New CT response criteria in non-small cell lung cancer: proposal and application in EGFR tyrosine kinase inhibitor therapy.
We aimed to devise new CT response criteria (new response criteria, NRC) in patients with non-small cell lung cancer (NSCLC) and to evaluate the efficacy of the criteria for stratifying patient responses and predicting patient survival compared to that of the traditional size-based criteria RECIST version 1.1. Our institutional review board approved this study with a waiver of informed consent. We enrolled 80 NSCLC patients as an experimental arm and treated them with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). Two blinded, independent radiologists assessed CT images for tumor response using the NRC, which were also validated in a separate arm (75 NSCLC patients). Tumor responses evaluated by RECIST 1.1 and the new criteria were compared from each other and correlated with patient survival. For statistical analyses, Kaplan-Meier method and kappa statistics were used. In the experimental arm (n=80), interobserver agreements for the assessment of patient response were excellent for both RECIST and NRC. Sixteen RECIST nonresponding patients achieved a designation of partial response according to NRC. In the validation arm (n=75), patients of optimal response (partial response) with the new criteria had median overall survival of 18.4 months compared with 8.5 months in patients with poor response (P=.04). However, RECIST failed to show survival difference between the two response groups. In NSCLC patients treated with EGFR-TKIs, new CT criteria reflecting additional morphological characteristics of target lesions are reproducible and have statistically significant association with overall survival.

title: A New and Simple Practical Plane Dividing Hepatic Segment 2 and 3 of the Liver: Evaluation of Its Validity
abstract: The conventional method of dividing hepatic segment 2 (S2) and 3 (S3) is subjective and CT interpretation is unclear. The purpose of our study was to test the validity of our hypothesis that the actual plane dividing S2 and S3 is a vertical plane of equal distance from the S2 and S3 portal veins in clinical situations.  We prospectively performed thin-section iodized-oil CT immediately after segmental chemoembolization of S2 or S3 in 27 consecutive patients and measured the angle of intersegmental plane on sagittal multiplanar reformation (MPR) images to verify its vertical nature. Our hypothetical plane dividing S2 and S3 is vertical and equidistant from the S2 and S3 portal veins (vertical method). To clinically validate this, we retrospectively collected 102 patients with small solitary hepatocellular carcinomas (HCC) on S2 or S3 the segmental location of which was confirmed angiographically. Two reviewers predicted the segmental location of each tumor at CT using the vertical method independently in blind trials. The agreement between CT interpretation and angiographic results was analyzed with Kappa values. We also compared the vertical method with the horizontal one.  In MPR images, the average angle of the intersegmental plane was slanted 15 degrees anteriorly from the vertical plane. In predicting the segmental location of small HCC with the vertical method, the Kappa value between CT interpretation and angiographic result was 0.838 for reviewer 1 and 0.756 for reviewer 2. Inter-observer agreement was 0.918. The vertical method was superior to the horizontal method for localization of HCC in the left lobe (p < 0.0001 for reviewers 1 and 2).  The proposed vertical plane equidistant from S2 and S3 portal vein is simple to use and useful for dividing S2 and S3 of the liver.

title: Volume-Based Parameter of 18F-FDG PET/CT in Malignant Pleural Mesothelioma: Prediction of Therapeutic Response and Prognostic Implications
abstract: BackgroundTo evaluate the importance of assessing volume-based parameter of 18F-FDG PET/CT in patients with malignant pleural mesothelioma (MPM) for the prediction of response and patient outcome early in the course of treatment.Materials and MethodsPatients (n = 13; M:F = 9:4, mean age, 54 years) with histopathologically proven MPM, all of whom were scheduled to undergo curative extrapleural pneumonectomy (EPP) or palliative chemotherapy, were included in this study. They were evaluated using integrated 18F-FDG PET/CT at baseline. Maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using PET/CT data. Relationships between tumor progression and PET parameters were statistically analyzed.ResultsOf the 13 patients, 8 (62%) developed disease recurrence after surgery or tumor progression after chemotherapy (median follow-up, 329 days; range, 28–536 days). Between subgroups with and without tumor progression, significant differences were noted in MTV (P = 0.045). On ROC curve analysis, MTV (AUC = 0.850, 95% confidence interval [95% CI] 0.550–0.977) and TLG (AUC = 0.800, 95% CI 0.494–0.960) showed good predictive performance for tumor progression. Multivariate analysis adjusted for treatment modality showed that MTV (HR 1.003, P = 0.025) and TLG (HR 1.001, P = 0.031) were independent factors associated with tumor progression. Time to tumor progression was shorter in patients with a high volume-based parameter of PET than in those with a low value.ConclusionsVolume-based parameters of 18F-FDG PET/CT have the potential to provide prognostic information in MPM patients who are receiving surgery or palliative chemotherapy.

title: Superficial venous aneurysm: reports of 3 cases and literature review.
abstract: The purpose of this series is to describe the ultrasonographic and computed tomographic (CT) findings of superficial venous aneurysms sometimes misdiagnosed as subcutaneous soft tissue tumors.



