The Ovarian-Adnexal Reporting and Data System (O-RADS) US Score Effect on Surgical Resection Rate.

Background The Ovarian-Adnexal Imaging Reporting and Data System (O-RADS) US risk score can be used to accurately stratify ovarian lesions based on morphologic characteristics. However, there are no large multicenter studies assessing the potential impact of using O-RADS US version 2022 risk score in patients referred for surgery for an ovarian or adnexal lesion. Purpose To retrospectively determine the proportion of patients with ovarian or adnexal lesions without acute symptoms who may have been managed conservatively by using the O-RADS US version 2022 risk score. Materials and Methods This multicenter retrospective study included patients with ovarian cystic lesions and nonacute symptoms who underwent surgical resection after US before the introduction of O-RADS US between January 2011 and December 2014. Investigators blinded to the final diagnoses recorded lesion imaging features and O-RADS US risk scores. The frequency of malignancy and the diagnostic performance of the risk score were calculated. The Mann-Whitney test and Fisher exact test were performed, with P < .05 indicating a statistically significant difference. Results A total of 377 patients with surgically resected lesions were included. Among the resected lesions, 42% (157 of 377) were assigned an O-RADS US risk score of 2. Of the O-RADS US 2 lesions, 54% (86 of 157) were nonneoplastic, 45% (70 of 157) were dermoids or other benign tumors, and less than 1% (one of 157) were malignant. Using O-RADS US 4 as the optimal threshold for malignancy prediction yielded a 94% (68 of 72) sensitivity, 64% (195 of 305) specificity, 38% (68 of 178) positive predictive value, and 98% (195 of 199) negative predictive value. Conclusion In patients without acute symptoms who underwent surgery for ovarian and adnexal lesions before the O-RADS US risk score was published, nearly half (42%) of surgically resected lesions retrospectively met the O-RADS US 2 version 2022 criteria. In these patients, imaging follow-up or conservative management could have been offered. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Fournier in this issue.

Radiology State-of-the-art Review: Endometriosis Imaging Interpretation and Reporting.

Endometriosis is a common condition impacting approximately 190 million individuals and up to 50% of women with infertility globally. The disease is characterized by endometrial-like tissue located outside of the uterine corpus, which causes cyclical hemorrhage, inflammation, and fibrosis. Based on clinical suspicion or findings at routine transvaginal pelvic US or other prior imaging, dedicated imaging for endometriosis may be warranted with MRI or advanced transvaginal US. Deep endometriosis (DE) in the pelvis includes evaluation for stromal and fibrotic components and architectural distortion resulting from fibrosis and tethering. It is a disease requiring a compartment-based, pattern-recognition approach. MRI has the benefit of global assessment of the pelvis and is effective in assessing for features of malignancy and for evaluating extrapelvic locations. Transvaginal US has the advantage of dynamic maneuvers to assess for adhesions and may achieve higher spatial resolution for assessing the depth of bowel wall invasion. T1-weighted MRI evaluation increases the specificity of diagnosis by identifying hemorrhagic components, but the presence of T1 signal hyperintensity is not essential for diagnosing DE. Endometriosis is a disease with a broad spectrum; understanding the mild through advanced manifestations, including malignancy evaluation, is within the scope and breadth of radiologists' interpretation.

Beta-Catenin-Mutated Hepatocellular Adenomas at Hepatobiliary Phase MRI: A Systematic Review and Meta-Analysis.

