STIM1 promotes acquired resistance to sorafenib by attenuating ferroptosis in hepatocellular carcinoma.

Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

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.

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 HCA subtypes and FNH on gadoxetate disodium­enhanced MRI. The algorithm included a pathway recommending biopsy for indeterminate lesions that could represent HCA with beta-catenin mutations (which are at risk of malignant transformation) or I-HCA with an atypical MRI appearance.

Fibroblast growth factor signaling in macrophage polarization: impact on health and diseases.

Fibroblast growth factors (FGFs) are a versatile family of peptide growth factors that are involved in various biological functions, including cell growth and differentiation, embryonic development, angiogenesis, and metabolism. Abnormal FGF/FGF receptor (FGFR) signaling has been implicated in the pathogenesis of multiple diseases such as cancer, metabolic diseases, and inflammatory diseases. It is worth noting that macrophage polarization, which involves distinct functional phenotypes, plays a crucial role in tissue repair, homeostasis maintenance, and immune responses. Recent evidence suggests that FGF/FGFR signaling closely participates in the polarization of macrophages, indicating that they could be potential targets for therapeutic manipulation of diseases associated with dysfunctional macrophages. In this article, we provide an overview of the structure, function, and downstream regulatory pathways of FGFs, as well as crosstalk between FGF signaling and macrophage polarization. Additionally, we summarize the potential application of harnessing FGF signaling to modulate macrophage polarization.

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.

Follow-up imaging and surgical costs associated with different guidelines for management of incidentally detected gallbladder polyps.

RATIONALE AND OBJECTIVES: To compare follow-up imaging and surgical cost implications of the Society of Radiologists in Ultrasound (SRU) guidelines, 2017 and 2022 European (EUR) guidelines, 2020 Canadian Association of Radiologists (CAR) recommendations, and 2013 American College of Radiology (ACR) White Paper for managing incidentally detected gallbladder polyps. MATERIALS AND METHODS: 253 consecutive patients with gallbladder polyps identified on ultrasound were independently reviewed by three radiologists for polyp size and morphology. Electronic medical records were reviewed for patient demographics, cholecystectomy (if performed) pathological findings, or any subsequent diagnosis of gallbladder cancer. For each patient, the following were calculated for each of the 5 guidelines studied: 1) number of recommended follow-up ultrasounds based on initial presentation, 2) number of surgical consultations recommended based on initial presentation, 3) number of surgical consultations recommended based on growth, and 4) associated imaging and surgical costs. Interrater agreement was calculated. RESULTS: The SRU 2022 guidelines suggested significantly fewer follow-up ultrasounds and surgical consultations, leading to a cost reduction of 96.5 % and 96.7 % compared to European 2022 and 2017, respectively; 86.5 % compared to CAR; and 86.2 % compared to ACR guidelines. With SRU Recommendations, the majority of gallbladder polyps would be classified as extremely low risk (68.4 %), 30.8 % low risk, and 0.8 % indeterminate risk. In our cohort, a single case of gallbladder cancer was identified (26 mm) which would be recommended for surgical consult by all guidelines. CONCLUSION: The SRU 2022 guidelines can lead to significant savings for patients, health systems, and society, while reducing unnecessary medical interventions for managing incidentally detected gallbladder polyps.

Gastrointestinal devices: common and uncommon foreign bodies.

Devices for the gastrointestinal tract are widely available and constantly advancing with less invasive techniques. They play a crucial role in diagnostic and therapeutic interventions and are commonly placed by interventional radiologists, gastroenterologists, and surgeons. These devices frequently appear in imaging studies, which verify their proper placement, identify any complications, or may be incidentally detected. Radiologists must be able to identify these devices at imaging and understand their intended purpose to assess their efficacy, detect complications such as incorrect positioning, and avoid misinterpreting them as abnormalities. Furthermore, many patients with these devices may require MRI, making assessing compatibility essential for safe patient care. This review seeks to provide a succinct and practical handbook for radiologists regarding both common and uncommon gastrointestinal devices. In addition to textual descriptions of clinical indications, imaging findings, complications, and MRI compatibility, the review incorporates a summary table as a quick reference point for key information and illustrative images for each device.