Two of the patients had an asymptomatic subcutaneous mass that gradually increased in size; the third patient had a superficial mass in the right antecubital fossa associated with pain and occasional edema. All of the patients were examined with ultrasonography, and 2 had CT scans.



In all cases, ultrasound examinations showed a well-defined heterogeneous echoic lesion that was contiguous with the adjacent superficial vein and easily compressed by the probe, whereas a Doppler study indicated a venous spectral wave without pulsation. Dynamic enhanced CT showed homogeneous enhancement in the late phase, with contiguity with the adjacent vein. Only the third patient had an internal, floating, heterogeneous, echoic mass-like lesion, suggesting a chronic thrombus in the lesion on ultrasonography. This patient underwent aneurysmectomy with end-to-end anastomosis.



Venous aneurysm should be included in the differential diagnosis of a subcutaneous mass, and an accurate understanding of the differences between superficial and deep venous aneurysms may help in diagnosis and treatment.

title: Diffusion-weighted imaging in transient global amnesia exposes the CA1 region of the hippocampus
abstract: IntroductionTransient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia without alteration of consciousness or personal identity. Interestingly, recent studies have reported a high frequency of small high-signal abnormalities in the hippocampus with diffusion-weighted (DW) imaging, and ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, known to be susceptible to ischemia.MethodsOver a 30-month period 34 patients with TGA underwent MRI including DW imaging within 4 days of symptom onset. Patients with high-signal abnormalities in the hippocampus on the initial DW images underwent subsequent DW and T2-weighted imaging in the coronal plane to identify the precise lesion locations.ResultsFourteen patients had small (1–3 mm) high-signal abnormalities in the hippocampus unilaterally on DW images. One of these patients had two lesions in one hippocampus and therefore in total 15 lesions were identified: four in the hippocampal head, and 11 in the body. Eleven lesions in ten patients with available coronal images were clearly demonstrated on both coronal DW and T2-weighted images and were localized to the lateral portion of the hippocampus, corresponding to the CA1 region.ConclusionLesions associated with TGA were localized exclusively to the lateral portion of the hippocampus corresponding to the CA1 region. This finding supports the ischemic etiology of TGA; however, the pathophysiological mechanism involved requires further study.

title: Classification of Focal Prostatic Lesions on Transrectal Ultrasound (TRUS) and the Accuracy of TRUS to Diagnose Prostate Cancer
abstract: To improve the diagnostic efficacy of transrectal ultrasound (TRUS)-guided targeted prostatic biopsies, we have suggested the use of a new scoring system for the prediction of malignancies regarding the characteristics of focal suspicious lesions as depicted on TRUS.  A total of 350 consecutive patients with or without prostate cancer who underwent targeted biopsies for 358 lesions were included in the study. The data obtained from participants were randomized into two groups; the training set (n = 240) and the test set (n = 118). The characteristics of focal suspicious lesions were evaluated for the training set and the correlation between TRUS findings and the presence of a malignancy was analyzed. Multiple logistic regression analysis was used to identify variables capable of predicting prostatic cancer. A scoring system that used a 5-point scale for better malignancy prediction was determined from the training set. Positive predictive values for malignancy prediction and the diagnostic accuracy of the scored components with the use of receiver operating characteristic curve analysis were evaluated by test set analyses.  Subsequent multiple logistic regression analysis determined that shape, margin irregularity, and vascularity were factors significantly and independently associated with the presence of a malignancy. Based on the use of the scoring system for malignancy prediction derived from the significant TRUS findings and the interactions of characteristics, a positive predictive value of 80% was achieved for a score of 4 when applied to the test set. The area under the receiver operating characteristic curve (AUC) for the overall lesion score was 0.81.  We have demonstrated that a scoring system for malignancy prediction developed for the characteristics of focal suspicious lesions as depicted on TRUS can help predict the outcome of TRUS-guided biopsies.

