Citations

Abstract Background: The GALAD score is a serum biomarker–based model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC. Methods: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed. Results: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93–97], which was higher than the AUC of ultrasound (0.82, P <0.01). At a cutoff of −0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88–0.96; cutoff −1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85–0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96–0.99; cutoff −0.18, sensitivity 95%, specificity 91%). Conclusions: The performance of the GALAD score was superior to ultrasound for HCC detection. The GALADUS score further enhanced the performance of the GALAD score. Impact: The GALAD score was validated in the United States.

Summary Cardiac surgery has been shown to be associated with increased risk of acute ischemic stroke. This report presents a case of a successful mechanical embolectomy procedure to treat a patient for an acute ischemic stroke, which was caused by the cardiac embolization of a ‘foreign body’ containing debris following a redo sternotomy procedure for mitral valve replacement and tricuspid valve annuloplasty.

Background: Flow diverters (FD) are increasingly used in the treatment of intracranial aneurysms. The risk of distal thromboembolic complications with FD is high, even in patients treated with dual antiplatelet therapy. The aim of the study was to understand the downstream vascular wall changes, by measuring the pulse wave velocity and vascular contractility following flow diverter treatment in a rabbit model. Methods: FD (Pipeline Embolic Device, Medtronic) were implanted in normal rabbits and sham-operated aorta were used as controls (n=5 for each group). Pulse wave imaging with ultra-fast ultrasound at 1600 frames per second (Vantage, Verasonics, Inc.) was performed in the vessel wall distal to FD, prior to device implantation and at 8 weeks follow up to measure the pulse wave propagation. Force contraction studies were conducted in the aortic rings using organ bath to assess the vascular functions. Results: The difference in pulse wave velocity (PWV) in the follow-up compared to pre-implantation was significantly higher (p=0.03,Fig 1A) in the distal vessels compared to sham controls (mean difference of PWV was 1.18 m/s and -0.37m/s, respectively as shown in Fig 1B). Conversely, the distal aortic segments to FD exhibited 55% increase in the level of vascular contractility compared to that of proximal segments (p=0.002). There is a significant positive correlation between mean PWV and mean vascular contractility. Conclusion: Our study found changes in the PWV after implantation of the FD, which correlated with vascular contractility. These results could explain vascular wall changes downstream following FD implantation.

Introduction: The composition of acute ischemic stroke (AIS) blood clots can impact their successful removal via endovascular therapy. Identification of the clot composition prior to endovascular treatment may influence the optimal treatment strategy. In this study, we aimed to investigate the relationship between the Hounsfield Unit intensity on CT and machine-learned characterization of clot composition. Methods: Prior to endovascular treatment, each patient had a non-contrast CT performed. Histopathological analysis of the clots was performed and clot composition was quantified via standard thresholding techniques using Adobe Photoshop. In addition, following representative cell labeling by an expert pathologist, image segmentation algorithms (Orbital Image Analysis, Actelion Ltd.) were trained on each case to quantify composition by cell type. The clots were categorized into 3 groups: red blood cell (RBC) dominant (>50%), RBC proportion equal to fibrin and fibrin dominant (>50%). Correlations between clot composition and Hounsfield Units (HU) density on CT were assessed. A positive Hyperdense Artery Sign was defined as ≥50 HU. Results: Twenty patients were included in the study. There was a significant correlation between clots quantified using Adobe Photoshop Image-Pro and Orbit image analysis ( ρ = 0.837, p < 0.001). A significant relationship was found between clot composition and the presence of a HAS sign, ( X 2 (2) = 6.496, p = 0.039). There is a significant positive correlation between percentage of RBC in the clot and the presence of a HAS sign ( ρ = 0.632, p = 0.002**). There is also a significant positive correlation between the presence of fibrin-rich and the absence of a HAS sign ( ρ = 0.600, p = 0.004**). Conclusion: Machine learning software can accurately quantify AIS clot composition. The Hounsfield unit density of an AIS clot on a non-contrast CT correlates with the composition of the clot. Measuring the HU of the clot on CT prior to endovascular intervention may inform the clinician of the clot type and help to determine the most appropriate treatment strategy for that clot.

