Comprehensive tissue deconvolution of cell-free DNA by deep learning for disease diagnosis and monitoring.

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

Characterization of Microwave Generator Energy and Ablation Volumes following Transarterial Embolization in an In Vivo Porcine Liver Model.

PURPOSE: To characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. MATERIALS AND METHODS: With Institutional Animal Care and Use Committee (IACUC) approval, 11 female swine underwent either right (n = 5) or left (n = 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound (US)-guided MWA was performed in each liver segment (left lateral, left medial, right medial, and right lateral) at either 30 W (n = 4 lobes), 60 W (n = 4), 65 W (n = 20), 90 W (n = 8), 120 W (n = 4), or 140 W (n = 4) continuously for 5 minutes. Postprocedural volumetric segmentation was performed on standardized multiphase T1 magnetic resonance (MR) imaging sequences. RESULTS: Mean AZVs in embolized lobes (15.8 mL ± SD 10.6) were significantly larger than those in nonembolized lobes (11.2 mL ± SD 6.5, P < .01). MWA energy demonstrated significant positive linear correlation with both embolized (R2 = 0.66, P < .01) and nonembolized (R2 = 0.64, P < .01) lobes. The slope of the linear models corresponded to a 0.95 mL/kJ (SD ± 0.16) and 0.54 mL/kJ (SD ± 0.09) increase in ablation volume per applied kilojoule of energy (E) in embolized and nonembolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the following interaction term: 0.42∗E∗(embolization status) (P = .031). CONCLUSIONS: Linear models demonstrated a near 1.8-fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to nonembolized lobes. Absolute AZV differences between embolized and nonembolized lobes were greater at higher-power MWA.

A Systematic Review of Neurophysiology-Based Localization Techniques Used in Deep Brain Stimulation Surgery of the Subthalamic Nucleus.

OBJECTIVE: This systematic review is conducted to identify, compare, and analyze neurophysiological feature selection, extraction, and classification to provide a comprehensive reference on neurophysiology-based subthalamic nucleus (STN) localization. MATERIALS AND METHODS: The review was carried out using the methods and guidelines of the Kitchenham systematic review and provides an in-depth analysis on methods proposed on STN localization discussed in the literature between 2000 and 2021. Three research questions were formulated, and 115 publications were identified to answer the questions. RESULTS: The three research questions formulated are answered using the literature found on the respective topics. This review discussed the technologies used in past research, and the performance of the state-of-the-art techniques is also reviewed. CONCLUSION: This systematic review provides a comprehensive reference on neurophysiology-based STN localization by reviewing the research questions other new researchers may also have.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model.

Airway-associated adipose tissue increases with body mass index and is a local source of pro-inflammatory adipokines that may contribute to airway pathology in asthma co-existing with obesity. Genetic susceptibility to airway adiposity was considered in the present study through kisspeptin/kisspeptin receptor signalling, known to modulate systemic adiposity and potentially drive airway remodelling. Therefore, the aim of the study was to determine the effects of kisspeptin/kisspeptin receptor signalling in the lung, focusing on airway-associated adipose tissue deposition and impact on airway structure-function. Wild-type, heterozygous and kisspeptin receptor knockout mice were studied at 6 or 8 weeks of age. Lung mechanics were assessed before and after methacholine challenge and were subsequently fixed for airway morphometry. A separate group of mice underwent glucose tolerance testing and bronchoalveolar lavage. At 6 weeks of age, kisspeptin/kisspeptin receptor signalling did not affect body adiposity, airway inflammation, wall structure or function. Despite no differences in body adiposity, there was a greater accumulation of airway-associated adipose tissue in knockout mice. By 8 weeks of age, female knockout mice displayed a non-diabetic phenotype with increased body adiposity but not males. Airway-associated adipose tissue area was also increased in both knockout females and males at 8 weeks of age, but again no other respiratory abnormality was apparent. In summary, airway-associated adipose tissue is decoupled from body adiposity in prepubescent mice which supports a genetic susceptibility to fatty deposits localised to the airway wall. There was no evidence that airway-associated adipose tissue drives pathology or respiratory impairment in the absence of other environmental exposures.

MR imaging biomarkers in HCC: outcomes correlation in liver transplant listed patients.

