Changes in kinetic heterogeneity of breast cancer via computer-aided diagnosis on MRI predict the pathological response to neoadjuvant systemic therapy.

OBJECTIVE: To evaluate whether the computer-aided diagnosis (CAD)-extracted kinetic heterogeneity of breast cancer on MRI and changes therein during treatment were associated with the pathological response to neoadjuvant systemic therapy (NST). MATERIALS AND METHODS: Consecutive patients with invasive breast cancer, who underwent NST followed by surgery between 2014 and 2020, were retrospectively evaluated. Using a commercial CAD system, kinetic features (angiovolume, peak enhancement, delayed enhancement profiles, and kinetic heterogeneity) of breast cancer were assessed with pre- and mid-treatment MRI. Multivariate logistic regression was used to identify the associations between CAD-extracted kinetic features and pathological complete response (pCR). RESULTS: A total of 130 patients (mean age, 55 years) were included, 37 (28.5%) of whom achieved a pCR. When the pre- and mid-treatment MRI data were compared, the pCR group exhibited greater changes in kinetic heterogeneity (86.14 ± 32.05% vs. 8.50 ± 141.01%, p < 0.001) and angiovolume (95.20 ± 14.29% vs. 19.89 ± 320.16%; p < 0.001) than the non-pCR group. Multivariate regression analysis showed that a large change in kinetic heterogeneity (odds ratio (OR) = 1.030, p < 0.001), age (OR = 0.931, p = 0.005), progesterone receptor negativity (OR = 7.831, p = 0.001), and HER2 positivity (OR = 3.455, p = 0.017) were associated with pCR. CONCLUSIONS: A greater change in the CAD-extracted kinetic heterogeneity of breast cancer between pre- and mid-treatment MRI was associated with a pCR in patients on NST. KEY POINTS: A greater change in kinetic heterogeneity was associated with a pathological complete response. Computer-aided diagnosis-extracted kinetic heterogeneity might serve as a quantitative biomarker of therapeutic efficacy.

Comparison of Fused Diffusion-Weighted Imaging Using Unenhanced MRI and Abbreviated Post-Contrast-Enhanced MRI in Patients with Breast Cancer.

Background and Objectives: To determine the percentage of breast cancers detectable by fused diffusion-weighted imaging (DWI) using unenhanced magnetic resonance imaging (MRI) and abbreviated post-contrast-enhanced MRI. Materials and Methods: Between October 2016 and October 2017, 194 consecutive women (mean age, 54.2 years; age range, 28-82 years) with newly diagnosed unilateral breast cancer, who underwent preoperative 3.0 T breast MRI with DWI, were evaluated. Both fused DWI and abbreviated MRI were independently reviewed by two radiologists for the detection of index cancer (which showed the most suspicious findings in both breasts), location, lesion conspicuity, lesion type, and lesion size. Moreover, the relationship between cancer detection and histopathological results of surgical specimens was evaluated. Results: Index cancer detection rates were comparable between fused DWI and abbreviated MRI (radiologist 1: 174/194 [89.7%] vs. 184/194 [94.8%], respectively, p = 0.057; radiologist 2: 174/194 [89.7%] vs. 183/194 [94.3%], respectively, p = 0.092). In both radiologists, abbreviated MRI showed a significantly higher lesion conspicuity than fused DWI (radiologist 1: 9.37 ± 2.24 vs. 8.78 ± 3.03, respectively, p < 0.001; radiologist 2: 9.16 ± 2.32 vs. 8.39 ± 2.93, respectively, p < 0.001). The κ value for the interobserver agreement of index cancer detection was 0.67 on fused DWI and 0.85 on abbreviated MRI. For lesion conspicuity, the intraclass correlation coefficients were 0.72 on fused DWI and 0.82 on abbreviated MRI. Among the histopathological factors, tumor invasiveness was associated with cancer detection on both fused DWI (p = 0.011) and abbreviated MRI (p = 0.004, radiologist 1), lymphovascular invasion on abbreviated MRI (p = 0.032, radiologist 1), and necrosis on fused DWI (p = 0.031, radiologist 2). Conclusions: Index cancer detection was comparable between fused DWI and abbreviated MRI, although abbreviated MRI showed a significantly better lesion conspicuity.

