Dual-energy computed tomography for predicting histological grading and survival in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: We evaluated the value of dual-energy computed tomography (DECT) parameters derived from pancreatic ductal adenocarcinoma (PDAC) to discriminate between high- and low-grade tumors and predict overall survival (OS) in patients. METHODS: Data were retrospectively collected from 169 consecutive patients with pathologically confirmed PDAC who underwent third-generation dual-source DECT enhanced dual-phase scanning before surgery between January 2017 and March 2023. Patients with prior treatments, other malignancies, small tumors, or poor-quality scans were excluded. Two radiologists evaluated three clinical and seven radiological features and measured sixteen DECT-derived parameters. Univariate and multivariate analyses were applied to select independent predictors. A prediction model and a corresponding nomogram were developed, and the area under the curve (AUC), calibration, and clinical applicability were assessed. The correlations between factors and OS were evaluated using Kaplan-Meier survival and Cox regression analyses. RESULTS: One hundred sixty-nine patients were randomly divided into training (n = 118) and validation (n = 51) cohorts, among which 43 (36.4%) and 19 (37.3%) had high-grade PDAC confirmed by pathology, respectively. The vascular invasion, normalized iodine concentration in the venous phase, and effective atomic number in the venous phase were independent predictors for histological grading. A nomogram was constructed to predict the risk of high-grade tumors in PDAC, with AUCs of 0.887 and 0.844 in the training and validation cohorts, respectively. The nomogram exhibited good calibration and was more beneficial than a single parameter in both cohorts. Pathological- and nomoscore-predicted high-grade PDACs were associated with poor OS (all p < 0.05). CONCLUSIONS: The nomogram, which combines DECT parameters and radiological features, can predict the histological grade and OS in patients with PDAC before surgery. KEY POINTS: Question Preoperative determination of histological grade in PDAC is crucial for guiding treatment, yet current methods are invasive and limited. Findings A DECT-based nomogram combining vascular invasion, normalized iodine concentration, and effective atomic number accurately predicts histological grade and OS in PDAC patients. Clinical relevance The DECT-based nomogram is a reliable, non-invasive tool for predicting histological grade and OS in PDAC. It provides essential information to guide personalized treatment strategies, potentially improving patient management and outcomes.

Development of TSHR-CAR NK-92 cells for Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is the predominant type of thyroid cancer, with some patients experiencing relapse, distant metastases, or refractoriness, revealing limited treatment options. Chimeric antigen receptor (CAR)-modified Natural Killer (NK) cells are revolutionary therapeutic agents effective against various resistant cancers. Thyroid-stimulating hormone receptor (TSHR) expression in DTC provides a unique tumor-specific target for CAR therapy. Here, we developed an innovative strategy for treating DTC using modified NK-92 cells armed with a TSHR-targeted CAR. The modified cells showed enhanced cytotoxicity against TSHR-positive DTC cell lines and exhibited elevated degranulation and cytokine release. After undergoing irradiation, the cells effectively halted their proliferative capacity while maintaining potent targeted killing ability. Transfer of these irradiation-treated cells into NSG mice with DTC tumors resulted in profound tumor suppression. NK-92 cells modified with TSHR-CAR offer a promising, off-the-shelf option for advancing DTC immunotherapy.

Pathological features of gastric­type endocervical adenocarcinoma: A report of two cases.

Gastric-type endocervical adenocarcinoma (GEA) is an uncommon form of uterine cervical adenocarcinoma with an unfavorable prognosis. The tumor consists of glands exhibiting a morphological resemblance to gastric cells and occasionally manifests features akin to pancreaticobiliary mucinous adenocarcinoma. GEA differs from the typical cervical cancer, particularly in its lack of association with the human papillomavirus. Immunophenotypic analysis suggests intestinal differentiation. The present study reports two cases of GEA occurring in postmenopausal individuals who were diagnosed in Lishui Central Hospital (Lishui, China) between January 2015 and January 2023. Microscopic examination revealed cysts lined with mucinous cells within the tumors. Immunohistochemical assays confirmed the positivity of the tumors for cytokeratin 7, mucin (MUC)5AC, and mutant tumor protein p53, while the results were negative for tumor suppressor p16, and in one case for paired box protein 8, consistent with characteristics of mucinous adenocarcinoma originating from the gastrointestinal tract. Programmed death-ligand 1 expression was also negative. The proto-oncogene K-ras was identified using amplification refractory mutation system polymerase chain reaction. Both cases were negative for mutations in codons 12 and 13 of exon 2, codon 61 of exon 3 and codon 146 of exon 4, but were positive for wild-type K-ras. Clinical follow-up revealed a potential association between histopathological features and resistance to chemotherapeutic drugs. The infrequency of this tumor type may contribute to diagnostic challenges.

