Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.5 to 3 fold increase. We also explored the potential involvement of the MeCP2 PEST domains in the proteasome-mediated regulation of MeCP2. Finally, we used the R294X mutant to gain further insight into the controversial competition between MeCP2 and histone H1 in the chromatin context. Interestingly, in R294X, MeCP2 E1 and E2 isoforms were differently affected, where the E1 isoform contributes to much of the overall protein increase observed, while E2 decreases by half. The modes of MeCP2 regulation, thus, appear to be differently regulated in the two isoforms.

MeCP2 ubiquitination and sumoylation, in search of a function†.

MeCP2 (Methyl CpG binding protein 2) is an intrinsically disordered protein that binds to methylated genome regions. The protein is a critical transcriptional regulator of the brain, and its mutations account for 95% of Rett syndrome (RTT) cases. Early studies of this neurodevelopmental disorder revealed a close connection with dysregulations of the ubiquitin system (UbS), notably as related to UBE3A, a ubiquitin ligase involved in the proteasome-mediated degradation of proteins. MeCP2 undergoes numerous post-translational modifications (PTMs), including ubiquitination and sumoylation, which, in addition to the potential functional outcomes of their monomeric forms in gene regulation and synaptic plasticity, in their polymeric organization, these modifications play a critical role in proteasomal degradation. UbS-mediated proteasomal degradation is crucial in maintaining MeCP2 homeostasis for proper function and is involved in decreasing MeCP2 in some RTT-causing mutations. However, regardless of all these connections to UbS, the molecular details involved in the signaling of MeCP2 for its targeting by the ubiquitin-proteasome system (UPS) and the functional roles of monomeric MeCP2 ubiquitination and sumoylation remain largely unexplored and are the focus of this review.

The sperm nuclear basic proteins of the sword fern (Polystichum munitum).

Sperm nuclear basic proteins (SNBPs) were isolated from extracted antheridia-rich male gametophytes raised from spores of the swordfern, Polystichum munitum. Electrophoretic (acetic acid-urea PAGE and SDS-PAGE) and chromatographic (rp-HPLC) characterization of the nuclear proteins exhibited the characteristics of the histone (H-type). In both types of gel electrophoresis, histones H1, H2A, and H2B showed an altered electrophoretic mobility corresponding to that which is routinely observed for the histones in other plants. Histones present during spermatogenesis of the fern P. munitum were compared with the few current SNBPs known to be present in higher and lower evolutionary plant clades. A transition from an early protamine (P-type) SNBPs in charophytes and bryophytes to the (H-type) SNBP observed here is reminiscent of similar reversions observed in the animal kingdom.

Protamines and the sperm nuclear basic proteins Pandora's Box of insects.

Insects are the largest group of animals when it comes to the number and diversity of species. Yet, with the exception of Drosophila, no information is currently available on the primary structure of their sperm nuclear basic proteins (SNBPs). This paper represents the first attempt in this regard and provides information about six species of Neoptera: Poecillimon thessalicus, Graptosaltria nigrofuscata, Apis mellifera, Nasonia vitripennis, Parachauliodes continentalis, and Tribolium castaneum. The SNBPs of these species were characterized by acetic acid urea gel electrophoresis (AU-PAGE) and high-performance liquid chromatography fractionated. Protein sequencing was obtained using a combination of mass spectrometry sequencing, Edman N-terminal degradation sequencing and genome mining. While the SNBPs of several of these species exhibit a canonical arginine-rich protamine nature, a few of them exhibit a protamine-like composition. They appear to be the products of extensive cleavage processing from a precursor protein which are sometimes further processed by other post-translational modifications that are likely involved in the chromatin transitions observed during spermiogenesis in these organisms.

PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

RECIST 1.1, mRECIST, and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab.