PURPOSE: To determine hepatocellular carcinoma (HCC) magnetic resonance imaging (MRI) biomarkers that enable the prediction of delisting from tumor progression versus successful transplantation in patients listed for orthotopic liver transplantation (OLT). METHODS: With IRB approval and HIPPA compliance, patients with HCC awaiting OLT who were delisted due to HCC progression from 2006 to 2015 were identified. Patients with adequate MR images for review were subsequently matched with a cohort of patients successfully bridged to OLT in the same time period. Matching considered the tumor stage and the dominant treatment strategy adopted to bridge the patient to OLT. Potential MRI features were evaluated by univariable and multivariable analysis using a conditional logistic model. RESULTS: There were 53 patients included in each cohort. On uni-variable analysis, significant unfavorable MR imaging features included T2 hyperintensity (odds ratio [OR], 19.0), infiltrative border (OR, 7.50), lobulated shape (OR, 4.5), T1 hypointensity (OR, 3.0), heterogeneous arterial enhancement (OR, 7.0), and corona venous enhancement (OR, 4.0). A significant favorable MR imaging feature was the presence of intralesional fat (OR = .36). The best multivariable logistic prediction model derived from the above notable features included only T1 and T2 signal intensity, border definition, and absence of intra-lesional fat as significant variables, with an area under the receiver operating characteristic curve (AUC) of .86 in the prediction of delisting. CONCLUSION: Select MR imaging features of HCC at presentation before any treatment are significantly associated with the risk of tumor progression regardless of tumor stage and treatment strategy in patients awaiting liver transplantation.

Hepatocellular Adenoma Subtypes Based on 2017 Classification System: Exploratory Study of Gadoxetate Disodium-Enhanced MRI Features With Proposal of a Diagnostic Algorithm.

BACKGROUND. The classification of hepatocellular adenomas (HCAs) was updated in 2017 on the basis of genetic and molecular analysis. OBJECTIVE. The purpose of this article was to evaluate features on gadoxetate disodium-enhanced MRI of HCA subtypes on the basis of the 2017 classification and to propose a diagnostic algorithm for determining subtype using these features. METHODS. This retrospective study included 56 patients (49 women, seven men; mean age, 37 ± 13 [SD] years) with histologically confirmed HCA evaluated by gadoxetate disodium-enhanced MRI from January 2010 to January 2021. Subtypes were reclassified using 2017 criteria: hepatocyte nuclear factor-1α mutated HCA (HHCA), inflammatory HCA (IHCA), ß-catenin exon 3 activated HCA (ß-HCA), mixed inflammatory and ß-HCA (ß-IHCA), sonic hedgehog HCA (shHCA), and unclassified HCA (UHCA). Qualitative MRI features were assessed. Liver-to-lesion contrast enhancement ratios (LLCERs) were measured. Subtypes were compared, and a diagnostic algorithm was proposed. RESULTS. The analysis included 65 HCAs: 16 HHCAs, 31 IHCAs, six ß-HCA, four ß-IHCA, five shHCA, and three UHCAs. HHCAs showed homogeneous diffuse intralesional steatosis in 94%, whereas all other HCAs showed this finding in 0% (p < .001). IHCAs showed the "atoll" sign in 58%, whereas all other HCAs showed this finding in 12% (p < .001). IHCAs showed moderate T2 hyperintensity in 52%, whereas all other HCAs showed this finding in 12% (p < .001). The ß-HCAs and ß-IHCAs occurred in men in 63%, whereas all other HCAs occurred in men in 4% (p < .001). The ß-HCAs and ß-IHCAs had a mean size of 10.1 ± 6.8 cm, whereas all other HCAs had a mean size of 5.1 ± 2.9 cm (p = .03). The ß-HCAs and ß-IHCAs showed fluid components in 60%, whereas all other HCAs showed this finding in 5% (p < .001). Hepatobiliary phase iso- or hyperintensity was observed in 80% of ß-HCAs and ß-IHCAs versus 5% of all other HCAs (p < .001). Hepatobiliary phase LLCER was positive in nine HCAs (eight ß-HCAs and ß-IHCAs; one IHCA). The shHCA and UHCA did not show distinguishing features. The proposed diagnostic algorithm had accuracy of 98% for HHCAs, 83% for IHCAs, and 95% for ß-HCAs or ß-IHCAs. CONCLUSION. Findings on gadoxetate disodium-enhanced MRI, including hepatobiliary phase characteristics, were associated with HCA subtypes using the 2017 classification. CLINICAL IMPACT. The algorithm identified common HCA subtypes with high accuracy, including those with ß-catenin exon 3 mutations.