Diffusion Kurtosis MR Imaging of Invasive Breast Cancer: Correlations With Prognostic Factors and Molecular Subtypes.

BACKGROUND: The associations between diffusion kurtosis imaging (DKI)-derived parameters and clinical prognostic factors of breast cancer have not been fully evaluated; this knowledge may have implications for outcome prediction and treatment strategies. PURPOSE: To determine associations between quantitative diffusion parameters derived from DKI and diffusion-weighted imaging (DWI) and the prognostic factors and molecular subtypes of breast cancer. STUDY TYPE: Retrospective. POPULATION: A total of 383 women (mean age, 53.8 years; range, 31-82 years) with breast cancer who underwent preoperative breast MRI including DKI and DWI. FIELD STRENGTH/SEQUENCE: A 3.0 T; DKI using a spin-echo echo-planar imaging (EPI) sequence (b values: 200, 500, 1000, 1500, and 2000 sec/mm2 ), DWI using a readout-segmented EPI sequence (b values: 0 and 1000 sec/mm2 ) and dynamic contrast-enhanced breast MRI. ASSESSMENT: Two radiologists (J.Y.K. and H.S.K. with 9 years and 1 year of experience in MRI, respectively) independently measured kurtosis, diffusivity, and apparent diffusion coefficient (ADC) values of breast cancer by manually placing a regions of interest within the lesion. Diffusion measures were compared according to nodal status, grade, and molecular subtypes. STATISTICAL TESTS: Kruskal-Wallis test, Mann-Whitney U test with Bonferroni correction, receiver operating characteristic (ROC) analysis, and multivariate logistic regression analysis. (Statistical significance level of P < 0.05). RESULTS: All diffusion measures showed significant differences according to axillary nodal status and histological grade. Kurtosis showed significant differences among molecular subtypes. The luminal subtype (median 1.163) showed a higher kurtosis value compared to the HER2-positive (median 0.962) or triple-negative subtypes (median 1.072). ROC analysis for differentiating HER2-positive from luminal subtypes revealed that kurtosis yielded the highest area under the curve of 0.781. In multivariate analyses, kurtosis remained a significant factor associated with differentiation between HER2-positive and luminal (odds ratio [OR] = 0.993), triple-negative and luminal (OR = 0.995), and HER2-positive and triple-negative subtypes (OR = 0.994). DATA CONCLUSION: Quantitative diffusion parameters derived from DKI and DWI are associated with prognostic factors for breast cancer. Moreover, DKI-derived kurtosis can help distinguish between the molecular subtypes of breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

Characterization of breast cancer subtypes based on quantitative assessment of intratumoral heterogeneity using dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging.

OBJECTIVE: To investigate whether intratumoral heterogeneity, assessed via dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI), reflects the molecular subtypes of invasive breast cancers. MATERIAL AND METHODS: We retrospectively evaluated data from 248 consecutive women (mean age ± standard deviation, 54.6 ± 12.2 years) with invasive breast cancer who underwent preoperative DCE-MRI and DWI between 2019 and 2020. To evaluate intratumoral heterogeneity, kinetic heterogeneity (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was assessed with DCE-MRI using a commercially available computer-aided diagnosis system. Apparent diffusion coefficients (ADCs) were obtained using a region-of-interest technique, and ADC heterogeneity was calculated using the following formula: (ADCmax-ADCmin)/ADCmean. Possible associations between imaging-based heterogeneity values and breast cancer subtypes were analyzed. RESULTS: Of the 248 invasive breast cancers, 61 (24.6%) were classified as luminal A, 130 (52.4%) as luminal B, 25 (10.1%) as HER2-enriched, and 32 (12.9%) as triple-negative breast cancer (TNBC). There were significant differences in the kinetic and ADC heterogeneity values among tumor subtypes (p < 0.001 and p = 0.023, respectively). The TNBC showed higher kinetic and ADC heterogeneity values, whereas the HER2-enriched subtype showed higher kinetic heterogeneity values compared to the luminal subtypes. Multivariate linear analysis showed that the HER2-enriched (p < 0.001) and TNBC subtypes (p < 0.001) were significantly associated with higher kinetic heterogeneity values. The TNBC subtype (p = 0.042) was also significantly associated with higher ADC heterogeneity values. CONCLUSIONS: Quantitative assessments of heterogeneity in enhancement kinetics and ADC values may provide biological clues regarding the molecular subtypes of breast cancer. KEY POINTS: • Higher kinetic heterogeneity was associated with HER2-enriched and triple-negative breast cancer. • Higher ADC heterogeneity was associated with triple-negative breast cancer. • Aggressive breast cancer subtypes exhibited higher intratumoral heterogeneity based on MRI.

