Gold Nanoparticles for Monitoring of Mesenchymal Stem-Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistula Maturation.

Mesenchymal stem cell (MSC)-seeded polymeric perivascular wraps have been shown to enhance arteriovenous fistula (AVF) maturation. However, the wraps' radiolucency makes their placement and integrity difficult to monitor. Through electrospinning, we infused gold nanoparticles (AuNPs) into polycaprolactone (PCL) wraps to improve their radiopacity and tested whether infusion affects the previously reported beneficial effects of the wraps on the AVF's outflow vein. Sprague Dawley rat MSCs were seeded on the surface of the wraps. We then compared the effects of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL + MSC wrap, PCL-Au wrap, and PCL-Au + MSC wrap-on AVF maturation in a Sprague Dawley rat model of chronic kidney disease (n = 3 per group). Via micro-CT, AuNP-infused wraps demonstrated a significantly higher radiopacity compared to that of the wraps without AuNPs. Wraps with and without AuNPs equally reduced vascular stenoses, as seen via ultrasonography and histomorphometry. In the immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of infiltration with smooth muscle cells (α-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) compared to that of the control and wraps without MSCs. In conclusion, AuNP infusion allows in vivo monitoring via micro-CT of MSC-seeded polymeric wraps over time, without compromising the benefits of the wrap for AVF maturation.

Effect of bead size and doxorubicin loading on tumor cellular injury after transarterial embolization and chemoembolization in a rat model of hepatocellular carcinoma.

Embolic agents used in transarterial embolization for intermediate stage hepatocellular carcinoma reduce blood flow into tumors and can deliver anticancer drugs. Tumor blood supply can be interrupted using doxorubicin-eluting beads (DEB-TACE) or non-loaded beads (TAE) of different calibers. In this preclinical study, we characterized the extent of remaining stressed tumor cells after treatment, hypoxia within the surviving tumor regions, and inflammatory immune cell infiltrates after embolization with 40-60 or 70-150 µm with non-loaded or doxorubicin-loaded beads at 3 and 7 days after treatment. TAE-treated tumors had more stressed and surviving tumor cells after 3 days, irrespective of bead size, compared with DEB-TACE-treated tumors. Hypoxic stress of residual cells increased after treatment with 70-150 µm beads without or with doxorubicin. Treatment with DEB-TACE of 70-150 µm resulted in increased inflammation and proliferation in the adjacent parenchyma. Inflammatory cell infiltrates were reduced at the periphery of tumors treated with 40-60 µm DEB-TACE.

Angiographic Atlas of the Visceral Vascular Anatomy in Translational Rat Models.

PURPOSE: To characterize angiographic and cross-sectional imaging anatomy of the rat visceral vasculature in 2 translational models. MATERIALS AND METHODS: Animal studies were conducted in accordance with institutional guidelines and approval of the Institutional Animal Care and Use Committees. Retrospective review of digital subtraction arteriography was performed in 65 Wistar and 50 Sprague-Dawley male rats through a left common carotid artery or right common femoral artery approach. MR imaging of the abdomen was performed on the rats to correlate imaging modalities. RESULTS: Aortography was performed in 3 locations, including cranial to the celiac artery, cranial to the renal arteries, and cranial to the caudal (inferior) mesenteric artery, enabling characterization of the visceral branch arteries in all 65 Wistar rats. Selective arteriography of first-, second-, and third-order branch vessels of the aorta was performed allowing characterization of normal and variant anatomy. Dedicated selective arteriography was performed of the celiac artery in 65 Wistar and 10 Sprague-Dawley rats, of the common hepatic artery in 65 Wistar and 50 Sprague-Dawley rats, and of the cranial mesenteric artery in 43 Wistar rats. MR imaging enabled correlation with the lobar and portal venous anatomy. CONCLUSIONS: Analysis of arteriography and MR imaging in these rat models will provide translational researchers with anatomic details needed to develop new endovascular protocols for small animal research in interventional radiology.

