Influence of antidepressant treatment on SLC6A4 methylation in Korean patients with major depression.

Genetic variation of the serotonin transporter gene (SLC6A4) has been suggested as potential mediator for antidepressant response in patients with depression. This study aimed to determine whether DNA methylation in SLC6A4 changes after antidepressant treatment and whether it affects treatment response in patients with depression. Overall, 221 Korean patients with depression completed 6 weeks of selective serotonin reuptake inhibitor (SSRI) monotherapy. DNA was extracted from venous blood pre- and post-treatment, and DNA methylation was analyzed using polymerase chain reaction. We used Wilcoxon's signed-rank test to verify the difference in methylation after treatment. Treatment response was assessed using the 17-item Hamilton Depression Rating Scale, and mRNA levels were quantified. After adjusting for relevant covariates, DNA methylation was significantly altered in specific CpG sites in SLC6A4 (p < .001 in CpG3, CpG4, and CpG5) following 6 weeks of treatment. Methylation change's magnitude (ΔDNA methylation) after drug treatment was not associated with treatment response or mRNA level change. SSRI antidepressants can influence SLC6A4 methylation in patients with depression. However, ΔDNA methylation at CpG3, CpG4, and CpG5 in SLC6A4 was not associated with treatment response. Future studies should investigate the integrative effect of other genetic variants and CpG methylation on gene transcription and antidepressant treatment response.

Feasibility of Endoscopic Resection in Early Gastric Cancer with Lymphovascular Invasion.

BACKGROUND: Lymphovascular invasion (LVI) is associated with the risk of lymph node metastasis (LNM) and poor survival in gastric cancer patients; however, it is unclear whether LVI is a non-curative criteria component in all patients. We evaluated the risk factors of LNM in LVI-positive early gastric cancer (EGC) patients and identified a subgroup with a negligible LNM risk to assess the feasibility of endoscopic resection in these patients. METHODS: The clinicopathologic and survival data of patients undergoing surgery for gastric cancer were reviewed; LVI-positive EGC patients were selected. Logistic regression analysis was used to test the associations of potential risk factors with LNM, and Kaplan-Meier analysis was used to compare survival curves. RESULTS: LVI was detected in 1243 (15.5%) patients. In the multivariate logistic analysis, larger tumor size (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.16-1.31; p < 0.001), presence of ulcer (OR 1.80, 95% CI 1.15-2.82; p = 0.010), undifferentiated histology (OR 1.64, 95% CI 1.25-2.16; p < 0.001), submucosal invasion (OR 2.28, 95% CI 1.38-3.76; p = 0.001), middle (OR 2.12, 95% CI 1.26-3.55; p = 0.004) or lower third location (OR 2.28, 95% CI 1.32-3.60; p = 0.002), and younger age (OR 0.98, 95% CI 0.97-0.99; p = 0.002) independently predicted LNM in LVI-positive EGC patients. LVI-positive patients fulfilling the absolute endoscopic resection criteria did not have LNM and there was no significant difference in the overall (p = 0.928) and disease-specific survival (p = 0.821) between these patients and those with LVI-negative EGC. CONCLUSIONS: Additional surgery after endoscopic resection might be unnecessary in LVI-positive patients meeting the absolute criteria for endoscopic resection.

Comprehensive Computed Tomography Radiomics Analysis of Lung Adenocarcinoma for Prognostication.

BACKGROUND: In this era of personalized medicine, there is an expanded demand for advanced imaging biomarkers that reflect the biology of the whole tumor. Therefore, we investigated a large number of computed tomography-derived radiomics features along with demographics and pathology-related variables in patients with lung adenocarcinoma, correlating them with overall survival. MATERIALS AND METHODS: Three hundred thirty-nine patients who underwent operation for lung adenocarcinoma were included. Analysis was performed using 161 radiomics features, demographic, and pathologic variables and correlated each with patient survival. Prognostic performance for survival was compared among three models: (a) using only clinicopathological data; (b) using only selected radiomics features; and (c) using both clinicopathological data and selected radiomics features. RESULTS: At multivariate analysis, age, pN, tumor size, type of operation, histologic grade, maximum value of the outer 1/3 of the tumor, and size zone variance were statistically significant variables. In particular, maximum value of outer 1/3 of the tumor reflected tumor microenvironment, and size zone variance represented intratumor heterogeneity. Integration of 31 selected radiomics features with clinicopathological variables led to better discrimination performance. CONCLUSION: Radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and has potential to improve prognosis assessment in clinical oncology. IMPLICATIONS FOR PRACTICE: Two radiomics features were prognostic for lung cancer survival at multivariate analysis: (a) maximum value of the outer one third of the tumor reflects the tumor microenvironment and (b) size zone variance represents the intratumor heterogeneity. Therefore, a radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and could play a larger role in clinical oncology.

Identification of risk factors for sessile and traditional serrated adenomas of the colon by using big data analysis.

