Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic lymphohistiocytosis (HLH) has a grave prognosis, little is known about the natural course of the disease. Patients who showed the clinical features of HLH as well as tissue-proven hemophagocytosis when seen at Asan Medical Center between 1999 and 2010 were included in this analysis. Patients with proven lymphoma were excluded. The median age of our 23 study patients was 49 years. Epstein-Barr virus was suspected to have caused HS in 16 (70%) patients and hepatitis A virus in one patient. Twenty-two patients were treated, 13 according to the HLH protocol and nine using immunosuppressive agents such as corticosteroid and/or cyclosporine. Five patients undertook allogeneic hematopoietic cell transplantation (HCT) during their treatment-dependent relapse (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41 days among those patients who died. The serum fibrinogen level ≥166 mg/dL determined at the initial visit was significantly associated with the survival time according to univariate analysis. The low histiocyte proportion in bone marrow and early initiation of treatment tended to correlate with a favorable outcome. On multivariate analysis, serum fibrinogen ≥166 mg/dL (hazard ratio, 0.175, P = 0.018) was an independent clinical factor for determining the patient survival time. Despite appropriate patient management, the outcome of HS featuring HLH was grave. The serum fibrinogen level at the initial presentation was significant, and selected patients obtained some benefit from allogeneic HCT.

Introduction: There are relatively few studies that compare the use of transrectal ultrasound (TRUS) to magnetic resonance imaging (MRI) to estimate the prostate volume. In this study, we compared the prostate volumes measured with MRI and TRUS with a surgical specimen volume. Patients and Methods: Seventy-three patients underwent TRUS examination of the prostate prior to radical prostatectomy. All specimens were weighed and measured when freshly excised. The corresponding volume measurements calculated using TRUS and MRI were compared retrospectively with the measured volumes of freshly excised prostate. Results: The volume measured with TRUS and MRI was linearly related to the radical prostatectomy volume. The estimated increase in the prostate volumes measured with TRUS and MRI per specimen volume was 0.9508 and 0.9331 by regression analysis, respectively. If the prostate volumes were <35 cm³, the prostate volumes measured with MRI overestimated the specimen volumes. If the prostate volumes were >35 cm³, the prostate volumes measured with MRI underestimated the specimen volumes. The classic ellipsoid formula was adequate for determining the prostate volume. Conclusions: In this study, MRI and TRUS gave different volumes. MRI is more accurate than TRUS for determining the prostate volume. However, because TRUS is inexpensive, noninvasive, and almost as accurate as MRI, it should be the preferred method for measuring the prostate volume.

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ROS1 rearrangement is a predictive biomarker for response to the tyrosine kinase inhibitor, crizotinib. We investigated the usefulness of ROS1 immunohistochemistry (IHC) for the detection of patients who harbor ROS1 rearrangements in two separate cohorts. We also compared ROS1 IHC with ALK IHC in terms of diagnostic performance to predict each gene rearrangement. In a retrospective cohort, IHC was performed in 219 cases of lung adenocarcinoma with already known genetic alterations. In a prospective cohort, we performed IHC for 111 consecutive cases of lung adenocarcinoma and confirmed the results by subsequent FISH. In the retrospective cohort, all 8 ROS1-rearranged tumors were immunoreactive, and 14 of 211 ROS1-wild cases were immunoreactive (sensitivity 100% and specificity 93.4%). In the prospective cohort, all IHC-negative cases were FISH-negative, and 5 of 34 ROS1 immunoreactive cases were ROS1-rearranged (sensitivity 100% and specificity 72.6%). In ROS1-wild tumors, ROS1 protein was more expressed in the tumors of ever-smokers than in those of never-smokers (p = 0.003). ALK IHC showed 100% sensitivity and 98.1 to 100% specificity in both patient cohorts. In conclusion, ROS1 IHC is highly sensitive, but less specific compared with ALK IHC for detection of the corresponding rearrangement. ROS1 IHC-reactive tumors, especially when the tumor is stained with moderate to strong intensity or a diffuse pattern, are recommended to undergo FISH to confirm the gene rearrangement.