Hepatocellular Adenomas: Molecular Basis and Multimodality Imaging Update.

Hepatocellular adenomas (HCAs) are a family of liver tumors that are associated with variable prognoses. Since the initial description of these tumors, the classification of HCAs has expanded and now includes eight distinct genotypic subtypes based on molecular analysis findings. These genotypic subtypes have unique derangements in their cellular biologic makeup that determine their clinical course and may allow noninvasive identification of certain subtypes. Multiphasic MRI performed with hepatobiliary contrast agents remains the best method to noninvasively detect, characterize, and monitor HCAs. HCAs are generally hypointense during the hepatobiliary phase; the ß-catenin-mutated exon 3 subtype and up to a third of inflammatory HCAs are the exception to this characterization. It is important to understand the appearances of HCAs beyond their depictions at MRI, as these tumors are typically identified with other imaging modalities first. The two most feared related complications are bleeding and malignant transformation to hepatocellular carcinoma, although the risk of these complications depends on tumor size, subtype, and clinical factors. Elective surgical resection is recommended for HCAs that are persistently larger than 5 cm, adenomas of any size in men, and all ß-catenin-mutated exon 3 HCAs. Thermal ablation and transarterial embolization are potential alternatives to surgical resection. In the acute setting of a ruptured HCA, patients typically undergo transarterial embolization with or without delayed surgical resection. This update on HCAs includes a review of radiologic-pathologic correlations by subtype and imaging modality, related complications, and management recommendations. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

CT-monitored minimal ablative margin control in single-session microwave ablation of liver tumors: an effective strategy for local tumor control.

OBJECTIVES: To investigate the usefulness of minimal ablative margin (MAM) control by intra-procedural contrast-enhanced CT (CECT) in microwave ablation (MWA) of liver tumors. METHODS: A total of 334 consecutive liver tumors (240 hepatocellular carcinomas [HCCs] and 94 colorectal liver metastases [CRLMs]) in 172 patients treated with percutaneous MWA were retrospectively included. MAM of each tumor was assessed after expected ablation completion using intra-procedural CECT, allowing within-session additional ablation to any potentially insufficient margin. On immediate post-MWA MRI, complete ablation coverage of tumor and final MAM status were determined. The cumulative local tumor progression (LTP) rate was estimated by using the Kaplan-Meier method. To identify predictors of LTP, Cox regression analysis with a shared frailty model was performed. RESULTS: Intra-procedural CECT findings prompted additional ablation in 18.9% (63/334) of tumors. Final complete ablation coverage of tumor and sufficient MAM were determined by MRI to be achieved in 99.4% (332/334) and 77.5% (259/334), and their estimated 6-month, 1-year, and 2-year LTP rates were 3.2%, 7.5%, and 12.9%; and 1.0%, 2.1%, and 6.9%, respectively. Insufficient MAM on post-MWA MRI, perivascular tumor location, and tumor size (cm) were independent risk factors for LTP (hazard ratio = 14.4, 6.0, and 1.1, p < 0.001, p = 0.003, and p = 0.011, respectively), while subcapsular location and histology (HCC vs CRLM) were not. CONCLUSIONS: In MWA of liver tumors, intra-procedural CECT monitoring of minimal ablative margin facilitates identification of potentially suboptimal margins and guides immediate additional intra-session ablation to maximize rates of margin-sufficient ablations, the latter being a highly predictive marker for excellent long-term local tumor control. KEY POINTS: • In MWA of liver tumors, intra-procedural CECT can identify potentially suboptimal minimal ablative margin, leading to immediate additional ablation in a single treatment session. • Achieving a finally sufficient ablative margin through the MWA with intra-procedural CECT monitoring of minimal ablative margin results in excellent local tumor control.

SMOKING, RURAL RESIDENCE AND DIABETES AS RISK FACTORS FOR PRESUMED OCULAR HISTOPLASMOSIS SYNDROME.

