Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Recombinant expression and tryptophan-assisted analysis of human sweet taste receptor T1R3's extracellular domain in sweetener interaction studies.

The human palate can discern multiple tastes; however, it predominantly perceives five fundamental flavors: sweetness, saltiness, sourness, bitterness, and umami. Sweetness is primarily mediated through the sweet taste receptor, a membrane-bound heterodimeric structure comprising T1R2-T1R3. However, unraveling the structural and mechanistic intricacies of the sweet taste receptor has proven challenging. This study aimed to address this knowledge gap by expressing an extracellular N-terminal domain encompassing the cysteine-rich domain of human hT1R3 (hT1R3-TMD) in Escherichia coli. The expressed protein was obtained as inclusion bodies, purified by metal affinity chromatography, and refolded using the dilution-refolding method. Through rigorous analysis, we confirmed the successful refolding of hT1R3-TMD and elucidated its structural characteristics using circular dichroism spectroscopy. Notably, the refolded protein was found to exist as either a monomer or a dimer, depending on its concentration. A tryptophan fluorescence quenching assay revealed that the dissociation constants for sucrose, sucralose, and brazzein were >9500 µM, 2380 µM and 14.3 µM, respectively. Our findings highlight the utility of this E. coli expression system for producing functional hT1R3-TMD for investigations and demonstrate the efficacy of the tryptophan fluorescence quenching assay in revealing complex interactions between sweet taste receptors and various sweeteners.

Primary Invasive Ductal Carcinoma Arising in Axillary Accessory Breast: A Case Report.

Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.

Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer.

OBJECTIVE: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. METHODS: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. RESULTS: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. CONCLUSION: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

Prognostic value of CT-based radiomics in grade 1-2 pancreatic neuroendocrine tumors.

BACKGROUND: Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS: This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS: Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.

Decoding cellular mechanism of recombinant adeno-associated virus (rAAV) and engineering host-cell factories toward intensified viral vector manufacturing.

Recombinant adeno-associated virus (rAAV) is one of the prominent gene delivery vehicles that has opened promising opportunities for novel gene therapeutic approaches. However, the current major viral vector production platform, triple transfection in mammalian cells, may not meet the increasing demand. Thus, it is highly required to understand production bottlenecks from the host cell perspective and engineer the cells to be more favorable and tolerant to viral vector production, thereby effectively enhancing rAAV manufacturing. In this review, we provided a comprehensive exploration of the intricate cellular process involved in rAAV production, encompassing various stages such as plasmid entry to the cytoplasm, plasmid trafficking and nuclear delivery, rAAV structural/non-structural protein expression, viral capsid assembly, genome replication, genome packaging, and rAAV release/secretion. The knowledge in the fundamental biology of host cells supporting viral replication as manufacturing factories or exhibiting defending behaviors against viral production is summarized for each stage. The control strategies from the perspectives of host cell and materials (e.g., AAV plasmids) are proposed as our insights based on the characterization of molecular features and our existing knowledge of the AAV viral life cycle, rAAV and other viral vector production in the Human embryonic kidney (HEK) cells.

Clinical Role of Upfront F-18 FDG PET/CT in Determining Biopsy Sites for Lung Cancer Diagnosis.