Fusion of high b-value diffusion-weighted and unenhanced T1-weighted images to diagnose invasive breast cancer: factors associated with false-negative results.

OBJECTIVES: We sought factors associated with false-negative results in the diagnosis of invasive breast cancer via non-contrast breast magnetic resonance imaging (MRI) using fused high b-value diffusion-weighted imaging (DWI) and unenhanced T1-weighted images (T1WI). METHODS: Between 2018 and 2019, 316 consecutive women (mean age, 54.6 years) with invasive breast cancer who underwent preoperative breast MRI, including fused high b-value DWI and unenhanced T1WI, were retrospectively evaluated. Malignancy confidence ratings of the most suspicious breast lesions evident on fused DWI were derived by two radiologists using a 6-point Likert-type scale. Both clinicopathological and imaging features were analyzed. Multivariate regression analysis was performed to identify factors associated with false-negative DWI results in the diagnosis of invasive breast cancer. RESULTS: Of the 316 breast cancers, fused DWI yielded 289 (91.5%) true-positive and 27 (8.5%) false-negative results. Multivariate analysis showed that small tumor size (≤ 1 cm) (odds ratio [OR], 5.95; 95% confidence interval [CI], 2.11, 16.81; p = 0.001), presence of calcifications in the tumor (OR, 3.41; 95% CI, 1.27, 9.15; p = 0.015), and a moderate/marked background diffusion signal (ORs, 4.23 and 19.18; 95% CI, 1.31, 13.67 and 6.51, 56.46; p = 0.016 and p < 0.001, respectively) were significantly associated with false-negative results. In subgroup analysis of 141 screening-detected cancers, a marked background diffusion signal (OR, 7.94; 95% CI, 2.30, 27.35; p = 0.001) remained significantly associated with false-negative results in the multivariate analysis. CONCLUSIONS: In addition to histopathological features, a higher background diffusion signal was associated with false-negative results in the diagnosis of invasive breast cancer via non-contrast MRI using fused high b-value DWI and unenhanced T1WI. KEY POINTS: • Subcentimeter tumors and presence of calcifications in the tumor are associated with false-negative diffusion-weighted imaging results in the diagnosis of invasive breast cancer. • A higher degree of background diffusion signal may lead to false-negative interpretation of diffusion-weighted imaging in patients with invasive breast cancer.

Ultrafast Dynamic Contrast-Enhanced MRI Using Compressed Sensing: Associations of Early Kinetic Parameters With Prognostic Factors of Breast Cancer.