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.

World Health Organization 2022 Classification Update: Radiologic and Pathologic Features of Papillary Renal Cell Carcinomas.

RATIONALE AND OBJECTIVES: To describe imaging and pathology features of newly defined papillary renal cell carcinoma (pRCC) based on the WHO 2022 update. MATERIALS AND METHODS: This retrospective study included 87 patients with 93 pathologically proven papillary renal cell carcinomas who underwent pre-treatment renal mass protocol CT or MRI. Baseline and post-treatment follow-up imaging was evaluated by two radiologists systematically based on established lexicon. RESULTS: At pathology, 63 (68%) were grade 1-2, 29 (31%) were grade 3-4, and 1 (%) was unreported. At surgical pathology, 84 (90%) were localized (≤pT2b), 5 (5%) were pT3a, and none were ≥pT3b; 4 (4%) had unknown pT stage (core biopsies). 33 (35%) had necrosis and 39 (41%) had hemorrhage. None had sarcomatoid or rhabdoid differentiation. At imaging, 73 (83%) were solid and 16 (17%) were cystic. Of 16 cystic masses, four were Bosniak class IIF (three were heterogeneously T1 hyperintense) and 12 were class IV. All were well-circumscribed. 92 (99%) were hypovascular. Median follow-up for 74 patients was 30 months (IQR 12-56). One untreated patient had non-regional nodal metastasis at presentation, and one patient had metastasis to lymph nodes and bones after surgery, but the patient had unresected renal masses elsewhere without pathology. Otherwise, no recurrence or metastases were detected. CONCLUSION: Most pRCCs present as a hypovascular, circumscribed, solid renal mass. A few pRCCs present as the newly defined Bosniak class IIF subtype. Our results can form the basis of a non-invasive, likelihood score to identify this relatively indolent pathology in the era of virtual biopsy and active surveillance.

Establishing a Point-of-Care Ultrasound Program: An Institutional Approach for Developing a Point-of-Care Ultrasound Program Infrastructure.

Point-of-care ultrasound (POCUS) is rapidly accelerating in adoption and applications outside the traditional realm of diagnostic radiology departments. Although the use of this imaging technology in a distributed fashion has great potential, there are many associated challenges. To address these challenges, the authors developed an enterprise-wide POCUS program at their institution (Stanford Health Care). Here, the authors share their experience, the governance organization, and their approaches to device and information security, training, and quality assurance. The authors also share the basic principles they use to guide their approach to manage these challenges. Through their work, the authors have learned that a foundational framework of defining POCUS and the different levels of POCUS use and delineating program management elements are critical. The authors hope that their experience will be helpful to others who are also interested in POCUS or in the process of creating POCUS programs at their institutions. With a clearly established framework, patient safety and quality of care are improved for everyone.

Study of the prediction of gamma passing rate in dosimetric verification of intensity-modulated radiotherapy using machine learning models based on plan complexity.

Objective: To predict the gamma passing rate (GPR) in dosimetric verification of intensity-modulated radiotherapy (IMRT) using three machine learning models based on plan complexity and find the best prediction model by comparing and evaluating the prediction ability of the regression and classification models of three classical algorithms: artificial neural network (ANN), support vector machine (SVM) and random forest (RF). Materials and methods: 269 clinical IMRT plans were chosen retrospectively and the GPRs of a total of 2340 fields by the 2%/2mm standard at the threshold of 10% were collected for dosimetric verification using electronic portal imaging device (EPID). Subsequently, the plan complexity feature values of each field were extracted and calculated, and a total of 6 machine learning models (classification and regression models for three algorithms) were trained to learn the relation between 21 plan complexity features and GPRs. Each model was optimized by tuning the hyperparameters and ten-fold cross validation. Finally, the GPRs predicted by the model were compared with measured values to verify the accuracy of the model, and the evaluation indicators were applied to evaluate each model to find the algorithm with the best prediction performance. Results: The RF algorithm had the optimal prediction effect on GPR, and its mean absolute error (MAE) on the test set was 1.81%, root mean squared error (RMSE) was 2.14%, and correlation coefficient (CC) was 0.72; SVM was the second and ANN was the worst. Among the classification models, the RF algorithm also had the optimal prediction performance with the highest area under the curve (AUC) value of 0.80, specificity and sensitivity of 0.80 and 0.68 respectively, followed by SVM and the worst ANN. Conclusion: All the three classic algorithms, ANN, SVM, and RF, could realize the prediction and classification of GPR. The RF model based on plan complexity had the optimal prediction performance which could save valuable time for quality control workers to improve quality control efficiency.

