•Volumetric tumor response assessment to targeted therapies is insufficient.•mp MRI enables assessment of therapy-induced changes of the tumor microenvironment.•Treatment response differs between ...tumor models with diverging grades of malignancy.•Different treatment approaches lead to an increase in intratumoral heterogeneity.
Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI).
Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology.
All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.
Display omitted
This work is devoted to the development of a mathematical model of the early stages of atherosclerosis incorporating processes of all time scales of the disease and to show their interactions. The ...cardiovascular mechanics is modeled by a fluid–structure interaction approach coupling a non-Newtonian fluid to a hyperelastic solid undergoing anisotropic growth and a change of its constitutive equation. Additionally, the transport of low-density lipoproteins and its penetration through the endothelium is considered by a coupled set of advection–diffusion-reaction equations. Thereby, the permeability of the endothelium is wall-shear stress modulated resulting in a locally varying accumulation of foam cells triggering a novel growth and remodeling formulation. The model is calibrated and applied to an murine-specific case study, and a qualitative validation of the computational results is performed. The model is utilized to further investigate the influence of the pulsatile blood flow and the compliance of the artery wall to the atherosclerotic process. The computational results imply that the pulsatile blood flow is crucial, whereas the compliance of the aorta has only a minor influence on atherosclerosis. Further, it is shown that the novel model is capable to produce a narrowing of the vessel lumen inducing an adaption of the endothelial permeability pattern.
Venous malformations tend to retain their slow-flow behavior, even in progressive disease or regression following therapy.
The aim of this study is to analyze the development of acquired hemodynamic ...relevant arterio-venous fistulae in patients with slow-flow malformations.
This study is a retrospective analysis based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with venous malformations and development of secondary arterio-venous fistulae were included. Indications for therapy of the vascular malformation were based on patients' symptoms and complications. The following endpoints were of clinical interest and were assessed: origin of development of arteriovenous fistula, development of secondary comorbidities as a result of the vascular malformation. For analysis we focused on descriptive statistics.
Out of 1213 consecutive patients with vascular malformations, in 6 patients perfusion changed from slow flow to arterio-venous fast-flow patterns. Four patients developed the fistula after local trauma in the area of the malformation, the other 2 patients developed the fistula due to progression of the disease and recurrent thrombophlebitis. These 2 patients had no trauma or interventions at the time of arterio-venous fistula development.
Acquired arterio-venous fast-flow fistula in patients with slow flow vascular malformation is very rare and might be a result of local trauma or the progression of the disease with recurrent thrombophlebitis. Specific evidence-based treatment options for these patients do not exist.
Summary
Background
Vascular malformations of the genitalia often go undetected in clinical examination. These vascular malformations can cause a variety of clinical symptoms such as swelling, pain ...and bleeding.
Aim
To characterize the distribution patterns of genital vascular malformations using magnetic resonance imaging (MRI) and to correlate these patterns with clinical findings in order to guide diagnostic decisions.
Methods
A retrospective analysis of MRIs of the pelvis and legs in 370 patients with vascular malformation was performed to determine the involvement of the internal and external genitalia.
Results
In 71 patients (19%), genital involvement could be identified by MRI. Of these, 11.3% (8 of 71) presented with internal involvement, 36.6% (26 of 71) with external involvement and 52.1% (37 of 71) with both internal and external involvement. Over half (57.1%) of the 49 patients with visible external genital signs detected during a clinical examination had additional internal genital involvement.
Conclusions
Genital involvement is a common finding in patients with vascular malformation of the legs and/or pelvis. Based on our data, we recommend MRI of the legs and pelvic region in patients with externally visible signs of a vascular malformation of the external genitalia in order to exclude additional internal involvement.
Purpose
To evaluate radiofrequency ablation (RFA) for closure of marginal veins in pediatric and adult patients with venous malformations.
Materials and methods
Medical records, imaging and procedure ...details were retrospectively reviewed in patients who underwent RFA of the marginal vein in a 17-month period. Additional sclerotherapy (
n
= 19) and coil embolization of the marginal vein were performed (
n
= 2).