OBJECTIVE. The purpose of this study was to investigate whether early kinetic parameters derived from ultrafast dynamic contrast-enhanced MRI (DCE-MRI) using compressed sensing are associated with prognostic factors for breast cancer. MATERIALS AND METHODS. We evaluated 201 consecutive women (mean age, 54.6 years) with breast cancer (168 invasive, 33 ductal carcinoma in situ) who underwent both ultrafast DCE-MRI using compressed sensing (temporal resolution, 4.7 seconds; spatial resolution, 0.8 × 1.1 × 0.9 mm) and surgery between 2018 and 2019. Early kinetic parameters (time to enhancement [TTE] and maximum slope [MS]) were measured in breast lesions by two radiologists using a software program and were correlated with histopathologic prognostic factors. The Mann-Whitney U test and linear regression analysis were used. RESULTS. The median TTE and MS values for breast cancer were 11.9 seconds and 7.7%/s, respectively. The median MS was significantly larger in invasive cancer lesions than in ductal carcinoma in situ lesions (8.4%/s vs 4.7%/s, p < .001). In women with invasive cancer, multivariate linear regression analyses showed that a larger tumor size (> 2 cm) (p = .048) and estrogen receptor-negative status (p < .001) were significantly associated with a shorter TTE. A higher histologic grade (grade 3) (p = .01) was significantly associated with a larger MS. We observed excellent interobserver agreement between two readers in the measurements of TTE and MS (intraclass correlation coefficients, 0.943 and 0.890, respectively). CONCLUSION. Ultrafast MRI-derived early enhancement parameters, such as TTE and MS, are associated with histopathologic prognostic factors in women with breast cancer.

Weekend catch-up sleep is associated with reduced metabolic derangements in Korean adults.

BACKGROUND: Deficits in sleep are associated with metabolic derangements, but the effect of sleep supplementation on metabolic derangements remains to be elucidated. This study aimed to investigate whether weekend catch-up sleep is associated with metabolic derangements in Korean adults. METHODS: A total of 10,749 individuals over 40 years old were identified from the 2016-2017 Korea National Health and Nutrition Examination Survey. Data on demographics, health behaviors, self-reported sleep duration, and physician-diagnosed metabolic diseases were used in this analysis. The odds ratio for each metabolic derangement was determined via stepwise multivariable logistic regression models. RESULTS: Short weekday sleep and insufficient weekend catch-up sleep were independently associated with an increased risk for all metabolic derangements, except hypertension. Individuals who did not make up sleep on the weekend were more likely to be obese and have type 2 diabetes or hypercholesterolemia.

Kinetic Heterogeneity of Breast Cancer Determined Using Computer-aided Diagnosis of Preoperative MRI Scans: Relationship to Distant Metastasis-Free Survival.

Background Higher peak enhancement and washout component values measured on preoperative breast MRI scans with computer-aided diagnosis (CAD) are presumed to be associated with worse recurrence-free survival. Purpose To investigate whether CAD-extracted kinetic features of breast cancer and the heterogeneity of these features at preoperative MRI are associated with distant metastasis-free survival in women with invasive breast cancer. Materials and Methods Consecutive women with newly diagnosed invasive breast cancer who underwent preoperative MRI were retrospectively evaluated between 2011 and 2012. A commercially available CAD system was used to extract the peak enhancement and delayed enhancement profiles of each breast cancer case from preoperative MRI data. The kinetic heterogeneity of these features (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was calculated to evaluate intratumoral heterogeneity. Cox proportional hazards models were used to investigate the associations between CAD-extracted kinetic features and distant metastasis-free survival after adjusting for clinical-pathologic factors. Results A total of 276 consecutive women (mean age, 53 years) were evaluated. In 28 of 276 (10.1%) women, distant metastasis developed at a median follow-up of 79 months. A higher degree of kinetic heterogeneity was observed in women with distant metastases than in those without distant metastases (mean, 0.70 ± 0.2 vs 0.43 ± 0.3; P < .001). Multivariable Cox proportional hazards analysis revealed that a higher degree of kinetic heterogeneity (hazard ratio [HR], 19.2; 95% confidence interval [CI]: 4.2, 87.1; P < .001), higher peak enhancement (HR, 1.001; 95% CI: 1.000, 1.002; P = .045), the presence of lymphovascular invasion (HR, 3.3; 95% CI: 1.5, 7.5; P = .004), and a higher histologic grade (ie, grade 3) (HR, 2.2; 95% CI: 1.0, 4.9; P = .044) were associated with worse distant metastasis-free survival. Conclusion Higher values of kinetic heterogeneity and peak enhancement as determined with computer-aided diagnosis of preoperative MRI were associated with worse distant metastasis-free survival in women with invasive breast cancer. © RSNA, 2020 See also the editorial by El Khouli and Jacobs in this issue.