BACKGROUND: Beta-catenin-mutated hepatocellular adenomas (ß-HCAs) can appear iso- to hyperintense at the hepatobiliary phase (HBP) at magnetic resonance imaging (MRI). Given the relatively lower prevalence of ß-HCAs, prior studies had limited power to show statistically significant differences in the HBP signal intensity between different subtypes. PURPOSE: To assess the diagnostic performance of HBP MRI to discriminate ß-HCA from other subtypes. STUDY TYPE: Systemic review and meta-analysis. POPULATION: Ten original studies were included, yielding 266 patients with 397 HCAs (9%, 36/397 ß-HCAs and 91%, 361/397 non-ß-HCAs). FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T, HBP. ASSESSMENT: PubMed, Web of Science, and Embase databases were searched from January 1, 2000, to August 31, 2023, for all articles reporting HBP signal intensity in patients with histopathologically proven HCA subtypes. QUADAS-2 was used to assess risk of bias and concerns regarding applicability. STATISTICAL TESTS: Univariate random-effects model was used to calculate pooled estimates. Heterogeneity estimates were assessed with I2 heterogeneity index. Meta-regression (mixed-effect model) was used to test for differences in the prevalence of HBP signal between HCA groups. The threshold for statistical significance was set at P < 0.05. RESULTS: HBP iso- to hyperintensity was associated with ß-HCAs (pooled prevalence was 72.3% in ß-HCAs and 6.3% in non-ß-HCAs). Pooled sensitivity and specificity were 72.3% (95% confidence interval 54.1-85.3) and 93.7% (93.8-97.7), respectively. Specificity had substantial heterogeneity with I2 of 83% due to one study, but not for sensitivity (I2 = 0). After excluding this study, pooled sensitivity and specificity were 77.4% (59.6-88.8) and 94.1% (88.9-96.9), with no substantial heterogeneity. One study had high risk of bias for patient selection and two studies were rated unclear for two domains. DATA CONCLUSION: Iso- to hyperintensity at HBP MRI may help to distinguish ß-HCA subtype from other HCAs with high specificity. However, there was heterogeneity in the pooled estimates. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.

OBJECTIVE AND DESIGN: Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD. METHODS: The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes. RESULTS: Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo. CONCLUSION: Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.

Outcomes of Bosniak Classification Version 2019 Class IIF Cystic Renal Masses at Imaging Surveillance.

BACKGROUND. Bosniak classification system version 2019 (v2019) recommends that class IIF masses undergo follow-up imaging at 6 months, 12 months, and then annually for 5 years. The frequency and timing of upgrade on follow-up imaging are incompletely understood. OBJECTIVE. The purpose of this article is to describe the temporal evolution of Bosniak v2019 class IIF cystic renal masses, with attention to outcomes at 6-month follow-up, the time to class upgrade, and malignant histologic diagnoses. METHODS. This retrospective study included 219 patients (91 women, 128 men; median age, 72 years) with 246 localized class IIF masses from January 2005 to June 2022. Patients underwent both a baseline and at least one follow-up renal-mass protocol contrast-enhanced CT or MRI examination. Two radiologists evaluated masses at all follow-up time points to categorize masses as downgraded (class I or II), stable (localized class IIF), or upgraded (class III or IV, solid, or category T3a, N1, or M1 or higher disease); a third radiologist resolved discrepancies. Incidence rate of upgrade was determined. Histopathologic outcomes were assessed for resected masses. RESULTS. Median follow-up was 28.4 months (IQR, 13.7-59.4 months). At 6-month follow-up, five (2%) masses were downgraded, 241 (98%) were stable, and none were upgraded. On the basis of final follow-up, 14 (6%) masses were downgraded, 223 (91%) were stable, and nine (4%) were upgraded. All upgrade events entailed a class increase to III (n = 7) or IV (n = 2); no mass became solid or developed T3, N1, or M1 disease. Among the nine upgraded masses, median time to upgrade was 53.5 months (IQR, 23.2-63.7 months). Incidence rate of upgrade was 3.006 per 100,000 person-days (95% CI, 1.466-5.516). Ten masses were resected; histopathology was benign in six and malignant in four. Of the four malignant masses, one was upgraded to class III after 15 months of preoperative follow-up imaging, and three remained class IIF on preoperative follow-up imaging. No resected malignant mass developed postoperative recurrence. CONCLUSION. Bosniak v2019 class IIF masses are unlikely to represent aggressive malignancy; only 4% were upgraded over time and never on initial 6-month follow-up. CLINICAL IMPACT. The currently recommended initial 6-month follow-up imaging examination for class IIF masses is of questionable clinical utility.

External Validation of a Five-Tiered CT Algorithm for the Diagnosis of Clear Cell Renal Cell Carcinoma: A Retrospective Five-Reader Study.