BACKGROUND AND AIM: Little is known about the risk factors associated with serrated polyps, because the early studies, which occurred before the new World Health Organization classification was introduced, included mixtures of serrated polyps. This study aimed to evaluate the risk factors associated with the presence of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) using big data analytics. METHODS: Using a case-control design, we evaluated the risk factors associated with the presence of SSAs and TSAs. Subjects who underwent colonoscopies from 2002 to 2012 as part of the comprehensive health screening programs undertaken at the Samsung Medical Center, Korea, participated in this study. RESULTS: Of the 48 677 individuals who underwent colonoscopies, 183 (0.4%) had SSAs and 212 (0.4%) had TSAs. The multivariate analysis determined that being aged ≥ 50 years (odds ratio [OR] 1.91, 95% confidential interval [CI] 1.27-2.90, P = 0.002) and a history of colorectal cancer among first-degree relatives (OR 3.14, 95% CI 1.57-6.27, P = 0.001) were significant risk factors associated with the presence of SSAs and that being aged ≥ 50 years (OR 2.61, 95% CI 1.79-3.80, P < 0.001), obesity (OR 1.63, 95% CI 1.12-2.36, P = 0.010), and a higher triglyceride level (OR 1.63, 95% CI 1.12-2.36, P = 0.010) were independent risk factors associated with the presence of TSAs. CONCLUSIONS: We used big data analytics to determine the risk factors associated with the presence of specific polyp subgroups, and individuals who have these risk factors should be carefully scrutinized for the presence of SSAs or TSAs during screening colonoscopies.

Synthesis of Enantiopure Mixed Alkyl-Aryl Vicinal Diamines by the Diaza-Cope Rearrangement: A Synthesis of (+)-CP-99,994.

The stereoselective synthesis of mixed alkyl-aryl vicinal diamines was demonstrated by the use of 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethene (hpen). A sequential addition of aryl and alkyl aldehyde to hpen gave a fused imidazolidine-dihydro-1,3-oxazine ring stereoselectively, which undergoes the diaza-Cope rearrangement to provide mixed vicinal diimines at elevated temperature in good yields and excellent stereoselectivity. We also showed that (+)-CP-99,994 can be readily prepared by the diaza-Cope rearrangement in overall 42% yield.

Atom-Precise Heteroatom Core-Tailoring of Nanoclusters for Enhanced Solar Hydrogen Generation.

While core-shell nanomaterials are highly desirable for realizing enhanced optical and catalytic properties, their synthesis with atomic-level control is challenging. Here, the synthesis and crystal structure of [Au12 Ag32 (SePh)30 ]4- , the first example of selenolated Au-Ag core-shell nanoclusters, comprising a gold icosahedron core trapped in a silver dodecahedron, which is protected by an Ag12 (SePh)30 shell, is presented. The gold core strongly modifies the overall electronic structure and induces synergistic effects, resulting in high enhancements in the stability and near-infrared-II photoluminescence. The Au12 Ag32 and its homometal analog Ag44 , show strong interactions with oxygen vacancies of TiO2 , facilitating the interfacial charge transfer for photocatalysis. Indeed, the Au12 Ag32 /TiO2 exhibits remarkable solar H2 production (6810 µmol g-1  h-1 ), which is ≈6.2 and ≈37.8 times higher than that of Ag44 /TiO2 and TiO2 , respectively. Good stability and recyclability with minimal catalytic activity loss are additional features of Au12 Ag32 /TiO2 . The experimental and computational results reveal that the Au12 Ag32 acts as an efficient cocatalyst by possessing a favorable electronic structure that aligns well with the TiO2 bands for the enhanced separation of photoinduced charge carriers due to the relatively negatively charged Au12 core. These atomistic insights will motivate uncovering of the structure-catalytic activity relationships of other nanoclusters.

Clinical Significance of Systemic Inflammation Markers in Newly Diagnosed, Previously Untreated Hepatocellular Carcinoma.

This study aimed to investigate the clinical significance of systemic inflammation markers (SIMs)-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-in patients with newly diagnosed, previously untreated hepatocellular carcinoma (HCC). The present study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC from a single institution. The training set included 6619 patients from 2005 to 2013 and the validation set included 2084 patients from 2014 to 2016. The SIMs as continuous variables significantly affected the overall survival (OS), and the optimal cut-off value of NLR, PLR, and LMR was 3.0, 100.0, and 3.0, respectively. There were significant correlations between SIMs and the albumin-bilirubin grade/Child-Turcotte-Pugh class (indicative of liver function status) and the staging system/portal vein invasion (indicative of the tumor burden). The OS curves were well stratified according to the prognostic model of SIMs and validated using the bootstrap method (1000 times, C-index 0.6367, 95% confidence interval (CI) 0.6274-0.6459) and validation cohort (C-index 0.6810, 95% CI 0.6570-0.7049). SIMs showed significant prognostic ability for OS, independent of liver function and tumor extent, although these factors were significantly correlated with SIMs in patients with newly diagnosed, previously untreated HCC.

