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Background: Ultrasound is increasingly being utilized in the diagnosis and treatment of adhesive capsulitis., Objective: To compare the therapeutic effects and advantages of combined handheld ultrasound and fluoroscopy-guided intra-articular corticosteroid injection with those of conventional ultrasound-guided corticosteroid injection in adhesive capsulitis of the shoulder., Methods: A total of 39 patients diagnosed with adhesive capsulitis of the shoulder were randomly assigned into two groups. Group A patients (n= 19) underwent combined handheld ultrasound and fluoroscopy-guided corticosteroid injection and group B patients (n= 20) underwent conventional ultrasound-guided corticosteroid injection to the intra-articular space of the shoulder twice. Treatment efficacy was assessed at 2 and 6 weeks after the final injection, based on the verbal numeric pain scale, Shoulder Pain and Disability Index, and range of motion. Secondary outcome measures were the accuracy and procedure time., Results: Both injection methods were effective in the treatment of adhesive capsulitis. No significant differences in treatment efficacy and injection accuracy were observed between the two groups (p> 0.05)., Conclusions: This study showed no statistical differences in treatment efficacy between 2 groups. However, the combined use of ultrasound and fluoroscopy can increase the accuracy of injection compared with conventional ultrasound alone.

This prospective study enrolled 147 women with invasive breast cancer who underwent low-dose breast CT (80 kVp, 25 mAs, 1.01-1.38 mSv) before treatment. From each tumor, we extracted eight perfusion parameters using the maximum slope algorithm and 36 texture parameters using the filtered histogram technique. Relationships between CT parameters and histological factors were analyzed using five machine learning algorithms. Performance was compared using the area under the receiver-operating characteristic curve (AUC) with the DeLong test. The AUCs of the machine learning models increased when using both features instead of the perfusion or texture features alone. The random forest model that integrated texture and perfusion features was the best model for prediction (AUC = 0.76). In the integrated random forest model, the AUCs for predicting human epidermal growth factor receptor 2 positivity, estrogen receptor positivity, progesterone receptor positivity, ki67 positivity, high tumor grade, and molecular subtype were 0.86, 0.76, 0.69, 0.65, 0.75, and 0.79, respectively. Entropy of pre- and postcontrast images and perfusion, time to peak, and peak enhancement intensity of hot spots are the five most important CT parameters for prediction. In conclusion, machine learning using texture and perfusion characteristics of breast cancer with low-dose CT has potential value for predicting prognostic factors and risk stratification in breast cancer patients.

There have been relatively few reports of bilateral internal auditory canal metastases of asymptomatic primary pulmonary adenocarcinoma presenting as unilateral sudden sensorineural hearing loss and vertigo. We report a case of a 60-year-old male patient who complained of sudden hearing loss in the right ear and vertigo. Upon a physical examination, no definite neurological signs or nystagmus were observed. Pure-tone audiometry showed deafness in the right ear at all frequencies and high-frequency sensorineural hearing loss in the left ear. The video head impulse test suggested bilateral vestibulopathy. Magnetic resonance imaging of the brain (with gadolinium contrast) revealed bilateral internal auditory canal enhancement and a variable-sized nodular and peripheral-enhancing lesion in the cerebrum and the right cerebellum. A computed tomographic and bronchoscopic biopsy identified asymptomatic primary pulmonary adenocarcinoma in the left upper lobe of the lungs. This is a rare report of bilateral internal auditory canal metastases in an asymptomatic patient with primary pulmonary adenocarcinoma who initially presented with symptoms of unilateral sudden sensorineural hearing loss with vertigo.

Backgrounds: Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies., Objectives: We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs)., Methods: We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 10 7 cells/2 mL), and six patients received a high dose (3.0 × 10 7 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study., Results: After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed., Conclusions: Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy., Trial Registration: ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017., (© 2021. The Author(s).)

Outdated-waste-carbon-fiber-reinforced olefin composites (oCFOCs) were fabricated with easily disposable polyolefin resins, polypropylene (PP), high-density polyethylene (HDPE), and low-density polyethylene (LDPE), by compressive molding using a hot press. The flexural and impact strengths of the oCFOCs from each respective resin type and oCF content, ranging from 35 to 70 wt.%, were increased by the aging treatment (120 °C and 95% humidity under a pressure of 0.8 MPa) until an aging time of three days, due to improved resin impregnation. For the oCFOC with PP, the hydrogen bond between PP and developed C-O groups due to the aging treatment and the existing silane layer of oCF is considered to assist cohesion between the resin and oCF. In particular, PP and 45 wt.% oCF content were the most effective conditions for improving the oCFOCs' mechanical properties, in addition to endowing the oCFOCs with good moldability and dimensional stability. Our results demonstrate that durable recycled composites can be manufactured using oCF and PP.

Calcium oxalate monohydrate (COM) crystal is the most common crystalline component of human kidney stones. The molecular-scale inhibitory mechanisms of COM crystal growth by urinary biomolecules such as citrate and osteopontin adsorbed onto the crystal surface are now well understood. However, the pathways by which dissolved calcium and oxalate ions are incorporated into the molecular step of the COM crystal surface, leading to COM crystal growth-a prerequisite to be elucidated for developing effective therapeutics to inhibit COM stones-remain unknown. Here, using in situ liquid-phase atomic microscopy along with a step kinetic model, we reveal the pathways of the calcium and oxalate ions into the COM molecular step via the growth speed analysis of the molecular steps with respect to their step width at the nanoscale. Our results show that, primarily, the ions are adsorbed onto the terrace of the crystal surface from the solution-the rate-controlling stage for the molecular step growth, i.e., COM crystal growth-and then diffuse over it and are eventually incorporated into the steps. This primary pathway of the ions is unaffected by the model peptide D-Asp 6 adsorbed on the COM crystal surface, suggesting that urinary biomolecules will not alter the pathway. These new findings rendering an essential understanding of the fundamental growth mechanism of COM crystal at the nanoscale provide crucial insights beneficial to the development of effective therapeutics for COM kidney stones.