Natural History of T1N0M0 Hepatocellular Carcinoma: Large-Scale Study in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) prognosis depends on clinicopathological features in addition to the treatment provided. We aimed to assess the natural history of TNM stage I HCC tumors which received different treatment over a period of 20 years. METHODS: Between 1992 and 2011, a total of 397 stage I HCC patients were included. Detailed information was retrieved from MD Anderson Cancer Center patients' medical records. The Kaplan-Meier method was used to calculate patients' overall survival (OS). Cox regression analysis was used to calculate the estimated hazard ratio and 95% confidence interval of different prognostic factors. RESULTS: Out of 397 patients, 67.5% were males, 42.8% had hepatitis-related HCC, and 59.7% had underlying cirrhosis. After adjustment for confounding factors, we found that all therapeutic modalities were associated with a significant mortality rate reduction with an OS of 63, 42.03, 34.3, and 22.1 months among patients treated with surgery, ablation, local, and systemic therapy, respectively. A restricted analysis of cirrhotic and noncirrhotic patients showed that ablative and local therapy were significantly associated with a longer OS compared to systemic therapy. CONCLUSION: TNM stage I HCC patients have a favorable prognosis regardless of the type of treatment. Notably, ablative and local therapy significantly improved OS compared to systemic therapy.

Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs.

OBJECTIVE: The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. METHODS: Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). RESULTS: All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. CONCLUSION: To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

A targeted next-generation sequencing assay detects a high frequency of therapeutically targetable alterations in primary and metastatic breast cancers: implications for clinical practice.

The aim of this study was to assess the frequency of potentially actionable genomic alterations in breast cancer that could be targeted with approved agents or investigational drugs in clinical trials using a next-generation sequencing-based genomic profiling assay performed in a Clinical Laboratory Improvement Amendments-certified and College of American Pathologists-accredited commercial laboratory. Methods. Fifty-one breast cancers were analyzed, including primary tumor biopsies of 33 stage I-II and 18 stage IV cancers (13 soft tissue, 3 liver, and 2 bone metastases). We assessed 3,230 exons in 182 cancer-related genes and 37 introns in 14 genes often rearranged in cancer for base substitutions, indels, copy number alterations, and gene fusions. The average median sequencing depth was 1,154×. Results. We observed 158 genomic alterations in 55 genes in 48 of 51 (94%) tumors (mean 3.1, range 0-9). The average number of potentially therapeutically relevant alterations was similar in primary (1.6, range 0-4) and in heavily pretreated metastatic cancers (2.0, range 0-4) (p = .24). The most common actionable alterations were in PIK3CA (n = 9, phosphatidylinositol 3-kinase [PI3K]/mammalian target of rapamycin [mTOR] inhibitors), NF1 (n = 7, PI3K/mTOR/mitogen-activated protein kinase inhibitors), v-akt murine thymoma viral oncogene homolog 1-3 (n = 7, PI3K/mTOR/AKT inhibitors), BRCA1/2 (n = 6, poly[ADP-ribose] polymerase inhibitors), and CCND1,2 and CCNE (n = 8)/cycline dependent kinase (CDK)6 (n = 1) (CDK4/6 inhibitors), KIT (n = 1, imatinib/sunitinib), ALK (n = 1, crizotinib), FGFR1,2 (n = 5, fibroblast growth factor receptor inhibitors), and EGFR (n = 2, epidermal growth factor receptor inhibitors). Our sequencing assay also correctly identified all six cases with HER2 (ERBB2) amplification by fluorescence in situ hybridization when tumor content was adequate. In addition, two known activating HER2 mutations were identified, both in unamplified cases. Conclusion. Overall, 84% of cancers harbored at least one genomic alteration linked to potential treatment options. Systematic evaluation of the predictive value of these genomic alterations is critically important for further progress in this field.

Irreversible electroporation of the lumbar vertebrae in a porcine model: is there clinical-pathologic evidence of neural toxicity?