Diffusion-weighted MRI of estrogen receptor-positive, HER2-negative, node-negative breast cancer: association between intratumoral heterogeneity and recurrence risk.

OBJECTIVES: To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay. METHODS: This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated. RESULTS: Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10-3 mm2/s vs. 0.746 × 10-3 mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3 mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors. CONCLUSIONS: The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer. KEY POINTS: • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.

Diffusion-weighted Imaging of Invasive Breast Cancer: Relationship to Distant Metastasis-free Survival.

Background Combined minimum apparent diffusion coefficient (ADC) and ADC difference value may improve the diagnostic performance of breast diffusion-weighted imaging (DWI) compared with mean ADC. Purpose To investigate whether ADC parameters at DWI are associated with distant metastasis-free survival in women with invasive breast cancer. Materials and Methods Between 2013 and 2014, 258 consecutive women (mean age ± standard deviation, 50.9 years ± 10.5; age range, 23-85 years) with newly diagnosed invasive breast cancer who underwent preoperative MRI with DWI were evaluated. All DWI examinations were retrospectively reviewed by two radiologists blinded to clinical information. The mean, minimum, and maximum ADCs were measured by manually placing regions of interest within the lesions, and the ADC difference value (the difference between minimum and maximum ADCs) was calculated to evaluate intratumoral heterogeneity. Cox proportional hazards models were used to determine the associations between ADC parameters and distant metastasis-free survival after adjustment for clinical-pathologic factors. Results In 25 of the 258 women (9.7%), distant metastasis developed at a median follow-up of 51 months. The ADC difference value was higher in women with distant metastasis than in those without distant metastasis (mean, 0.743 × 10-3 mm2/sec vs 0.566 × 10-3 mm2/sec, respectively; P < .001). Multivariable Cox proportional hazards analysis showed that a higher ADC difference value (>0.698 × 10-3 mm2/sec) (hazard ratio [HR], 4.5; 95% confidence interval [CI]: 2.0, 10.0; P < .001), presence of axillary node metastasis (HR, 3.3; 95% CI: 1.2, 9.3; P = .02), and estrogen receptor negativity (HR, 2.6; 95% CI: 1.2, 5.7; P = .02) were associated with poorer distant metastasis-free survival. Conclusion A higher apparent diffusion coefficient difference value at diffusion-weighted imaging is associated with poorer distant metastasis-free survival of women with invasive breast cancer. © RSNA, 2019 See also the editorial by Taourel in this issue.

Hepatitis C virus genotype 3 was associated with the development of hepatocellular carcinoma in Korea.

Although hepatitis C virus (HCV) genotype 3 infection is thought to be an important risk factor for hepatocellular carcinoma (HCC), current evidence is limited because only a few Western studies have evaluated the occurrence of HCC in patients with HCV genotype 3 infection. We evaluated the impact of genotype 3 and non-3 on HCC incidence and on disease progression in chronic HCV patients; this is the first study reporting such findings in an Asian population. We performed a retrospective cohort study using the data of 1448 consecutive chronic HCV patients evaluated at three centres in Korea between January 2005 and December 2016. Of these, 604, 675 and 169 had genotype 1, genotype 2 and genotype 3 HCV infections, respectively. Over a mean follow-up period of 53.2 months, 75 and 143 patients of all the patients developed HCC and experienced disease progression, respectively. The incidences of HCC were 1.10, 0.92 and 2.50 per 100 person-years, and those of disease progression were 1.95, 1.62 and 6.72 per 100 person-years for HCV genotypes 1, 2 and 3, respectively. In multivariate Cox regression analysis, genotype 3 was associated with an increased risk of HCC (hazard ratio [HR] = 4.26, 95% confidence interval [CI] = 2.02-8.97) and an increased risk of disease progression (HR = 4.88, 95%; CI = 2.94-8.08). Our study proposes that HCV genotype 3 is an independent risk factor for HCC and disease progression in chronic HCV patients.

Risk stratification of ductal carcinoma in situ using whole-lesion histogram analysis of the apparent diffusion coefficient.