Background: Although inflammatory breast cancer (IBC) has poor overall survival (OS), there is little information about using imaging features for predicting the prognosis. Computed tomography (CT)-based texture analysis, a non-invasive technique to quantify tumor heterogeneity, could be a potentially useful imaging biomarker. The aim of the article was to investigate the usefulness of chest CT-based texture analysis to predict OS in IBC patients. Methods: Of the 3,130 patients with primary breast cancers between 2006 and 2016, 104 patients (3.3%) with IBC were identified. Among them, 98 patients who underwent pre-treatment contrast-enhanced chest CT scans, got treatment in our institution, and had a follow-up period of more than 2 years were finally included for CT-based texture analysis. Texture analysis was performed on CT images of 98 patients, using commercially available software by two breast radiologists. Histogram-based textural features, such as quantification of variation in CT attenuation (mean, standard deviation, mean of positive pixels [MPP], entropy, skewness, and kurtosis), were recorded. To dichotomize textural features for survival analysis, receiver operating characteristic curve analysis was used to determine cutoff points. Clinicopathologic variables, such as age, node stage, metastasis stage at the time of diagnosis, hormonal receptor positivity, human epidermal growth factor receptor 2 positivity, and molecular subtype, were assessed. A Cox proportional hazards model was used to determine the association of textural features and clinicopathologic variables with OS. Results: During a mean follow-up period of 47.9 months, 41 of 98 patients (41.8%) died, with a median OS of 20.0 months. The textural features of lower mean attenuation, standard deviation, MPP, and entropy on CT images were significantly associated with worse OS, as was the M1 stage among clinicopathologic variables (all P- values < 0.05). In multivariate analysis, lower mean attenuation (hazard ratio [HR], 3.26; P = 0.003), lower MPP (HR, 3.03; P = 0.002), and lower entropy (HR, 2.70; P = 0.009) on chest CT images were significant factors independent from the M1 stage for predicting worse OS. Conclusions: Lower mean attenuation, MPP, and entropy on chest CT images predicted worse OS in patients with IBC, suggesting that CT-based texture analysis provides additional predictors for OS., Competing Interests: BG is the Co-Founder/Co-Inventor of TexRAD texture analysis software used in this study and a shareholder (not an employee) of Feedback Plc., a UK based company which owns, develops and markets the TexRAD texture analysis software. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Song, Seo, Cho, Woo, Ganeshan, Kim and Cha.)

Purpose: To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) for additional MR-detected enhancing lesions and to determine whether or not kinetic pattern results comparable to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast can be obtained using the quantitative analysis of CEUS., Materials and Methods: In this single-center prospective study, a total of 71 additional MR-detected breast lesions were included. CEUS examination was performed, and lesions were categorized according to the Breast Imaging-Reporting and Data System (BI-RADS). The sensitivity, specificity, and diagnostic accuracy of CEUS were calculated by comparing the BI-RADS category to the final pathology results. The degree of agreement between CEUS and DCE-MRI kinetic patterns was evaluated using weighted kappa., Results: On CEUS, 46 lesions were assigned as BI-RADS category 4B, 4C, or 5, while 25 lesions category 3 or 4A. The diagnostic performance of CEUS for enhancing lesions on DCE-MRI was excellent, with 84.9% sensitivity, 94.4% specificity, and 97.8% positive predictive value. A total of 57/71 (80%) lesions had correlating kinetic patterns and showed good agreement (weighted kappa = 0.66) between CEUS and DCE-MRI. Benign lesions showed excellent agreement (weighted kappa = 0.84), and invasive ductal carcinoma (IDC) showed good agreement (weighted kappa = 0.69)., Conclusion: The diagnostic performance of CEUS for additional MR-detected breast lesions was excellent. Accurate kinetic pattern assessment, fairly comparable to DCE-MRI, can be obtained for benign and IDC lesions using CEUS., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)

Background: The aim of this study was to evaluate the efficacy of early amiodarone-based pharmacological cardioversion for postoperative atrial fibrillation (POAF) following off-pump coronary bypass grafting (OPCAB)., Methods: A total of 507 patients who underwent OPCAB between 2015 and 2017 were categorized into POAF (n=94) and no-POAF (n=413) groups. Patients in the POAF group were treated according to the following institutional protocol: 150 mg loading dose of intravenous amiodarone, followed by oral administration with sequential maintenance doses at 600, 400, and 200 mg per day. If sinus rhythm was restored before discharge, patients were discharged without amiodarone or anticoagulants, except for dual antiplatelets., Results: Before discharge at index hospitalization, 97.8% of POAF patients had restored sinus rhythm. Independent risk factors for POAF were age, unstable angina, prior percutaneous transluminal coronary angioplasty, and left atrial diameter. The mean follow-up duration was 41.1±12.8 months. Freedom from overall mortality and composite events, including mortality, major bleeding requiring admission and cerebrovascular events, were similar between the 2 groups. Results were consistent after propensity-score matching., Conclusions: Amiodarone-based rapid pharmacological cardioversion of POAF resulted in a high sinus rhythm conversion rate (97.9%). Rate of late adverse cardiovascular events including stroke, were low even without anticoagulation. As optimal treatment and anticoagulation guidelines for POAF after OPCAB have not yet been established, amiodarone-based treatment protocols may be considered as a useful option., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-466). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Recently, ovarian cancer research has evolved considerably because of the emerging recognition that rather than a single disease, ovarian carcinomas comprise several different histotypes that vary by etiologic origin, risk factors, molecular profiles, therapeutic approaches and clinical outcome. Despite significant progress in our understanding of the etiologic heterogeneity of ovarian cancer, as well as important clinical advances, it remains the eighth most frequently diagnosed cancer in women worldwide and the most fatal gynecologic cancer. The International Agency for Research on Cancer and the United States National Cancer Institute jointly convened an expert panel on ovarian carcinoma to develop consensus research priorities based on evolving scientific discoveries. Expertise ranged from etiology, prevention, early detection, pathology, model systems, molecular characterization and treatment/clinical management. This report summarizes the current state of knowledge and highlights expert consensus on future directions to continue advancing etiologic, epidemiologic and prognostic research on ovarian carcinoma., (Published by Oxford University Press 2021.)

Studies have shown bacteria influence the initiation and progression of cancers arising in sites that harbor rich microbial communities, such as the colon. Little is known about the potential for the microbiome to influence tumorigenesis at sites considered sterile, including the upper female genital tract. The recent identification of distinct bacterial signatures associated with ovarian carcinomas suggests microbiota in the gut, vagina, or elsewhere might contribute to ovarian cancer pathogenesis. Here, we tested whether altering the microbiome affects tumorigenesis in a mouse model of high-grade serous carcinoma (HGSC) based on conditional oviduct-specific inactivation of the Brca1 , Trp53 , Rb1 , and Nf1 tumor suppressor genes. Cohorts of control ( n = 20) and antibiotic-treated ( n = 23) mice were treated with tamoxifen to induce tumor formation and then monitored for 12 months. The antibiotic cocktail was administered for the first 5 months of the monitoring period in the treatment group. Antibiotic-treated mice had significantly fewer and less advanced tumors than control mice at study endpoint. Antibiotics induced changes in the composition of the intestinal and vaginal microbiota, which were durable in the fecal samples. Clustering analysis showed particular groups of microbiota are associated with the development of HGSC in this model. These findings demonstrate the microbiome influences HGSC pathogenesis in an in vivo model that closely recapitulates the human disease. Because the microbiome can modulate efficacy of cancer chemo- and immunotherapy, our genetically engineered mouse model system may prove useful for testing whether altering the microbiota can improve the heretofore poor response of HGSC to immunotherapies. SIGNIFICANCE: This study provides strong in vivo evidence for a role of the microbiome in ovarian cancer pathogenesis., (©2021 American Association for Cancer Research.)

Background: Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered., Methods: The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case-control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted., Results: Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50-0.85). There was a statistically significant trend of decreasing risk with increasing duration of use ( P trend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk., Conclusions: DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted., Impact: The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect., (©2021 American Association for Cancer Research.)

