Differentiation between non-hypervascular pancreatic neuroendocrine tumour and pancreatic ductal adenocarcinoma on dynamic computed tomography and non-enhanced magnetic resonance imaging

Purpose: To determine the differentiating features between non-hypervascular pancreatic neuroendocrine tumour (PNET) and pancreatic ductal adenocarcinoma (PDAC) on dynamic computed tomography (CT) and non-enhanced magnetic resonance imaging (MRI). Material and methods: We enrolled 102 patients with non-hypervascular PNET (n = 15) or PDAC (n = 87), who had undergone dynamic CT and non-enhanced MRI. One radiologist evaluated all images, and the results were subjected to univariate and multivariate analyses. To investigate reproducibility, a second radiologist re-evaluated features that were significantly different between PNET and PDAC on multivariate analysis. Results: Tumour margin (well-defined or ill-defined) and enhancement ratio of tumour (ERT) showed significant differences in univariate and multivariate analyses. Multivariate analysis revealed a predominance of well-defined tumour margins in non-hypervascular PNET, with an odds ratio of 168.86 (95% confidence interval [CI]: 10.62-2685.29; p < 0.001). Furthermore, ERT was significantly lower in non-hypervascular PNET than in PDAC, with an odds ratio of 85.80 (95% CI: 2.57-2860.95; p = 0.01). Sensitivity, specificity, and accuracy were 86.7%, 96.6%, and 95.1%, respectively, when the tumour margin was used as the criteria. The values for ERT were 66.7%, 98.9%, and 94.1%, respectively. In reproducibility tests, both tumour margin and ERT showed substantial agreement (margin of tumour, κ = 0.6356; ERT, intraclass correlation coefficients (ICC) = 0.6155). Conclusions: Non-hypervascular PNET showed well-defined margins and lower ERT compared to PDAC, with significant differences. Our results showed that non-hypervascular PNET can be differentiated from PDAC via dynamic CT and non-enhanced MRI

Evaluating the malignant potential of intraductal papillary mucinous neoplasms of the pancreas : added value of non-enhanced endoscopic ultrasound to supplement non-enhanced magnetic resonance imaging

Purpose: To evaluate the diagnostic performance of combining non-enhanced magnetic resonance imaging (MRI) and non-enhanced endoscopic ultrasonography (EUS) for assessing the malignant potential of lesions in patients with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Material and methods: Data from 38 patients histopathologically diagnosed with IPMN adenomas or IPMN adenocarcinomas were retrospectively analysed. Preliminary univariate and multivariate analyses were conducted to identify statistically significant associations. Three blinded radiologists evaluated the image sets to assess the diagnostic performance of combined use of non-enhanced MRI and EUS as opposed to non-enhanced MRI alone in distinguishing malignant from benign lesions. Observer performance and interobserver variability were determined using receiver-operating-characteristic curve analysis and weighted κ statistics. Results: Multivariate analyses identified a significant difference between the abrupt change in the main pancreatic duct (MPD) calibre with distal pancreatic atrophy and the signal intensity of lesion-to-spinal cord ratio on MRI; a significant difference was observed in MPD size on EUS. Diagnostic performance assessments of the image sets did not differ significantly between the blinded radiologists. Conclusions: The clinical utility of non-enhanced EUS may be attributive in evaluating IPMN that has already been evaluated by non-enhanced MRI

3D quantitative analysis of diffusion-weighted imaging for predicting the malignant potential of intraductal papillary mucinous neoplasms of the pancreas

Purpose: To investigate the predictors of intraductal papillary mucinous neoplasms of the pancreas (IPMNs) with high-grade dysplasia, using 2-dimensional (2D) analysis and 3-dimensional (3D) volume-of-interest-based apparent diffusion coefficient (ADC) histogram analysis. Material and methods: The data of 45 patients with histopathologically confirmed IPMNs with high-grade or lowgrade dysplasia were retrospectively assessed. The 2D analysis included lesion-to-spinal cord signal intensity ratio (LSR), minimum ADC value ($ADC_{min}$), and mean ADC value ($ADC_{mean}$). The 3D analysis included the overall mean ($ADC_{overall mean}$), mean of the bottom 10th percentile ($ADC_{mean0-10}$), mean of the bottom 10-25th percentile ($ADC_{mean10-25}$), mean of the bottom 25-50th percentile ($ADC_{mean25-50}$), skewness ($ADC_{skewness}$), kurtosis ($ADC_{kurtosis}$), and entropy ($ADC_{entropy}$). Diagnostic performance was compared by analysing the area under the receiver operating characteristic curve (AUC). Inter-rater reliability was assessed by blinded evaluation using the intraclass correlation coefficient. Results: There were 16 and 29 IPMNs with high- and low-grade dysplasia, respectively. The LSR, $ADC_{overall mean}$, $ADC_{mean0-10}$, $ADC_{mean10-25}$, $ADC_{mean25-50}$, and $ADC_{entropy}$ showed significant between-group differences (AUC = 72-93%; p < 0.05). Inter-rater reliability assessment showed almost perfect agreement for LSR and substantial agreement for $ADC_{overall mean}$ and $ADC_{entropy}$. Multivariate logistic regression showed that $ADC_{overall mean}$ and $ADC_{entropy}$ were significant independent predictors of malignancy (p < 0.05), with diagnostic accuracies of 80% and 73%, respectively. Conclusion: $ADC_{overall mean}$ and $ADC_{entropy}$ from 3D analysis may assist in predicting IPMNs with high-grade dysplasia

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Ramos Cells Using Bio-phantoms

The roles of cell density, extracellular space, intracellular factors, and apoptosis induced by the molecularly targeted drug rituximab on the apparent diffusion coefficient (ADC) values were investigated using bio-phantoms. In these bio-phantoms, Ramos cells (a human Burkittｾs lymphoma cell line) were encapsulated in gellan gum. The ADC values decreased linearly with the increase in cell density, and declined steeply when the extracellular space became less than 4 μm. The analysis of ADC values after destruction of the cellular membrane by sonication indicated that approximately 65% of the ADC values of normal cells originate from the cell structures made of membranes and that the remaining 35% originate from intracellular components. Microparticles, defined as particles smaller than the normal cells, increased in number after rituximab treatments, migrated to the extracellular space and significantly decreased the ADC values of bio-phantoms during apoptosis. An in vitro study using bio-phantoms was conducted to quantitatively clarify the roles of cellular factors and of extracellular space in determining the ADC values yielded by tumor cells and the mechanism by which apoptosis changes those values

Clinical Guides for aHUS

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS

PDCD4 Knockdown Induces Senescence in Hepatoma Cells by Up-Regulating the p21 Expression

While the over-expression of tumor suppressor programmed cell death 4 (PDCD4) induces apoptosis, it was recently shown that PDCD4 knockdown also induced apoptosis. In this study, we examined the cell cycle regulators whose activation is affected by PDCD4 knockdown to investigate the contribution of PDCD4 to cell cycle regulation in three types of hepatoma cells: HepG2, Huh7 (mutant p53 and p16-deficient), and Hep3B (p53- and Rb-deficient). PDCD4 knockdown suppressed cell growth in all three cell lines by inhibiting Rb phosphorylation via down-regulating the expression of Rb itself and CDKs, which phosphorylate Rb, and up-regulating the expression of the CDK inhibitor p21 through a p53-independent pathway. We also found that apoptosis was induced in a p53-dependent manner in PDCD4 knockdown HepG2 cells (p53+), although the mechanism of cell death in PDCD4 knockdown Hep3B cells (p53-) was different. Furthermore, PDCD4 knockdown induced cellular senescence characterized by β-galactosidase staining, and p21 knockdown rescued the senescence and cell death as well as the inhibition of Rb phosphorylation induced by PDCD4 knockdown. Thus, PDCD4 is an important cell cycle regulator of hepatoma cells and may be a promising therapeutic target for the treatment of hepatocellular carcinoma

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Jurkat Cells Using Bio-phantoms

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis

〈Originals〉Trib1 and Trib2 inhibit granulocytic differentiation by suppressing Akt pathway

[Abstract] Background :Overexpression of Tribbles homolog 1 (Tribl) and Tribbles homolog 2 (Trib2) in hematopoietic stem/progenitor cells evokes acute myeloid leukemia (AML) in murine transplantation models. Degradation of CCAAT-enhancer-binding-protein α (C/EBPα) plays a crucial role in Trib1 or Trib2-induced AML. However, because C/EBPα knockout mice do not develop AML, it is likely that Trib1 and Trib2 influence other signaling pathways besides C/EBPα. Elevated Akt phosphorylation is considered to contribute to the development of AML. In contrast, two groups recently reported that reduced Akt activity is involved in the pathogenesis of leukemia. We performed this study to reveal the role of Akt signaling in Trib family-induced AML.Methods : G-CSF-induced granulocytic differentiation of 32D cells was assessed morphologically and phenotypically. G-CSF-induced signaling wasassessed by Westernblotting. Results : Overexpression of Trib1 or Trib2 inhibited GCSF-induced granulocytic differentiation of 32D cells, which was accompanied by reduced Akt phosphorylation. Also, an Akt inhibitor API-2 blocked G-CSF-induced granulocytic differentiation independently of C/EBPα degradation.　Furthermore, retroviral C/EBPα restoration did not completely abolish the differentiation block caused by Trib1 and Trib2. Conclusion :Trib1 and Trib2 block granulocytic differentiation, at least partially, by suppressing Akt phosphorylation

Are implicit attitudes toward dishonesty associated with self-serving dishonesty? Implications for the reliability of the IAT

Experiments assessing the prevalence and magnitude of dishonesty have provided a large body of empirical findings regarding the cognitive nature of honesty. However, the personal factors that regulate dishonest behavior have yet to be fully clarified. This study examined two factors that potentially inhibit dishonesty—implicit attitudes toward dishonesty and executive control. In Study 1, the participants completed the Implicit Association Test (IAT), which measured their implicit attitudes toward dishonesty, and a working memory (WM) task, which was used to index executive control. The participants subsequently completed an incentivized coin-flip prediction task wherein they were given real and repeated opportunities for dishonest reward acquisition and punishment avoidance. The results revealed that individuals showing stronger negative implicit attitudes toward dishonesty engaged in a lower frequency of dishonest behavior for punishment avoidance, although this effect was marginal. In contrast, WM capacity was not associated with variations in dishonest reward acquisition and punishment avoidance. A follow-up experiment on other-serving dishonesty, where dishonest reward acquisition and punishment avoidance were credited to two other anonymous participants, revealed that neither implicit attitudes toward dishonesty nor WM capacity was associated with dishonest behavior. An additional preregistered experiment in Study 2 demonstrated that the association between implicit attitudes toward dishonesty and self-serving dishonesty for punishment avoidance was again marginal. While it is tempting to conclude that implicit attitudes toward dishonesty are associated with self-serving dishonesty, the present study provides only weak evidence that should be interpreted with great caution. Implications for the reliability of the IAT are discussed