Radiomic Feature-Based Nomogram: A Novel Technique to Predict EGFR-Activating Mutations for EGFR Tyrosin Kinase Inhibitor Therapy.

OBJECTIVES: To develop and validate a radiomic feature-based nomogram for preoperative discriminating the epidermal growth factor receptor (EGFR) activating mutation from wild-type EGFR in non-small cell lung cancer (NSCLC) patients. MATERIAL: A group of 301 NSCLC patients were retrospectively reviewed. The EGFR mutation status was determined by ARMS PCR analysis. All patients underwent nonenhanced CT before surgery. Radiomic features were extracted (GE healthcare). The maximum relevance minimum redundancy (mRMR) and LASSO, were used to select features. We incorporated the independent clinical features into the radiomic feature model and formed a joint model (i.e., the radiomic feature-based nomogram). The performance of the joint model was compared with that of the other two models. RESULTS: In total, 396 radiomic features were extracted. A radiomic signature model comprising 9 selected features was established for discriminating patients with EGFR-activating mutations from wild-type EGFR. The radiomic score (Radscore) in the two groups was significantly different between patients with wild-type EGFR and EGFR-activating mutations (training cohort: P<0.0001; validation cohort: P=0.0061). Five clinical features were retained and contributed as the clinical feature model. Compared to the radiomic feature model alone, the nomogram incorporating the clinical features and Radscore exhibited improved sensitivity and discrimination for predicting EGFR-activating mutations (sensitivity: training cohort: 0.84, validation cohort: 0.76; AUC: training cohort: 0.81, validation cohort: 0.75). Decision curve analysis demonstrated that the nomogram was clinically useful and surpassed traditional clinical and radiomic features. CONCLUSIONS: The joint model showed favorable performance in the individualized, noninvasive prediction of EGFR-activating mutations in NSCLC patients.

Application of artificial neural networks in detection and diagnosis of gastrointestinal and liver tumors.

As a form of artificial intelligence, artificial neural networks (ANNs) have the advantages of adaptability, parallel processing capabilities, and non-linear processing. They have been widely used in the early detection and diagnosis of tumors. In this article, we introduce the development, working principle, and characteristics of ANNs and review the research progress on the application of ANNs in the detection and diagnosis of gastrointestinal and liver tumors.

Preparation of a Polypyrrole/Graphene Oxide Composite Electrode by Electrochemical Codeposition for Capacitor Deionization.

In this paper, a polypyrrole/graphene oxide (PPy/GO) composite electrode, applied to the capacitive deionization process for removing heavy metal ions, was prepared by one-step electrochemical codeposition. The PPy/GO composite electrode has a dense sheet structure, and PPy is spherical and uniformly distributed on the surface of GO sheets. The experimental results show that the PPy/GO composite electrode has a higher capacitance (186.67 F/g) and a lower charge transfer resistance (1.626 Ω·cm2) than the PPy electrode. The adsorption capacity of the PPy/GO composite electrode is 41.51 mg/g, which is about 2.67 times (15.52 mg/g) that of the PPy electrode. After five adsorption/desorption treatments, the adsorption capacity was maintained at about 98.0%, and the regeneration rate was 94.7%. Therefore, the electrode has good cycle stability and regenerability. In addition, the adsorption capacity of different metal ions follows the order Ag+ < Cd2+ < Cu2+ < Pb2+ < Fe3+, indicating that the PPy/GO composite electrode has stronger adsorption capacity for the added state, and the adsorption capacity for ions with the same valence state decreases with the increase in ion hydration radius. The PPy/GO composite electrode has a good prospect for the removal of heavy metal ions in industrial wastewater.