Background: In diffusion-weighted imaging (DWI) of breast MRI, simultaneous multislice acceleration techniques can be used for readout-segmented echo planar imaging (rs-EPI) to shorten the scan time., Purpose: To compare the image quality, apparent diffusion coefficient (ADC) value, and scan time of rs-EPI and simultaneous multislice rs-EPI (SMS rs-EPI) sequences., Study Type: Retrospective., Subjects: In all, 134 consecutive women (mean age: 55.3 years) with invasive breast cancer who underwent preoperative MRI., Field Strength/ Sequences: 3.0T; rs-EPI sequence, prototypic SMS rs-EPI sequence and dynamic contrast-enhanced MRI (DCE-MRI) sequence ASSESSMENT: For quantitative comparison, two radiologists independently measured the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), lesion contrast, and apparent diffusion coefficient (ADC). For qualitative comparison, image quality, lesion conspicuity, and reader preference were assessed with a reference of DCE-MRI., Statistical Tests: Paired t-tests and Mann-Whitney tests were used., Results: For SNR and CNR, there were no differences between the sequences (P = 0.342 and 0.665 for reader 1; P = 0.606 and P = 0.116 for reader 2). Lesion contrast of SMS rs-EPI was higher than that of rs-EPI (P < 0.05 for both reader 1 and reader 2). Mean tumor ADC was similar in rs-EPI and SMS rs-EPI sequences (0.98 ± 0.22 vs. 1.00 ± 0.22; P = 0.291 for reader 1, 0.98 ± 0.21 vs. 1.00 ± 0.22; P = 0.418 for reader 2). Regarding qualitative comparison, image quality and lesion conspicuity were higher in SMS rs-EPI than in rs-EPI (both P < 0.05 for both readers). The two readers regarded SMS rs-EPI as superior or equal to rs-EPI in over 90% of cases. The acquisition time was 4:30 minutes for rs-EPI and 2:31 minutes for SMS rs-EPI., Data Conclusion: The SMS rs-EPI sequence resulted in a similar ADC value and better image quality than the rs-EPI sequence in a 44.1% reduced scan time., Level of Evidence: 4 TECHNICAL EFFICACY: 3., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objective: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC., Methods: We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27)., Results: The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004)., Conclusion: GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

Background: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical., Methods: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients., Results: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness., Conclusions: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

This study aimed to compare the surgical outcomes and morbidities of retrosigmoid and translabyrinthine approaches for large vestibular schwannoma (VS), with a focus on cerebellar injury and morbidities. Eighty-six consecutive patients with large VS, with a maximal extrameatal diameter > 3.0 cm, were reviewed between August 2010 and September 2018. The surgical outcomes, operating time, volume change of perioperative cerebellar edema, and inpatient rehabilitation related to cerebellar morbidities were compared between the two approaches. In total, 53 and 33 patients underwent the retrosigmoid and translabyrinthine approaches, respectively. The median follow-up time was 34.5 months. Surgical outcomes, including the extent of resection, tumor recurrence, and facial nerve preservation, showed no significant differences between the two groups. Patients who underwent the retrosigmoid approach showed a marginal trend for postoperative lower cranial nerve (LCN) dysfunction (P = 0.068). Although the approaching procedure time was longer in the translabyrinthine group, the tumor resection time was significantly longer in the retrosigmoid group (P = 0.001). The median change in the volume of the perioperative cerebellar edema was significantly larger in the retrosigmoid group (P < 0.001) and significantly related to the retrosigmoid approach, solid VS, and tumor resection time. Most cerebellar and LCN deficits were transient; however, the patients in the retrosigmoid group underwent inpatient rehabilitation more than those in the translabyrinthine group (P = 0.018). Both surgical approaches show equivalent surgical outcomes. Notably, the translabyrinthine approach for large VS has advantages in that it reduces cerebellar injury and related morbidities.

Background: Shear wave elastography (SWE) is an ultrasound technique for the noninvasive quantification of tissue stiffness. The hypoxic tumor microenvironment promotes tumor stiffness and is associated with poor prognosis in cancer. We aimed to investigate the correlation between tumor hypoxia and histologic biomarkers and tumor stiffness measured by SWE in breast cancer., Methods: From June 2016 to January 2018, 82 women with invasive breast cancer who underwent SWE before treatment were enrolled. Average tumor elasticity (E average ) and tumor-to-fat elasticity ratio (E ratio ) were extracted from SWE. Immunohistochemical staining of glucose transporter 1 (GLUT1) was used to assess tumor hypoxia in breast cancer tissues and automated digital image analysis was performed to assess GLUT1 activities. Spearman correlation and logistic regression analyses were performed to identify associations between GLUT1 expression and SWE values, histologic biomarkers, and molecular subtypes. The Mann-Whitney U test, t test, or Kruskal-Wallis test was used to compare SWE values and histologic features according to the GLUT1 expression (≤the median vs > median)., Results: E average (r = 0.676) and E ratio (r = 0.411) correlated significantly with GLUT1 expression (both p <  0.001). E average was significantly higher in cancers with estrogen receptor (ER)-, progesterone receptor (PR)-, Ki67+, and high-grade (p <  0.05). E ratio was higher in cancers with Ki67+, lymph node metastasis, and high-grade (p <  0.05). Cancers with high GLUT1 expression (>median) had higher E average (mean, 85.4 kPa vs 125.5 kPa) and E ratio (mean, 11.7 vs 17.9), and more frequent ER- (21.7% vs 78.3%), PR- (26.4% vs 73.1%), Ki67+ (31.7%% vs 68.3%), human epidermal growth factor receptor 2 (HER2) + (25.0% vs 75.0%), high-grade (28.6% vs 71.4%), and HER2-overexpressing (25.0% vs 75.0%) and triple-negative (23.1% vs 76.9%) subtypes (p <  0.05). Multivariable analysis showed that E average was independently associated with GLUT1 expression (p <  0.001)., Conclusions: Tumor stiffness on SWE is significantly correlated with tumor hypoxia as well as histologic biomarkers. In particular, E average on SWE has independent prognostic significance for tumor hypoxia in the multivariable analysis and can potentially be used as a noninvasive imaging biomarker to predict prognosis and pretreatment risk stratification in breast cancer patients.

Mesonephric adenocarcinoma is a rare tumor, accounting for <1% of cervical cancers. Well-differentiated mesonephric adenocarcinoma can be difficult to distinguish from diffuse mesonephric hyperplasia. Herein, we report a case of well-differentiated mesonephric adenocarcinoma with an FGFR2 mutation not previously reported in the literature. Nonselective tyrosine kinase inhibitors or FGFR2 inhibitors may represent options for targeted therapy.