PURPOSE: This study aimed to investigate the impact of FDG PET/CT timing for biopsy site selection in patients with stage IV lung cancer regarding complications and diagnostic yield. METHODS: This retrospective analysis was performed on 1297 patients (924 men and 373 women with a mean age of 71.4 ± 10.2 years) who underwent percutaneous needle biopsy (PNB) for stage IV lung cancer diagnosis in two hospitals. Data collected included the patient's characteristics, order date of the biopsy and PET/CT exams, biopsy target site (lung or non-lung), guidance modality, complications, sample adequacy, and diagnostic success. Based on the order date of the PNB and PET/CT exams, patients were categorized into upfront and delayed PET/CT groups. RESULTS: PNB for non-lung targets resulted in significantly lower rates of minor (8.1% vs. 16.2%), major (0.2% vs. 3.4%), and overall complications (8.3% vs. 19.6%) compared to PNB for lung targets (p < 0.001 for all types of complications). Compared to the delayed PET/CT group, the upfront PET/CT group exhibited a lower probability of lung target selection of PNB (53.9% vs. 67.1%, p < 0.001), including a reduced incidence of major complications (1.0% vs. 2.9%, p = 0.031). Moreover, there was no significant difference in the occurrence of minor and total complications between the two groups. Upfront PET/CT and delayed PET/CT groups showed no significant difference regarding sample adequacy and diagnostic success. CONCLUSIONS: Upfront PET/CT may have an impact on the selection of the biopsy site for patients with advanced lung cancer, which could result in a lower rate of major complications with no change in the diagnostic yield. Upfront PET/CT demonstrates potential clinical implications for enhancing the safety of lung cancer diagnosis in clinical practice.

Achieving imaging and computational reproducibility on multiparametric MRI radiomics features in brain tumor diagnosis: phantom and clinical validation.

OBJECTIVES: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis. METHODS: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs). RESULTS: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869). CONCLUSION: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL. CLINICAL RELEVANCE STATEMENT: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology. KEY POINTS: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility.

Suboptimal hepatobiliary phase image in gadoxetic acid-enhanced liver MRI for the evaluation of the HCC: Predictive factors.

To determine the relevant laboratory values for hepatobiliary phase (HBP) imaging and predictive factors for suboptimal HBP images on gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) for the evaluation of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD). This study included 307 patients with CLD who underwent gadoxetic acid-enhanced liver MRI for HCC evaluation. The liver-portal vein contrast ratio and liver-spleen contrast ratio were calculated from the measurements of the HBP images. In this study, a suboptimal HBP image was defined as the presence of a bright portal vein or a liver-spleen contrast ratio of <1.5. Correlation, comparison, and receiver operating characteristic analyses were performed between the measured parameters on the HBP images and hepatic and renal function tests. The estimated glomerular filtration rate did not correlate with any measured or calculated values on the HBP images. On receiver operating characteristic analysis, the optimal cutoff value for the bright portal vein was an albumin level of 4.05 g/dL (area under the curve, 0.971; sensitivity, 65%; specificity, 82%). The optimal cutoff value of the suboptimal HBP image was a serum direct bilirubin level of 0.83 mg/dL (area under the curve, 0.830; sensitivity, 69%; specificity, 84%). On gadoxetic acid-enhanced MRI for the evaluation of HCC in patients with CLD, suboptimal HBP images were most strongly correlated with serum direct bilirubin levels. Renal function was not associated with suboptimal HBP imaging. Although the sensitivity is low, suboptimal HBP images can be predicted before gadoxetic acid-enhanced liver MRI can be performed.

Reducing false positives in deep learning-based brain metastasis detection by using both gradient-echo and spin-echo contrast-enhanced MRI: validation in a multi-center diagnostic cohort.