PURPOSE: To evaluate the effects of irreversible electroporation (IRE) in the porcine spine. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Twenty computed tomographically guided IRE ablations in either a transpedicular location or directly over the posterior cortex were performed in the lumbar vertebrae of 10 pigs by a single operator. T1- and T2-weighted magnetic resonance (MR) imaging was performed with and without contrast material 2 or 7 days after ablation. Mathematical modeling was performed to estimate the extent of ablation. Clinical, radiologic, pathologic, and simulation findings were analyzed. The Miller low-bias back transformation was used to construct 95% confidence intervals for the mean absolute percentage difference between the maximum length and width of the ablation zone on MR images and pathologic measurements by using square-root-transformed data. RESULTS: Bipolar IRE electrode placement and ablation were successful in all cases. The mean distances from the IRE electrode to the posterior wall of the vertebral body or the exiting nerve root were 2.93 mm ± 0.77 (standard deviation) and 7.87 mm ± 1.99, respectively. None of the animals had neurologic deficits. Well-delineated areas of necrosis of bone, bone marrow, and skeletal muscle adjacent to the vertebral body were present. Histopathologic changes showed outcomes that matched with simulation-estimated ablation zones. The percentage absolute differences in the ablation measurements between MR imaging and histopathologic examination showed the following average errors: 24.2% for length and 28.8% for width measurements on T2-weighted images, and 26.1% for length and 33.3% for width measurements on T1-weighted contrast material-enhanced images. CONCLUSION: IRE ablation in the porcine spine is feasible and safe and produces localized necrosis with minimal neural toxicity. Signal intensity changes on images acquired with standard MR imaging sequences demonstrate the ablation zone to be larger than that at histopathologic examination.

Evaluation of liver fibrosis and hepatic venous pressure gradient with MR elastography in a novel swine model of cirrhosis.

PURPOSE: To assess the correlation among MR elastography (MRE) measured liver stiffness (LS), liver fibrosis, and hepatic venous pressure gradient (HVPG) in a swine model of cirrhosis. MATERIALS AND METHODS: Three swine served as controls, and liver fibrosis was induced in eight swine by transarterial embolization. LS and HVPG were obtained at baseline and 4 weeks (prenecropsy) following induction of liver fibrosis. RESULTS: Four weeks following the induction of liver cirrhosis, experimental animals developed an increase in HVPG of 8.0±6.4 mmHg compared with 0.3±1.2 mmHg for controls (P=0.08). Over the same timeframe, mean MRE-measured LS increased 0.82±0.39 kPa for experimental swine and 0.1±0.05 kPa for controls (P=0.01). A positive correlation was observed between increases in HVPG and LS (ρ=0.682; P=0.02). Liver fibrosis was measured on explanted livers at 4 weeks and yielded mean fibrosis scores of 2.8 for experimental animals and 0 for controls (P=0.0016). A positive correlation was observed between higher LS and liver fibrosis (ρ=0.884; P=0.0003). CONCLUSION: MRE is a reliable noninvasive technique to measure LS in a swine model of cirrhosis. Significant positive correlations were observed between LS and HVPG as well as LS and fibrosis.

Stem cell-mediated delivery of SPIO-loaded gold nanoparticles for the theranosis of liver injury and hepatocellular carcinoma.

The treatment of liver injuries or hepatocellular carcinoma (HCC) has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system. As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic magnetic resonance (MR)-active contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MR imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNP-loaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP-loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.

Pre-procedural and intra-procedural computerized tomography: providing a roadmap for successful adrenal venous sampling procedures.