Purpose: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival., Methods: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery., Results: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival., Conclusions: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism., Competing Interests: Declaration of Competing Interest Usha Menon has stocks in Abcodia awarded to her by University College London., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The treatment methodology as well as efficacy of stereotactic radiosurgery on numerous brain metastases has not been clearly established despite it being a primary modality for brain metastasis treatment. This study aimed to evaluate the efficacy of two-staged gamma knife radiosurgery (GKS) for patients with more than 10 metastatic lesions., Patients and Methods: Staged GKS was applied to 52 patients diagnosed with numerous metastases when a single radiosurgery was unbearable, or the exposed brain volume was excessive. Large clinically significant lesions in the eloquent area were treated in first GKS. The remainders were radiated in second GKS within a 4-week interval. The study evaluated three primary outcomes: 1) the radiological response at second GKS and 3-month follow up, 2) treatment-related side effects, and 3) survival after staged GKS treatment., Results: Irradiated lesions of 17 (32.7 %) patients showed radiological response on MRI at second GKS. Lesions non-treated at first GKS progressed in 13 (25.0 %) patients during the same period. At the 3-month follow-up, 5 (9.6 %) and 7 (13.5 %) patients were partially responsive and stable, respectively. Given that some patients expired from mostly non-neurological causes before the third follow-up, we could not detect an un-biased radiological progression. Nine (17.3 %) among 52 patients suffered grade 1-3 toxicity until the second GKS, whereas 4 (15.4 %) among 26 survivors suffered grade 1-2 CNS toxicity, but the relationship between irradiation and toxicity remained unclear. Survival rates for 52 patients at 3, 6, 12, 18 and 24 months were 63.9 %, 44.1 %, 23.3 %, 17.8 %, and 13.3 %, respectively. Longer survival after staged GKS treatment was observed in patients with KPS ≥ 80 rather than <70, RPA II rather than III, and PIV < 7000 mm 3 . However, the number of target lesions more or less than 10 was not correlated with survival., Conclusion: Although the clinical benefit as well as survival gain could not be clearly presented in this study, two-staged GKS for numerous metastases seems to benefit the patients' convenience and risk avoidance. Selected patients, especially with no other treatment options, can be candidates for this treatment protocol., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to evaluate the potential of radiomics as an imaging biomarker for glioblastoma (GBM) patients and explore the molecular rationale behind radiomics using a radio-genomics approach. A total of 144 primary GBM patients were included in this study (training cohort). Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model, which we validated using an independent validation cohort. GBM patients were consensus clustered to reveal inherent phenotypic subtypes. GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis ("heterogenous enhancing", "rim-enhancing necrotic", and "cystic" subtypes). Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation and flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis). This study showed that imaging subtypes derived from radiomics successfully recapitulated the genomic underpinnings of GBMs and thereby confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation.

Background: Recently, ultrasound- (US-) guided selective nerve root block (SNRB) has been reported to have similar effects compared to fluoroscopy- (FL-) guided cervical epidural steroid injection (CESI). There is no published study comparing the therapeutic efficacy and safety of interlaminar- (IL-) CESI and transforaminal- (TF-) CESI with US-guided SNRB. Our retrospective study aimed to compare the mid-term effects and advantages of the US-guided SNRB, FL-guided IL-CESI, and TF-CESI for radicular pain in the lower cervical spine through assessment of pain relief and functional improvement., Methods: Patients with radicular pain in the lower cervical spine who received guided SNRB ( n  = 44) or FL-guided IL ( n  = 41) or TF-CESI ( n  = 37) were included in this retrospective study. All procedures were performed using a FL or US. The complication frequencies during the procedures, adverse event, treatment effects, and functional improvement were compared at 1, 3, and 6 months after the last injection., Results: Both the Neck Disability Index (NDI) and Verbal Numeric Scale (VNS) scores showed improvements at 1, 3, and 6 months after the last injection in all groups, with no significant differences between groups ( P < 0.05). Furthermore, the treatment success rate at all time points was not significantly different between groups. Logistic regression analysis revealed that the injection method (US- or FL-guided), cause, sex, age, number of injections, and pain duration were not independent predictors of treatment success. Blood was aspirated before injection in 7% ( n  = 3), 14% ( n  = 6), and 0% patients in the FL-guided IL, TF, and US-guided groups, respectively. In 2 patients of FL-guided IL and 7 of FL-guided TF group, intravascular contrast spread was noted during injection., Conclusions: Our results suggest that, compared with FL-guided IL and TF-CESI, US-guided SNRB has a low intravascular injection rate; it is unlikely that serious complications will occur. Also, US-guided SNRB requires a shorter administration duration while providing similar pain relief and functional improvements. Therefore, for the treatment of patients with lower cervical radicular pain, US-guided SNRB should be considered as a prior epidural steroid injection., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jin Hyuk Jang et al.)

Introduction: The clinical benefit of stereotactic radiosurgery (SRS) in the treatment of malignant glioma remains controversial. We analyzed failure patterns of malignant gliomas following SRS to identify the clinical implications of SRS against these malignancies., Materials and Methods: We retrospectively reviewed 58 consecutive patients who received SRS with a gamma knife for their malignant glioma from January 2013 to December 2018. A total of 51 patients were available for analysis of failure patterns. Failure patterns were defined by the recurrent tumors' spatial relation to SRS target as follows: in-field local recurrence, remote recurrence, and leptomeningeal seeding. If patients demonstrated several types of failure patterns simultaneously, we categorized them as a combined failure pattern., Results: In-field local recurrence was found in 47.1% of patients. Other types of failure patterns were as follows: remote recurrence (19.6%), leptomeningeal seeding (13.7%), and combined failure pattern (19.6%). The majority of patients (52.9%) experienced disease progression beyond the radiation field of SRS, which implies limited efficacy of local therapy against these invasive tumors. The prognosis of patients differed according to failure pattern and patients with local recurrence had better survival outcomes compared to other types of disease progression (p-value = 0.0015, log-rank test)., Conclusions: This study illustrated that SRS could not improve survival of malignant gliomas significantly even when it had some effect within radiation field. Our findings support utilizing a multidisciplinary treatment strategy to improve the prognosis of malignant gliomas and suggest that SRS is one element of that treatment strategy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS., Methods: From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space., Results: Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up., Conclusions: Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

Background: Computer-aided detection (CAD) can detect breast lesions by using an enhancement threshold. Threshold means the percentage of increased signal intensity in post-contrast imaging compared to precontrast imaging. If the pixel value of the enhanced tumor increases above the set threshold, CAD provides the size of the tumor, which is calculated differently depending on the set threshold. Therefore, CAD requires the accurate setting of thresholds. We aimed to compare the diagnostic accuracy of tumor size measurement using MRI and CAD with 3 most commonly used thresholds and to identify which threshold is appropriate on CAD in breast cancer patients., Methods: A total of 130 patients with breast cancers (80 invasive cancers and 50 ductal carcinoma in situ [DCIS]) who underwent preoperative MRI with CAD and surgical treatment were included. Tumor size was manually measured on first contrast-enhanced MRI and acquired by CAD using 3 different thresholds (30, 50, and 100%) for each tumor. Tumor size measurements using MRI and CAD were compared with pathological sizes using Spearman correlation analysis. For comparison of size discrepancy between imaging and pathology, concordance was defined as estimation of size by imaging within 5 mm of the pathological size. Concordance rates were compared using Chi-square test., Results: For both invasive cancers and DCIS, correlation coefficient rho (r) between tumor size on imaging and pathology was highest at CAD with 30% threshold, followed by MRI, CAD with 50% threshold, and CAD with 100% threshold (all p <  0.05). For invasive cancers, the concordance rate of 72.5% at CAD with 30% threshold showed no difference with that of 62.5% at MRI (p = 0.213). For DCIS, the concordance rate of 30.0% at CAD with 30% threshold showed no difference with that of 36.0% at MRI (p = 0.699). Compared to MRI, higher risk of underestimation was noted when using CAD with 50% or 100% threshold for invasive cancers and when using CAD with 100% threshold for DCIS., Conclusion: For CAD analysis, 30% threshold is the most appropriate threshold whose accuracy is comparable to manual measurement on MRI for tumor size measurement. However, clinicians should be aware of the higher risk of underestimation when using CAD with 50% threshold for tumor staging in invasive cancers.