OBJECTIVES: We aimed to compare the early responder rates, defined as complete or partial responders, using response evaluation criteria in solid tumors (RECIST) 1.1, modified RECIST (mRECIST), and Choi criteria in advanced HCC patients treated with atezolizumab-bevacizumab (atezo-bev), and to correlate them with progression-free survival (PFS) and overall survival (OS). METHODS: This retrospective study included advanced HCC patients treated with ≥ 3 cycles of atezo-bev. Two reviewers assessed responses using RECIST 1.1, mRECIST, and Choi criteria at 1st follow-up imaging. Kaplan-Meier curves with log-rank tests evaluated and compared PFS and OS. Cox proportional hazard models identified survival outcome predictors. Kappa statistics assessed inter-reader agreement. RESULTS: We evaluated 77 patients (65 men; mean age, 62.8 ± 12.3 years). Choi's criteria revealed the highest early responders rate (53.2%), exceeding mRECIST (32.5-33.8%) and RECIST 1.1 (24.7-26.0%), with an excellent agreement in all criteria (κ, 0.85-0.95). Across criteria, a consistent number of patients progressed (23-26) and was associated with significantly poor OS (ps ≤ 0.049). Responders by any criteria showed longer PFS (ps ≤ 0.009), and 1-year OS (ps ≤ 0.01). Choi criteria linked to significantly better OS without landmark (p = 0.003), with 1-year OS rates at 76.9% for responders vs 38.1% for non-responders. Cox analysis identified responders by Choi criteria as a significant OS predictor. CONCLUSION: Choi criteria identified more early responders than RECIST 1.1 and mRECIST, significantly correlating with improved OS. Choi criteria could be considered as a formal response assessment criterion for the emerging atezo-bev systemic treatment. CLINICAL RELEVANCE STATEMENT: For atezo-bev treatment of advanced HCC, more comprehensive response criteria, such as Choi criteria, could be effective in identifying early responders and predicting survival outcomes along with RECIST 1.1 and mRECIST. KEY POINTS: Choi criteria identified a higher rate of early responders compared to mRECIST and RECIST1.1 following atezo-bev treatment. Responders by all criteria had longer PFS and 1-year OS, and only those by Choi criteria experienced longer OS without landmark time. Choi criteria, with RECIST 1.1 and mRECIST, is an effective response assessment tool for atezo-bev treatment.

KRT18 as a Novel Biomarker of Urothelial Papilloma While Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.

INTRODUCTION: Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood. METHODS: We conducted an in-depth proteomic analysis of papillary urothelial lesions (n=31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry. RESULTS: In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n=120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis. CONCLUSION: This is the first study that successfully revealed UP's comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.

Artificial intelligence model for enhancing the accuracy of transvaginal ultrasound in detecting endometrial cancer and endometrial atypical hyperplasia.

OBJECTIVES: Transvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective of this study was to enhance the diagnostic accuracy of transvaginal ultrasound through the integration of artificial intelligence. By using transvaginal ultrasound images, we aimed to develop an artificial intelligence based automated segmentation model and an artificial intelligence based classifier model. METHODS: Patients with postmenopausal bleeding undergoing transvaginal ultrasound and endometrial sampling at Mayo Clinic between 2016 and 2021 were retrospectively included. Manual segmentation of images was performed by four physicians (readers). Patients were classified into cohort A (atypical hyperplasia/cancer) and cohort B (benign) based on the pathologic report of endometrial sampling. A fully automated segmentation model was developed, and the performance of the model in correctly identifying the endometrium was compared with physician made segmentation using similarity metrics. To develop the classifier model, radiomic features were calculated from the manually segmented regions-of-interest. These features were used to train a wide range of machine learning based classifiers. The top performing machine learning classifier was evaluated using a threefold approach, and diagnostic accuracy was assessed through the F1 score and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 302 patients were included. Automated segmentation-reader agreement was 0.79±0.21 using the Dice coefficient. For the classification task, 92 radiomic features related to pixel texture/shape/intensity were found to be significantly different between cohort A and B. The threefold evaluation of the top performing classifier model showed an AUC-ROC of 0.90 (range 0.88-0.92) on the validation set and 0.88 (range 0.86-0.91) on the hold-out test set. Sensitivity and specificity were 0.87 (range 0.77-0.94) and 0.86 (range 0.81-0.94), respectively. CONCLUSIONS: We trained an artificial intelligence based algorithm to differentiate endometrial atypical hyperplasia/cancer from benign conditions on transvaginal ultrasound images in a population of patients with postmenopausal bleeding.

Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer.

Muscle-invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high-throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in-house patient-derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform-based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype (TUBB6 migration, P = .0509 and P < .0001; invasion, P = .0002 and P = .0044; TGFBI migration, P = .0214 and P = .0026; invasion, P < .0001 and P = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein-based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P < .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.

Estimating postsurgical outcomes of patients with a single hepatocellular carcinoma using gadoxetic acid-enhanced MRI: risk scoring system development and validation.

OBJECTIVES: To develop and validate risk scoring systems using gadoxetic acid-enhanced liver MRI features and clinical factors that predict recurrence-free survival (RFS) of a single hepatocellular carcinoma (HCC). METHODS: Consecutive 295 patients with treatment-naïve single HCC who underwent curative surgery were retrospectively enrolled from two centers. Cox proportional hazard models developed risk scoring systems whose discriminatory powers were validated using external data and compared to the Barcelona Clinic Liver Cancer (BCLC) or American Joint Committee on Cancer (AJCC) staging systems using Harrell's C-index. RESULTS: Independent variables-tumor size (per cm; hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.02-1.13; p = 0.005), targetoid appearance (HR, 1.74; 95% CI: 1.07-2.83; p = 0.025), radiologic tumor in vein or tumor vascular invasion (HR, 2.59; 95% CI: 1.69-3.97; p < 0.001), the presence of a nonhypervascular hypointense nodule on the hepatobiliary phase (HR, 4.65; 95% CI: 3.03-7.14; p < 0.001), and pathologic macrovascular invasion (HR, 2.60; 95% CI: 1.51-4.48; p = 0.001)-with tumor markers (AFP ≥ 206 ng/mL or PIVKA-II ≥ 419 mAU/mL) derived pre- and postoperative risk scoring systems. The risk scores showed comparably good discriminatory powers in the validation set (C-index, 0.75-0.82) and outperformed the BCLC (C-index, 0.61) and AJCC staging systems (C-index, 0.58; ps < 0.05). The preoperative scoring system stratified the patients into low-, intermediate-, and high-risk for recurrence, whose 2-year recurrence rate was 3.3%, 31.8%, and 85.7%, respectively. CONCLUSION: The developed and validated pre- and postoperative risk scoring systems can estimate RFS after surgery for a single HCC. KEY POINTS: • The risk scoring systems predicted RFS better than the BCLC and AJCC staging systems (C-index, 0.75-0.82 vs. 0.58-0.61; ps < 0.05). • Five variables-tumor size, targetoid appearance, radiologic tumor in vein or vascular invasion, the presence of a nonhypervascular hypointense nodule on the hepatobiliary phase, and pathologic macrovascular invasion-combined with tumor markers derived risk scoring systems predicting postsurgical RFS for a single HCC. • In the risk scoring system using preoperatively-available factors, patients were classified into three distinct risk groups, with 2-year recurrence rates in the low-, intermediate-, and high-risk groups being 3.3%, 31.8%, and 85.7% in the validation set.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.

Methods for sampling wound fluid from venous leg ulcers for molecular analyses: A scoping review.

Determining the precise role of molecular factors present in venous leg ulcer exudate will expedite the identification of biomarkers that can optimally guide treatment. However, there is now no standardized approach for collecting, processing and storing wound fluid samples for molecular analyses. This scoping review was conducted to integrate and summarize the multiple types of methods being used currently in studies of venous leg ulcers for collecting, processing and storing wound fluid prior to analysis. PubMed, CINAHL, EMBASE and Scopus databases were searched for eligible studies between 2012 and 2022. Nineteen studies were selected for this scoping review. Five primary methodological categories for wound fluid sampling were identified. The most commonly used collection method involved extracting the fluid from various absorbent materials, and the majority of studies centrifuged wound fluid before storing it at ultra-low temperatures. This review found the wound fluid sampling methods among the included studies to be heterogeneous. Moreover, the data revealed no definitive patterns. There is a critical need to develop standardized wound fluid sampling methods in research to facilitate accurate comparisons of biomarker data across studies and a more rapid determination of biomarkers that can most effectively guide delivery of tailored venous leg ulcer treatments.