OBJECTIVES: To develop a deep learning (DL) for detection of brain metastasis (BM) that incorporates both gradient- and turbo spin-echo contrast-enhanced MRI (dual-enhanced DL) and evaluate it in a clinical cohort in comparison with human readers and DL using gradient-echo-based imaging only (GRE DL). MATERIALS AND METHODS: DL detection was developed using data from 200 patients with BM (training set) and tested in 62 (internal) and 48 (external) consecutive patients who underwent stereotactic radiosurgery and diagnostic dual-enhanced imaging (dual-enhanced DL) and later guide GRE imaging (GRE DL). The detection sensitivity and positive predictive value (PPV) were compared between two DLs. Two neuroradiologists independently analyzed BM and reference standards for BM were separately drawn by another neuroradiologist. The relative differences (RDs) from the reference standard BM numbers were compared between the DLs and neuroradiologists. RESULTS: Sensitivity was similar between GRE DL (93%, 95% confidence interval [CI]: 90-96%) and dual-enhanced DL (92% [89-94%]). The PPV of the dual-enhanced DL was higher (89% [86-92%], p < .001) than that of GRE DL (76%, [72-80%]). GRE DL significantly overestimated the number of metastases (false positives; RD: 0.05, 95% CI: 0.00-0.58) compared with neuroradiologists (RD: 0.00, 95% CI: - 0.28, 0.15, p < .001), whereas dual-enhanced DL (RD: 0.00, 95% CI: 0.00-0.15) did not show a statistically significant difference from neuroradiologists (RD: 0.00, 95% CI: - 0.20-0.10, p = .913). CONCLUSION: The dual-enhanced DL showed improved detection of BM and reduced overestimation compared with GRE DL, achieving similar performance to neuroradiologists. CLINICAL RELEVANCE STATEMENT: The use of deep learning-based brain metastasis detection with turbo spin-echo imaging reduces false positive detections, aiding in the guidance of stereotactic radiosurgery when gradient-echo imaging alone is employed. KEY POINTS: •Deep learning for brain metastasis detection improved by using both gradient- and turbo spin-echo contrast-enhanced MRI (dual-enhanced deep learning). •Dual-enhanced deep learning increased true positive detections and reduced overestimation. •Dual-enhanced deep learning achieved similar performance to neuroradiologists for brain metastasis counts.

A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report.

Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.

Assessment of diagnostic performance of risk factors affecting extraprostatic extension: Role of zonal level of prostate cancer.

OBJECTIVE: Extraprostatic extension (EPE) serves as a crucial marker of prostate cancer aggressiveness and independently predicts the likelihood of biochemical recurrence (BCR), exhibiting a strong correlation with the histologic severity of EPE. Therefore, this study aimed to investigate the probability of EPE along the zonal level of the prostate by measuring tumor contact length (TCL) using multiparametric magnetic resonance imaging (mpMRI). MATERIALS AND METHODS: Records of 308 patients who had undergone radical prostatectomy (RP) were identified. Tumor levels in the prostate were categorized as apex, mid-gland, and base, after which the correlation between TCL measured using MRI and microscopic EPE on pathologic specimens was evaluated. Univariable and multivariable logistic regression analyses were performed to assess the association among tumor origin, index tumor diameter, and TCL measured using MRI and microscopic EPE in RP specimens. RESULTS: Among the 214 patients included, 45 apical cancers (21%), 87 mid-gland cancers (41%), and 82 base cancers (38%) were observed. Pathological reports revealed that 18 (40.0%) apex, 31 (35.6%) mid-gland, and 50 (61.0%) base tumors were pT3a. Multivariable analysis demonstrated that the zonal level of the tumor, especially the base level, was an independent predictive factor for EPE (P < 0.001), and the AUC value of the base tumor was 0.858. CONCLUSION: Prostate cancers arising from the base were more likely to exhibit EPE than those arising from the mid-gland and apex of the prostate gland. Therefore, identifying the origin of the zonal level of prostate cancer may help guide treatment decisions and predict clinical prognosis.

Primary Peritoneal Psammocarcinoma Misdiagnosed as an Heterotopic Ossification: A Case Report.

Primary peritoneal psammocarcinoma is a rare type of serous carcinoma that is characterized by the massive formation of psammoma bodies and the invasion of adjacent organs. A 55-year-old female who previously underwent a hysterectomy presented to the emergency room with severe abdominal pain. Contrast-enhanced CT revealed an intra-abdominal calcific mass. Initially, it was thought to be a heterotopic ossification due to the previous pelvic surgery with intact ovaries. However, this was diagnosed as a primary peritoneal psammocarcinoma. Primary peritoneal psammocarcinoma is a very rare disease entity that should be considered a differential diagnosis in patients with normal ovaries, massive ossification in the pelvic cavity, and calcific peritoneal nodules.

Functional significance of serine 13 in the active site of glutathione S-transferase F3 from Oryza sativa.