Abstract Background: Endometrioid carcinoma (EC) and clear cell carcinoma (CC) histotypes of epithelial ovarian cancer are understudied compared with the more common high-grade serous carcinomas (HGSC). We therefore sought to characterize EC and CC transcriptomes in relation to HGSC. Methods: Following bioinformatics processing and gene abundance normalization, differential expression analysis of RNA sequence data collected on fresh-frozen tumors was completed with nonparametric statistical analysis methods (55 ECs, 19 CCs, 112 HGSCs). Association of gene expression with progression-free survival (PFS) was completed with Cox proportional hazards models. Eight additional multi-histotype expression array datasets (N = 852 patients) were used for replication. Results: In the discovery set, tumors generally clustered together by histotype. Thirty-two protein-coding genes were differentially expressed across histotype (P &lt; 1 × 10−10) and showed similar associations in replication datasets, including MAP2K6, KIAA1324, CDH1, ENTPD5, LAMB1, and DRAM1. Nine genes associated with PFS (P &lt; 0.0001) showed similar associations in replication datasets. In particular, we observed shorter PFS time for CC and EC patients with high gene expression for CCNB2, CORO2A, CSNK1G1, FRMD8, LIN54, LINC00664, PDK1, and PEX6, whereas, the converse was observed for HGSC patients. Conclusions: The results suggest important histotype differences that may aid in the development of treatment options, particularly those for patients with EC or CC. Impact: We present replicated findings on transcriptomic differences and how they relate to clinical outcome for two of the rarer ovarian cancer histotypes of EC and CC, along with comparison with the common histotype of HGSC. Cancer Epidemiol Biomarkers Prev; 27(9); 1101–9. ©2018 AACR.

Abstract1q21 gain is a common cytogenetic abnormality featuring high‐risk multiple myeloma (HRMM). However, the molecular mechanism underlying the adverse prognostic effect of 1q21 gain remains largely unclear. Here, we report that ARNT/HIF‐1β, a 1q21 gene, is highly expressed in HRMM and induced by microenvironmental hypoxia, which confers drug resistance and correlates with inferior outcome. Analysis of the gene expression profile database revealed that ARNT expression was upregulated in MM and increased with disease progression or in HRMM subtypes (particularly 1q21 gain), while correlated to shorter overall survival. In a cohort of 40 MM patients, qPCR further validated that ARNT expression was higher in MM patients than normal donors. MM cells carrying 1q21 gain or acquired drug resistance displayed a robust increase in HIF‐1β protein level. Hypoxia induced HIF‐1β expression via a NF‐κB‐dependent process. Notably, HIF‐1β overexpression impaired bortezomib sensitivity, whereas shRNA knockdown of ARNT reversed hypoxia‐mediated drug resistance. Together, these findings suggest that ARNT/HIF‐1β might represent a novel biomarker for risk stratification and prognosis of HRMM patients, as well as a potential therapeutic target for overcoming 1q21 gain‐ or microenvironment‐mediated and acquired drug resistance in MM.

AbstractIntroductionTo evaluate the outcomes of video‐assisted thoracoscopic surgery (VATS) during transvenous lead extractions (TLEs).Methods and resultsNinety‐one high‐risk patients who underwent TLE in the operating room from January 1, 2015, to March 31, 2017, were included in the study. Of these, 9 patients underwent VATS during TLE. Their clinical characteristics, indications for lead extraction, and complications associated with TLE in the 9 patients who had VATS were compared with those for the 82 patients who did not have VATS. The mean (SD) age of the study patients was 61 (17) years (64.8% were male). The lead dwell time, number of leads extracted, and clinical comorbidities were similar between the 2 groups. Superior vena cava (SVC) tear occurred in 2 of the 9 patients in VATS group and in 1 of the 82 in the non‐VATS group (22.2% vs. 1.2%, P = 0.03). Of the 2 patients in the VATS group who had SVC tears, in 1 the tear was visualized immediately and there was no hemodynamic compromise. In the other patient, the SVC tear was within the pericardium; the blood pressure recovered quickly after sternotomy and repair. Both patients had complete lead extraction and survived hospitalization. The patient in the non‐VATS group who had an SVC tear had a successful repair but died of postoperative complications.ConclusionsUtilization of VATS to facilitate TLE is beneficial for early recognition of SVC tear and timely surgical repair in select high‐risk patients.

SummaryBackgroundHepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.MethodsThis was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.ResultsApproximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).ConclusionsAnti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.