Outcomes of Repeat Conventional Transarterial Chemoembolization in Patients with Liver Metastases.

INTRODUCTION AND OBJECTIVES: Although unlimited sessions of conventional transarterial chemoembolization (cTACE) may be performed for liver metastases, there is no data indicating when treatment becomes ineffective. This study aimed to determine the optimal number of repeat cTACE sessions for nonresponding patients before abandoning cTACE in patients with liver metastases. MATERIALS AND METHODS: In this retrospective, single-institutional analysis, patients with liver metastases from neuroendocrine tumors (NET), colorectal carcinoma (CRC), and lung cancer who underwent consecutive cTACE sessions from 2001 to 2015 were studied. Quantitative European Association for Study of the Liver (qEASL) criteria were utilized for response assessment. The association between the number of cTACE and 2-year, 5-year, and overall survival was evaluated to estimate the optimal number of cTACE for each survival outcome. RESULTS: Eighty-five patients underwent a total of 186 cTACE sessions for 117 liver metastases, of which 30.7% responded to the first cTACE. For the target lesions that did not respond to the first, second, and third cTACE sessions, response rates after the second, third, and fourth cTACE sessions were 33.3%, 23%, and 25%, respectively. The fourth cTACE session was the optimal number for 2-year survival (HR 0.40; 95%CI: 0.16-0.97; p=0.04), 5-year survival (HR 0.31; 95%CI: 0.11-0.87; p=0.02), and overall survival (HR 0.35; 95%CI: 0.13-0.89; p=0.02). CONCLUSIONS: Repeat cTACE in the management of liver metastases from NET, CRC, and lung cancer was associated with improved patient survival. We recommend at least four cTACE sessions before switching to another treatment for nonresponding metastatic liver lesions.

Assessing interventional radiology specialty knowledge and perception amongst Tanzanian medical students before and after exposure to an immersive curriculum.

AIMS: This study aims to assess the impact that delivering an introductory interventional radiology (IR) lecture series has on the knowledge and perception of the specialty among medical students in a resource-limited setting with, until recently, no IR presence. MATERIALS AND METHODS: An introductory four-hour lecture series in IR was delivered to third-year medical students in Tanzania. Prior to and following the lecture series, participants completed a 27-item paper-based survey assessing their knowledge and perception of the specialty. RESULTS: Out of a class of 213, the pre- and post-lecture survey was returned by 148 (69.5%) and 151 (70.9%) respondents, respectively. 94.5% of respondents indicated that they were aware of IR as a specialty. Among respondents, 97.3% expressed interest in having IR lectures integrated into their curriculum, compared to 29.0% that reported having any prior IR training. 27.3% believed their knowledge in IR compared to other specialties was either "good" or "excellent", which improved to 43.3% (p<0.001). Identification that IR physicians consult patients directly, have outpatient clinics, have inpatient beds, and do rounds improved from 55.4% to 81.1% (p<0.001), 49.7% to 60.3% (p=0.066), 48.3% to 66.7% (p=0.001), and 52.0% to 66.2% (p=0.013), respectively. CONCLUSION: By introducing short lectures on IR-relevant topics, knowledge and perception of IR improved among Tanzanian medical students. Early education and exposure to IR should be prioritized to promote the continued growth of the specialty in this setting.

Creating a Sustainable Foundation for IR Services and Training in Sub-Saharan Africa: 5-Year Update on the Road2IR Initiative.

PURPOSE: To evaluate the growth and quality of an interventional radiology (IR) training model designed for resource-constrained settings and implemented in Tanzania as well as its overall potential to increase access to minimally invasive procedures across the region. MATERIALS AND METHODS: IR training in Tanzania began in October 2018 through monthly deployment of visiting teaching teams for hands-on training combined with in-person and remote lectures. A competency-based 2-year Master of Science in IR curriculum was inaugurated at the nation's main teaching hospital in October 2019, with the first 2 classes graduating in 2021 and 2022. Procedural data, demographics, and clinical outcomes were collected and analyzed throughout the duration of this program. RESULTS: From October 2018 to July 2022, 1,595 procedures were performed in Tanzania: 1,236 nonvascular and 359 vascular, all with local fellows as primary interventional radiologists. Of these, 97.2% were technically successful, 95.2% were without adverse events, and 28.9% were performed independently by Tanzanian fellows and faculty with no difference in adverse event and technical success rates (P = .63 and P = .90, respectively), irrespective of procedural class. Ten IR physicians graduated from this program during the study period, followed by another 3 per year going forward. Partner training programs in Uganda and Rwanda mirroring this model commenced in 2023 and 2024, respectively. CONCLUSIONS: The reported training model offers a practical and effective solution to meet many of the challenges associated with the lack of access to IR in sub-Saharan Africa.