Plant glutathione S-transferase (GST, EC 2.5.1.18) is an enzyme that detoxifies various electrophilic compounds including herbicides and organic pollutants by catalyzing the formation of conjugates with reduced glutathione (GSH). Although the structure and function of the GST subunits in rice, an important food in Asia, are not well understood, they are crucial for herbicide development. To investigate the role of active site residues in rice Phi-class GSTF3 (OsGSTF3), evolutionarily conserved serine residues were replaced with alanine using site-directed mutagenesis to obtain the mutants S13A, S38A, S69A, and S169A. These four mutants were expressed in Escherichia coli and purified to electrophoretic homogeneity using immobilized GSH affinity chromatography. Mutation of Ser13 to Ala resulted in substantial reductions in specific activities and kcat/Km values for the GSH-[1-chloro-2,4-dinitrobenzene (CDNB)] conjugation reaction. In contrast, mutations of Ser38, Ser69, and Ser169 to Ala had little effect on the activities and kinetic parameters. Additionally, the mutation of Ser13 to Ala significantly affected the KmGSH and I50 values of S-hexylglutathione and S-(2,4-dinitrophenyl)glutathione, which compete with GSH and the product of GSH-CDNB conjugation, respectively. A pH-log (kcat/KmCDNB) plot was used to estimate the pKa value of GSH in the enzyme-GSH complex of the wild-type enzyme, which was approximately 6.9. However, the pKa value of GSH in the enzyme-GSH complex of the S13A mutant was approximately 8.7, which was about 1.8 pK units higher than that of the wild-type enzyme. OsGSTF3 was also crystallized for crystallographic study, and the structure analyses revealed that Ser13 is located in the active site and that its side chain is in close proximity to the thiol group of glutathione bound in the enzyme. Based on these substitution effects on kinetic parameters, the dependence of kinetic parameters on the pH and 3-dimensional structure, it was suggested that Ser13 in rice OsGSTF3 is the residue responsible for catalytic activity by lowering the pKa of GSH in the enzyme-GSH complex and enhancing the nucleophilicity of the GSH thiol in the active site.

Diagnostic performance of synthetic relaxometry for predicting neurodevelopmental outcomes in premature infants: a feasibility study.

OBJECTIVES: To investigate the predictability of synthetic relaxometry for neurodevelopmental outcomes in premature infants and to evaluate whether a combination of relaxation times with clinical variables or qualitative MRI abnormalities improves the predictive performance. METHODS: This retrospective study included 33 premature infants scanned with synthetic MRI near or at term equivalent age. Based on neurodevelopmental assessments at 18-24 months of corrected age, infants were classified into two groups (no/mild disability [n = 23] vs. moderate/severe disability [n = 10]). Clinical and MRI characteristics associated with moderate/severe disability were explored, and combined models incorporating independent predictors were established. Ultimately, the predictability of relaxation times, clinical variables, MRI findings, and a combination of the two were evaluated and compared. The models were internally validated using bootstrap resampling. RESULTS: Prolonged T1-frontal/parietal and T2-parietal periventricular white matter (PVWM), moderate-to-severe white matter abnormality, and bronchopulmonary dysplasia were significantly associated with moderate/severe disability. The overall predictive performance of each T1-frontal/-parietal PVWM model was comparable to that of individual MRI finding and clinical models (AUC = 0.71 and 0.76 vs. 0.73 vs. 0.83, respectively; p > 0.27). The combination of clinical variables and T1-parietal PVWM achieved an AUC of 0.94, sensitivity of 90%, and specificity of 91.3%, outperforming the clinical model alone (p = 0.049). The combination of MRI finding and T1-frontal PVWM yielded AUC of 0.86, marginally outperforming the MRI finding model (p = 0.09). Bootstrap resampling showed that the models were valid. CONCLUSIONS: It is feasible to predict adverse outcomes in premature infants by using early synthetic relaxometry. Combining relaxation time with clinical variables or MRI finding improved prediction. CLINICAL RELEVANCE STATEMENT: Synthetic relaxometry performed during the neonatal period may serve as a biomarker for predicting adverse neurodevelopmental outcomes in premature infants. KEY POINTS: • Synthetic relaxometry based on T1 relaxation time of parietal periventricular white matter showed acceptable performance in predicting adverse outcome with an AUC of 0.76 and an accuracy of 78.8%. • The combination of relaxation time with clinical variables and/or structural MRI abnormalities improved predictive performance of adverse outcomes. • Synthetic relaxometry performed during the neonatal period helps predict adverse neurodevelopmental outcome in premature infants.