Results
A total of 23 marginal veins were treated in 20 patients. Mean age at treatment was 16 years ± 9.4 (1–37 years). Pre-procedural magnetic resonance imaging revealed thoracoabdominal marginal veins in 3 patients. A type I marginal vein (draining in the great saphenous vein below the popliteal vein) was identified in 1 and type IIa/IIb (draining in a median/lateral accessory saphenous vein) in 2/8 cases. Type III (draining into the profunda femoral vein) was detected in 8, and type IV (draining into gluteal veins) in 1. Mean diameter of the marginal veins was 13.2 mm ± 4 (7–20 mm). Patency was found in 1 during follow-up (22 months ± 9.8). Complete or partial occlusion was achieved in 94.5% of the veins. One patient showed signs of thrombophlebitis after the procedure, and another incomplete paresis of the peroneal nerve.
Conclusion
RFA is effective as minimally invasive treatment of the marginal venous system. These veins should be treated early in life. Marginal veins with large diameter, residual tributaries and the intrafascial courses usually require adjunct coil embolization and sclerotherapy.
Level of Evidence
Case series, Level IV.
Purpose
To evaluate the incidence of acute renal failure and chronic kidney disease due to occlusion of accessory renal arteries during endovascular aneurysm repair of infrarenal abdominal aortic ...aneurysm.
Material and Methods
We retrospectively reviewed the course of 181 patients (mean age, 71, SD ± 9 years) who underwent EVAR of infrarenal abdominal aortic aneurysm. The renal vessel anatomy was analyzed in all pre- and postoperative CT scans. Diameter and origin of accessory renal arteries were evaluated. Renal function was determined by pre- and postoperative serum creatinine and eGFR levels. Long-term follow-up (>3 months) of patients was available in 121 cases (66.9%). Acute kidney injury and chronic kidney failure were defined according to guidelines of “Kidney Disease: Improving Global Outcomes” (KDIGO).
Results
In 65 of 181 patients (33.9%), 82 accessory renal arteries were identified preoperatively. In 19 of 181 patients (10.5%), one or more accessory renal arteries were covered and subsequently occluded by the implanted stent-graft device. Neither acute kidney injury (10.3% vs 12.5%;
p
= .785) nor chronic kidney disease (10.7% vs 15.38%;
p
= .452) was detected significantly more often in patients with covered accessory renal artery. The only significant predictor of acute kidney injury was the preoperative serum creatinine level (1.12 mg/dl vs. 0.98 mg/dl;
p
= .03). Significant predictors for chronic kidney disease were preoperative serum creatinine, eGFR, and impaired renal function (
p
< .001).
Conclusion
Coverage of accessory renal artery due to stent-graft does not lead either to temporary acute kidney injury after endovascular aneurysm repair or to chronic kidney disease.
Level of Evidence
Level II b.
Abstract Background Locoregional interventional bridging treatment (IBT) before liver transplantation (LT) is an accepted neoadjuvant approach in liver transplant patients with hepatocellular ...carcinoma (HCC). However, the effect of postinterventional tumor necrosis on posttransplantation outcome is known. Methods A total of 93 consecutive liver transplant patients with HCC were included in this prospective trial. Fifty-nine patients underwent pretransplantation IBT, by either transarterial chemoembolization (n = 51) or radiofrequency ablation (n = 8). The extent of tumor necrosis assessed at explant pathology (≥50% tumor necrosis rate = extended post-IBT tumor necrosis; <50% tumor necrosis rate = less extended tumor necrosis) and its impact on recurrence-free survival in the context of other prognostic relevant histopathologic variables were analyzed in uni- and multivariate analyses. Results Extended tumor necrosis was assessed in 44 patients among the IBT population, and tumor necrosis rate was <50% in 15 patients of the IBT and 34 patients of the non-IBT population, respectively. Five-year recurrence-free survival rates were 96% in patients with and 55% in patients without extended tumor necrosis rates ( P < .001). Recurrence-free survival rates were similar between patients with HCC meeting the Milan criteria (85%) and those exceeding the Milan criteria but demonstrating extended post-IBT tumor necrosis on explant pathology (80%). On multivariate analysis, only microvascular invasion (odds ratio 6.4) and extended postinterventional tumor necrosis (odds ratio 9.2) were identified as independent histopathologic predictors of recurrence-free outcome ( P < .05). Conclusions Extended tumor necrosis should be the major objective of neoadjuvant IBT in liver transplant patients with HCC, because it significantly improves posttransplantation outcome. Thereby, even patients with HCC beyond the Milan criteria may achieve excellent survival rates.
PDF