Multidetector CT of Extrahepatic Bile Duct Cancer: Diagnostic Performance of Tumor Resectability and Interreader Agreement.

Background In extrahepatic bile duct (EHD) cancer, accurate assessment of resectability is essential for curative surgery, but pertinent guidelines from the perspectives of radiologists are yet to be developed. Purpose To investigate the performance of multiphasic CT in the assessment of longitudinal tumor extent, vascular invasion, and resectability of EHD cancer according to the Korean Society of Abdominal Radiology consensus recommendation and to evaluate the interreader agreement. Materials and Methods This retrospective study included patients with EHD cancer who underwent multiphasic CT examinations with section thickness of 3 mm or less before surgery from January 2016 to December 2018. Four abdominal radiologists independently evaluated the overall and biliary segment-wise longitudinal tumor extent, the presence of hepatic artery and/or portal vein invasion, and the resectability according to the Korean Society of Abdominal Radiology recommendations. The diagnostic performance was assessed with sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. Interreader agreement was determined using κ statistics. Results A total of 112 patients (mean age ± SD, 61 years ± 11; 73 men) were evaluated. The accuracy of the overall longitudinal tumor extent assessment ranged from 56.3% (63 of 112 patients) to 74.1% (83 of 112 patients). The sensitivity for detecting secondary confluence involvement (n = 62) was lower than that for the primary confluence or intrapancreatic duct (n = 115; 38.5%-75% vs 72.1%-96.3%, respectively). Vascular invasion (n = 17) had moderate sensitivity (28.6%-71.4%) and high specificity (77.5%-99.0%). For predicting negative-margin (R0) resection (n = 85), the sensitivity and specificity ranged from 71.8% to 96.5% and from 11.1% to 66.7%, respectively, and the areas under the receiver operating characteristic curve ranged from 0.69 to 0.80. Interreader agreements for tumor extent, vascular invasion, and resectability had κ values of 0.65-0.89, 0.21-0.64, and 0.35-0.56, respectively. Conclusion For the preoperative evaluation of extrahepatic bile duct cancer, the Korean Society of Abdominal Radiology consensus recommendation enabled systematic assessment of longitudinal tumor extent and vascular invasion with acceptable performance in predicting negative-margin resection with use of multiphasic CT and with fair to good interreader agreement. © RSNA, 2022 Online supplemental material is available for this article.

A systematic review on the use of artificial intelligence in gynecologic imaging - Background, state of the art, and future directions.

OBJECTIVE: Machine learning, deep learning, and artificial intelligence (AI) are terms that have made their way into nearly all areas of medicine. In the case of medical imaging, these methods have become the state of the art in nearly all areas from image reconstruction to image processing and automated analysis. In contrast to other areas, such as brain and breast imaging, the impacts of AI have not been as strongly felt in gynecologic imaging. In this review article, we: (i) provide a background of clinically relevant AI concepts, (ii) describe methods and approaches in computer vision, and (iii) highlight prior work related to image classification tasks utilizing AI approaches in gynecologic imaging. DATA SOURCES: A comprehensive search of several databases from each database's inception to March 18th, 2021, English language, was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Ovid Cochrane Database of Systematic Reviews and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We performed an extensive literature review with 61 articles curated by three reviewers and subsequent sorting by specialists using specific inclusion and exclusion criteria. TABULATION, INTEGRATION, AND RESULTS: We summarize the literature grouped by each of the three most common gynecologic malignancies: endometrial, cervical, and ovarian. For each, a brief introduction encapsulating the AI methods, imaging modalities, and clinical parameters in the selected articles is presented. We conclude with a discussion of current developments, trends and limitations, and suggest directions for future study. CONCLUSION: This review article should prove useful for collaborative teams performing research studies targeted at the incorporation of radiological imaging and AI methods into gynecological clinical practice.

Into the future: A pilot study combining imaging with molecular profiling to predict resectability in ovarian cancer.