Assessment of Required Patient Travel to Receive Interventional Radiology Services in the Resource-Limited Setting of Tanzania.

This study aimed to evaluate the geographic patient profile of a country's first interventional radiology (IR) service in sub-Saharan Africa. From October 2018 to August 2022, travel time (1,339 patients) and home region (1,184 patients) were recorded from 1,434 patients who underwent IR procedures at Tanzania's largest referral center. Distances traveled by road were calculated from the administrative capital of each region using a web mapping platform (google.com/maps). The effect of various factors on distance and time traveled were assessed. Patients from all 31 regions in Tanzania underwent IR procedures. The mean and maximum calculated distance traveled by patients were 241.6 km and 1,387 km, respectively (Sk2 = 1.66); 25.0% of patients traveled for over 6 hours for their procedure. Patients traveled furthest for genitourinary procedures (mean = 293.4 km) and least for angioplasty and stent placement (mean = 123.9 km) (P < .001). To increase population access and reduce travel times, geographic data should be used to decentralize services.

Comparative Analysis of Percutaneous Drainage versus Operative Drainage of Intra-Abdominal Abscesses in a Resource-Limited Setting: The Tanzanian Experience.

Background: Intra-abdominal abscesses (IAAs) are a major cause of morbidity and mortality worldwide. While image-guided percutaneous abscess drainage (PAD) has become the standard of care in many countries, over half of the global population does not have access to interventional radiology (IR) and are left with surgery as the only option for source control. Objective: The purpose of this study is to evaluate the development, implementation, and role of a PAD service in a resource-limited setting. Method: A retrospective cohort study was performed on all patients who underwent percutaneous or surgical abscess drainage (SAD) of IAAs at Tanzania's national referral hospital from 10/2018 to 4/2021. Patients were identified through a match case search of institutional records and inclusion was confirmed through manual chart review. Demographics, patient presentation, procedural data, and clinical outcomes were recorded in a password-encrypted database and compared between groups. Findings: Sixty-three patients underwent abscess drainage: 32 percutaneously and 31 surgically. In the PAD group, there was a 100% technical success rate and a 0% complication rate. In the SAD group, there was a 64.5% technical success rate and ten deaths within 30 days (32.3%), and one additional complication requiring major therapy (3.2%) (p < 0.001). Conclusion: Results from this study demonstrate that PAD can be performed with high technical success and without complication by trained IR physicians in Tanzania. The development of a successful PAD program exemplifies the drastic need to support the growth of IR services in this setting.

ClotTriever system for mechanical thrombectomy of deep vein thrombosis.

There is increasing evidence that early and comprehensive removal of thrombus in deep vein thrombosis is associated with improved outcomes, including decreased incidence of post-thrombotic syndrome and debilitating long-term symptoms. Catheter-directed thrombolysis is effective for the rapid removal of clot, but it is associated with high bleeding risk. Percutaneous mechanical thrombectomy is a highly effective method for the removal of clot without the use of systemic or catheter-directed thrombolytic therapy. The Inari ClotTriever system (Inari Medical Inc., CA, USA) is a thrombectomy device, which is approved for deep vein thrombosis by the US FDA in 2017. Herein we review the current treatment strategies using the ClotTriever system, its specifications, indications and current state of literature.

Deep venous thrombosis is a common disease that causes blood clots in the veins. Complete removal of clot is associated with better outcomes, including decreased incidence of post-thrombotic syndrome (symptoms including leg heaviness, pain, cramping, swelling and discomfort). The ClotTriever system (Inari Medical, Inc., CA, USA) is a device approved for the removal of clot in veins without using clot-busting medications that increase bleeding risk. This review describes the types of devices, indications and current research.