OBJECTIVES: To investigate the value of the whole-lesion histogram apparent diffusion coefficient (ADC) metrics for differentiating low-risk from non-low-risk ductal carcinoma in situ (DCIS). METHODS: The authors identified 93 women with pure DCIS who had undergone preoperative MR imaging and diffusion-weighted imaging from 2013 to 2016. Histogram analysis of pixel-based ADC data of the whole tumour volume was performed by two radiologists using a software tool. The results were compared between low-risk and non-low-risk DCIS. Associations between quantitative ADC metrics and low-risk DCIS were evaluated by receiver operating characteristics (ROC) curve and logistic regression analyses. RESULTS: In whole-lesion histogram analysis, mean ADC and 5th, 50th and 95th percentiles of ADC were significantly different between low-risk and non-low-risk DCIS (1.522, 1.207, 1.536 and 1.854 × 10-3 mm2/s versus 1.270, 0.917, 1.261 and 1.657 × 10-3 mm2/s, respectively; p = .004, p = .003, p = .004 and p = .024, respectively). ROC curve analysis for differentiating low-risk DCIS revealed that 5th percentile ADC yielded the largest area under the curve (0.786) among the metrics of whole-lesion histogram, and the optimal cut-off point was 1.078 × 10-3 mm2/s (sensitivity 80%, specificity 75.9%, p = .001). Multivariate regression analysis revealed that a high 5th percentile of ADC (> 1.078× 10-3 mm2/s; odds ratio [OR] = 10.494, p = .016), small tumour size (≤ 2 cm; OR = 12.692, p = .008) and low Ki-67 status (< 14%; OR = 10.879, p = .046) were significantly associated with low-risk DCIS. CONCLUSIONS: Assessment with whole-lesion histogram analysis of the ADC could be helpful for identifying patients with low-risk DCIS. KEY POINTS: • Whole-lesion histogram ADC metrics could be helpful for differentiating low-risk from non-low-risk DCIS. • A high 5th percentile ADC was a significant factor associated with low-risk DCIS. • Risk stratification of DCIS is important for their management.

CK2 downregulation induces senescence-associated heterochromatic foci formation through activating SUV39h1 and inactivating G9a.

Cellular senescence is an irreversible form of cell cycle arrest and senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHF). Here, we present evidence that CK2 downregulation induces trimethylation of histone H3 Lys 9 (H3K9me3), selective binding of HP1γ to H3K9me3, formation of SAHF, and reduction of cyclin D1 expression in HCT116 and MCF-7 cells. CK2 downregulation-mediated H3K9me3 is associated with induction of H3K9 trimethylase SUV39h1 as well as reduction of H3K9 dimethylase G9a and GLP in cells. In addition, Pharmacological inhibition of SUV39h1 and G9a overexpression significantly attenuated induction of senescence-associated ß-galactosidase (SA-ß-gal) activity, H3K9me3 and SAHF formation in CK2-downregulated cells. Moreover, CK2 downregulation induced H3K9me3 in nematodes. Taken together, these results demonstrate that CK2 downregulation leads to H3K9me3 and SAHF formation by increasing SUV39h1 and decreasing G9a.

Diffusion tensor magnetic resonance imaging of breast cancer: associations between diffusion metrics and histological prognostic factors.

