Objectives
To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have ...clinical significance.
Methods
The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group
n
= 56, MVI-negative group
n
= 57). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan–Meier survival curves and compared using the log-rank test.
Results
The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282–0.971;
p
= 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749–75.098;
p
= 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164–0.631;
p
= 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio HR, 0.402; 95% CI, 0.189–0.854,
p
= 0.013).
Conclusion
A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI.
Key Points
• Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor.
• cHCC-CCA with MVI may have a higher risk of early recurrence after surgery.
• Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.
Computational modeling and simulations are increasingly being used to complement experimental testing for analysis of safety and efficacy of medical devices. Multiple voxel- and surface-based whole- ...and partial-body models have been proposed in the literature, typically with spatial resolution in the range of 1-2 mm and with 10-50 different tissue types resolved. We have developed a multimodal imaging-based detailed anatomical model of the human head and neck, named "MIDA". The model was obtained by integrating three different magnetic resonance imaging (MRI) modalities, the parameters of which were tailored to enhance the signals of specific tissues: i) structural T1- and T2-weighted MRIs; a specific heavily T2-weighted MRI slab with high nerve contrast optimized to enhance the structures of the ear and eye; ii) magnetic resonance angiography (MRA) data to image the vasculature, and iii) diffusion tensor imaging (DTI) to obtain information on anisotropy and fiber orientation. The unique multimodal high-resolution approach allowed resolving 153 structures, including several distinct muscles, bones and skull layers, arteries and veins, nerves, as well as salivary glands. The model offers also a detailed characterization of eyes, ears, and deep brain structures. A special automatic atlas-based segmentation procedure was adopted to include a detailed map of the nuclei of the thalamus and midbrain into the head model. The suitability of the model to simulations involving different numerical methods, discretization approaches, as well as DTI-based tensorial electrical conductivity, was examined in a case-study, in which the electric field was generated by transcranial alternating current stimulation. The voxel- and the surface-based versions of the models are freely available to the scientific community.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extensive evidence suggests that the human ability to adaptively implement a wide variety of tasks is preferentially a result of the operation of a fronto-parietal brain network (FPN). We ...hypothesized that this network's adaptability is made possible by flexible hubs: brain regions that rapidly update their pattern of global functional connectivity according to task demands. Using recent advances in characterizing brain network organization and dynamics, we identified mechanisms consistent with the flexible hub theory. We found that the FPN's brain-wide functional connectivity pattern shifted more than those of other networks across a variety of task states and that these connectivity patterns could be used to identify the current task. Furthermore, these patterns were consistent across practiced and novel tasks, suggesting that reuse of flexible hub connectivity patterns facilitates adaptive (novel) task performance. Together, these findings support a central role for fronto-parietal flexible hubs in cognitive control and adaptive implementation of task demands.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose
Surgical exploration and bowel resection are frequently required for treating non-occlusive mesenteric ischemia. Intraoperative evaluation of intestinal perfusion is subjective and ...challenging. In this feasibility study, ICG fluorescence angiography was performed in order to evaluate intestinal perfusion in patients with acute mesenteric ischemia.
Methods
This is a retrospective analysis of 52 patients who were operated for acute mesenteric ischemia using ICG fluorescence angiography. Patients with occlusive disease requiring recanalization were excluded. The SPY and PinPoint imaging systems were used for open and laparoscopic surgery, respectively. Intraoperative macroscopic assessment of perfusion was compared with the ICG angiography results.
Results
Surgical exploration was performed for ischemia of the colon (
n
= 12), the small bowel (
n
= 23), or both (
n
= 16). One patient had ischemia of the esophagus and stomach. All patients had a preoperative CT angiography to rule out stenosis or occlusion of the mesenteric vessels. In 18 cases (34.6%), ICG fluorescence angiography provided information that was supplemental to macroscopic evaluation, but most patients did not survive the postoperative course. However, in six of those cases (11.5%), ICG angiography led to a major change in operative strategy resulting in a significant clinical benefit for those patients. For two cases, ICG fluorescence produced false negative results.
Discussion
ICG tissue angiography is feasible and technically reliable for evaluating intestinal perfusion in acute mesenteric ischemia and led to a significant clinical benefit in 11% of our patients. A relevant discrepancy between surgical visual assessment and fluorescence angiography was found in 35% of the cases, which may help to define resection margins more accurately and thus support surgical decision-making.
Transient receptor potential (TRP) cation channels are emerging in vascular biology. In particular, the expression of the capsaicin receptor (TRPV1) was reported in vascular smooth muscle cells. This ...study characterized the arteriolar TRPV1 function and expression in the rat. TRPV1 mRNA was expressed in various vascular beds. Six commercially available antibodies were tested for TRPV1 specificity. Two of them were specific (immunostaining was abolished by blocking peptides) for neuronal TRPV1 and one recognized vascular TRPV1. TRPV1 was expressed in blood vessels in the skeletal muscle, mesenteric and skin tissues, as well as in the aorta and carotid arteries. TRPV1 expression was found to be regulated at the level of individual blood vessels, where some vessels expressed, while others did not express TRPV1 in the same tissue sections. Capsaicin (a TRPV1 agonist) evoked constrictions in skeletal muscle arteries and in the carotid artery, but had no effect on the femoral and mesenteric arteries or the aorta. In blood vessels, TRPV1 expression was detected in most of the large arteries, but there were striking differences at level of the small arteries. TRPV1 activity was suppressed in some isolated arteries. This tightly regulated expression and function suggests a physiological role for vascular TRPV1.
Tumor endothelial markers (TEMs) that are highly expressed in human tumor vasculature compared with vasculature in normal tissue hold clear therapeutic potential. We report that the C-type lectin ...CLEC14A is a novel TEM. Immunohistochemical and immunofluorescence staining of tissue arrays has shown that CLEC14A is strongly expressed in tumor vasculature when compared with vessels in normal tissue. CLEC14A overexpression in tumor vessels was seen in a wide range of solid tumor types. Functional studies showed that CLEC14A induces filopodia and facilitates endothelial migration, tube formation and vascular development in zebrafish that is, CLEC14A regulates pro-angiogenic phenotypes. CLEC14A antisera inhibited cell migration and tube formation, suggesting that anti-CLEC14A antibodies may have anti-angiogenic activity. Finally, in endothelial cultures, expression of CLEC14A increased at low shear stress, and we hypothesize that low shear stress due to poor blood flow in the disorganized tumor vasculature induces expression of CLEC14A on tumor vessels and pro-angiogenic phenotypes.
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models ...as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies.
► PlGF inhibition phenocopies genetic deficiency in tumor models and ocular angiogenesis ► PlGF inhibition blocks vessel abnormalization rather than density in certain tumors ► Anti-mouse and anti-human PlGF antibodies are specific and efficacious ► Anti-PlGF treatment lacks efficacy in some cancer models
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