OBJECTIVE: We sought to determine the predictive value of combining tumor molecular subtype and computerized tomography (CT) imaging for surgical outcomes after primary cytoreductive surgery in advanced stage high-grade serous ovarian cancer (HGSOC) patients. METHODS: We identified 129 HGSOC patients who underwent pre-operative CT imaging and post-operative tumor mRNA profiling. A continuous CT-score indicative of overall disease burden was defined based on six imaging measurements of anatomic involvement. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors and classified as mesenchymal (MES) subtype (36%) or non-MES subtype (64%). Fischer exact tests and multivariate logistic regression examined residual disease and surgical complexity. RESULTS: Women with higher CT-scores were more likely to have MES subtype tumors (p = 0.014). MES subtypes and a high CT-score were independently predictive of macroscopic disease and high surgical complexity. In multivariate models adjusting for age, stage and American Society of Anesthesiologists (ASA) score, patients with a MES subtype and high CT-score had significantly elevated risk of macroscopic disease (OR = 26.7, 95% CI = [6.42, 187]) and were more likely to undergo high complexity surgery (OR = 9.53, 95% CI = [2.76, 40.6], compared to patients with non-MES tumor and low CT-score. CONCLUSION: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women unlikely to have resectable disease and likely to require high complexity surgery. Along with other clinical factors, these may refine predictive scores for resection and assist treatment planning. Investigating methods for pre-surgical molecular subtyping is an important next step.

Liver Imaging-Reporting and Data System treatment response algorithm predicts postsurgical recurrence in locoregional therapy-treated hepatocellular carcinoma.

OBJECTIVES: In HCC, locoregional therapy (LRT) is performed as a bridging or downstaging treatment before curative surgery. The impact of the LI-RADS Treatment Response (LR-TR) algorithm on surgical outcomes remains unknown. We aimed to evaluate radiologic and clinical factors predicting recurrence-free survival (RFS) and overall survival (OS) after curative surgery for LRT-treated HCC. MATERIALS AND METHODS: Consecutive HCC patients who underwent liver transplantation or curative resection after LRT from 2010 to 2016 and had baseline and follow-up post-LRT CT/MRI up to the point of surgery were included. The LR-TR category at the time of surgery and other features were assessed using Cox proportional hazard models. RFS was estimated and compared using the Kaplan-Meier method with log-rank tests. RESULTS: We evaluated 73 patients with 115 lesions. The LR-TR viable category at the time of surgery (hazard ratio [HR], 3.84; 95% confidence interval [CI]: 1.04, 14.16), preoperative AFP > 200 ng/mL (HR, 3.63; 95% CI: 1.63, 8.10), LRT sessions > 3 (HR, 4.99; 95% CI: 1.73, 14.38), and resection (HR, 3.35; 95% CI: 1.39, 8.09) independently predicted recurrence. The risk score categorized the patients into poor, intermediate, and favorable-risk groups with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). Outside Milan at the time of surgery (HR, 5.79; 95% CI: 1.94, 17.07) and recurrence within the first postoperative year (HR, 17.66; 95% CI: 6.42, 48.56) predicted death. CONCLUSION: In LRT-treated HCC, non-LR-TR viable disease achieved within fewer LRT sessions and removed by liver transplantation recurred less. KEY POINTS: • The Liver Imaging Reporting and Data System treatment response (LR-TR) viable disease (hazard ratio [HR], 3.84; p = 0.043), preoperative serum AFP level > 200 ng/mL (HR, 3.63; p = 0.002), more than three locoregional treatment (LRT) sessions (HR, 4.99; p = 0.003), and resection compared to liver transplantation (HR, 3.35; p = 0.001) were the independent predictors for postsurgical recurrence in LRT-treated HCCs. • A scoring system combining LR-TR categories and key clinical factors stratifies the patients into poor, intermediate, and favorable recurrence risk groups, with 1-year RFS rates of 35.0%, 78.3%, and 97.0%, respectively (p < 0.001). • Outside Milan at the time of surgery (HR, 5.79; p = 0.001) and recurrence within the first postoperative year (HR, 17.66; p < 0.001) were associated with poor overall survival.

Identification of intratumoral fluid-containing area by magnetic resonance imaging to predict prognosis in patients with pancreatic ductal adenocarcinoma after curative resection.