PURPOSE: To investigate the relationship of smoking, urbanicity, and diabetes to presumed ocular histoplasmosis syndrome (POHS) and associated choroidal neovascularization (CNV). METHODS: Medical records of 751 adult patients with POHS were reviewed, including 603 patients without CNV and 148 patients with CNV. Age-matched and gender-matched controls were randomly selected from the same practice for comparison. Statistical comparisons of smoking history, urbanicity, and diabetic history were performed using chi-square and conditional logistic regression analyses. RESULTS: Increased rates of current or former smoking, rural residence, and diabetes were found in patients with POHS compared with controls. POHS patients with CNV had increased rates of current or former smoking and rural residence as compared with controls. CONCLUSION: A history of current or past smoking is associated with an increased risk of developing both POHS alone and POHS with CNV. We did not find a significant additional risk of smoking on the development of CNV in patients with POHS. Patients living in rural locations are more likely than those in urban locations to develop both POHS and POHS with CNV. Diabetics may be more likely to develop POHS than nondiabetics.

Optimization of Intraoperative Neural Monitoring of the Recurrent Laryngeal Nerve in Thyroid Surgery.

The application of intraoperative neural monitoring (IONM) has been widely accepted to improve surgical outcomes after thyroid surgery. The malfunction of an IONM system might interfere with surgical procedures. Thus, the development of anesthesia modalities aimed at ensuring functional neuromonitoring is essential. Two key issues should be taken into consideration for anesthetic management. Firstly, most patients undergo recurrent laryngeal nerve monitoring via surface electrodes embedded in an endotracheal tube. Thus, advanced video-assisted devices might optimize surface electrode positioning for improved neuromonitoring signaling accuracy. Secondly, neuromuscular blocking agents are routinely used during thyroid surgery. The ideal neuromuscular block should be deep enough for surgical relaxation at excision and recovered enough for an adequate signal f nerve stimulation. Proper neuromuscular block management could be achieved by titration doses of muscle relaxants and reversal agents.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Optimizing Spatial Biopsy Sampling for the Detection of Prostate Cancer.

PURPOSE: The appropriate number of systematic biopsy cores to retrieve during magnetic resonance imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling approach that reduces required core count while maintaining diagnostic performance. MATERIALS AND METHODS: We collected data from a cohort of 971 men who underwent MRI-ultrasound fusion targeted biopsy for suspected prostate cancer. A regional targeted biopsy (RTB) was evaluated retrospectively; only cores within 2 cm of the margin of a radiologist-defined region of interest were considered part of the RTB. We compared detection rates for clinically significant prostate cancer (csPCa) and cancer upgrading rate on final whole mount pathology after prostatectomy between RTB, combined, MRI-targeted, and systematic biopsy. RESULTS: A total of 16,459 total cores from 971 men were included in the study data sets, of which 1,535 (9%) contained csPCa. The csPCa detection rates for systematic, MRI-targeted, combined, and RTB were 27.0% (262/971), 38.3% (372/971), 44.8% (435/971), and 44.0% (427/971), respectively. Combined biopsy detected significantly more csPCa than systematic and MRI-targeted biopsy (p <0.001 and p=0.004, respectively) but was similar to RTB (p=0.71), which used on average 3.8 (22%) fewer cores per patient. In 102 patients who underwent prostatectomy, there was no significant difference in upgrading rates between RTB and combined biopsy (p=0.84). CONCLUSIONS: A RTB approach can maintain state-of-the-art detection rates while requiring fewer retrieved cores. This result informs decision making about biopsy site selection and total retrieved core count.

Image-Guided Percutaneous Thermal Ablation of Oligometastatic Ovarian and Non-Ovarian Gynecologic Tumors.