Conventional vs. Drug-Eluting Beads Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma-A Propensity Score Weighted Comparison of Efficacy and Safety.

This study compared the efficacy and safety of conventional transarterial chemoembolization (cTACE) with drug-eluting beads (DEB)-TACE in patients with unresectable hepatocellular carcinoma (HCC). This retrospective analysis included 370 patients with HCC treated with cTACE (n = 248) or DEB-TACE (n = 122) (January 2000-July 2014). Overall survival (OS) was assessed using uni- and multivariate Cox proportional hazards models and Kaplan-Meier analysis. Additionally, baseline imaging was assessed, and clinical and laboratory toxicities were recorded. Propensity score weighting via a generalized boosted model was applied to account for group heterogeneity. There was no significant difference in OS between cTACE (20 months) and DEB-TACE patients (24.3 months, ratio 1.271, 95% confidence interval 0.876-1.69; p = 0.392). However, in patients with infiltrative disease, cTACE achieved longer OS (25.1 months) compared to DEB-TACE (9.2 months, ratio 0.366, 0.191-0.702; p = 0.003), whereas DEB-TACE proved more effective in nodular disease (39.4 months) than cTACE (18 months, ratio 0.458, 0.308-0681; p = 0.007). Adverse events occurred with similar frequency, except for abdominal pain, which was observed more frequently after DEB-TACE (101/116; 87.1%) than cTACE (119/157; 75.8%; p = 0.02). In conclusion, these findings suggest that tumor morphology and distribution should be used as parameters to inform decisions on the selection of embolic materials for TACE for a more personalized treatment planning in patients with unresectable HCC.

Catheter-directed embolectomy for massive pulmonary embolism in a pediatric patient.

Pulmonary embolisms can affect 0.9 in 100,000 children and carry high risk for mortality. However, management of pediatric pulmonary embolism is largely derived from adult studies and treatment often includes local or systemic thrombolytics or anticoagulation, which may pose unique bleeding risks in children and adolescents compared with adults. This report describes a case in which catheter-directed embolectomy was used to successfully manage a pediatric patient with high-risk/massive pulmonary embolism. This case suggests that catheter-directed embolectomy is an effective therapy in patients outside the adult population and more research is required to expand inclusion criteria for current catheter-directed embolectomy treatment paradigms. Moreover, this case emphasizes the need for dedicated pediatric pulmonary embolism response teams to best serve the pediatric population.

Optimization of the BCLC Staging System for Locoregional Therapy for Hepatocellular Carcinoma by Using Quantitative Tumor Burden Imaging Biomarkers at MRI.

Background Patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC) represent a highly heterogeneous patient collective with substantial differences in overall survival. Purpose To evaluate enhancing tumor volume (ETV) and enhancing tumor burden (ETB) as new criteria within the Barcelona Clinic Liver Cancer (BCLC) staging system for optimized allocation of patients with intermediate- and advanced-stage HCC to undergo transarterial chemoembolization (TACE). Materials and Methods In this retrospective study, 682 patients with HCC who underwent conventional TACE or TACE with drug-eluting beads from January 2000 to December 2014 were evaluated. Quantitative three-dimensional analysis of contrast-enhanced MRI was performed to determine thresholds of ETV and ETB (ratio of ETV to normal liver volume). Patients with ETV below 65 cm3 or ETB below 4% were reassigned to BCLC Bn, whereas patients with ETV or ETB above the determined cutoffs were restratified or remained in BCLC Cn by means of stepwise verification of the median overall survival (mOS). Results This study included 494 patients (median age, 62 years [IQR, 56-71 years]; 401 men). Originally, 123 patients were classified as BCLC B with mOS of 24.3 months (95% CI: 21.4, 32.9) and 371 patients as BCLC C with mOS of 11.9 months (95% CI: 10.5, 14.8). The mOS of all included patients (including the BCLC B and C groups) was 15 months (95% CI: 12.3, 17.2). A total of 152 patients with BCLC C tumors were restratified into a new BCLC Bn class, in which the mOS was then 25.1 months (95% CI: 21.8, 29.7; P < .001). The mOS of the remaining patients (ie, BCLC Cn group) (n = 222; ETV ≥65 cm3 or ETB ≥4%) was 8.4 months (95% CI: 6.1, 11.2). Conclusion Substratification of patients with intermediate- and advanced-stage hepatocellular carcinoma according to three-dimensional quantitative tumor burden identified patients with a survival benefit from transarterial chemoembolization before therapy. © RSNA, 2022 Online supplemental material is available for this article.