Growth Kinetics of Pancreatic Neuroendocrine Neoplasms by Histopathologic Grade.

OBJECTIVES: The aims of the study are to describe the growth kinetics of pathologically proven, treatment-naive pancreatic neuroendocrine neoplasms (panNENs) at imaging surveillance and to determine their association with histopathologic grade and Ki-67. METHODS: This study included 100 panNENs from 95 patients who received pancreas protocol computed tomography or magnetic resonance imaging from January 2005 to July 2022. All masses were treatment-naive, had histopathologic correlation, and were imaged with at least 2 computed tomography or magnetic resonance imaging at least 90 days apart. Growth kinetics was assessed using linear and specific growth rate, stratified by grade and Ki-67. Masses were also assessed qualitatively to determine other possible imaging predictors of grade. RESULTS: There were 76 grade 1 masses, 17 grade 2 masses, and 7 grade 3 masses. Median (interquartile range) linear growth rates were 0.06 cm/y (0-0.20), 0.40 cm/y (0.22-1.06), and 2.70 cm/y (0.41-3.89) for grade 1, 2, and 3 masses, respectively (P < 0.001). Linear growth rate correlated with Ki-67 with r2 of 0.623 (P < 0.001). At multivariate analyses, linear growth rate was the only imaging feature significantly associated with grade (P = 0.009). CONCLUSIONS: Growth kinetics correlate with Ki-67 and grade. Grade 1 panNENs grow slowly versus grade 2-3 panNENs.

Opportunities and considerations for studying liver disease with microphysiological systems on a chip.

Advances in microsystem engineering have enabled the development of highly controlled models of the liver that better recapitulate the unique in vivo biological conditions. In just a few short years, substantial progress has been made in creating complex mono- and multi-cellular models that mimic key metabolic, structural, and oxygen gradients crucial for liver function. Here we review: 1) the state-of-the-art in liver-centric microphysiological systems and 2) the array of liver diseases and pressing biological and therapeutic challenges which could be investigated with these systems. The engineering community has unique opportunities to innovate with new liver-on-a-chip devices and partner with biomedical researchers to usher in a new era of understanding of the molecular and cellular contributors to liver diseases and identify and test rational therapeutic modalities.

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.

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.

BACKGROUND: Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects. METHODS: Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats. RESULTS: Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies. CONCLUSION: ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.

Risk of malignancy in T1-hyperintense Bosniak version 2019 class II and IIF cystic renal masses.