Imaging-Based Versus Pathologic Survival Stratifications of Diffuse Glioma According to the 2021 WHO Classification System.

OBJECTIVE: Imaging-based survival stratification of patients with gliomas is important for their management, and the 2021 WHO classification system must be clinically tested. The aim of this study was to compare integrative imaging- and pathology-based methods for survival stratification of patients with diffuse glioma. MATERIALS AND METHODS: This study included diffuse glioma cases from The Cancer Genome Atlas (training set: 141 patients) and Asan Medical Center (validation set: 131 patients). Two neuroradiologists analyzed presurgical CT and MRI to assign gliomas to five imaging-based risk subgroups (1 to 5) according to well-known imaging phenotypes (e.g., T2/FLAIR mismatch) and recategorized them into three imaging-based risk groups, according to the 2021 WHO classification: group 1 (corresponding to risk subgroup 1, indicating oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, and 1p19q-co-deleted), group 2 (risk subgroups 2 and 3, indicating astrocytoma, IDH-mutant), and group 3 (risk subgroups 4 and 5, indicating glioblastoma, IDHwt). The progression-free survival (PFS) and overall survival (OS) were estimated for each imaging risk group, subgroup, and pathological diagnosis. Time-dependent area-under-the receiver operating characteristic analysis (AUC) was used to compare the performance between imaging-based and pathology-based survival model. RESULTS: Both OS and PFS were stratified according to the five imaging-based risk subgroups (P < 0.001) and three imaging-based risk groups (P < 0.001). The three imaging-based groups showed high performance in predicting PFS at one-year (AUC, 0.787) and five-years (AUC, 0.823), which was similar to that of the pathology-based prediction of PFS (AUC of 0.785 and 0.837). Combined with clinical predictors, the performance of the imaging-based survival model for 1- and 3-year PFS (AUC 0.813 and 0.921) was similar to that of the pathology-based survival model (AUC 0.839 and 0.889). CONCLUSION: Imaging-based survival stratification according to the 2021 WHO classification demonstrated a performance similar to that of pathology-based survival stratification, especially in predicting PFS.

Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma.

Background: Tumor budding is considered a prognostic factor in several solid cancer types. However, we lack comprehensive information on the importance of tumor budding in cholangiocarcinoma. Therefore, we aimed to assess the prognostic value of tumor budding in intrahepatic and extrahepatic cholangiocarcinomas and to evaluate its correlations with other clinicopathological parameters. Methods: We monitored 219 patients who underwent surgery for intrahepatic or extrahepatic cholangiocarcinoma at the Pusan National University Hospital between 2012 and 2021. Tumor budding was evaluated using the International Tumor Budding Consensus Conference scoring system. Tumor budding was classified into low (0-4), intermediate (5-9), and high (≥10). For statistical analysis, tumor budding was divided into two groups based on the cut-off value of 10 (lower: 0-9 vs. higher: ≥10). The correlations between clinicopathological parameters were examined using the chi-square and Fisher's exact test. The prognostic values of the variables were analyzed using the log-rank test and Cox regression analysis. Results: Low, intermediate, and high tumor buddings were identified in 135 (61.6%), 63 (28.8), and 21 (9.6%), patients, respectively. Higher tumor budding was related to the presence of lymphatic invasion (p = 0.017), higher tumor grade (p = 0.001), higher N category (p = 0.034). In the univariable and multivariable analyses, higher tumor budding was associated with shorter disease-free survival in 97 (44.3%) patients who underwent R0 resection (p < 0.001 and p = 0.011). Tumor budding did not significantly correlate with disease-specific survival in entire patients. Conclusion: Tumor budding may serve as a prognostic factor for intrahepatic and extrahepatic cholangiocarcinomas treated with R0 resection.