BACKGROUND AND PURPOSE: Adrenal venous sampling (AVS) is used for the diagnosis of primary hyperaldosteronism. Technical difficulties with right adrenal vein (RAV) catheterization can lead to erroneous results. Our purpose was to delineate the location of the RAV on pre-procedural CT imaging in relation to the location identified during AVS and to report on the impact of successful RAV cannulation with and without the use of intra-procedural CT scanning. METHODS: Retrospective case series including patients who underwent AVS from October 2000 to September 2022. Clinical and laboratory values were abstracted from the electronic medical record. Successful cannulation of the RAV was defined as a selectivity index > 3. RESULTS: 110 patients underwent 124 AVS procedures. Pre-AVS CT imaging was available for 118 AVS procedures. The RAV was identified in 61 (51.7%) CT datasets. Biochemical confirmation of successful RAV cannulation occurred in 98 (79.0%) of 124 AVS procedures. There were 52 (85.2%) procedures in which the RAV was identified on pre-AVS CT and there was biochemical confirmation of successful RAV sampling. Among these 52 procedures, the RAV was localized during AVS at the same anatomic level or within 1 vertebral body level cranial to the level identified on pre-AVS CT in 98.1% of cases. The rate of successful RAV cannulation was higher in patients who underwent intra-procedural CT (93.8% versus 63.9%), P < 0.01. CONCLUSIONS: Pre-AVS and intra-procedural CT images provide an invaluable roadmap that resulted in a higher rate of accurate identification of the RAV and successful AVS procedures; in particular, search for the RAV orifice during AVS can be limited to 1 vertebral body cranial to the level identified on pre-AVS CT imaging and successful cannulation can be confidently verified with intra-procedural CT.

Percutaneous intraportal application of adipose tissue-derived mesenchymal stem cells using a balloon occlusion catheter in a porcine model of liver fibrosis.

PURPOSE: To investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis. MATERIALS AND METHODS: Transcatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals. MSCs were allowed to dwell for 10 minutes using prolonged balloon inflation. Five control animals received a sham injection of normal saline in a similar fashion. Hepatic venous pressure gradient (HVPG) was measured immediately before necropsy. Specimens from all accessible lobes were obtained with ultrasound-guided percutaneous 18-gauge biopsy 2 hours after cell application. All animals were euthanized within 4 weeks. Fluorescent microscopy was used to assess the presence and distribution of cells. RESULTS: Liver injury and fibrosis were successfully induced in all animals. MSCs (6-10 × 10(7)) were successfully delivered into the portal vein in the six experimental animals. Cell application was not associated with vascular complications. HVPG showed no instances of portal hypertension. GFP-expressing MSCs were visualized in biopsy specimens and were distributed primarily within the sinusoidal spaces; however, 4 weeks after implantation, MSCs could not be identified in histologic specimens. CONCLUSIONS: A percutaneous endovascular approach for cell delivery using a balloon occlusion catheter proved safe for intraportal MSC application in a large animal model of liver fibrosis.

Gastroduodenal artery recanalization after transcatheter fibered coil embolization for prevention of hepaticoenteric flow: incidence and predisposing technical factors in 142 patients.

BACKGROUND: Prophylactic occlusion of extrahepatic vessels prior to radioembolization or chemotherapy infusion is an effective method to prevent gastrointestinal complications. Unfortunately, vascular recanalization can occur. PURPOSE: To retrospectively determine the rate and technical factors associated with gastroduodenal artery (GDA) recanalization after transcatheter occlusion with fibered coils. MATERIAL AND METHODS: Patients with hepatic malignancy who underwent fibered coil occlusion of the GDA origin for radioembolization or hepatic arterial chemotherapy infusion with at least one subsequent hepatic angiogram between March 2006 and January 2011 were included. One hundred and forty-two patients (men, 71; women, 71) met study criteria. Hepatic arteriograms were reviewed to determine the frequency of arterial recanalization. Additional parameters included: patients' demographics, GDA diameter, length of coil pack, distance between GDA origin and most cephalad coil, persistent flow at the conclusion of the initial GDA occlusion procedure, platelet count, and international normalized ratio (INR). Chi-square test and pooled t-test were used to compare the two groups. Prospective multivariate analysis was performed with a logistic regression model. RESULTS: Twenty-nine of 142 patients (20.4%) experienced GDA recanalization. The distance between the GDA origin and most cephalad coil was significantly greater in the recanalization group than in the non-recanalization group (9.6 mm vs. 12.6 mm, P = 0.01). A prospective multivariate analysis established that the further the coil was from the origin the more likely the GDA was to recanalize. The two groups did not differ on the basis of any other factors examined. CONCLUSION: GDA origin recanalization after fibered coil occlusion is common. The distance between the GDA origin and most cephalad coil appears to be a predisposing factor for recanalization. Familiarity with this phenomenon is beneficial to reduce the likelihood of gastrointestinal tract complications during hepatic locoregional therapy.