BACKGROUND. In 2022, a five-tiered CT algorithm was proposed for predicting whether a small (cT1a) solid renal mass represents clear cell renal cell carcinoma (ccRCC). OBJECTIVE. The purpose of this external validation study was to evaluate the proposed CT algorithm for diagnosis of ccRCC among small solid renal masses. METHODS. This retrospective study included 93 patients (median age, 62 years; 42 women, 51 men) with 97 small solid renal masses that were seen on corticomedullary phase contrast-enhanced CT performed between January 2012 and July 2022 and subsequently underwent surgical resection. Five readers (three attending radiologists, two clinical fellows) independently evaluated masses for the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score; these scores were used to derive the CT score by use of the previously proposed CT algorithm. The CT score's sensitivity, specificity, and PPV for ccRCC were calculated at threshold of 4 or greater, and the NPV for ccRCC was calculated at a threshold of 3 or greater (consistent with thresholds in studies of the MRI-based clear cell likelihood score and the CT algorithm's initial study). The CT score's sensitivity and specificity for papillary RCC were calculated at a threshold of 2 or less. Interreader agreement was assessed using the Gwet agreement coefficient (AC1). RESULTS. Overall, 61 of 97 masses (63%) were malignant and 43 of 97 (44%) were ccRCC. Across readers, CT score had sensitivity ranging from 47% to 95% (pooled sensitivity, 74% [95% CI, 68-80%]), specificity ranging from 19% to 83% (pooled specificity, 59% [95% CI, 52-67%]), PPV ranging from 48% to 76% (pooled PPV, 59% [95% CI, 49-71%]), and NPV ranging from 83% to 100% (pooled NPV, 90% [95% CI, 84-95%]), for ccRCC. A CT score of 2 or less had sensitivity ranging from 44% to 100% and specificity ranging from 77% to 98% for papillary RCC (representing nine of 97 masses). Interreader agreement was substantial for attenuation score (AC1 = 0.70), poor for heterogeneity score (AC1 = 0.17), fair for five-tiered CT score (AC1 = 0.32), and fair for dichotomous CT score at a threshold of 4 or greater (AC1 = 0.24 [95% CI, 0.14-0.33]). CONCLUSION. The five-tiered CT algorithm for evaluation of small solid renal masses was tested in an external sample and showed high NPV for ccRCC. CLINICAL IMPACT. The CT algorithm may be used for risk stratification and patient selection for active surveillance by identifying patients unlikely to have ccRCC.

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.

Nyquist sampling theorem and Bosniak classification, version 2019: effect of thin axial sections on categorization and agreement.

OBJECTIVE: To determine if CT axial images reconstructed at current standard of care (SOC; 2.5-3 mm) or thin (≤ 1 mm) sections affect categorization and inter-rater agreement of cystic renal masses assessed with Bosniak classification, version 2019. METHODS: In this retrospective single-center study, 3 abdominal radiologists reviewed 131 consecutive cystic renal masses from 100 patients performed with CT renal mass protocol from 2015 to 2021. Images were reviewed in two sessions: first with SOC and then the addition of thin sections. Individual and overall categorizations are reported, latter of which is based on majority opinion with 3-way discrepancies resolved by a fourth reader. Major categorization changes were defined as differences between classes I-II, IIF, or III-IV. RESULTS: Thin sections led to a statistically significant major category change with class II for all readers individually (p = 0.004-0.041; McNemar test), upgrading 10-17% of class II masses, most commonly to class IIF followed by III. Modal reason for upgrades was due to identification of additional septa followed by larger measurement of enhancing features. Masses categorized as class I, III, or IV on SOC sections were unaffected, as were identification of protrusions. Inter-rater agreements using weighted Cohen's kappa were 0.679 for SOC and 0.691 for thin sections (both substantial). CONCLUSION: Thin axial sections upgraded up to one in six class II masses to IIF or III through identification of additional septa or larger feature. Other classes, including III-IV, were unaffected. Inter-rater agreements were substantial regardless of section thickness. KEY POINTS: • Thin axial sections (≤ 1 mm) compared to standard of care sections (2.5-3 mm) led to identification of additional septa but did not affect identification of protrusions. • Thin axial sections (≤ 1 mm) compared to standard of care sections (2.5-3 mm) can upgrade a small proportion of cystic renal masses from class II to IIF or III when applying Bosniak classification, version 2019. • Inter-rater agreements were substantial regardless of section thickness.

Outcomes of LI-RADS US-2 Subthreshold Observations Detected on Surveillance Ultrasound.