OBJECTIVES: To investigate whether quantitative diffusion metrics derived from diffusion tensor imaging (DTI) are associated with histological prognostic factors in breast cancer patients. METHODS: This retrospective study was approved by the institutional review board, and informed consent was waived. Between 2016 and 2017, 251 consecutive women (mean age, 53.8 years) with breast cancer (230 invasive, 21 in situ) who underwent preoperative magnetic resonance (MR) imaging with DTI were identified. Diffusion gradients were applied in 20 directions (b values, 0 and 1,000 s/mm2). DTI metrics - mean diffusivity (MD) and fractional anisotropy (FA) - were measured for breast lesions and contralateral normal breast by two radiologists and were correlated with histological findings using the Mann-Whitney U-test and linear regression analysis. RESULTS: MD and FA were significantly lower for breast cancers than for normal fibroglandular tissues (1.03 ± 0.25×10-3 mm2/s vs. 1.60 ± 0.19×10-3 mm2/s, p < 0.001 and 0.29 ± 0.09 vs. 0.33 ± 0.06, p < 0.001, respectively). Significant differences were observed in MD between invasive cancer and ductal carcinoma in situ lesions (p < 0.001). Multivariate linear analysis showed that larger size (>2 cm) (p = 0.007), high histological grade (grade 3) (p = 0.045) and axillary node metastasis (p = 0.009) were significantly associated with lower MD in invasive breast cancer patients. Larger size (p < 0.001) and high histological grade (p = 0.025) were significantly associated with lower FA. CONCLUSIONS: DTI-derived diffusion metrics, such as MD and FA, are associated with histological prognostic factors in breast cancer patients. KEY POINTS: • MD was significantly lower for breast cancers than for normal breast tissues. • FA was significantly lower for breast cancers than for normal breast tissues. • Reduced DTI metrics were associated with poor prognostic factors of breast cancer. • DTI may provide valuable information concerning biological aggressiveness in breast cancer.

Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience.

BACKGROUND: Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. METHODS: A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. RESULTS: The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. CONCLUSIONS: Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

Age is related to neurological outcome in patients with out-of-hospital cardiac arrest (OHCA) receiving therapeutic hypothermia (TH).

INTRODUCTION: In this study, we retrospectively reviewed the patients' outcomes after cardiac arrest based on age in one center, to determine whether geriatric patients had worse outcomes. METHODS: This was a single-center, retrospective cohort study. The patients admitted to the intensive care unit on successful resuscitation after OHCA were retrospectively identified and evaluated. RESULTS: This was a retrospective cohort study of patients over 18years of-age with return of spontaneous circulation (ROSC) (>24h) after cardiac arrest who were admitted to the emergency intensive care unit (EICU) and received post-cardiac arrest care between March 2007 and December 2013. Finally, a total of 295 patients were enrolled during the study period; of these, 79 patients (36.6%) had a good cerebral performance category (CPC). In stepwise multivariate analysis, young age (per 10years) (odds ratio [OR] 1.42, 95% CI 1.00-1.99, p=0.044), high hemoglobin level (per 1g/dL) (OR 1.31, 95% CI 1.07-1.60, p=0.008), non-diabetic patients (OR 15.21, 95% CI 1.85-125.3, p=0.01), cardiogenic cardiac arrest (OR 8.68, 95% CI 3.72-20.30, p<0.001), pre-hospital cardiopulmonary resuscitation (CPR) by bystander (OR 3.61, 95% CI 1.23-10.57, p=0.019), short time from collapsed to ACLS (per 1min) (OR 1.12, 95% CI 1.06-1.18, p<0.001) had good CPC at 6-month post-admission. CONCLUSION: Elderly patients with OHCA had a poor neurological outcome; but several other factors were also related with the outcome. In decision-making for resuscitation, physicians should consider the patients' physiologic factors as well as age.

Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease-free survival. Conclusion Higher values of CAD-measured peak enhancement and washout component at preoperative MR imaging were significantly associated with poorer disease-free survival of patients with primary operable breast cancer. © RSNA, 2017.

Comparing the Clinical Features and Outcomes of Acute Hepatitis E Viral Infections with Those of Acute Hepatitis A, B, and C Infections in Korea.

OBJECTIVES: This study investigated the etiology of acute viral hepatitis and compared the clinical features of hepatitis E virus (HEV) infections with those of other acute viral hepatitis infections in Korea. METHODS: This study included 2,357 consecutive patients who were diagnosed with acute hepatitis, based on acute illness with jaundice or elevated alanine aminotransferase levels (>100 IU/L), between January 2007 and January 2016. Acute viral infections were observed in 23 (19.8%) patients with HEV, 49 (42.2%) patients with hepatitis A virus, 28 (24.1%) patients with hepatitis B virus, and 16 (13.8%) patients with hepatitis C virus. RESULTS: The incidence of acute HEV infection was higher among older patients (median age: 49 years) and male patients (69.6%), and was associated with the consumption of undercooked or uncooked meat (43.5%). Half of the acute HEV infections involved underlying liver disease, such as alcoholic liver disease, chronic hepatitis B, common bile duct stones, and autoimmune hepatitis. Two HEV-infected patients were diagnosed with Guillain-Barré syndrome, although no patients developed fulminant hepatitis. CONCLUSION: Our findings indicate that HEV infection in Korea is frequently transmitted through the consumption of raw meat and may cause acute or chronic liver disease.