PURPOSE: To assess the safety, feasibility, and efficacy of percutaneous thermal ablation (TA) in the treatment of metastatic gynecologic (GYN) tumors. MATERIALS AND METHODS: A study cohort of 42 consecutive women (mean age, 59. years; range, 25-78 years) with metastatic GYN tumors (119 metastatic tumors) treated with radiofrequency (n = 47 tumors), microwave (n = 47 tumors), or cryogenic (n = 30 tumors) ablation from over 2,800 ablations performed from January 2001 to January 2019 was identified. The primary GYN neoplasms consisted of ovarian (27 patients; 77 tumors; mean tumor diameter [MTD], 2.50 cm), uterine (7 patients; 26 tumors; MTD, 1.89 cm), endometrial (5 patients; 10 tumors; MTD, 2.8 cm), vaginal (2 patients; 5 tumors; MTD, 2.40 cm), and cervical (1 patient; 1 tumor; MTD, 1.90 cm) cancers. In order of descending frequency, metastatic tumors treated by TA were located in the liver or liver capsule (74%), lungs (13%), and peritoneal implants (9%). Single tumors were also treated in the kidneys, rectus muscle, perirectal soft tissue (2.5%), and retroperitoneal lymph nodes (1.6%). All efficacy parameters of TA and definitions of major and minor adverse events are categorized by the latest Society of Interventional Radiology reporting standards. RESULTS: The median follow-up of treated patients was 10 months. After the initial ablation, 95.6% of the patients achieved a complete tumor response confirmed by contrast-enhanced magnetic resonance imaging or computed tomography. On surveillance imaging, 8.5% of the ablated tumors developed local progression over a median follow-up period of 4.1 months. Five of 8 tumors with local recurrence underwent repeated treatment over a mean follow-up period of 18 months, and 4 of 5 tumors achieved complete eradication after 1 additional treatment session that resulted in a secondary efficacy of 80%. The overall technique efficacy of TA was 96.2% over a median follow-up period of 10 months. CONCLUSIONS: TA was safe and effective for the local control of metastatic GYN tumors in the lungs, abdomen, and pelvis, with an overall survival rate of 37.5 months and a local progression-free survival rate of 16.5 months, with only 4.8% of treated patients experiencing a major adverse event.

Histogram-based analysis of cerebral blood flow using arterial spin labeling MRI in de novo brain gliomas: relationship to histopathologic grade and molecular markers.

PURPOSE: We developed multiple histogram-based CBF indices and evaluated their association with histopathologic grade in de novo brain tumor patients. Furthermore, the associations between these advanced CBF indices and molecular markers, including IDH1 mutation, ATRX loss, and 1p/19q co-deletion were also investigated. METHODS: Thirteen de novo brain tumor patients (age 21-68 years, 9 M/4F) who were enrolled in our prospective study were scanned on 3 T MRI using a pCASL perfusion sequence following IRB-approved written informed consent. All patients have since undergone surgical intervention with tissue sampling for histopathologic tumor grading and molecular marker assessment. Tumor region of interest (ROI) were manually delineated on FLAIR images including the full extent of the tumor and peritumoral edema. Fourteen rCBF indices were derived from the histogram of the voxels with the ROI. Multi-linear regression was then used to compare rCBF indices with histopathologic tumor grade and molecular markers. RESULTS: Averaged rCBF in top 10 and top 20 voxels (p < 0.004), but not the entire tumor ROI, was positively associated with WHO tumor grade. After accounting for tumor grade, the presence of 1p/19q co-deletion was associated with higher rCBF in top voxels, as well as with standard deviation of rCBF in the tumor ROI (p < 0.001). ATRX retention was related to higher rCBF, and this effect appears to be present in both higher-perfusion (p < 0.004) and low-perfusion (p < 0.05) voxels. IDH mutation was not significantly associated with any of the CBF indices investigated. CONCLUSION: ASL MRI may provide useful supplemental noninvasive imaging assessment of brain tumor grade and molecular marker status.

Evaluating patient knowledge and use of medication disposal in a Chinatown community pharmacy.