Impact of Chemoembolic Regimen on Immune Cell Recruitment and Immune Checkpoint Marker Expression following Transcatheter Arterial Chemoembolization in a VX2 Rabbit Liver Tumor Model.

PURPOSE: To characterize the effects of commonly used transcatheter arterial chemoembolization (TACE) regimens on the immune response and immune checkpoint marker expression using a VX2 rabbit liver tumor model. MATERIALS AND METHODS: Twenty-four VX2 liver tumor-bearing New Zealand white rabbits were assigned to 7 groups (n = 3 per group) undergoing locoregional therapy as follows: (a) bicarbonate infusion without embolization, (b) conventional TACE (cTACE) using a water-in-oil emulsion containing doxorubicin mixed 1:2 with Lipiodol, drug-eluting embolic-TACE with either (c) idarubicin-eluting Oncozene microspheres (40 µm) or (d) doxorubicin-eluting Lumi beads (40-90 µm). For each therapy arm (b-d), a tandem set of 3 animals with additional bicarbonate infusion before TACE was added, to evaluate the effect of pH modification on the immune response. Three untreated rabbits served as controls. Tissue was harvested 24 hours after treatment, followed by digital immunohistochemistry quantification (counts/µm2 ± SEM) of tumor-infiltrating cluster of differentiation 3+ T-lymphocytes, human leukocyte antigen DR type antigen-presenting cells (APCs), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway axis expression. RESULTS: Lumi-bead TACE induced significantly more intratumoral T-cell and APC infiltration than cTACE and Oncozene-microsphere TACE. Additionally, tumors treated with Lumi-bead TACE expressed significantly higher intratumoral immune checkpoint markers compared with cTACE and Oncozene-microsphere TACE. Neoadjuvant bicarbonate demonstrated the most pronounced effect on cTACE and resulted in a significant increase in intratumoral cluster of differentiation 3+ T-cell infiltration compared with cTACE alone. CONCLUSIONS: This preclinical study revealed significant differences in evoked tumor immunogenicity depending on the choice of chemoembolic regimen for TACE.

Establishment of an interdisciplinary vascular anomalies program in Tanzania, East Africa.

Purpose: The aim of this project is the sustainable implementation of a vascular anomalies (VA) program in Tanzania. Materials and methods: In 2021 the first interdisciplinary VA program was initiated at Muhimbili National Hospital (MNH), Dar Es Salaam, Tanzania in a stepwise approach. During the planning phase the clinical need for minimally-invasive therapies of VAs and the preexisting structures were assessed by the local Interventional Radiology (IR) team at MNH. During the initiation phase, an IR team from two German VA centers joined the interdisciplinary team at MNH for clinical workup, image-guided procedures and follow-up. VA patients were recruited from existing patient records or seen at clinics as de novo presentations following nationwide advertisement. In the post-processing phase joined online conferences for follow-up and support in management of new patients were established. Further follow-up was supported by attending providers from other established VA centers, traveling to bolster the primary operators of MNH. Results: The first interdisciplinary VA program was successfully launched in Tanzania. Minimally-invasive treatments were successfully trained, by performing ultrasound-guided sclerotherapy with polidocanol and bleomycin in twelve patients with slow-flow malformations, one endovascular embolization of a high-flow malformation, and medical treatment of an aggressive infantile hemangioma. Regular online follow-up presentations have been initiated. Follow-up evaluation and required treatment was sustained when appropriate. Conclusion: The presented "hands-on" training set the ground for the first interdisciplinary VA program in Tanzania. This framework is expected to establish comprehensive and sustainable care of patients with VAs in East Africa and can serve as a blueprint for other sites.