BACKGROUND. Ultrasound LI-RADS version 2017 recommends that patients with US-2 subthreshold observations undergo repeat surveillance ultrasound in 3-6 months and return to routine surveillance if the observation shows no growth for 2 years. However, outcomes of US-2 observations are unknown. OBJECTIVE. The purpose of this article was to determine imaging outcomes of US-2 observations detected on surveillance ultrasound examinations. METHODS. This retrospective study included 175 patients (median age, 59 years; 70 women, 105 men) at high risk for hepatocellular carcinoma (HCC) with US-2 observations (i.e., subcentimeter observations) on surveillance ultrasound. Observations were classified on follow-up ultrasound performed 2 or more years later as showing no correlate, stable (if remaining subcentimeter), or progressed (if measuring ≥ 10 mm, meeting US-3 criteria). Observations were classified on follow-up multiphasic CT or MRI (stratified as < 2-year vs ≥ 2-year follow-up) as showing no correlate or, if showing a correlate, using CT/MRI LI-RADS version 2018. RESULTS. A total of 111 patients had follow-up ultrasound after 2 or more years and 106 had follow-up CT or MRI (79 before 2 years, 27 after 2 years). On the basis of final follow-up examinations, 173 of 175 observations were stable on follow-up ultrasound 2 or more years later (n = 68); showed no correlate on follow-up ultrasound, CT, or MRI (n = 88); or were classified as LR-1 or LR-2 on CT or MRI (n = 17). The remaining 2 of 175 observations were LR-3 on CT or MRI. No observations progressed to US-3 on follow-up ultrasound or were classified as LR-4 or greater on CT or MRI. A correlate was observed in 25 of the 106 follow-up CT or MRI examinations (LR-1 or LR-2 in 23; LR-3 in two). Eight patients developed HCC at a median of 2.0 years after initial US-2 observation detection; all HCCs were in separate locations from the baseline observations and were preceded by a surveillance ultrasound that could not reidentify the baseline observation. In three patients who underwent liver transplant, the explant showed no dysplastic nodule or HCC. CONCLUSION. US-2 subthreshold observations are unlikely to progress or become HCC and commonly have no correlate on follow-up imaging. CLINICAL IMPACT. Because of the low progression rate of US-2 subthreshold observations, it is unclear if an extended period of intensive surveillance, as recommended by multiple professional societies, is warranted.

Growth Kinetics and Progression Rate of Bosniak Classification Version 2019 Class III and IV Cystic Renal Masses on Imaging Surveillance.

BACKGROUND. Active surveillance is increasingly used as first-line management for localized renal masses. Triggers for intervention primarily reflect growth kinetics, which have been poorly investigated for cystic masses defined by the Bosniak classification version 2019 (v2019). OBJECTIVE. The purpose of this study was to determine growth kinetics and incidence rates of progression of class III and IV cystic renal masses, as defined by the Bosniak classification v2019. METHODS. This retrospective study included 105 patients (68 men, 37 women; median age, 67 years) with 112 Bosniak v2019 class III or IV cystic renal masses on baseline renal mass protocol CT or MRI examinations performed from January 2005 to September 2021. Mass dimensions were measured. Progression was defined as any of the following: linear growth rate (LGR) of 5 mm/y or greater (representing the clinical guideline threshold for intervention), volume doubling time less than 1 year, T category increase, or N1 or M1 disease. Class III and IV masses were compared. Time to progression was estimated using Kaplan-Meier curve analysis. RESULTS. At baseline, 58 masses were class III and 54 were class IV. Median follow-up was 403 days. Median LGR for class III masses was 0.0 mm/y (interquartile range [IQR], -1.3 to 1.8 mm/y) and for class IV masses was 2.3 mm/y (IQR, 0.0-5.7 mm/y) (p < .001). LGR was at least 5 mm/y in four (7%) class III masses and 15 (28%) class IV masses (p = .005). Two patients, both with class IV masses, developed distant metastases. Incidence rate of progression for class III masses was 11.0 (95% CI, 4.5-22.8) and for class IV masses 73.6 (95% CI, 47.8-108.7) per 100,000 person-days of follow-up. Median time to progression was undefined for class III masses given the small number of progression events and 710 days for class IV masses. Hazard ratio of progression for class IV relative to class III masses was 5.1 (95% CI, 2.5-10.8; p < .001). CONCLUSION. During active surveillance of cystic masses evaluated using the Bosniak classification v2019, class IV masses grew faster and were more likely to progress than class III masses. CLINICAL IMPACT. In comparison with current active surveillance guidelines that treat class III and IV masses similarly, future iterations may incorporate relatively more intensive surveillance for class IV masses.

Prevalence of Malignancy and Histopathological Association of Bosniak Classification, Version 2019 Class III and IV Cystic Renal Masses.