MicroRNA-155-5p suppresses PD-L1 expression in lung adenocarcinoma.

MiR-155-5p is a key oncogenic microRNA that maintains immune homeostasis and mediates cross-talk between inflammation and tumorigenesis. High expression of programmed death ligand-1 (PD-L1) also plays an important role in immune tolerance in tumors. The present study aimed to explore the relationship between miR-155-5p and PD-L1 in lung adenocarcinoma (LUAD) cells A549 and H1650. The expression levels of miR-155-5p and PD-L1 in LUAD patients were detected by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and mimics of miR-155-5p were used to model increased expression in A549 or H1650 cells. After 24 h, we measured levels of PD-L1 by qRT-PCR, western blotting and flow cytometry. In addition, we identified two sites in the PD-L1 3'-UTR (5'-AGCAUUA-3' and 5'-GCAUUAA-3') that can be bound by miR-155-5p using TargetScan (http://www.targetscan.org). Compared to normal tissue, miR-155-5p was overexpressed in tumor tissue (P = 0.0456), whereas the expression of PD-L1 was not significantly different (P = 0.1349). The expression levels of miR-155-5p and PD-L1 were negatively correlated (r = -0.6409, P = 0.0459 and r = -0.7544, P = 0.0117). Exogenous overexpression of miR-155-5p decreased the mRNA, total protein and membrane protein expression levels of PD-L1 both in A549 and H1650 cells (P < 0.05). Taken together, our data suggest that miR-155-5p may suppress the expression of PD-L1 in LUAD.

Value of TSCT Features for Differentiating Preinvasive and Minimally Invasive Adenocarcinoma From Invasive Adenocarcinoma Presenting as Subsolid Nodules Smaller Than 3 cm.

BACKGROUND: To distinguish preinvasive (adenocarcinoma in situ/atypical adenomatous hyperplasia) and minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IA) appearing as solitary subsolid nodules (SSNs) less than 3 cm based on thin-section computed tomography (TSCT) features to guide therapeutic approaches. METHODS: A total of 154 lesions that were histopathologically confirmed to have pre/minimally invasive adenocarcinoma (hereafter pre/MIA) and IA presenting as part-solid nodules (PSNs) or pure ground-glass nodules (pGGNs) were retrospectively reviewed. The TSCT features, including diameter, area, CT value, shape, air bronchogram, margins, and location, were compared and assessed. Receiver operating characteristic analyses were conducted to determine the cut-off values for the qualitative variables and their diagnostic performances. RESULTS: Of 154 nodules, 89 IA, 53 MIA, eight adenocarcinoma in situ, and four atypical adenomatous hyperplasia lesions were found. Univariate and multivariate logistic regression of the pre/MIA and IA lesions were compared and analyzed among PSNs and pGGNs. Among pGGNs, a significant difference was found in the area (p = 0.004, odds ratio [OR] = 0.124, 95% confidence interval [CI] = 0.300-0.515) between the pre/MIA and IA groups. In PSNs, significant differences were found in the diameter (p = 0.001, OR = 0.171, 95% CI = 0.063-0.467) and CT value (p = 0.001, OR = 0.996, 95% CI = 0.993-0.998) between the pre/MIA and IA groups. According to the corresponding receiver operating characteristic curves, the optimal cut-off tumor area in pGGNs to differentiate pre/MIA from IA was 0.595 cm2. A higher CT value of the lesion (≥ -298.500 HU) and a larger diameter (≥1.450 cm) in PSNs were significantly associated with IA. CONCLUSION: Imaging features from TSCT contribute to distinguishing pre/MIA from IA in solitary subsolid nodules and may contribute to guide the clinical management of these lesions.

Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study.