Defining subventricular zone involvement to predict the survival of patients in isocitrate dehydrogenase-wild type glioblastoma: validation in a prospective registry.

OBJECTIVES: The prognostic value of subventricular zone distance (SVD) is unclear because of different definitions and lack of evaluation of clinical survival models. The aim of this study was to define SVD and evaluate its prognostic value in a survival nomogram for glioblastoma. METHODS: This retrospective study included 158 (SVD biomarker) from historical glioblastoma patients and 187 (survival modeling) with IDH-wild type glioblastoma from a prospective registry (NCT02619890). SVD was assessed by two radiologists: definition 1, the distance between the tumor edge to subventricular zone (SVZ); definition 2, the distance between the tumor centroid to SVZ; definition 3, enhancement at the ventricular wall. The associations between SVD and overall survival (OS) were evaluated using multivariable Cox proportional hazards regression analysis. Performance of an updated SVD survival model was compared with that of the Radiation Therapy Oncology Group (RTOG) 0525 nomogram. RESULTS: SVD according to both definition 1 (hazard ratio [HR]: 0.97, 95% CI: 0.94-0.99; p = .011) and definition 2 (HR: 0.96, 0.94-0.98, p < .001) was adversely associated with OS. Definition 1 was adversely associated with PFS (HR: 0.96, 0.94-0.99, p = .008) and showed the highest reproducibility (intraclass correlation coefficient, 0.90). The SVD-updated model showed similar to better performance than the RTOG model for predicting OS of up to 3 years (AUC: 0.735-0.738 vs. 0.687-0.708), with higher time-dependent specificity for 1-year (89.9% vs. 70.6%) and 3-year OS (93.3% vs. 80.0%). CONCLUSION: SVZ distance is an independent adverse prognostic factor in patients with IDH-wild type glioblastoma. Updating the survival model with SVZ provides better time-dependent specificity and reproducibility. KEY POINTS: • Subventricular zone distance (SVD) measurement from tumor edge showed high reproducibility. • Longer SVD was independently associated with longer overall survival. • Adding SVD improved time-dependent specificity for survival model in a prospective registry.

Atypical Radiological Findings of Capillary Hemangioma in Right Atrium: A Case Report.

BACKGROUND: Cardiac hemangiomas account for only 2.8% of primary cardiac tumors and are caused by the abnormal proliferation of endothelial cells and excess blood vessels. Typical radiological findings of cardiac hemangioma demonstrate intense contrast enhancement. CASE PRESENTATION: Here we report the case of a 69-year-old man who presented with a right atrial mass found incidentally with multimodal imaging findings, including echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI). This case presented with poor enhancement within right atrial mass on dynamic contrast-enhanced CT scan and gadolinium-enhanced first-pass perfusion image of cardiac MRI. After surgical resection, the pathologic diagnosis of cardiac capillary hemangioma was made. CONCLUSION: Cardiac hemangioma could be included in the differential diagnosis for cardiac neoplasms demonstrating poor enhancements on CT and MRI scans.

Parasitic Leiomyoma with Lymphatic Dilatation in Trocar Port-Site of Abdominal Wall: A Case Report.

Uterine leiomyoma is the most common benign pelvic tumor in female and being symptomatic is an indication for surgical removal. As laparoscopic surgery has been developed, some cases related to parasitic leiomyomas in the port site have been reported. A 40-year-old female who a history of previous laparoscopic surgery to remove uterine myoma 2 years ago visited in outpatient clinic of general surgery with palpable mass in left lower abdomen. Contrast enhanced abdomen CT and pelvis MRI were done to evaluate the mass. It was diagnosed parasitic leiomyoma in pathologic study after surgical removal and parasitic leiomyoma should be considered when patient visited presenting abdominal mass with the history of laparoscopic myomectomy.