PURPOSE: Bosniak Classification, version 2019 (v2019) describes 2 types of class III and IV masses each: 1) thick, wall/septa ≥4 mm (III-WS), 2) obtuse protrusion ≤3 mm (III-OP), 3) obtuse protrusion ≥4 mm (IV-OP), and 4) acute protrusion of any size (IV-AP). The purposes of this study were to determine the prevalence of malignancy and histopathological features of class III and IV masses and subclasses. MATERIALS AND METHODS: In this institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study, 3 fellowship-trained abdominal radiologists (R1-3) reviewed cystic renal masses that had tissue pathology and preoperative renal mass protocol computerized tomography or magnetic resonance imaging. Classes based on v2019 and prior classification systems were retrospectively re-assigned and associated with malignancy, aggressive histologic features (necrosis or high Fuhrman grade) and radiological progression following resection. RESULTS: The final sample included 79 masses (59 malignant, 20 benign) from 74 patients. Based on v2019, prevalence of malignancy ranged from 56% to 61% (mean 60%) for class III and 83% to 83% (mean 83%) for class IV (p=0.036, 0.013, 0.036 for 3 fellowship-trained abdominal radiologists). Prevalence of malignancy within subclasses were: III-WS (overall 49%; range 47%-53%); III-OP (76%; 71%-85%); IV-OP (78%; 75%-87%); IV-AP (87%; 82%-95%; p=0.029, 0.001, 0.005). All readers were more likely to classify malignancies with aggressive histologic features as class IV (88% to 100%) rather than class III (0% to 12%; p=0.012, <0.001, 0.002), corresponding to a negative predictive value of 96% to 100%. After treatment (mean followup length 1,210 days), 1 patient developed metastases. CONCLUSIONS: Bosniak Classification, version 2019 can help risk stratification of class III-IV masses by identifying those likely to be malignant and have aggressive histologic features.

Bosniak Classification of Cystic Renal Masses Version 2019: Comparison of Categorization Using CT and MRI.

BACKGROUND. Bosniak classification version 2019 proposed refinements for cystic renal mass characterization and now formally incorporates MRI, which may improve concordance with CT. OBJECTIVE. The purpose of this study is to compare concordance of CT and MRI in evaluation of cystic renal masses using Bosniak classification version 2019. METHODS. Three abdominal radiologists retrospectively reviewed 68 consecutive cystic renal masses from 45 patients assessed with both CT and MRI renal mass protocols within a year between 2005 and 2019. CT and MRI were reviewed independently and in separate sessions, using both the original and 2019 versions of Bosniak classification systems. RESULTS. Using Bosniak classification version 2019, cystic renal masses were classified into 12 category I, 19 category II, 13 category IIF, four category III, and 20 category IV by CT and eight category I, 15 category II, 23 category IIF, nine category III, and 13 category IV by MRI. Among individual features, MRI showed more septa (p < 0.001, p = 0.046, p = 0.005; McNemar test) for all three radiologists, although both CT and MRI showed a similar number of protrusions (p = 0.823, p = 1.0, p = 0.302) and maximal septa and wall thickness (p = 1.0, p = 1.0, p = 0.145). Of the discordant cases with version 2019, MRI led to a higher categorization in 12 masses. The reason for upgrade was most commonly because of protrusions identified only on MRI (n = 4), an increased number of septa (n = 3), and a new category: heterogeneously T1-weighted hyperintensity (n = 3). Neither modality was more likely to lead to a categorization change for either version 2019 (p = 0.502; McNemar test) or the original (p = 0.823) Bosniak classification system. Overall interrater agreement was substantial for both CT (κ = 0.745) and MRI (κ = 0.655) using version 2019 and was slightly higher than that of the original system for CT (κ = 0.707) and MRI (κ = 0.623). CONCLUSION. CT and MRI were concordant in the majority of cases using Bosniak classification version 2019, and category changes by modality were not statistically significant. Interrater agreements were substantial for both CT and MRI. CLINICAL IMPACT. Bosniak classification version 2019 as applied to cystic renal masses has substantial interrater agreement and does not lead to systematic category upgrades with either CT or MRI.

A DNA Aptameric Ligand of Human Transferrin Receptor Generated by Cell-SELEX.

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.

Detection of Circulating Tumor-Related Materials by Aptamer Capturing and Endogenous Enzyme-Signal Amplification.