BACKGROUND: Drug take-back programs (TBPs) provide the opportunity to safely dispose of unused or expired medications (UEMs), potentially reducing the risk of environmental harm and morbidity. Data on patient perceptions and participation are limited, especially in underserved Asian populations. OBJECTIVE: This study aimed to evaluate medication disposal perceptions and behaviors through a free mail-in medication disposal program among patients in a Chinatown community pharmacy. METHODS: An institutional review board-approved Web-based survey was developed in English and Mandarin. Student pharmacists tabled at a Chinatown community pharmacy in Boston, Massachusetts. The patients were educated about safe medication disposal practices and invited to take the anonymous survey assessing medication disposal needs, practices, and beliefs accessed in person by using a quick response code. On survey completion, the patients were offered a disposal envelope. Envelope tracking numbers were used to evaluate medication disposal over a 9-month follow-up period. RESULTS: Sixty-two patients of Asian descent completed the survey, and 42 (67.7%) accepted an envelope. Forty-seven patients (75.8%) reported having access to UEMs. More than half indicated that TBPs were important to alleviate the risk of medication and environmental consequences despite low previous use (6.5%). Most patients felt more aware of TBPs (72.6%), an increased sense of the importance of TBPs (74.2%), and intent to participate in TBPs (69.4%), including using the envelope (75.8%). Three (4.8%) patients disposed of medications using the study-provided envelope during the 9-month follow-up. CONCLUSION: Patient education about TBPs and their importance may be effective in increasing TBP awareness in a population with low TBP use. Free disposal envelopes did not seem to be highly used within 9 months of receipt despite interest and access to UEMs. Future research should continue offering programs at no charge, evaluating barriers to free TBP use, and implementing follow-up procedures to increase envelope use.

Physiological modulation of endogenous BRCA1 p220 abundance suppresses DNA damage during the cell cycle.

Endogenous BRCA1 p220 expression peaks in S and G2 when it is activated, and the protein participates in certain key DNA damage responses. In contrast, its expression is markedly reduced in G0/G1. While variations in transcription represent a significant part of p220 expression control, there is at least one other relevant process. We found that a microRNA, miR-545, that is expressed throughout the cell cycle down-modulates endogenous p220 mRNA and protein abundance directly in both G0/G1 and S/G2. When miR-545 function was inhibited by a specific antagomir, endogenous p220 expression increased in G0/G1, and aberrant p220-associated DNA damage responses and de novo DNA strand breaks accumulated. Analogous results were observed upon inhibition of miR-545 function in S/G2. Both sets of antagomir effects were mimicked by infecting cells with a p220 cDNA-encoding adenoviral vector. Thus, strand breaks were a product of p220 overexpression, and their prevention by miR-545 depends on its modulation of p220 expression. Breaks were also dependent on aberrant, overexpressed p220-driven recruitment of RAD51 to either spontaneously arising or mutagen-based DNA damage sites. Hence, when its level is not physiologically maintained, endogenous p220 aberrantly directs at least one DNA repair protein, RAD51, to damage sites, where their action contributes to the development of de novo DNA damage. Thus, like its loss, a surfeit of endogenous p220 function represents a threat to genome integrity.

Percutaneous thermal ablation of subcapsular hepatocellular carcinomas: influence of tumor-surface contact and protrusion on therapeutic efficacy and safety.

PURPOSE: To evaluate therapeutic efficacy and complication of percutaneous thermal ablation of subcapsular hepatocellular carcinomas (HCCs), and how these may be influenced by the degree of tumor to liver surface contact and tumor protrusion from liver surface. MATERIALS AND METHODS: Our retrospective study was approved by the Institutional Review Board. Between January 2006 and December 2013, 290 patients (82 women, 208 men; mean age, 64.5 years; range, 33-89 years) with 474 subcapsular (within 1 cm to the liver surface) HCCs (mean size, 23.7 mm; range, 6-71 mm) underwent percutaneous thermal ablation. The HCCs were divided into surface contact group (n = 243) and non-surface contact group (n = 231). The former was further subdivided into exophytic and non-exophytic HCCs. Technical success, primary technique efficacy, local tumor progression (LTP), and secondary technique efficacy rates were analyzed and compared by the chi-square test or Fisher exact test. Prognostic factors for LTP and secondary technique efficacy were assessed using the Cox regression model. Major complications were also assessed. RESULTS: With median follow-up of 15 months (range, 1-87 months), technical success and primary technique efficacy were 98.7% and 95.7% % in the non-surface contact group; 96.4% and 94.0% in the non-exophytic group; and 100% and 94.7% in the exophytic group (p > 0.05). Tumor size > 3 cm was a significant predictor for LTP, but not for secondary efficacy. Overall major complication rate was 3.8% (24/624) and was not different among the three groups. CONCLUSION: Subcapsular HCCs can be effectively treated with thermal ablation techniques. Degree of tumor-surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. KEY POINTS: • Subcapsular HCCs can be effectively treated with thermal therapy when proper image-guided technique and assistive techniques are applied. • Degree of tumor surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. • Major complications after percutaneous thermal ablation of subcapsular HCCs such as tumor seeding can be minimized by avoiding breach of the tumor capsule exposed to the peritoneal surface and use of tract ablation.