BACKGROUND: A recent genome-wide association study has identified 12 genetic variants robustly associated with body fat percentage (BF%) with diverse cardiometabolic consequences. We developed three genetic risk scores (GRSs) according to the associations of the 12 individual variants with type 2 diabetes (T2D) and test the GRSs' associations with insulin resistance and T2D in the Atherosclerosis Risk in Communities Study. METHODS: In 6895 European-American participants, we calculated GRS-I as the number of BF%-increasing alleles from variants associated with increased risk of T2D, GRS-D from variants associated with decreased risk of T2D, and GRS-ALL from all 12 variants. Linear and logistic regression models were used to evaluate associations of the GRSs with insulin resistance and risk of T2D, respectively, adjusted for age, sex, smoking, and drinking, and additionally for body mass index (BMI). RESULTS: GRS-D was significantly associated with decreased levels of fasting insulin (P = 0.014) and homeostasis assessment of insulin resistance (P = 0.023). While GRS-I was not associated with insulin resistance measures, it was with T2D (P = 0.002). Further adjustment for BMI did not substantially change the above associations. GRS-ALL was inversely associated with insulin resistance after controlling for covariates including BMI; GRS-ALL was not associated with T2D. CONCLUSION: Genetically determined BF% has differential effects on cardiometabolic risk, which may partly explain the heterogeneity in obesity-induced cardiometabolic risk and have implications for developing new strategies mitigating obesity-induced cardiometabolic consequences.

Malignant changes in adenomyosis in patients with endometrial adenocarcinoma: A case series.

The aim of the study is to describe the clinical characteristics and prognosis of malignant transformation of adenomyosis in patients with endometrial cancer.In this retrospective descriptive study, the clinical data of patients with endometrial cancer (n = 127) who were admitted at our hospital between January 2006 and December 2013 were evaluated.Among the 127 patients with endometrial cancer, 24 patients had endometrial cancer concurrently with adenomyosis. Among these 24 patients, 3 were diagnosed with malignant transformation of adenomyosis. Postoperative pathological investigations in the cancer+adenomyosis group revealed endometrial adenocarcinoma of Grade I (n = 21) and II (n = 3). The patients with malignant transformation of adenomyosis were relatively younger than the other patients. In those 3 patients, both the estrogen and progesterone receptors were strongly expressed in eutopic endometrium and were weakly positive in ectopic endometrium.Although adenomyosis is usually benign, it might also be a precursor of malignant disease. As the incidence of adenomyosis malignant transformation is low, and its clinical manifestations are nonspecific, it may only be confirmed by postoperative pathological examination. Further investigations on larger sample size may provide additional data about prognosis of adenomyosis malignant transformation.

High expression of angiogenic factor AGGF1 is an independent prognostic factor for hepatocellular carcinoma.

BACKGROUND: Angiogenesis plays a critical role in tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) has been recently identified as a novel initiator of angiogenesis. However, the function and the prognostic values of AGGF1 in hepatocellular carcinoma remain poorly understood. Our aim is to provide more information to assist design the angiogenesis therapy that targets AGGF1 in HCC. RESULTS: AGGF1-positive frequency in HCC tissues was significantly higher than in peritumor tissues. The high expression of AGGF1 expression in HCC tissue was well associated with the increased expression of VEGF and the high microvessel density (MVD). AGGF1 expression predicts a poor prognosis and AGGF1 was an independent prognostic factor for DFS. METHODS: The expression levels of AGGF1, vascular endothelial growth factor (VEGF) and microvessel density (MVD) were identified by immunohistochemistry in 79 HCC tumor tissues and 24 corresponding peritumor tissues. The expression level of AGGF1 and MVD were quantified by counting the positively stained endothelial cells in the HCC and the peritumor tissue on the immunohistochemically stained tissue slides. The prognostic value of AGGF1 was evaluated by survival analysis. CONCLUSIONS: Our study shows that AGGF1 is identified as the independent prognostic factor for the disease-free survival (DFS) of patients after the surgical resection. contribute to tumor angiogenesis in HCC, which indicates that AGGF1 may be a new potential therapeutic target for anti-angiogenesis treatment for patients with HCC.

Gastric bronchogenic cysts: A case report and literature review.

Gastric bronchogenic cysts are rare lesions, first described in 1956, with only 34 cases reported in the literature to date. The present study described a case of bronchogenic cyst of the stomach in a 17-year-old female who presented with periodic epigastric pain. In addition, the study analyzed the existing literature on these lesions. Gastric bronchogenic cysts are more common in females (female:male ratio, 21:14) and the median age of their development is 43 years. In total, 48.57% of the 34 previously reported cases were identified incidentally, and the remainder presented mainly with epigastric pain. Cyst sizes varied between 1.7 and 15 cm. In 3 cases, preoperative diagnosis was performed using needle biopsy, whereas several studies were initially misdiagnosed as stromal tumors. In 85% of the cases (31/35), cyst resection was performed, with laparoscopy used in 4 of the cases. The findings of the present study and literature review suggested that bronchogenic cysts of the stomach are rare, and surgical resection is warranted to treat symptoms and prevent malignant transformation.

Posterior mediastinal ectopic meningioma: a case report.

Primary ectopic meningiomas occurring in the mediastinal region are extremely rare. So far, only five cases of primary mediastinal meningioma have been reported in the literatures. The imaging characteristics and the clinicopathological significance of mediastinal psammomatous meningioma have not been detailed. Here, we report the case of a 42-year-old male with primary posterior mediastinal psammomatous meningioma. The clinical features, imaging, and pathological findings are carefully analyzed, and the relevant literatures were reviewed.

Gastric schwannoma: CT findings and clinicopathologic correlation.

PURPOSE: The purpose of this study was to evaluate the computed tomography (CT) imaging characteristics of gastric schwannoma. METHODS: Eight cases of gastric schwannomas confirmed by surgery and pathology were retrospectively analyzed by CT. We reviewed the CT findings of gastric schwannomas for the following characteristics: tumor location, size, contour, margin, growth pattern, enhancement pattern, the presence or absence of necrosis, and perigastric lymph nodes. RESULTS: The tumors were located in the lesser curvature of gastric body (n = 5) and greater curvature of the gastric antrum (n = 3) with a median size of 4.8 cm (range 1.7-11.4 cm). Gastric schwannomas appeared as submucosal tumors with CT features of ovoid (7/8 patients), well-defined (8/8) and exophytic (4/8) or mixed (3/8) growth patterns. On dynamic CT examination, the tumors displayed homogeneous enhancement in seven cases and heterogeneous enhancement in one case. Solid parts of eight tumors demonstrated mild enhancement during the arterial phase and strengthened progressive enhancement during the venous and delayed phases. Two cases had perigastric lymph nodes. CONCLUSIONS: Gastric schwannomas typically manifested as ovoid, well-defined, exophytic, or mixed growth pattern masses on CT. Homogeneous progressive enhancement on dynamic CT is a characteristic finding of gastric schwannoma.

Localization of the calcium-regulated citrate transport process in proximal tubule cells.

Urinary citrate is an important inhibitor of calcium-stone formation. Most of the citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport. The present studies address several fundamental properties of this novel process: the polarity of the transport process, the location of the calcium-sensitivity and whether NaDC1 is present in OK cells. OK cells grown on permeable supports exhibited apical >basolateral citrate transport. Apical transport of both citrate and succinate was sensitive to extracellular calcium whereas basolateral transport was not. Apical calcium, rather than basolateral, was the predominant determinant of changes in transport. Also 2,3-dimethylsuccinate, previously identified as an inhibitor of basolateral dicarboxylate transport, inhibited apical citrate uptake. Although the calcium-sensitive transport process in OK cells is functionally not typical NaDC1, NaDC1 is present in OK cells by Western blot and PCR. By immunolocalization studies, NaDC1 was predominantly located in discrete apical membrane or subapical areas. However, by biotinylation, apical NaDC1 decreases in the apical membrane with lowering calcium. In sum, OK cells express a calcium-sensitive/regulated dicarboxylate process at the apical membrane which responds to variations in apical calcium. Despite the functional differences of this process compared to NaDC1, NaDC1 is present in these cells, but predominantly in subapical vesicles.