Circulating tumor-related materials (CTRMs) shed from original or metastatic tumors, carry a lot of tumor information and are considered as important markers for cancer diagnosis and metastasis prognosis. Herein, we report a colorimetric detection strategy for CTRMs based on aptamer-based magnetic isolation and endogenous alkaline phosphatase (AP)-signal amplification. This strategy exhibited high sensitivity and selectivity toward the CTRMs that express AP heterodimers (the target of aptamer, a potential tumor marker). For clinical samples, this CTRM assay significantly discriminated colorectal cancer patients (n = 50) from healthy individuals (n = 39, p < 0.0001). The receiver operating characteristic (ROC) analysis indicated the sensitivity and specificity reached 92% and 82%, respectively, at the optimal cutoff point, the area under the curve of ROC reached 0.93, suggesting great potential for colorectal cancer diagnosis and therapeutic monitoring. Compared with CTC assays, this strategy is simple and has the potential for point-of-care testing.

Differentiation of Hepatocellular Adenoma Subtypes and Focal Nodular Hyperplasia on Gadoxetate Disodium-Enhanced MRI: An Updated Diagnostic Algorithm.

This study evaluated an updated diagnostic algorithm for distinguishing hepatocellular adenoma (HCA) subtypes from focal nodular hyperplasia (FNH) on gadoxetate disodium­enhanced MRI. The algorithm included a pathway recommending biopsy for indeterminate lesions that could represent HCA with ß-catenin mutations (which are at risk of malignant transformation) or inflammatory HCA with an atypical MRI appearance.

Imaging of Neurite Network with an Anti-L1CAM Aptamer Generated by Neurite-SELEX.

Neurite outgrowth is the critical step of nervous development. Molecular probes against neurites are essential for evaluation of the nervous system development, compound neurotoxicity, and drug efficacy on nerve regeneration. To obtain a neurite probe, we developed a neurite-SELEX strategy and generated a DNA aptamer, yly12, that strongly binds neurites. The molecular target of yly12 was identified to be neural cell adhesion molecule L1 (L1CAM), a surface antigen expressed in normal nervous system and various cancers. Here, yly12 was successfully applied to image the three-dimensional network of neurites between live cells, as well as the neurite fibers on normal brain tissue section. This aptamer was also found to have an inhibitory effect on neurite outgrowth between cells. Given the advantages of aptamers, yly12 hold great potential as a molecular tool in the field of neuroscientific research. The high efficiency of neurite-SELEX suggests that SELEX against a subcellular structure instead of the whole cells is more effective in obtaining the desired aptamers.

Translabial US: Preoperative Detection of Midurethral Sling Erosion in Stress Urinary Incontinence.

Purpose To evaluate the performance of translabial (TL) US in preoperative detection of sling erosion into pelvic organs with cystourethroscopic and surgical correlation. Materials and Methods The study cohort included women who underwent surgery at a subspecialty center (from 2008 to 2016) for suspected mesh complications in the setting of previous midurethral sling placement for stress urinary incontinence (from 1999 to 2012) with available preoperative TL US imaging. Clinical information, the finding of sling erosion identified intraoperatively and at cystourethroscopy, and blinded dual-reader radiologic analysis of the TL US studies for mesh location (intraluminal, mural, or extramural) relative to pelvic organs (bladder, urethra, vagina, or rectum) were evaluated. The diagnostic performance of TL US was correlated with the reference standard of surgical findings. The consensus of two radiologists was recorded, and interobserver agreement was evaluated with the κ statistic. Results Of the 124 women who were suspected of having sling erosion (mean age, 57.5 years ± 11.1 [standard deviation]), 15 women (12.1%) had sling erosion into the urethra or bladder at surgery. Sensitivity and specificity for erosion at TL US were 53% (95% confidence interval: 45%, 62%) and 100% (95% confidence interval: 97%, 100%), respectively, when erosion was defined as only intraluminal mesh products. Sensitivity and specificity for erosion at TL US were 93% (95% confidence interval: 89%, 98%) and 72% (95% confidence interval: 65%, 80%), respectively, when erosion was defined as visualizing either intraluminal or intramural mesh products. Interobserver agreement (κ value) was 0.95. Cystourethroscopy had 67% sensitivity and 100% specificity for sling erosion. Conclusion Preoperative translabial US can be used to detect sling erosion into the lower urinary tract, with sensitivity up to 93% and specificity up to 100%. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Benson and Phillips in this issue.

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PURPOSE: We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. MATERIALS AND METHODS: We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. RESULTS: Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. CONCLUSIONS: In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker.