Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Purpose: We assessed the proportion of patients with a focal intrahepatic stricture (FIHS) that was a precursor lesion or malignancy and visualized only as a duct dilatation. Materials and Methods: This retrospective study assessed patients who underwent surgery or biopsy for an FIHS on CT or MRI between January 2010 and March 2022. The number and proportion of non-precursor benign lesions, precursors, and malignancies were calculated.Clinical variables and imaging features were compared between non-premalignant benign and premalignant/malignant FIHSs. Results: Twenty-eight patients with confirmed histopathological diagnoses were identified, including 15 men (54.0%) and 13 women (46.0%). The median age of all patients at the first imaging diagnosis was 65 ± 9.54 (range, 43–78) years. Of the 28 patients with FIHSs, 9 (32%) were diagnosed with cholangiocarcinoma and 7 (25%) were diagnosed with precursor lesions, which included six intraductal papillary neoplasms of the bile duct and one biliary intraepithelial neoplasm. Accordingly, 16 (57%) patients had malignant or precursor lesions, and 12 (43%) were diagnosed with non-precursor benign lesions. None of the clinical variables and imaging features used for analysis showed a statistically significant difference between the non-premalignant benign and premalignant/malignant FIHS groups (p > 0.05). Conclusion FIHSs visualized only as duct dilatation can harbor malignant or precursor lesions.

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson’s disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors.Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

Background: Preeclampsia (PE) is a hypertensive pregnancy disorder linked to placental dysfunction, often involving pathological lesions like acute atherosis, decidual vasculopathy, accelerated villous maturation, and fibrinoid deposition. However, there is no gold standard for the pathological diagnosis of PE and this limits the ability of clinicians to distinguish between PE and non-PE pregnancies. Recent advances in computational pathology have provided the opportunity to automate pathological analysis for diagnosis, classification, prediction, and prediction of disease progression. In this study, we assessed whether computational pathology could be used to identify PE placentas. Methods: A total of 168 placental whole-slide images (WSIs) of patients from Seoul National University Hospital (comprising 84 PE cases and 84 normal controls) were used for model development and internal validation. For external validation of the model, 76 placental slides (including 38 PE cases and 38 normal controls) were obtained from the Boramae Medical Center (BMC). To establish standard criteria for diagnosing PE and distinguishing it from controls using placental WSIs, patch characteristics and quantification of terminal and intermediate villi were employed. In unsupervised learning, K-means clustering was conducted as a feature obtained through an Auto Encoder to extract the ratio of each cluster for each WSI. For supervised learning, quantitative assessments of the villi were obtained using a U-Net-based segmentation algorithm. The prediction model was developed using an ensemble method and was compared with a clinical feature model developed by using placental size features. Results: Using ensemble modeling, we developed a model to identify PE placentas.The model showed good performance (area under the precision-recall curve [AUPRC], 0.771; 95% confidence interval [CI], 0.752–0.790), with 77.3% of sensitivity and 71.1% of specificity, whereas the clinical feature model showed an AUPRC 0.713 (95% CI, 0.694–0.732) with 55.6% sensitivity and 86.8% specificity. External validation of the predictive model employing the BMC-derived set of placental slides also showed good discrimination (AUPRC, 0.725; 95% CI, 0.720–0.730). Conclusion The proposed computational pathology model demonstrated a strong ability to identify preeclamptic placentas. Computational pathology has the potential to improve the identification of PE placentas.

Objective: This study investigated the feasibility and prognostic relevance of threshold-based quantification of myocardial delayed enhancement (MDE) on CT in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods: Forty-three patients with NIDCM (59.3 ± 17.1 years; 21 male) were included in the study and underwent cardiac CT and MRI. MDE was quantified manually and with a threshold-based quantification method using cutoffs of 2, 3, and 4 standard deviations (SDs) on three sets of CT images (100 kVp, 120 kVp, and 70 keV). Interobserver agreement in MDE quantification was assessed using the intraclass correlation coefficient (ICC). Agreement between CT and MRI was evaluated using the Bland-Altman method and the concordance correlation coefficient (CCC). Patients were followed up for the subsequent occurrence of the primary composite outcome, including cardiac death, heart transplantation, heart failure hospitalization, or appropriate use of an implantable cardioverter-defibrillator. The Kaplan–Meier method was used to estimate event-free survival according to MDE levels. Results: Late gadolinium enhancement (LGE) was observed in 29 patients (67%, 29/43), and the mean LGE found with the 5-SD threshold was 4.1% ± 3.6%. The 4-SD threshold on 70-keV CT showed excellent interobserver agreement (ICC = 0.810) and the highest concordance with MRI (CCC = 0.803). This method also yielded the smallest bias with the narrowest range of 95% limits of agreement compared to MRI (bias, -0.119%; 95% limits of agreement, -4.216% to 3.978%). During a median follow-up of 1625 days (interquartile range, 712–1430 days), 10 patients (23%, 10/43) experienced the primary composite outcome. Event-free survival significantly differed between risk subgroups divided by the optimal MDE cutoff of 4.3% (log-rank P = 0.005). Conclusion The 4-SD threshold on 70-keV monochromatic CT yielded results comparable to those of MRI for quantifying MDE as a marker of myocardial fibrosis, which showed prognostic value in patients with NIDCM.

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). Conclusions After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Background/Aims: Helicobacter pylori (H. pylori) infection highly correlates with erythematous/exudative gastritis, which is one of the endoscopic findings of the Sydney classification system. The present study aimed to evaluate the association between endoscopic severity of erythematous/exudative gastritis and H. pylori infection. Methods: We prospectively enrolled asymptomatic adults who were diagnosed with erythematous/exudative gastritis during screening esophagogastroduodenoscopy. A rapid urease test was performed in all participants to diagnose H. pylori infection. The severity of erythematous/exudative gastritis was determined based on the Sydney classification system. Two investigators independently evaluated the endoscopic findings. The primary endpoint was H. pylori infection rate according to the severity of erythematous/exudative gastritis (mild vs. moderate-to-severe). Results: A total of 177 patients with erythematous/exudative gastritis were included. The rate of H. pyloriinfection was 86.4% in all patients. Of 177 included patients, 78 were at mild degree, 48 were at moderate degree, and 51 were at severe degree. The inter-observer variation was 4.6% and kappa value was 0.593. H. pylori infection rate was similar between patients with mild erythematous/exudative gastritis and those with moderate-to-severe erythematous/exudative gastritis (91.0% vs. 82.8%, p=0.115). Even after adjusting potential confounding variables, the severity of erythematous/exudative gastritis was not associated with H. pylori infection rate. Conclusions H. pylori infection is commonly observed in patients with erythematous/exudative gastritis. However, the severity of erythematous/exudative gastritis is not associated with H. pylori infection rate.