Identifying enhancement-based staging markers on baseline MRI in patients with colorectal cancer liver metastases undergoing intra-arterial tumor therapy.

OBJECTIVES: To determine if three-dimensional whole liver and baseline tumor enhancement features on MRI can serve as staging biomarkers and help predict survival of patients with colorectal cancer liver metastases (CRCLM) more accurately than one-dimensional and non-enhancement-based features. METHODS: This retrospective study included 88 patients with CRCLM, treated with transarterial chemoembolization or Y90 transarterial radioembolization between 2001 and 2014. Semi-automated segmentations of up to three dominant lesions were performed on pre-treatment MRI to calculate total tumor volume (TTV) and total liver volumes (TLV). Quantitative 3D analysis was performed to calculate enhancing tumor volume (ETV), enhancing tumor burden (ETB, calculated as ETV/TLV), enhancing liver volume (ELV), and enhancing liver burden (ELB, calculated as ELV/TLV). Overall and enhancing tumor diameters were also measured. A modified Kaplan-Meier method was used to determine appropriate cutoff values for each metric. The predictive value of each parameter was assessed by Kaplan-Meier survival curves and univariable and multivariable cox proportional hazard models. RESULTS: All methods except whole liver (ELB, ELV) and one-dimensional/non-enhancement-based methods were independent predictors of survival. Multivariable analysis showed a HR of 2.1 (95% CI 1.3-3.4, p = 0.004) for enhancing tumor diameter, HR 1.7 (95% CI 1.1-2.8, p = 0.04) for TTV, HR 2.3 (95% CI 1.4-3.9, p < 0.001) for ETV, and HR 2.4 (95% CI 1.4-4.0, p = 0.001) for ETB. CONCLUSIONS: Tumor enhancement of CRCLM on baseline MRI is strongly associated with patient survival after intra-arterial therapy, suggesting that enhancing tumor volume and enhancing tumor burden are better prognostic indicators than non-enhancement-based and one-dimensional-based markers. KEY POINTS: • Tumor enhancement of colorectal cancer liver metastases on MRI prior to treatment with intra-arterial therapies is strongly associated with patient survival. • Three-dimensional, enhancement-based imaging biomarkers such as enhancing tumor volume and enhancing tumor burden may serve as the basis of a novel prognostic staging system for patients with liver-dominant colorectal cancer metastases.

Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial.

BACKGROUND: The use of the ethiodized oil- Lipiodol in conventional trans-arterial chemoembolization (cTACE) ensures radiopacity to visualize drug delivery in the process of providing selective drug targeting to hepatic cancers and arterial embolization. Lipiodol functions as a carrier of chemo drugs for targeted therapy, as an embolic agent, augmenting the drug effect by efflux into the portal veins as well as a predictor for the tumor response and survival. PURPOSE: To prospectively evaluate the role of 3D quantitative assessment of intra-procedural Lipiodol deposition in liver tumors on CBCT immediately after cTACE as a predictive biomarker for the outcome of cTACE. MATERIALS & METHODS: This was a post-hoc analysis of data from an IRB-approved prospective clinical trial. Thirty-two patients with hepatocellular carcinoma or liver metastases underwent contrast enhanced CBCT obtained immediately after cTACE, unenhanced MDCT at 24 h after cTACE, and follow-up imaging 30-, 90- and 180-days post-procedure. Lipiodol deposition was quantified on CBCT after cTACE and was characterized by 4 ordinal levels: ≤25%, >25-50%, >50-75%, >75%. Tumor response was assessed on follow-up MRI. Lipiodol deposition on imaging, correlation between Lipiodol deposition and tumor response criteria, and correlation between Lipiodol coverage and median overall survival (MOS) were evaluated. RESULTS: Image analysis demonstrated a high degree of agreement between the Lipiodol deposition on CBCT and the 24 h post-TACE CT, with a Bland-Altman plot of Lipiodol deposition on imaging demonstrated a bias of 2.75, with 95%-limits-of-agreement: -16.6 to 22.1%. An inverse relationship between Lipiodol deposition in responders versus non-responders for two-dimensional EASL reached statistical significance at 30 days (p = 0.02) and 90 days (p = 0.05). Comparing the Lipiodol deposition in Modified Response Evaluation Criteria in Solid Tumors (mRECIST) responders versus non-responders showed a statistically significant higher volumetric deposition in responders for European Association for the Study of the Liver (EASL)-30d, EASL-90d, and quantitative EASL-180d. The correlation between the relative Lipiodol deposition and the change in enhancing tumor volume showed a negative association post-cTACE (30-day: p < 0.001; rho = -0.63). A Kaplan-Meier analysis for patients with high vs. low Lipiodol deposition showed a MOS of 46 vs. 33 months (p = 0.05). CONCLUSION: 3D quantification of Lipiodol deposition on intra-procedural CBCT is a predictive biomarker of outcome in patients with primary or metastatic liver cancer undergoing cTACE. There are spatial and volumetric agreements between 3D quantification of Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT could suggest that acquiring MDCT 24 h after cTACE is redundant. Importantly, the demonstrated relationship between levels of tumor coverage with Lipiodol and degree and timeline of tumor response after cTACE underline the role of Lipiodol as an intra-procedural surrogate for tumor response, with potential implications for the prediction of survival.