OBJECTIVES: To compare the prognosis of pancreatic ductal adenocarcinoma (PDAC) after curative resection according to the type of intratumoral fluid-containing area identified on MRI. METHODS: This retrospective study included 112 consecutive patients who underwent upfront surgery with margin-negative resection between 2012 and 2019. All patients underwent MRI within 1 month before surgery. Three radiologists independently assessed the MRI findings, determined whether intratumoral fluid-containing areas were present, and classified all intratumoral fluid-containing areas by type (i.e., imaging necrosis or neoplastic mucin cysts). Recurrence-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and the Cox proportional hazards model. Histopathological differences according to the type of intratumoral fluid-containing area were assessed. RESULTS: Of the 112 PDAC patients, intratumoral fluid-containing areas were identified on MRI in 33 (29.5%), among which 18 were classified as imaging necrosis and 15 as neoplastic mucin cysts. PDAC patients with imaging necrosis demonstrated significantly shorter RFS (mean 6.1 months versus 47.3 months; p < .001) and OS (18.4 months versus 55.0 months, p = .001) than those with neoplastic mucin cysts. Multivariable analysis showed that only the type of intratumoral fluid-containing area was significantly associated with RFS (hazard ratio, 2.25 and 0.38; p = .009 and p = .046 for imaging necrosis and neoplastic mucin cysts, respectively). PDAC with imaging necrosis had more frequent histological necrosis, more aggressive tumor differentiation, and higher tumor cellularity than PDAC with neoplastic mucin cysts (p ≤ .02). CONCLUSION: The detection and discrimination of intratumoral fluid-containing areas on preoperative MRI may be useful in predicting the prognosis of PDAC patients after curative resection. KEY POINTS: • Pancreatic ductal adenocarcinoma (PDAC) patients with imaging necrosis demonstrated significantly shorter survival than those with neoplastic mucin cysts after curative resection. • Multivariable analysis showed that only the type of intratumoral fluid-containing area identified on MRI was significantly associated with recurrence-free survival. • PDAC with imaging necrosis had more frequent histological necrosis, more aggressive tumor differentiation, and higher tumor cellularity than PDAC with neoplastic mucin cysts.

Imaging of the Bulbourethral (Cowper) Gland: Abnormalities and Differential Diagnosis.

Normal Cowper glands and ducts are imperceptible at imaging. However, abnormalities of the Cowper glands and ducts are increasingly seen owing to increasing use of cross-sectional imaging. In this article, the authors present a comprehensive review of the normal anatomy of the Cowper glands and ducts and the clinical and imaging findings of conditions that affect them in an effort to help lead to appropriate diagnosis and management. A Cowper duct syringocele is a congenital or acquired dilatation of the Cowper duct in the bulb of the corpus spongiosum. Retrograde urethrography is the standard test to diagnose a communicating (open) Cowper duct syringocele, and MRI is used for further morphologic assessment. Cowperitis refers to inflammation of the gland and/or duct, and recurrent cowperitis is usually associated with an underlying syringocele, a urethral fistulous connection to the Cowper gland, or a perianal fistula. MRI allows detection of the underlying structural abnormality and the superimposed inflammation. Cowper stones are typically radiopaque and are found in both the Cowper gland and duct. A Cowper gland hemorrhagic cyst may be incidentally detected at MRI of the prostate, and follow-up MRI may be required to ensure evolution of hemorrhage and exclude an underlying neoplasm. Cowper gland carcinoma is rare and includes adenocarcinoma and adenoid cystic carcinoma subtypes. Transperineal US may be used for initial evaluation and CT and/or MRI are necessary for further characterization and staging. Cowper gland hyperplasia is a rare entity with few previous reports that may be incidentally detected at imaging and may mimic malignancy. ©RSNA, 2022.

Retrospective analysis of current guidelines for hepatocellular carcinoma diagnosis on gadoxetic acid-enhanced MRI in at-risk patients.