We developed an automatic opening and closing chamber system (AOCC) based on an open-flow dynamic method (open-flow AOCC). The AOCC can be used during all four seasons, even at the surface of relatively deep snow. We compared the open-flow AOCC with two closed dynamic methods [the AOCC configured as a closed dynamic system (closed dynamic AOCC) and the LI-6400 system] under field conditions. The closed dynamic-AOCC and LI-6400 measurements were about 15.4% and 5.2% lower, respectively, than the values obtained with the open-flow AOCC. There was a significant difference in soil respiration rate between the open-flow AOCC and the closed dynamic AOCC system. In contrast, no significant difference in soil respiration rate was detected between the open-flow AOCC and the LI-6400 system. In the field, the openflow AOCC permitted continuous long-term measurements under a range of temperature conditions and did a good job of reflecting the marked daily and seasonal variations in soil respiration as a function of soil temperature.

BackgroundEGFR mutation-induced cell proliferation causes changes in tumor biology and tumor metabolism, which may reflect tumor marker concentration and 18F-FDG uptake on PET/CT. Direct aspirates of primary lung tumors contain different concentrations of tumor markers than serum tumor markers, and may correlate better with EGFR mutation than serum tumor markers.The purpose of this study is to investigate an association between cytologic tumor markers and FDG uptake with EGFR mutation status in non-small cell lung cancer (NSCLC).MethodsWe prospectively collected tumor aspirates of 61 patients who underwent EGFR mutation analysis. Serum and cytologic CYFRA 21-1, CEA, and SCCA levels were measured and correlated with EGFR gene mutations. FDG PET/CT was performed on 58 patients for NSCLC staging, and SUV was correlated with EGFR mutation status.ResultsThirty (50 %) patients had EGFR mutation and 57 patients had adenocarcinoma subtype. Univariate analysis showed that female gender, never smoker, high levels of cytologic CYFRA 21-1 (c-CYFRA) and lower maximum standard uptake value (SUVmax) were correlated with EGFR mutations. ROC generated cut-off values of 20.8 ng/ml for c-CYFRA and SUVmax of 9.6 showed highest sensitivity for EGFR mutation detection. Multivariate analysis revealed that female gender [hazard ratio (HR): 18.15, p = 0.025], higher levels of c-CYFRA (HR: 7.58, and lower SUVmax (HR: 0.08, p = 0.005) were predictive of harboring EGFR mutation.ConclusionsThe cytologic tumor marker c-CYFRA was positively associated with EGFR mutations in NSCLC. EGFR mutation-positive NSCLCs have relatively lower glycolysis compared with NSCLCs without EGFR mutation.

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While acute treatment with beetroot juice (BRJ) containing nitrate (NO3 (-)) can lower systolic blood pressure (SBP), afterload, and myocardial O2 demand during submaximal exercise, effects of chronic supplementation with BRJ (containing a relatively low dose of NO3 (-), 400 mg) on cardiac output (CO), SBP, total peripheral resistance (TPR), and the work of the heart in response to dynamic exercise are not known. Thus, in 14 healthy males (22 ± 1 yr), we compared effects of 15 days of both BRJ and nitrate-depleted beetroot juice (NDBRJ) supplementation on plasma concentrations of NOx (NO3 (-)/NO2 (-)), SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), CO, TPR, and rate pressure product (RPP) at rest and during progressive cycling exercise. Endothelial function was also assessed via flow-mediated dilation (FMD). BRJ supplementation increased plasma NOx from 83.8 ± 13.8 to 167.6 ± 13.2 μM. Compared with NDBRJ, BRJ reduced SBP, DBP, MAP, and TPR at rest and during exercise (P < 0.05). In addition, RPP was decreased during exercise, while CO was increased, but only at rest and the 30% workload (P < 0.05). BRJ enhanced FMD-induced increases in brachial artery diameter (pre: 12.3 ± 1.6%; post: 17.8 ± 1.9%). We conclude that 1) chronic supplementation with BRJ lowers blood pressure and vascular resistance at rest and during exercise and attenuates RPP during exercise and 2) these effects may be due, in part, to enhanced endothelium-induced vasodilation in contracting skeletal muscle. Findings suggest that BRJ can act as a dietary nutraceutical capable of enhancing O2 delivery and reducing work of the heart, such that exercise can be performed at a given workload for a longer period of time before the onset of fatigue.