Role of 3D quantitative tumor analysis for predicting overall survival after conventional chemoembolization of intrahepatic cholangiocarcinoma.

This study was designed to assess 3D vs. 1D and 2D quantitative tumor analysis for prediction of overall survival (OS) in patients with Intrahepatic Cholangiocarcinoma (ICC) who underwent conventional transarterial chemoembolization (cTACE). 73 ICC patients who underwent cTACE were included in this retrospective analysis between Oct 2001 and Feb 2015. The overall and enhancing tumor diameters and the maximum cross-sectional and enhancing tumor areas were measured on baseline images. 3D quantitative tumor analysis was used to assess total tumor volume (TTV), enhancing tumor volume (ETV), and enhancing tumor burden (ETB) (ratio between ETV and liver volume). Patients were divided into low (LTB) and high tumor burden (HTB) groups. There was a significant separation between survival curves of the LTB and HTB groups using enhancing tumor diameter (p = 0.003), enhancing tumor area (p = 0.03), TTV (p = 0.03), and ETV (p = 0.01). Multivariate analysis showed a hazard ratio of 0.46 (95%CI: 0.27-0.78, p = 0.004) for enhancing tumor diameter, 0.56 (95% CI 0.33-0.96, p = 0.04) for enhancing tumor area, 0.58 (95%CI: 0.34-0.98, p = 0.04) for TTV, and 0.52 (95%CI: 0.30-0.91, p = 0.02) for ETV. TTV and ETV, as well as the largest enhancing tumor diameter and maximum enhancing tumor area, reliably predict the OS of patients with ICC after cTACE and could identify ICC patients who are most likely to benefit from cTACE.

Reliable prediction of survival in advanced-stage hepatocellular carcinoma treated with sorafenib: comparing 1D and 3D quantitative tumor response criteria on MRI.