Updated 10-year outcomes of percutaneous radiofrequency ablation as first-line therapy for single hepatocellular carcinoma < 3 cm: emphasis on association of local tumor progression and overall survival.

OBJECTIVES: The purpose of this study was to evaluate the 10-year overall survival and local tumor progression (LTP) of percutaneous radiofrequency ablation (RFA) for single nodular hepatocellular carcinoma (HCC) < 3 cm using a large longitudinal hospital registry and clinical factors associated with overall survival and LTP. METHODS: A total of 467 newly diagnosed patients with single nodular HCC < 3 cm who underwent RFA as first-line therapy between January 2008 to December 2016 were analyzed. Overall survival and LTP were estimated using the Kaplan-Meier method. Cox regression and competing risks Cox regression analysis were performed to identify prognostic factors for overall survival and LTP, respectively. RESULTS: The 5- and 10-year overall survival rates after RFA were 83.7% and 74.2%, respectively. LTP (hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.19-3.47) was one of the important factors for overall survival after RFA. The 5- and 10-year LTP rates after RFA were 20.4% and 25.1%, respectively. Periportal location (subdistribution HR, 2.29; 95% CI, 1.25-4.21), subphrenic location (2.25, 1.34-3.86), size ≥ 1.5-< 2.0 cm (1.88, 1.05-3.39), and size ≥ 2.0 cm (2.10, 1.14-3.86) were independent factors for LTP. CONCLUSION: Ten-year therapeutic outcomes of percutaneous RFA as first-line therapy were excellent for single HCC < 3 cm. LTP was an important prognostic factor for overall survival after RFA. Periportal and subphrenic location of HCCs and tumor size were predictors for the development of LTP after RFA. KEY POINTS: • Updated 10-year survival outcome of percutaneous radiofrequency ablation as first-line therapy for single hepatocellular carcinoma < 3 cm was higher than previously reported. • Local tumor progression was an important prognostic factor for overall survival after percutaneous radiofrequency ablation. • Periportal and subphrenic location of hepatocellular carcinomas and tumor size were predictors for the development of local tumor progression after percutaneous radiofrequency ablation.

Efficacy of 3T Multiparametric MR Imaging followed by 3T in-Bore MR-Guided Biopsy for Detection of Clinically Significant Prostate Cancer Based on PIRADSv2.1 Score.

PURPOSE: To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). MATERIALS AND METHODS: This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4. RESULTS: 3T IB-MRGB detected PCa and csPCa in 69.1% (262 of 379) and 50.3% (193 of 379) of patients, respectively. The PCa and csPCa detection rates per target were 64.2% (305 of 475) and 43.8% (208 of 475), respectively. The rate of urosepsis, treated with intravenous antibiotics, was 1% (4 patients). In TRUS biopsy negative results and biopsy-naïve subcohorts, csPCa was found in 36.8% (39 of 106) and 52.8% (65 of 123), respectively. In 50.7% (76 of 150) of the active surveillance subcohort, 3T IB-MRGB upgraded the GS assigned in prior TRUS biopsies. Positive predictive values of PIRADSv2.1 categories 3, 4, and 5 for csPCa detection were 24.8%, 44.4%, and 67.1%, respectively. Higher PIRADSv2.1 categories were significantly associated with PCa (odds ratio [OR], 3.97; 95% confidence interval [CI], 2.98-5.28) and csPCa (OR, 1.41; 95% CI, 1.03-1.94) detection. Of 137 PIRADSv2 category 3 lesions, 28 were downgraded to PIRADSv2.1 category 2, in which there were no occurrences of csPCa in histology. CONCLUSIONS: Use of 3T IB-MRGB resulted in detection of csPCa in 50.9% of individuals. 3T IB-MRGB has a high diagnostic yield in individuals with negative TRUS biopsy results and those under active surveillance. The PIRADSv2.1 category is a strong predictor of PCa and csPCa detection.