 patients were diagnosed with PC (PC size in 41 patients: 11-20 mm; 10 patients: ≤10 mm). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (11-20 mm) detection were 95%/83%/94%, 78%/83%/79%, and 73%/33%/68%, respectively. The diagnostic ability of CH-EUS was significantly superior compared with MDCT and MRI (p = 0.002 and p = 0.007, respectively). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (≤10 mm) detection were 70%/100%/77%, 20%/100%/38%, and 50%/100%/62%, respectively. The diagnostic ability of CH-EUS tended to be superior to that of MDCT (p = 0.025). The sensitivity of MDCT for PC (≤10 mm) detection was significantly lower than that for PC (11-20 mm) detection (20% vs. 78%; p = 0.001). CH-EUS, compared to MDCT and MRI, is useful for diagnosing small PCs.

Diffusion-weighted MRI predicts the histologic response for neoadjuvant therapy in patients with pancreatic cancer: a prospective study (DIFFERENT trial).

PURPOSE: Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS: We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS: Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P < 0.001/< 0.0001). The post-treatment cutoff value of ADC at the site of vascular contact for discriminating histological response of tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.42 × 10-3 mm2/s. It predicts R0 with 88% sensitivity, 50% specificity, and 61% accuracy. For histological response, the post-treatment whole-tumor ADC cutoff value for discriminating between tumor destruction of ≤ 50% and tumor destruction of > 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS: Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.

Efficacy of EGFR-TKIs with or without upfront brain radiotherapy for EGFR-mutant NSCLC patients with central nervous system metastases.

BACKGROUND: Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR-mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR-TKIs in patients with EGFR-mutant NSCLC with newly diagnosed brain metastases. METHODS: We retrospectively analyzed the data of EGFR-mutant NSCLC patients with CNS metastases who received EGFR-TKIs as a first-line therapy. RESULTS: A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR-TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3-9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1-30.1). The overall response rate of the CNS was 37%. The median CNS progression-free survival (PFS) was 13.2 months (95% CI: 10.0-16.2). Brain radiotherapy prior to EGFR-TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS-PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. CONCLUSION: EGFR-TKI showed a favorable effect for EGFR-mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS-PFS were observed with upfront brain radiotherapy.