title: Rapid direct PCR for ABO blood typing.
abstract: Many different molecular typing methods have been reported to complement routine serological ABO blood typing in forensics. However, these ABO genotyping methods are often time-consuming and call for an initial DNA isolation step that requires the use of expensive kits or reagents. We report here a rapid direct ABO genotyping method that eliminates the need for DNA extraction from fresh blood, hair, and body fluid stains before PCR. Using a fast PCR instrument and an optimized polymerase, the genotyping method-which employs a multiplex allele-specific primer set for the simultaneous detection of three single-nucleotide polymorphism (SNP) sites (nucleotides 261, 526, and 803)-identifies A, B, O01/O02, O03, and cis-AB01 alleles in around 70 min from sample collection to electropherogram. Not only will this ABO genotyping method be efficiently used in forensic practice for rapid screening of samples before full-blown multilocus short tandem repeat profiling, but it will also demonstrate an example of rapid direct genotyping of SNPs that offers the advantages of time- and cost-efficiency, convenience, and reduced contamination during DNA analysis.

title: Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation product concentration (Balance).
abstract: In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome.



Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay . safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up.



The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions.



This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.

title: Prevalence and risk factors of masked hypertension identified by multiple self-blood pressure measurement.
abstract: With great interest we read the article by O'Brien,1 comprehensively reviewing implementation of out-of-office blood pressure (BP) measurement, ie, ambulatory BP measurement and self-BP measurement (SBPM), for more precise evaluation and management of hypertension. Clearly, ambulatory BP measurement provides a greater amount of BP information and, thus, can be more sensitive than SBPM. However, ambulatory BP measurement is more expensive and may cause discomfort, interfering with subjects’ normal activity, which limit its routine use.2 Here, we introduce our investigation of the diurnal BP pattern and its determining factors by implementing a multiple SBPM strategy.

A total of 5009 hypertension patients in 500 primary care clinics in Korea, whose recent BP during the last 2 visits was stable without change in medication, were enrolled. This study was performed by multicenter, prospective, observational design. To minimize possible confounding factors and to compare the differential effect of various classes of antihypertensive agents, 2 strategies were used. First, enrolled patients were …

title: A stereoselective enyne cross metathesis.
abstract: [reaction: see text] Intermolecular enyne metathesis reaction of alkynes with olefins catalyzed by second-generation Grubbs catalyst (1) proceeded stereoselectively under ethylene atmosphere to produce 1,3-disubstituted butadienes with E stereochemistry.

title: Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells.
abstract: Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) induces apoptosis in non-small-cell lung cancer (NSCLC) cells in vitro and in vivo. However, Ras-mediated signaling pathways could develop resistance to apoptotic activities of IGFBP-3 in NSCLC cells. We thus evaluated the therapeutic potential of the combination of IGFBP-3 and SCH66336, a farnesyltransferase inhibitor that blocks Ras activation, in NSCLC cell lines.



The effects of the combination of adenoviral IGFBP-3 (Ad-IGFBP3) and SCH66336 on proliferation and apoptosis of NSCLC cell lines (H1299, H596, A549, H460, H358, H322, and H226B) were assessed in vitro and in vivo by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometry-based terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, western blot analyses, and an NSCLC xenograft tumor model. The specific effects of Ad-IGFBP 3 and SCH66336 on mitogen-activated protein kinase and Akt were assessed by using adenoviral vectors that express constitutively active MEK1 or constitutively active Akt. Synergy was assessed by median effect analysis.



The combination of Ad-IGFBP3 and SCH66336 had synergistic antiproliferative effects in five cell lines (H1299, H596, A549, H460, and H322). Antiproliferative effects were accompanied by increased apoptosis in H460 cells in vitro. Overexpression of a constitutively active Akt but not a constitutively active MEK-1 rescued H460 cells from apoptosis induced by single or combined treatment of Ad-IGFBP3 and SCH66336. In H1299 tumor xenografts, Ad-IGFBP3 and SCH66336 was associated with decreased tumor volume, increased apoptosis, and decreased Akt levels.



The combination of Ad-IGFBP3 and SCH66336 decreased Akt expression and increased apoptosis in NSCLC cells in vitro and in vivo. Simultaneous treatment with IGFBP-3 and SCH66336 may have the potential to be an effective therapeutic strategy in NSCLC.