BACKGROUND: Bosniak classification version 2019 includes cystic masses in class II and IIF based partly on their hyperintense appearance at T1-weighted MRI. The prevalence of malignancy in non-enhancing heterogeneously T1-hyperintense masses is unknown, nor whether the pattern of T1 hyperintensity affects malignancy likelihood. PURPOSE: To determine the malignancy proportion among six patterns of T1 hyperintensity within non-enhancing cystic renal masses. METHODS: This retrospective, single-institution study included 72 Bosniak class II and IIF, non-enhancing, T1-hyperintense cystic renal masses. Diagnosis was confirmed by histopathology or by follow-up imaging demonstrating 5-year size and morphologic stability, decreased in size by ≥ 30%, resolution, or Bosniak down-classification. Six patterns of T1 hyperintensity were pre-defined: homogeneous (pattern A), fluid-fluid level (pattern B), peripherally markedly T1-hyperintense (pattern C), containing a T1-hyperintense non-enhancing nodule (pattern D), peripherally T1-hypointense (pattern E), and heterogeneously T1-hyperintense without a distinct pattern (pattern F). Three readers independently assigned each mass to a pattern. Individual and mean malignancy proportion were determined. Mann-Whitney test and Fischer's exact test compared the likelihood of malignancy between patterns. Inter-reader agreement was analyzed with Gwet's agreement coefficient (AC). RESULTS: Among 72 masses, the mean number of masses assigned was 11 (15%) to pattern A, 21 (29%) to pattern B, 6 (8%) to pattern C, 7 (10%) to pattern D, 5 (7%) to pattern E, and 22 (31%) to pattern F. Five of 72 masses (7%) were malignant; none was assigned pattern A, B, or D. Mean malignancy proportion was 5% (0/9, 1/6, and 0/4) for pattern C, 13% (0/4, 1/3, and 1/7) for pattern E, and 18% (5/20, 3/21, and 4/25) for pattern F. Malignant masses were more likely assigned to pattern E or F (p = 0.003-0.039). Inter-reader agreement was substantial (Gwet's AC: 0.68). CONCLUSION: Bosniak version 2019 class IIF masses that are non-enhancing and heterogeneously T1-hyperintense with a fluid-fluid level are likely benign. Those that are non-enhancing and heterogeneously T1-hyperintense without a distinct pattern have a malignancy proportion up to 25% (5/20).

Diagnostic performance of the "drooping" sign in CT diagnosis of exophytic renal angiomyolipoma.

OBJECTIVE: To evaluate the prevalence of angular interface and the "drooping" sign in exophytic renal angiomyolipomas (AMLs) and the diagnostic performance in differentiating exophytic lipid-poor AMLs from other solid renal masses. METHODS: This IRB-approved, two-center study included 185 patients with 188 exophytic solid renal masses < 4 cm with histopathology and pre-operative CT within 30 days of surgical resection or biopsy. Images were reviewed for the presence of angular interface and the "drooping" sign qualitatively by three readers blinded to the final diagnosis, with majority rules applied. Both features were assessed quantitatively by cohort creators (who are not readers) independently. Free-marginal kappa was used to assess inter-reader agreement and agreement between two methods assessing each feature. Fisher's exact test, Mann-Whitney test, and multivariable logistic regression with two-tailed p < 0.05 were used to determine statistical significance. Diagnostic performance was assessed. RESULTS: Ninety-four patients had 96 AMLs, and 91 patients had 92 non-AMLs. Seventy-four (77%) of AMLs were lipid-poor based on quantitative assessment on CT. The presence of angular interface and the "drooping" sign by both qualitative and quantitative assessment were statistically significantly associated with AMLs (39% (qualitative) and 45% (quantitative) vs 15% (qualitative) and 13% (quantitative), and 48% (qualitative) and 43% (quantitative) vs 4% (qualitative) and 1% (quantitative), respectively, all p < 0.001) in univariable analysis. In multivariable analysis, only the "drooping" sign in either qualitative or quantitative assessment was a statistically significant predictor of AMLs (both p < 0.001). Inter-reader agreement for the "drooping" sign was moderate (k = 0.55) and for angular interface was fair (k = 0.33). Agreement between the two methods of assessing the "drooping" sign was substantial (k = 0.84) and of assessing the angular interface was moderate (k = 0.59). The "drooping" sign both qualitatively and quantitatively, alone or in combination of angular interface, had very high specificity (96-100%) and positive predictive value (PPV) (89-100%), moderate negative predictive value (62-68%), but limited sensitivity (23-49%) for lipid-poor AMLs. CONCLUSION: The "drooping" sign by both qualitative and quantitative assessment is highly specific for lipid-rich and lipid-poor AMLs. This feature alone or in combination with angular interface can aid in CT diagnosis of lipid-poor AMLs with very high specificity and PPV.

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.