Liver Cancer Vascularity Driven by Extracellular Matrix Stiffness: Implications for Imaging Research.

BACKGROUND: Extracellular matrix stiffness represents a barrier to effective local and systemic drug delivery. Increasing stiffness disrupts newly formed vessel architecture and integrity, leading to tumor-like vasculature. The resulting vascular phenotypes are manifested through different cross-sectional imaging features. Contrast-enhanced studies can help elucidate the interplay between liver tumor stiffness and different vascular phenotypes. PURPOSE: This study aims to correlate extracellular matrix stiffness, dynamic contrast-enhanced computed tomography, and dynamic contrast-enhancement ultrasound imaging features of 2 rat hepatocellular carcinoma tumor models. METHODS AND MATERIALS: Buffalo-McA-RH7777 and Sprague Dawley (SD)-N1S1 tumor models were used to evaluate tumor stiffness by 2-dimensional shear wave elastography, along with tumor perfusion by dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography. Atomic force microscopy was used to calculate tumor stiffness at a submicron scale. Computer-aided image analyses were performed to evaluate tumor necrosis, as well as the percentage, distribution, and thickness of CD34+ blood vessels. RESULTS: Distinct tissue signatures between models were observed according to the distribution of the stiffness values by 2-dimensional shear wave elastography and atomic force microscopy ( P < 0.05). Higher stiffness values were attributed to SD-N1S1 tumors, also associated with a scant microvascular network ( P ≤ 0.001). Opposite results were observed in the Buffalo-McA-RH7777 model, exhibiting lower stiffness values and richer tumor vasculature with predominantly peripheral distribution ( P = 0.03). Consistent with these findings, tumor enhancement was significantly greater in the Buffalo-McA-RH7777 tumor model than in the SD-N1S1 on both dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography ( P < 0.005). A statistically significant positive correlation was observed between tumor perfusion on dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography in terms of the total area under the curve and % microvessel tumor coverage ( P < 0.05). CONCLUSIONS: The stiffness signatures translated into different tumor vascular phenotypes. Two-dimensional shear wave elastography and dynamic contrast-enhanced ultrasonography adequately depicted different stromal patterns, which resulted in unique imaging perfusion parameters with significantly greater contrast enhancement observed in softer tumors.

Gold Nanoparticles for Monitoring of Mesenchymal Stem Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistulas.

Background: To address high rates of arteriovenous fistula (AVF) failure, a mesenchymal stem cell (MSC)-seeded polymeric perivascular wrap has been developed to reduce neointimal hyperplasia (NIH) and enhance AVF maturation in a rat model. However, the wrap's radiolucency makes its placement and integrity difficult to monitor. Purpose: In this study, we infused gold nanoparticles (AuNPs) into the polymeric perivascular wrap to improve its radiopacity and tested the effect of infusion on the previously reported beneficial effects of the polymeric wrap on the AVF outflow vein. Materials and Methods: We fabricated a polymeric perivascular wrap made of polycaprolactone (PCL) infused with AuNPs via electrospinning. Sprague-Dawley rat mesenchymal stem cells (MSCs) were seeded on the surface of the wraps. We then compared the effect of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL+MSC wrap, PCL-Au wrap, and PCL-Au+MSC wrap-on AVF maturation in a Sprague-Dawley rat model of chronic kidney disease (n=3 per group). Statistical significance was defined as p<.05, and one-way analysis of variance was performed using GraphPad Prism software. Results: On micro-CT, AuNP-infused wraps demonstrated significantly higher radiopacity compared to wraps without AuNPs. On ultrasonography, wraps with and without AuNPs equally reduced the wall-to-lumen ratio of the outflow vein, a marker of vascular stenosis. On histomorphometric analysis, wraps with and without AuNPs equally reduced the neointima-to- lumen ratio of the outflow vein, a measure of NIH. On immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of smooth muscle cells (α-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) infiltration when compared to control and wraps without MSCs. Conclusion: Gold nanoparticle infusion allows the in vivo monitoring via micro-CT of a mesenchymal stem cell-seeded polymeric wrap over time without compromising the benefits of the wrap on arteriovenous fistula maturation. Summary Statement: Gold nanoparticle infusion enables in vivo monitoring via micro-CT of the placement and integrity over time of mesenchymal stem cell-seeded polymeric wrap supporting arteriovenous fistula maturation. Key Results: Gold nanoparticle (AuNP)-infused perivascular wraps demonstrated higher radiopacity on micro-CT compared with wraps without AuNPs after 8 weeks.AuNP-infused perivascular wraps equally improved the wall-to-lumen ratio of the outflow vein (a marker of vascular stenosis) when compared with wraps without AuNPs, as seen on US.AuNP-infused perivascular wraps equally reduced the neointima-to-lumen ratio of the outflow vein (a measure of neointimal hyperplasia) when compared with wraps without AuNPs, as seen on histomorphometry.

Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in a Rat Model of Chronic Kidney Disease.

Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three-dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve ultrasonographic (i.e., luminal diameter, wall-to-lumen ratio, and flow rate) and histologic (i.e., neointima-to-lumen ratio, neointima-to-media ratio) parameters compared to control, with PCL+MSC demonstrating further improvement in these parameters compared to PCL alone. Moreover, only PCL+MSC significantly reduces 18 F-fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.

Salvage Locoregional Therapy Following Progression After Radiotherapy for Hepatocellular Carcinoma Is Associated with Improved Outcomes.

PURPOSE: To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. METHODS: This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015-2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. RESULTS: A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4-54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child-Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). CONCLUSIONS: Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.

A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis.

BACKGROUND: To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. METHODS: This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. RESULTS: CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). CONCLUSION: CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

CT-guided adrenal biopsy: comparison of ipsilateral decubitus versus prone patient positioning for biopsy approach.

OBJECTIVES: To compare ipsilateral decubitus and prone patient positioning for performing computed tomography guided adrenal biopsy using the requirements for out-of-plane approach (OOP) and the needle insertion time (NIT) as a surrogate for procedure complexity. METHODS: The study included 106 adrenal biopsies performed in 104 patients with lesions measuring ≤ 4 cm that were divided into two groups: Ipsilateral decubitus (Group I) and prone (Group II) positions. The frequency of use of an OOP biopsy path and the NIT were recorded as well as diagnostic yield, adverse events and transgression of organs to approach the target lesion. RESULTS: Groups I and II comprised 54 and 50 patients, respectively. The use of the OOP approach was significantly less frequent (P < 0.01) in Group I (n = 4) compared to Group II (n = 38). NIT was statistically shorter (P < 0.01) in Group I (9 min and 43 s) compared to Group II (19 min and 7 s). There were fewer organs traversed in Group I versus Group II. Diagnostic yield and post-biopsy complications were equal in both groups. CONCLUSION: Ipsilateral adrenal biopsy approach is a less complex, equally reliable and safe compared to the prone approach based on the less frequent use of the OOP approach and the shorter NIT. KEY POINTS: • Ipsilateral adrenal biopsy decubitus positioning provides a direct, non-transpulmonary path for sampling • Ipsilateral decubitus positioning reduces the need for potentially dangerous out-of-plane approaches (OOP) • Ipsilateral decubitus and prone positioning are equally reliable and safe techniques.

Temporary balloon occlusion of the common hepatic artery for administration of yttrium-90 resin microspheres in a patient with patent hepatoenteric collaterals.

The most common serious complication of yttrium-90 ((90)Y) therapy is gastrointestinal ulceration caused by extrahepatic microsphere dispersion. The authors describe the use of a balloon catheter for temporary occlusion of the common hepatic artery to reverse hepatoenteric flow for lobar administration of resin microspheres when coil embolization of a retroportal artery was impossible. At 9 months after treatment, the patient had no gastrointestinal side effects and showed a partial response.