Background Radiogenomic investigations for breast cancer provide an understanding of tumor heterogeneity and discover image phenotypes of genetic variation. However, there is little research on the correlations between US features of breast cancer and whole-transcriptome profiling. Purpose To explore US phenotypes reflecting genetic alteration relevant to breast cancer treatment and prognosis by comparing US images of tumor with their RNA sequencing results. Materials and Methods From January to October 2016, B-mode and vascular US images in 31 women (mean age, 49 years ± 9 [standard deviation]) with breast cancer were prospectively analyzed. B-mode features included size, shape, echo pattern, orientation, margin, and calcifications. Vascular features were evaluated by using microvascular US and contrast agent-enhanced US: vascular index, vessel morphologic features, distribution, penetrating vessels, enhancement degree, order, margin, internal homogeneity, and perfusion defect. RNA sequencing was conducted with total RNA obtained from a surgical specimen by using next-generation sequencing. US features were compared with gene expression profiles, and ingenuity pathway analysis was used to analyze gene networks, enriched functions, and canonical pathways associated with breast cancer. The P value for differential expression was extracted by using a parametric F test comparing nested linear models. Results Thirteen US features were associated with various patterns of 340 genes ( P < .05). Nonparallel orientation at B-mode US was associated with upregulation of TFF1 (log twofold change [log2FC] = 4.0; P < .001), TFF3 (log2FC = 2.5; P < .001), AREG (log2FC = 2.6; P = .005), and AGR3 (log2FC = 2.6; P = .003). Complex vessel morphologic structure was associated with upregulation of FZD8 (log2FC = 2.0; P = .01) and downregulation of IGF1R (log2FC = -2.0; P = .006) and CRIPAK (log2FC = -2.4; P = .01). The top networks with regard to orientation or vessel morphologic structure were associated with cell cycle, death, and proliferation. Conclusion Compared with RNA sequencing, B-mode and vascular US features reflected genomic alterations associated with hormone receptor status, angiogenesis, or prognosis in breast cancer. © RSNA, 2020 Online supplemental material is available for this article .

Our goal is to fabricate flexible magnetic polymer composites as antenna substrates for very high frequency (VHF)/low ultra high frequency (UHF) antennas for unmanned aerial vehicles (UAVs) and medical devices. Magnetodielectric materials, which have permeability ( μ ) similar to permittivity ( ε ), have attracted great attention, because they facilitate miniaturization of microwave devices while keeping or enhancing electromagnetic characteristics. Mechanically millled Ba 1.5 Sr 1.5 Co 2 Fe 24 O 41 (Ba 1.5 Sr 1.5 Z) hexaferrite particles were used to increase permeability in the interesting frequency band. The microwave properties of Ba 1.5 Sr 1.5 Z composites were predicted and measured. Hansen's zero-order analysis of antenna bandwidth and electromagnetic field simulation showed that the hexaferrite-based flexible composite could enhance a bandwidth and achieve the miniaturization of antennas as well. The magnetic antenna substrates can be a good solution to integrate antennas into the UAVs whose dimensions are comparable to or larger than communication wavelength.

Robust preclinical models of ovarian high-grade serous carcinoma (HGSC) are needed to advance our understanding of HGSC pathogenesis and to test novel strategies aimed at improving clinical outcomes for women with the disease. Genetically engineered mouse models of HGSC recapitulating the likely cell of origin (fallopian tube), underlying genetic defects, histology, and biologic behavior of human HGSCs have been developed. However, the degree to which the mouse tumors acquire the somatic genomic changes, gene expression profiles, and immune microenvironment that characterize human HGSCs remains unclear. We used integrated molecular characterization of oviductal HGSCs arising in the context of Brca1, Trp53, Rb1 , and Nf1 ( BPRN ) inactivation to determine whether the mouse tumors recapitulate human HGSCs across multiple domains of molecular features. Targeted DNA sequencing showed the mouse BPRN tumors, but not endometrioid carcinoma-like tumors based on different genetic defects (e.g., Apc and Pten ), acquire somatic mutations and widespread copy number alterations similar to those observed in human HGSCs. RNA sequencing showed the mouse HGSCs most closely resemble the so-called immunoreactive and mesenchymal subsets of human HGSCs. A combined immuno-genomic analysis demonstrated the immune microenvironment of BPRN tumors models key aspects of tumor-immune dynamics in the immunoreactive and mesenchymal subtypes of human HGSC, with enrichment of immunosuppressive cell subsets such as myeloid-derived suppressor cells and regulatory T cells. The findings further validate the BPRN model as a robust preclinical experimental platform to address current barriers to improved prevention, diagnosis, and treatment of this often lethal cancer. SIGNIFICANCE: The acquired gene mutations, broad genomic alterations, and gene expression and immune cell-tumor axis changes in a mouse model of oviductal serous carcinoma closely mirror those of human tubo-ovarian high-grade serous carcinoma., (©2019 American Association for Cancer Research.)

Objectives: Surgical resection of nonfunctioning pituitary adenoma (NFPA) invading the cavernous sinus (CS) remains a challenging and significant factor associated with incomplete resection. The residual tumor in CS is usually treated with adjuvant stereotactic radiosurgery (SRS), but there is little information concerning SRS as an initial treatment for CS-invading NFPA. In this study, we investigated the tumor control rate and clinical outcomes of the patients who received primary gamma knife radiosurgery (GKRS) for CS-invading NFPA., Methods: This was a single-institute retrospective analysis of 11 patients. CS invasion of tumor was categorized using the modified Knosp grading system. The median tumor volume and maximal diameter were 1.6 cm3 (range 0.4-6.5) and 17.2 mm (range 11.6-23.3), respectively. The median clinical follow-up period was 48.5 months (range 16.4-177.8). The median prescription dose at tumor margin was 15 Gy (range 11-25) and median prescription isodose was 50% (range 45-50). The maximum radiation dose to optic chiasm and optic nerve were 7.2 Gy (range 3.4-9.2) and 7.5 Gy (range 4.5-11.5), respectively., Results: Tumor control was achieved in all patients. The median tumor volume and maximal diameter at last follow-up were 0.4 cm3 (range 0.1-2.3) and 11.4 mm (range 4.7-19.5), respectively. The median volume reduction rate was 52% (range 33-88). Six patients showed downgrading of modified Knosp grade after GKRS. No patients developed GKRS-related complications such as hypopituitarism or visual disturbance., Conclusions: SRS may be an alternative primary treatment option for CS-invading NFPA if there is no urgent and absolute indication for surgery such as optic apparatus compression., (© 2020 S. Karger AG, Basel.)

