A
bstract
We report on the response of a high light-output NaI(Tl) crystal to nuclear recoils induced by neutrons from an Am-Be source and compare the results with the response to electron recoils ...produced by Compton-scattered 662 keV γ-rays from a
137
Cs source. The measured pulse-shape discrimination (PSD) power of the NaI(Tl) crystal is found to be significantly improved because of the high light output of the NaI(Tl) detector. We quantify the PSD power with a quality factor and estimate the sensitivity to the interaction rate for weakly interacting massive particles (WIMPs) with nucleons, and the result is compared with the annual modulation amplitude observed by the DAMA/LIBRA experiment. The sensitivity to spin-independent WIMP-nucleon interactions based on 100 kg·year of data from NaI detectors is estimated with simulated experiments, using the standard halo model.
Aim To compare the diagnostic performances of gadoxetic acid-enhanced magnetic resonance imaging (MRI) and multiphasic multidetector computed tomography (MDCT) in the detection of hepatocellular ...carcinoma (HCC) in patients with chronic liver disease. Materials and methods Institutional review board approval was obtained for this study and informed consent was obtained from all patients. Fifty-one patients (43 men, eight women; age range 32–80 years) with 73 HCCs underwent gadoxetic acid-enhanced MRI and multiphasic MDCT. Two readers independently analysed each image in three separate reading sessions. The alternative free-response receiver operating characteristic (AFROC) method was used to analyse the diagnostic accuracy. Positive and negative predictive values and sensitivity were evaluated. Results A total of 73 HCCs were detected in 51 patients. Although not significant ( p > 0.05), the areas under the receiver operating characteristic curves were 0.877 and 0.850 for MDCT, 0.918 and 0.911 for dynamic MRI, and 0.905 and 0.918 for combined interpretation of dynamic and hepatobiliary phase MR images. Differences in sensitivity, specificity, and positive and negative predictive values between the readers were not statistically significant ( p > 0.05). Combined interpretation of dynamic and hepatobiliary phase MRI images was more useful than MDCT in the detection of HCC lesions ≤1 cm in diameter for one reader ( p = 0.043). Conclusion Gadoxetic acid-enhanced MRI and MDCT show similar diagnostic performances for the detection of HCC in patients with chronic liver disease. However, the combined interpretation of dynamic and hepatobiliary phase MRI images may improve diagnostic accuracy in the detection of HCC lesions ≤1 cm in diameter.
Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report ...the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty‐five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs 280.0 minutes; P < .001) and the percentage with multiple bile duct openings was higher (53.3% vs 26.2%; P = .010) in the PLDRH group. However, the length of postoperative hospital stay (8.4 vs 8.2 days; P = .495) and rate of complications (11.9% vs 8.9%; P = .733) and re‐hospitalizations (4.8% vs 4.4%; P = 1.000) were similar in both groups. PLDH, including PLDRH, is feasible when performed by a highly experienced surgeon and transplant team. Further evaluation, including long‐term results, may support these preliminary findings of comparative outcomes for donors undergoing PLDRH and CDRH.
Compared with the open approach, pure laparoscopic donor hepatectomy, primarily right hepatectomy, is a feasible procedure when performed by a highly experienced surgeon and transplantation team.
Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, ...and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009–2013). One hundred and twenty‐six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA/l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.
► The study examined effect of composting operation on decline of veterinary antibiotics (VAs) sourced from animal manure. ► The organic matter provided a wide range of additional binding for VAs ...sites during composting. ► Sawdust was one potential organic source able to initiate efficient composting. ► Concentrations of tetracyclines, sulfonamides and macrolides declined to reasonable levels.
A wide variety of antibiotics have been detected in natural water samples and this is of potential concern because of the adverse environmental effects of such antibiotic residues. One of the main sources of antibiotics effluence to the surrounding environment is livestock manures which often contain elevated concentrations of veterinary antibiotics (VAs) which survive digestion in the animal stomach following application in animal husbandry practices. In Korea, livestock manures are normally used for compost production indicating that there is potential for antibiotic release to the environment through compost application to agricultural lands. Therefore, reduction of the amount of VAs in composts is crucial. The purpose of this study was to understand the influence of the composting process and the components of the compost on the levels of three common classes of antibiotics (tetracyclines, sulfonamides, and macrolides). Composted materials at different stages of composting were collected from compost manufacturing plants and the variation in antibiotic concentrations was determined. Three different antibiotics, chlortetracycline (CTC), sulfamethazine (SMZ), and tylosin (TYL) at three different concentrations (2, 10, and 20
mg
kg
−1) were also applied to a mixture of pig manure and sawdust and the mixtures incubated using a laboratory scale composting apparatus to monitor the changes in antibiotic concentrations during composting together with the physicochemical properties of the composts. During composting, in both field and lab-scale investigations, the concentrations of all three different antibiotics declined below the relevant Korean guideline values (0.8
mg
kg
−1 for tetracyclines, 0.2
mg
kg
−1 for sulfonamides and 1.0
mg
kg
−1 for macrolides). The decline of tetracycline and sulfonamide concentrations was highly dependent on the presence of sawdust while there was no influence of sawdust on TYL decline.
Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune ...evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer.
Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (N = 24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString® (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (N = 37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival.
In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (APhigh), and this was used to define the APhigh tertile of the second cohort (13 APhigh of 37). APhigh tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, P = 0.03). Median progression-free survival was lower in the APhigh group (55 versus 180 days, P = 0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival hazard ratio 0.29, 95% confidence interval 0.099–0.85, P = 0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response.
A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy.
ClinicalTrials.gov Identifier: NCT#02589496
Targeting oncogenic genomic aberrations is an established therapeutic strategy in multiple tumor types. Molecular classification has uncovered a number of novel targets, and rapamycin-insensitive ...companion of mTOR (RICTOR) amplification has been identified in lung cancer. Further investigation assessing the therapeutic potential ofRICTOR amplification as a novel target across advanced cancers is needed.
Tumor samples from 640 patients with metastatic solid tumors, primarily gastrointestinal and lung cancers were prospectively subjected to a next-generation sequencing (NGS) assay to identify molecular targets. Samples with NGS-detectedRICTOR amplification were confirmed with FISH. ARICTOR-amplified patient-derived cell (PDC) line was generated and used to investigate the effectiveness of selective AKT, mTORC1, and mTORC1/2 inhibition.
NGS identified 13 (2%) of 640 patients withRICTOR-amplified tumors (6 gastric, 3 NSCLC, 1 SCLC, 1 CRC, 1 sarcoma, 1 MUO). Of the 13 patients, seven patients had RICTOR protein overexpression by IHC. The prevalence of RICTOR amplification in gastric cancer by NGS was 3.8% (6/160). FISH testing confirmed amplification (RICTOR/control >2) in 5/13 (38%) of samples, including four gastric cancers and one lung cancer. Treatment of aRICTOR amplified PDC with a selective AKT (AZD5363), selective mTORC1 (everolimus), dual mTORC1/2 (AZD2014), and the multi-target kinase inhibitor pazopanib demonstrated preferential sensitivity to the mTORC1/2 inhibitor (AZD2014). Knockdown ofRICTOR reversed PDC sensitivity to AZD2014, validating the importance ofRICTOR amplification to the PDC line.
RICTOR amplification is a rare but therapeutically relevant genomic alteration across solid tumors. Our results support further pre-clinical and clinical investigation with AZD2014 inRICTOR amplified gastric cancer and highlights the importance of genomic profiling.
Summary Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to ...reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable—even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.
Aim To evaluate recurrence rate and associated risk factors for recurrence after ethanol ablation (EA) in patients with predominantly cystic thyroid nodules. Materials and methods This observational ...study was approved by the Ethics Committee of the Institutional Review Board and informed consent for procedures was obtained. From April 2009 to April 2013, 107 consecutive patients with predominantly cystic nodules were treated using EA. Recurrence was defined as nodules showing a residual solid portion with internal vascularity, cosmetic problems remaining, or persistent symptoms, and patients who requested additional therapy to resolve their symptomatic or cosmetic problems. Delayed recurrence was defined as treated nodules that showed no recurrent features at 1 month, but showed newly developed recurrent features during the longer follow-up period. Multivariate analysis was used for variables to demonstrate the independent factors related to volume reduction. Results One month after EA, 18.7% of patients (20/107) showed recurrence. Among 87 patients with non-recurrence, 24.1% (21/87) showed delayed recurrence. The total recurrence rate was 38.3% (41/107). Patients with recurrence ( n = 41) were treated using radiofrequency ablation ( n = 28), second EA ( n = 4), and refused further treatment ( n = 9). These patients responded well to repeat EA and radiofrequency ablation. Multivariate analysis demonstrated that the initial nodule volume (>20 ml; p < 0.036) and vascularity (grade >1; p < 0.049) were independent predictors of volume reduction at last follow-up. Conclusions The results revealed that although EA seemed to be effective during the initial period, delayed recurrence should be considered during longer-term follow-up. The independent predictors of recurrence were initial volume (>20 ml) and vascularity.
We present a search for low-mass (< or = 20 GeV /c super(2)) weakly interacting massive particles (WIMPs), strong candidates of dark matter particles, using the low-background CsI(Tl) detector array ...of the Korea Invisible Mass Search experiment. With a total data exposure of 24,524.3 kg days, we search for WIMP interaction signals produced by nuclei recoiling from WIMP-nuclear elastic scattering with visible energies between 2 and 4 keVee (electron-equivalent energy). The observed energy distribution of candidate events is consistent with null signals, and upper limits of the WIMP-proton spin-independent interaction are set with a 90% confidence level. The observed limit covers most of the low-mass region of parameter space favored by the DAMA annual modulation signal assuming the standard halo model.
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