OBJECTIVE: To evaluate and compare the diagnostic performance of the updated HCC guidelines using gadoxetic acid-enhanced MRI. METHODS: In this study, patients at risk of HCC who underwent gadoxetic acid-enhanced MRI following US/CT surveillance were retrospectively recruited from 3 centers. Three radiologists independently evaluated hepatic nodule imaging features relevant to the diagnostic criteria outlined in each guideline. Per-lesion sensitivity, specificity, and accuracy were compared between guidelines using logistic regression with a generalized estimating equation. Inter-observer agreements on imaging features were determined using Fless κ statistics. RESULTS: Altogether, 447 nodules (310 HCCs, 20 combined hepatocellular-cholangiocarcinomas, 2 cholangiocarcinomas, and 115 benign entities) measuring 1-3 cm from 386 patients were assessed. The KLCA-NCC and APASL guidelines showed the highest sensitivity (82.3-90.6%, p < .001) and accuracy (83.9-88.6%) among the five guidelines. The OPTN/UNOS guideline showed the highest specificity (94.9-97.1%), followed by the AASLD/LI-RADS, EASL, KLCA-NCC, and APASL guidelines, with significant difference only with the APASL guideline. The diagnostic performance of the updated AASLD/LI-RADS and EASL guidelines and of the KLCA-NCC and APASL guidelines was comparable (p > .05). Inter-observer agreement was substantial to almost perfect (κ = 0.73-0.87). CONCLUSIONS: For the diagnosis of HCC using gadoxetic acid-enhanced MRI, the KLCA-NCC and APASL guidelines showed the highest sensitivity and accuracy. The OPTN/UNOS guideline showed the highest specificity. Acknowledging their relative strengths and weaknesses could help adapt the diagnostic criteria according to the clinical context. KEY POINTS: • APASL and KLCA-NCC provided significantly the highest sensitivity and accuracy, followed by AASLD/LI-RADS and EASL in an endemic area for hepatitis B. • OPTN/UNOS showed the highest specificity, followed by AASLD/LI-RADS, EASL, KLCA-NCC, and APASL guidelines, with significant difference only with APASL. • Broadened definition of arterial hyperenhancement, washout, and the size of the lesion eligible to apply diagnostic criteria may improve the diagnostic performance for HCC in an endemic area for hepatitis B.

Diagnostic performance of Liver Imaging Reporting and Data System treatment response algorithm: a systematic review and meta-analysis.

OBJECTIVE: To systematically determine the accuracy of Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm for diagnosing the viability of hepatocellular carcinoma (HCC) treated with locoregional therapy (LRT). METHODS: Original studies reporting the diagnostic accuracy of LR-TR algorithm on dynamic contrast-enhanced computed tomography or magnetic resonance imaging (MRI) were identified in MEDLINE and EMBASE up to June 1, 2020. The meta-analytic summary sensitivity and specificity of LR-TR algorithm were calculated using a bivariate random-effects model. Subgroup analyses and meta-regression analysis were performed to explore study heterogeneity. RESULTS: We found six studies reporting the accuracy of LR-TR viable category (601 observations in 453 patients). The meta-analytic pooled sensitivity and specificity of LR-TR viable category were 63% (95% confidence interval [CI], 39-81%; I2 = 88%) and 96% (95% CI, 91-99%; I2 = 76%), respectively. The meta-analytic pooled sensitivity and specificity of LR-TR viable or equivocal category combined were 71% (95% CI, 55-84%; I2 = 89%) and 87% (95% CI, 73-94% I2 = 80%), respectively. Studies which used only MRI showed a trend towards higher sensitivity (71% [95% CI, 46-88%]) with a comparable specificity (95% [95% CI, 86-99%]) of LR-TR viable category compared to the whole group. The type of reference standard and study design were significantly associated with study heterogeneity (p ≤ 0.01). CONCLUSIONS: The LR-TR viable category had high specificity but suboptimal sensitivity for diagnosing the viability of HCC after LRT. Substantial study heterogeneity was noted, and it was significantly associated with the type of reference standard and study design. KEY POINTS: • The meta-analytic pooled sensitivity and specificity of LR-TR viable category were 63% (95% CI, 39-81%) and 96% (95% CI, 91-99%), respectively. • The meta-analytic pooled sensitivity and specificity of LR-TR viable or equivocal category combined were 71% (95% CI, 55-84%) and 87% (95% CI, 73-94%), respectively. • The type of reference standard and study design were the factors significantly influencing study heterogeneity (p ≤ 0.01).