Purpose: Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major concern. We aimed to investigate the clinical efficacy and safety of fractionated SRS (fSRS) versus single-session SRS (sSRS) for malignant gliomas., Methods: We retrospectively reviewed 58 malignant glioma patients who underwent gamma knife SRS from January 2015 to December 2018. Forty-one underwent sSRS, and 17 underwent fSRS. Median dose for fSRS was 28 Gy (range 24-35 Gy), with a median dose of 6 Gy per fraction (range 5-7 Gy). Patients received 4 or 5 fractions on consecutive days. Median dose for sSRS was 18 Gy (range 11-25 Gy), with a median isodose of 50% (range 50-65%). Mean target volumes were 5.9 and 19.3 cc for sSRS and fSRS, respectively (p < 0.001, two-sided t test)., Results: After SRS, median progression-free survival (PFS) was 4.5 and 4.6 months (p = 0.58), and median overall survival (OS) was 12.7 and 12.6 months for sSRS and fSRS (p = 0.41), respectively (log-rank test). The incidence of clinically significant radiation necrosis was 20.5% (8/39) and 18.8% (3/16) for sSRS and fSRS, respectively (p = 1, Fisher's exact test)., Conclusion: fSRS for malignant glioma conferred local control and survival comparable with conventional sSRS. The radiation necrosis incidence was comparable between groups when a parallel biological effective dose was administered to the larger target volumes in the fSRS group. fSRS can be a better alternative to sSRS if re-irradiation is considered for large malignant gliomas.

Radiogenomics investigates the relationship between imaging phenotypes and genetic expression. Breast cancer is a heterogeneous disease that manifests complex genetic changes and various prognosis and treatment response. We investigate the value of machine learning approaches to radiogenomics using low-dose perfusion computed tomography (CT) to predict prognostic biomarkers and molecular subtypes of invasive breast cancer. This prospective study enrolled a total of 723 cases involving 241 patients with invasive breast cancer. The 18 CT parameters of cancers were analyzed using 5 machine learning models to predict lymph node status, tumor grade, tumor size, hormone receptors, HER2, Ki67, and the molecular subtypes. The random forest model was the best model in terms of accuracy and the area under the receiver-operating characteristic curve (AUC). On average, the random forest model had 13% higher accuracy and 0.17 higher AUC than the logistic regression. The most important CT parameters in the random forest model for prediction were peak enhancement intensity (Hounsfield units), time to peak (seconds), blood volume permeability (mL/100 g), and perfusion of tumor (mL/min per 100 mL). Machine learning approaches to radiogenomics using low-dose perfusion breast CT is a useful noninvasive tool for predicting prognostic biomarkers and molecular subtypes of invasive breast cancer.

Somatic APC (adenomatous polyposis coli), TP53, KRAS mutations are present in roughly 80%, 60%, and 40%, respectively, of human colorectal cancers (CRCs). Most TP53 mutant alleles in CRCs encode missense mutant proteins with loss-of-function (LOF) of p53's transcriptional activity and dominant negative (DN) effects on wild-type p53 function. Missense mutant p53 proteins have been reported to exert gain-of-function (GOF) effects in cancer. We compared the phenotypic effects of the common human cancer-associated TP53 R273H missense mutation to p53 null status in a genetically engineered mouse CRC model. Inactivation of one allele of Apc together with activation of a Kras mutant allele in mouse colon epithelium instigated development of serrated and hyperplastic epithelium and adenomas (AK mice). Addition of a Trp53 R270H or Trp53 null mutant allele to the model (AKP mice) led to markedly shortened survival and increased tumor burden relative to that of AK mice, including adenocarcinomas in AKP mice. Comparable life span and tumor burden were seen in AKP mice carrying Trp53 R270H or Trp53 null alleles, along with similar frequencies of spontaneous metastasis to lymph nodes, lung, and liver. The fraction of adenocarcinomas with submucosa or deeper invasion was higher in AKP 270/fl mice than in AKP fl/fl mice, but the incidence of adenocarcinomas per mouse did not differ significantly between AKP fl/fl and AKP 270/fl mice. In line with their comparable biological behaviors, mouse primary tumors and tumor-derived organoids with the Trp53 R270H or Trp53 null alleles had highly similar gene expression profiles. Human CRCs with TP53 R273 missense mutant or null alleles also had essentially homogeneous gene expression patterns. Our findings indicate the R270H/R273H p53 mutant protein does not manifest definite GOF biological effects in mouse and human CRCs, suggesting possible GOF effects of mutant p53 in cancer phenotypes are likely allele-specific and/or context-dependent.

Purpose: The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS) for large brain metastases (BMs) according to different interfraction intervals., Methods: Between September 2016 and May 2018, a total of 45 patients who underwent FGKRS for BMs were enrolled in this study. They were divided into two groups (standard fractionation over 3 consecutive days with a 24-h interfraction interval versus prolonged fractionation over 4 or 5 days with an interfraction interval of at least 48-h). BMs with ≥ 2 cm in maximum diameter or ≥ 5 cm 3 in volume were included in analysis., Results: Among 52 BMs treated with 3-fraction GKRS, 25 (48.1%) were treated with standard fractionation scheme, and 27 (51.9%) with prolonged fractionation scheme. The median follow-up period was 10.5 months (range 5-25). Local tumor control rates of the standard group were 88.9% at 6 months and 77.8% at 12 months, whereas those of the prolonged group were 100% at 6 and 12 months (p = 0.023, log-rank test). In multivariate analysis, fractionation scheme (hazard ratio [HR] 0.294, 95% CI 0.099-0.873; p = 0.027) and tumor volume (HR 0.200, 95% CI 0.051-0.781; p = 0.021) were revealed as the only significant factors affecting the local tumor control after 3-fraction GKRS., Conclusions: Our preliminary tumor control results suggest a promising role of 3-fraction GKRS with an interfraction interval of at least 48-h. This fractionation regimen could be an effective and safe treatment option in the management of large BMs.