Initial blood pH during cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients: a multicenter observational registry-based study.

BACKGROUND: When an out-of-hospital cardiac arrest (OHCA) patient receives cardiopulmonary resuscitation (CPR) in the emergency department (ED), blood laboratory test results can be obtained by using point-of-care testing during CPR. In the present study, the relationship between blood laboratory test results during CPR and outcomes of OHCA patients was investigated. METHODS: This study was a multicenter retrospective analysis of prospective registered data that included 2716 OHCA patients. Data from the EDs of three university hospitals in different areas were collected from January 2009 to December 2014. Univariate and multivariable analyses were conducted to elucidate the factors associated with survival to discharge and neurological outcomes. A final analysis was conducted by including patients who had no prehospital return of spontaneous circulation and those who underwent rapid blood laboratory examination during CPR. RESULTS: Overall, 2229 OHCA patients were included in the final analysis. Among them, the rate of survival to discharge and a good Cerebral Performance Categories Scale score were 14% and 4.4%, respectively. The pH level was independently related to survival to hospital discharge (adjusted OR 6.287, 95% CI 2.601-15.197; p < 0.001) and good neurological recovery (adjusted OR 15.395, 95% CI 3.439-68.911; p < 0.001). None of the neurologically intact patients had low pH levels (< 6.8) or excessive potassium levels (> 8.5 mEq/L) during CPR. CONCLUSIONS: Among the blood laboratory test results during CPR of OHCA patients, pH and potassium levels were observed as independent factors associated with survival to hospital discharge, and pH level was considered as an independent factor related to neurological recovery.

The Relationship Between the Decreased Rate of Initial Blood Glucose and Neurologic Outcomes in Survivors of Out-of-Hospital Cardiac Arrest Receiving Therapeutic Hypothermia.

BACKGROUND: Hyperglycemia in out-of-hospital cardiac arrest (OHCA) survivors is associated with poor outcomes. However, in the control of initial hyperglycemia, an adequate strategy to improve patients' neurologic outcomes remains undetermined. Prior to the establishment of such strategy, we need to determine whether a decreased rate of initial blood glucose (BG) affects patient outcomes. METHODS: One hundred and forty-five adult non-traumatic OHCA survivors treated with therapeutic hypothermia between April 2007 and December 2011 were enrolled in this single-center retrospective cohort study. Based on the cerebral performance category (CPC) at 6 months after OHCA, study populations were categorized as "Good CPC group" (favorable outcome, CPC1 and CPC2) and "Poor CPC group" (unfavorable outcome, CPC3-CPC5). Variables related to BG were obtained, and the rate of BG change was calculated. RESULTS: In the Good CPC group, the time required to attain target BG levels was shorter [7.4 (2.97-18.13) vs. 13.17 (7.55-27.0) h, p < 0.001], and the average rate of glucose decrease until the attainment of target BG levels was faster [17.06 (6.67-34.49) vs. 8.33 (4.26-18.55) mg/dl/h, p = 0.005] than in the Poor CPC group. Using multivariate analysis, the faster rate (odds ratio 1.074; 95% confidence interval 1.029-1.12; p = 0.001) and the shorter time (odds ratio 13.888; 95% confidence interval 2.271-84.906; p = 0.004) required to attain target BG levels were independently related to favorable neurologic outcomes. CONCLUSIONS: Faster rates of initial BG decrease and the shorter time required to attain target BG levels were associated with favorable neurologic outcome in survivors of OHCA receiving therapeutic hypothermia.