The impact of unplanned reoperations in head and neck cancer surgery on survival.

OBJECTIVES: Unplanned reoperation causes physical and psychological stress in patients and it costs more in terms of medical, economic and social resource. The purpose of the study was to evaluate the incidence, risk factors and clinical significance of unplanned reoperation (any unscheduled surgery within 30 days from the initial surgery) in patients who had undergone head and neck cancer (HNC) surgery. MATERIALS AND METHODS: A total of 574 consecutive patients who had received surgery for HNC with or without flap reconstruction from 2010 to 2015 were analyzed. Clinical and biochemical characteristics, cause of unplanned reoperation, cancer subsites, and previous treatment history were compared between unplanned reoperation group (n = 60) and control group (n = 514). Multivariable analyses were performed to identify risk factors for unplanned reoperation. Clinical significance was evaluated by multivariable survival analyses using Cox proportional hazard model. RESULTS: Overall rate of unplanned reoperation was 10.5%. Flap complication (40.0%) was the most common cause, followed by infection (16.7%), necrosis (11.7%), and bleeding (8.3%). Higher N (N2) classification, long operation time and previous treatment before surgery were identified as risk factors for unplanned reoperation. Based on multivariable survival analyses, recurrence-free survival was significantly decreased in unplanned reoperation group (Hazard ratio = 1.85, 95% confidence interval [1.23-2.80]), but not overall survival. CONCLUSION: Unplanned reoperation significantly decreased recurrence-free survival in patients with HNC surgery. Thus, careful surgical/ perioperative management is needed to reduce unplanned reoperation in HNC patients with advanced nodal disease, long operation time or previous treatment history.

Imaging genotyping of functional signaling pathways in lung squamous cell carcinoma using a radiomics approach.

Imaging features can be useful for identifying distinct genomic differences and have predictive power for certain phenotypes attributed to genomic mutations. We aimed to identify predictive imaging biomarkers that underpin genomic alterations and clinical outcomes in lung squamous cell carcinoma (SQCC) using a radiomics approach. In 57 patients with lung SQCC who underwent preoperative computed tomography (CT) and whole-exome DNA sequencing, 63 quantitative imaging features were extracted from CT and 73 clinicoradiological features including imaging features were classified into 8 categories: clinical, global, histogram-based, lung cancer-specific, shape, local, regional, and emphysema. Mutational profiles for core signaling pathways of lung SQCC were classified into five categories: redox stress, apoptosis, proliferation, differentiation, and chromatin remodelers. Range and right lung volume was significantly associated with alternation of apoptosis and proliferation pathway (p = 0.03, and p = 0.03). Energy was associated with the redox stress pathway (p = 0.06). None of the clinicoradiological features showed any significant association with the alteration of differentiation and chromatin remodelers pathway. This study showed that radiomic features indicating five different functional pathways of lung SQCC were different form one another. Radiomics approaches to lung SQCC have the potential to noninvasively predict alterations in core signaling pathways and clinical outcome.

Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND/AIMS: Antiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear. METHODS: A retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled. RESULTS: The median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new-onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort. CONCLUSIONS: Overall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients.

Decoding Tumor Phenotypes for ALK, ROS1, and RET Fusions in Lung Adenocarcinoma Using a Radiomics Approach.

Quantitative imaging using radiomics can capture distinct phenotypic differences between tumors and may have predictive power for certain phenotypes according to specific genetic mutations. We aimed to identify the clinicoradiologic predictors of tumors with ALK (anaplastic lymphoma kinase), ROS1 (c-ros oncogene 1), or RET (rearranged during transfection) fusions in patients with lung adenocarcinoma.A total of 539 pathologically confirmed lung adenocarcinomas were included in this retrospective study. The baseline clinicopathologic characteristics were retrieved from the patients' medical records and the ALK/ROS1/RET fusion status was reviewed. Quantitative computed tomography (CT) and positron emission tomography imaging characteristics were evaluated using a radiomics approach. Significant features for the fusion-positive tumor prediction model were extracted from all of the clinicoradiologic features, and were used to calculate diagnostic performance for predicting 3 fusions' positivity. The clinicoradiologic features were compared between ALK versus ROS1/RET fusion-positive tumors to identify the clinicoradiologic similarity between the 2 groups.The fusion-positive tumor prediction model was a combination of younger age, advanced tumor stage, solid tumor on CT, higher values for SUV(max) and tumor mass, lower values for kurtosis and inverse variance on 3-voxel distance than those of fusion-negative tumors (sensitivity and specificity, 0.73 and 0.70, respectively). ALK fusion-positive tumors were significantly different in tumor stage, central location, SUV(max), homogeneity on 1-, 2-, and 3-voxel distances, and sum mean on 2-voxel distance compared with ROS1/RET fusion-positive tumors.ALK/ROS1/RET fusion-positive lung adenocarcinomas possess certain clinical and imaging features that enable good discrimination of fusion-positive from fusion-negative lung adenocarcinomas.