Most high-grade serous carcinomas are thought to arise from Fallopian tube epithelium (FTE), but some likely arise outside of the tube, perhaps from ectopic tubal-type epithelium known as endosalpingiosis. Importantly, the origin of endosalpingiosis is poorly understood. The proximity of the tubal fimbriae to the ovaries has led to the proposal that disruptions in the ovarian surface that occur during ovulation may allow detached FTE to implant in the ovary and form tubal-type glands and cysts. An alternative model suggests that cells present in ectopic locations outside the Müllerian tract retain the capacity for multi-lineage differentiation and can form glands with tubal-type epithelium. We used double transgenic Ovgp1-iCreER T2 ;R26R LSL-eYFP mice, which express an eYFP reporter protein in OVGP1-positive tissues following transient tamoxifen (TAM) treatment, to track the fate of oviductal epithelial cells. Cohorts of adult mice were given TAM to activate eYFP expression in oviductal epithelium, and ovaries were examined at time points ranging from 2 days to 12 months post-TAM. To test whether superovulation might increase acquisition of endosalpingiosis, additional cohorts of TAM-treated mice underwent up to five cycles of superovulation and ovaries were examined at 1, 6, and 12 months post-TAM. Ovaries were sectioned in their entirety to identify endosalpingiosis. Immunohistochemical staining for PAX8, tubulin, OVGP1, and eYFP was employed to study endosalpingiosis lesions. Ovarian endosalpingiosis was identified in 14.2% of TAM-treated adult mice. The endosalpingiotic inclusion glands and cysts were lined by secretory and ciliated cells and expressed PAX8, tubulin, OVGP1, and eYFP. Neither age nor superovulation was associated with a significant increase in endosalpingiosis. Endosalpingiosis was also occasionally present in the ovaries of pre-pubertal mice. The findings imply that ovarian endosalpingiosis in the mouse does not likely arise as a consequence of detachment and implantation of tubal epithelium and other mechanisms may be relevant. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Sternal wound complications could increase the hospital cost while decreasing the satisfaction of surgery. Furthermore, it can potentially also lead to life-threatening mediastinitis especially after coronary artery bypass grafting using bilateral internal thoracic artery (BITA). Skill levels of suture technique vary among surgeons and may contribute to an increased wound complication rate. Thus, standardization of surgical wound closure could potentially decrease the surgeon factor. The aim of the study is to compare the wound complication rate between non-invasive surgical skin closure devices (zip surgical skin closure device, Zipline Medical, Campbell, CA, USA) and conventional suture closure., Methods: Three hundred seventy-nine patients who underwent off-pump coronary artery bypass grafting (OPCAB) using BITAs at our institution between 2016 and 2018 were included in this study. Patients were divided into two groups; the Zipline group (zip-group, N=100), and conventional group (con-group, N=279). Following propensity score matching, 95 con-group patients were matched to 169 zip-group patients., Results: The average age and history of cancer were significantly higher in the zip-group (P=0.021 and P=0.023, respectively). However, after propensity score matching, no differences were observed in the demographic data between the groups. In total patients (unmatched), although there was no significant difference in the incidence of deep sternal wound infection (DSWI) between the two groups (zip vs. con, 0% vs. 1.1%, P=0.569), the incidence of post-operative superficial sternal wound infection (SSWI) or dehiscence was significantly higher in the con-group than in the zip-group (1.0% vs. 7.9%, P=0.013). The results were consistent in the matched patients. (DSWI: 0% vs. 0.6%, P>0.999; SSWI or dehiscence: 1.1% vs. 7.1%, P=0.036). Multivariable analysis revealed use of the zip surgical skin closure device showed a preventive effect against wound complications [odds ratio (OR): 0.128, 95% confidence interval (CI): 0.017-0.976, P=0.029]., Conclusions: Zip surgical skin closure devices could decrease superficial wound complication rates compared to conventional suture techniques in OPCAB using BITAs., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Objective: Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM., Methods: The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival., Results: Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5-25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%-29%) in the 9-Gy group, and 37% (95% CI 1%-58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1-51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1-29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups., Conclusions: In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

The insufficient electrical conductivity and mechanical stretchability of conventional graphene fibers based on reduced graphene oxide liquid crystals (rGO-LCs) has limited their applications to numerous textile devices. Here, we report a simple method to fabricate multifunctional fibers with mechanically strong rGO cores and highly conductive CVD graphene shells (rGO@Gr fibers), which show an outstanding electrical conductivity as high as ∼137 S cm-1 and a failure strain value of 21%, which are believed to be the highest values among polymer-free graphene fibers. We also demonstrate the use of the rGO@Gr fibers for high power density supercapacitors with enhanced mechanical stability and durability, which would enable their practical applications in various smart wearable devices in the future.

Rationale: Sarcomatoid carcinoma is a rare variant of squamous cell carcinoma (SCC) with poor prognosis. Previous radiation has been reported as one of the etiologic factors., Patient Concerns: We describe a case of a 57-year-old man presented with a painless mass in the left supraclavicular area. Five years before, he was diagnosed with SCC in floor of mouth (FOM) and underwent radiotherapy (RT)., Diagnoses: Sonography-guided biopsy on the supraclavicular lymph node revealed diffuse spindle cell proliferation with a focus of squamous differentiation. Local recurrence on primary site or distant metastasis was not obvious on both computed tomography (CT) of the neck and F-fluorodeoxyglucose positron emission tomography CT. The final diagnosis was confirmed as sarcomatoid carcinoma via surgery., Interventions: The patient underwent surgery including explorative resection of the mouth floor, excision of the submandibular gland, and modified radical neck dissection. Following surgery, the patient received adjuvant radiation therapy., Outcomes: There were no complications according to the surgery. Six months after adjuvant therapy, distant metastasis to liver was identified. The patient is currently undergoing palliative chemotherapy., Lessons: This may be the first reported case of sarcomatoid carcinoma arising from early-stage SCC in FOM that was previously treated with RT alone. When RT is performed as a single modality for oral SCC, even in an early stage, rigorous follow-up should be performed.

Objective: Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS., Methods: The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non-small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3-5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6-10 Gy) with a 50% isodose line., Results: On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9-94 weeks). During the follow-up period, local recurrence occurred in 5 lesions., Conclusions: The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

Objectives: The aim of this study was to investigate the feasibility of using low-dose perfusion computed tomography (CT) in breast cancers for quantification of tumor vascularity and to correlate perfusion indexes with prognostic biomarkers., Materials and Methods: This preliminary study was approved by our institutional review board. Signed informed consent was obtained from all 70 enrolled patients with invasive breast cancers. Low-dose perfusion CT was performed with the patient in the prone position using a spectral CT device set at 80 kVp and 30 mAs (1.30-1.40 mSv). Images were analyzed using commercial software applying the maximum slope algorithm. On CT perfusion maps, perfusion (mL/min per 100 mL), blood volume (mL/100 g), time-to-peak enhancement (second), and peak enhancement intensity (HU) were measured in the tumor, normal breast glandular tissues, and fat. Tumor grade, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, CT perfusion indexes of the tumor and normal glandular tissues or fat were compared using the Wilcoxon signed-rank test, and CT indexes were correlated with histological characteristics using the Mann-Whitney U or Kruskal-Wallis tests. We also correlated CT indexes with magnetic resonance imaging enhancement characteristics., Results: In breast cancers, perfusion, blood volume, and peak enhancement intensity values were significantly higher, and time to peak was shorter than in normal glandular tissues and fat (P < 0.001). Perfusion increased significantly in high-grade, ER-, or HER2+ cancers (P < 0.05). Time to peak decreased in ER-, HER2+, and high-grade cancers or in those with high Ki67 levels (P < 0.05). Peak enhancement intensity significantly increased in high-grade cancers (P < 0.05). HER2 overexpressing cancers showed significantly higher perfusion and shorter time to peak than luminal-type cancers (P < 0.05). Perfusion increased and time to peak decreased significantly in cancers with washout enhancement patterns on magnetic resonance imaging., Conclusions: Low-dose perfusion CT in the prone position is feasible to quantify tumor vascularity in breast cancers, and CT perfusion indexes are significantly correlated with prognostic biomarkers and molecular subtypes of breast cancer.

Objective: The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation., Methods: We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study., Results: Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up., Conclusion: GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.