OBJECTIVES: To compare 1D and 3D quantitative tumor response criteria applied to DCE-MRI in patients with advanced-stage HCC undergoing sorafenib therapy to predict overall survival (OS) early during treatment. METHODS: This retrospective analysis included 29 patients with advanced-stage HCC who received sorafenib for at least 60 days. All patients underwent baseline and follow-up DCE-MRI at 81.5 ± 29.3 days (range 35-140 days). Response to sorafenib was assessed in 46 target lesions using 1D criteria RECIST1.1 and mRECIST. In addition, a segmentation-based 3D quantification of absolute enhancing lesion volume (vqEASL) was performed on the arterial phase MRI, and the enhancement fraction of total tumor volume (%qEASL) was calculated. Accordingly, patients were stratified into groups of disease control (DC) and disease progression (DP). OS was evaluated using Kaplan-Meier curves with log-rank test and Cox proportional hazards regression model. RESULTS: The Kaplan-Meier analysis revealed that stratification of patients in DC vs. DP according to mRECIST (p = 0.0371) and vqEASL (p = 0.0118) successfully captured response and stratified OS, while stratification according to RECIST and %qEASL did not correlate with OS (p = 0.6273 and p = 0.7474, respectively). Multivariable Cox regression identified tumor progression according to mRECIST and qEASL as independent risk factors of decreased OS (p = 0.039 and p = 0.006, respectively). CONCLUSIONS: The study identified enhancement-based vqEASL and mRECIST as reliable predictors of patient survival early after initiation of treatment with sorafenib. This data provides evidence for potential advantages 3D quantitative, enhancement-based tumor response analysis over conventional techniques regarding early identification of treatment success or failure. KEY POINTS: • Tumor response criteria on MRI can be used to predict survival benefit of sorafenib therapy in patients with advanced HCC. • Stratification into DC and DP using mRECIST and vqEASL significantly correlates with OS (p = 0.0371 and p = 0.0118, respectively) early after initiation of sorafenib, while stratification according to RECIST and %qEASL did not correlate with OS (p = 0.6273 and p = 0.7474, respectively). • mRECIST (HR = 0.325, p = 0.039. 95%CI 0.112-0.946) and qEASL (HR = 0.183, p = 0.006, 95%CI 0.055-0.613) are independent prognostic factors of survival in HCC patients undergoing sorafenib therapy.

Idarubicin-Loaded ONCOZENE Drug-Eluting Bead Chemoembolization in a Rabbit Liver Tumor Model: Investigating Safety, Therapeutic Efficacy, and Effects on Tumor Microenvironment.

PURPOSE: To investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-µm and 100-µm drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model. MATERIALS AND METHODS: Twelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-µm (n = 5) or 100-µm (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24-72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia. Laboratory parameters and histopathologic ex vivo analysis included fluorescence confocal microscopy and immunohistochemistry. RESULTS: DCE MR imaging demonstrated a similar degree of devascularization of embolized tumors for both microsphere sizes (mean arterial enhancement, 8% ± 12 vs 36% ± 51 in controls; P = .07). Similarly, DWI showed postprocedural increases in diffusion across the entire lesion (apparent diffusion coefficient, 1.89 × 10-3 mm2/s ± 0.18 vs 2.34 × 10-3 mm2/s ± 0.18 in liver; P = .002). BIRDS demonstrated profound tumor acidosis at baseline (mean pHe, 6.79 ± 0.08 in tumor vs 7.13 ± 0.08 in liver; P = .02) and after chemoembolization (6.8 ± 0.06 in tumor vs 7.1 ± 0.04 in liver; P = .007). Laboratory and ex vivo analyses showed central tumor core penetration and greater increase in liver enzymes for 40-µm vs 100-µm microspheres. Inhibition of cell proliferation, intratumoral hypoxia, and limited idarubicin elution were equally observed with both sphere sizes. CONCLUSIONS: Noninvasive multiparametric MR imaging visualized chemoembolic effects in tumor and tumor microenvironment following DEE chemoembolization. Devascularization, increased hypoxia, coagulative necrosis, tumor acidosis, and limited idarubicin elution suggest ischemia as the predominant therapeutic mechanism. Substantial size-dependent differences indicate greater toxicity with the smaller microsphere diameter.

Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury.

Anatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway. We show that ascending dorsal root ganglion (DRG) axons branch in the spinal grey matter and substantially increase the number of these collaterals following injury. These sensory fibers exhibit synapsin-positive varicosities, indicating their integration into spinal networks. Using a monosynaptic circuit tracing with rabies viruses injected into the cuneate nucleus, we show the presence of spinal cord neurons that provide a detour pathway to the original target area of DRG axons. Notably the number of contacts between DRG collaterals and those spinal neurons increases by more than 300% after injury. We then characterized these interneurons and showed that the lesion triggers a remodeling of the connectivity pattern. Finally, using re-lesion experiments after initial remodeling of connections, we show that these detour circuits are responsible for the recovery of tactile and proprioceptive function. Taken together our study reveals that detour circuits represent a common blueprint for axonal rewiring after injury.