Objective: To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD)., Materials and Methods: Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed., Results: Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS ( p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively ( p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD ( p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD ( p < 0.05)., Conclusion: US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD., Competing Interests: Author Bo Kyoung Seo has received research grants from Korea government and Canon Medical Systems Korea Co.,Ltd. The remaining authors declare that they have no conflict of interest., (Copyright © 2019 The Korean Society of Radiology.)

Purpose: Currently in diagnostic setting for breast cancer, FFDM and DBT are performed conjunctively. However, performing two imaging modalities may increase radiation exposure by double. Two-dimensional reconstructed images created from DBT with 2DSM, has a potential to replace conventional FFDM in concerning both radiation dosage and image quality. With increasing concerns for individual radiation exposure, studies analyzing radiation dosage in breast imaging modalities are needed. This study compared radiation dosage and image quality between DBT + 2DSM versus FFDM., Methods and Materials: 374 patients (mean age 52 years) who underwent both DBT and FFDM were retrospectively reviewed. Radiation dosage data were obtained by radiation dosage scoring and monitoring program Radimetrics (Bayer HealthCare, Whippany, NJ). Entrance dose and mean glandular doses in each breast were obtained for both modalities. To compare image quality of DBT + 2DSM and FFDM, a 5-point scoring system for lesion clarity was assessed. The parameters of radiation dosage (entrance dose, mean glandular dose) and image quality (lesion clarity scoring) were compared., Results: For entrance dose, DBT had lower mean dosage (14.8 mGy) compared with FFDM (21.8 mGy, p-value < 0.0001). Mean glandular doses for both breasts were lower in DBT (Left 1.74, Right 2.1) compared with FFDM (Left 2.85, Right 2.74, p-value < 0.0001). Lesion clarity score was higher in DBT with 2DSM (mean score 4.03) compared with FFDM (3.82, p-value < 0.0001)., Conclusion: DBT showed lower radiation entrance dose and mean glandular doses to both breasts compared with FFDM. DBT + 2DSM had better image quality than FFDM, suggesting that DBT with 2DSM has potential as an alternative to FFDM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The molecular events driving low-grade endometrioid endometrial carcinoma (LGEC) development-like in many cancers-are incompletely understood. Hence, here we performed multiregion, comprehensive somatic molecular profiling of routinely processed formalin-fixed, paraffin-embedded (FFPE) material from 13 cases of LGEC totaling 64 minute, spatially defined cell populations ranging from presumed precursor lesions through invasive LGEC. Shared driving PTEN, PIK3R1 , or PIK3CA mutations support clonal origin of the samples in each case, except for two cases with two clonally distinct neoplastic populations, consistent with unexpected multiclonality in LGEC development. Although substantial heterogeneity in driving somatic alterations was present across populations in nearly all cases, these alterations were usually clonal in a given population, supporting continued selection and clonal sweeping of driving alterations in populations with both precursor and LGEC histology. Importantly, CTNNB1 mutational status, which has been proposed as both prognostic and predictive in LGEC, was frequently heterogeneous and subclonal, occurring both exclusively in precursor or cancer populations in different cases. Whole-transcriptome profiling of coisolated RNA from 12 lesions (from 5 cases) was robust and confirmed histologic and molecular heterogeneity, including activated Wnt signaling in CTNNB1 -mutant versus wild-type populations. Taken together, we demonstrate clinically relevant multiclonality and intratumoral heterogeneity during LGEC development with important implications for diagnosis, prognosis, and therapeutic prediction. More broadly, our methodology is broadly scalable to enable high-throughput genomic and transcriptomic characterization of precursor and invasive cancer populations from routine FFPE specimens. IMPLICATIONS: Multiregion profiling of LGEC populations using a highly scalable approach demonstrates clinically relevant multiclonality and intratumoral heterogeneity., (©2019 American Association for Cancer Research.)

Objective: To investigate the correlation of kinetic features of breast cancers on computer-aided diagnosis (CAD) of preoperative 3T magnetic resonance imaging (MRI) data and clinical-pathologic factors in breast cancer patients., Materials and Methods: Between July 2016 and March 2017, 85 patients (mean age, 54 years; age range, 35-81 years) with invasive breast cancers (mean, 1.8 cm; range, 0.8-4.8 cm) who had undergone MRI and surgery were retrospectively enrolled. All magnetic resonance images were processed using CAD, and kinetic features of tumors were acquired. The relationships between kinetic features and clinical-pathologic factors were assessed using Spearman correlation test and binary logistic regression analysis., Results: Peak enhancement and angio-volume were significantly correlated with histologic grade, Ki-67 index, and tumor size: r = 0.355 ( p = 0.001), r = 0.330 ( p = 0.002), and r = 0.231 ( p = 0.033) for peak enhancement, r = 0.410 ( p = 0.005), r = 0.341 ( p < 0.001), and r = 0.505 ( p < 0.001) for angio-volume. Delayed-plateau component was correlated with Ki-67 ( r = 0.255 [ p = 0.019]). In regression analysis, higher peak enhancement was associated with higher histologic grade (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.001-1.008; p = 0.024), and higher delayed-plateau component and angio-volume were associated with higher Ki-67 (O r = 1.051; 95% CI: 1.011-1.094; p = 0.013 for delayed-plateau component, OR = 1.178; 95% CI: 1.023-1.356; p = 0.023 for angio-volume)., Conclusion: Of the CAD-assessed kinetic features, higher peak enhancement may correlate with higher histologic grade, and higher delayed-plateau component and angio-volume correlate with higher Ki-67 index. These results support the clinical application of kinetic features in prognosis assessment., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

We sought to evaluate the outcomes of postoperative three-month dual antiplatelet therapy in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) following off-pump coronary artery bypass grafting (OPCAB) with exclusively arterial grafts. Between 2013⁻2016, dual antiplatelet therapy (DAPT) with either aspirin + clopidogrel (ASA + CPD group, n = 100) or aspirin + ticagrelor (ASA + TCG group, n = 169) was prescribed postoperatively in 269 NSTE-ACS patients after total arterial OPCAB. Patients with indications for other oral anticoagulants were excluded from the study. Three-month DAPT was completed in 259 patients (96%); ASA + CPD group ( n = 94) vs. ASA + TCG group ( n = 165). A one-to-one propensity score matching was performed. Unadjusted comparison between the groups showed no significant difference in overall survival ( P = 0.253) and composite outcome of major adverse cerebrovascular and cardiovascular event (MACCE) and major bleeding ( P = 0.276). The rate of freedom from composite outcome at one year in the ASA + CPD and ASA + TCG groups was 91 ± 3% and 93 ± 2%, respectively. In multivariable analysis, being in the ASA + TCG group did not increase the risk of the composite outcome of MACCE and major bleeding ( P = 0.972, hazard ratio: 1.0, 95% confidence interval: 0.4⁻2.3). Propensity score-matched comparison (76 pairs) showed no significant difference in the overall survival ( P = 0.423) and composite outcome between the groups ( P = 0.442). In the setting of exclusive arterial grafting, post-OPCAB three-month DAPT showed acceptable outcomes in patients with NSTE-ACS. There was no significant difference in overall survival or composite outcome of MACCE and major bleeding between the ASA + CPD and ASA + TCG groups.