Practical Considerations When Choosing Chemoembolization versus Radioembolization for Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common liver-directed therapies (LDTs) for unresectable HCC. While both deliver intra-arterial treatment directly to the site of the tumor, they differ in mechanisms of action and side effects. Several studies have compared their side effect profile, time to progression, and overall survival data, but often these lack practical considerations when choosing which treatment modality to use. Many factors can impact operator's choice for treatment, and the choice depends on treatment availability, cost, insurance coverage, operator's comfort level, patient-specific factors, tumor location, tumor biology, and disease stage. This review discusses survival data, time to progression data, as well as more practical patient and tumor characteristics for personalized LDT with TACE or TARE.

Intrahepatic cholangiocarcinoma: a dose threshold evaluation in those undergoing transarterial radioembolization.

Background: Intrahepatic cholangiocarcinoma (ICC) is a rare primary hepatic malignancy. One of the treatment strategies which has shown some promise is transarterial radioembolization (TARE). However, data on dose thresholds, arguably the most important aspect of the procedure itself, is still limited. The study aims to evaluate the relationship between dose to tumor and radiologic response in intrahepatic cholangiocarcinoma patients undergoing transarterial radioembolization. Methods: Twenty-patients who underwent treatment for 26 tumors were retrospectively reviewed. Radiologic response at 3-month was evaluated and post yttrium-90 bremsstrahlung single photon emission computerized tomography computed tomography was evaluated to determine tumor dose. Other factors such as particle load and activity per particle were evaluated. Results: The mean tumor dose for those with progressive disease or stable disease, partial response, and complete response (CR) by European Association for the Study of Liver (EASL) criteria for the glass cohort was 294±0, 465.4±292.4 and 951.8±666.5 Gy respectively (P=0.039). A receiver operating characteristic (ROC) curve analysis of tumor dose demonstrated an area under the curve (AUC) of 0.738 (P=0.038) with Youden-index analysis demonstrated a cutoff point of >541.7 Gy (sensitivity: 55.56%; specificity: 92.86%) for the glass cohort. Significantly longer survival was noted in those who achieved a CR [HR: 4.79 (95% CI: 1.41-16.25)] and those treated with glass as compared to resin [HR: 5.02 (95% CI: 1.23-20.55), P=0.025]. Of the 17 treatments in 13 patients which were done concomitantly with chemotherapy 7/17 (41.2%) required a delay in chemotherapy, however all patients reinitiated chemotherapy after a delay. Conclusions: There appears to be a relationship between tumor dose and radiologic response, with this study suggesting a target of ≥541.7 Gy being warranted in patients receiving treatment with glass microspheres.

Radiation induces long-term muscle fibrosis and promotes a fibrotic phenotype in fibro-adipogenic progenitors.

BACKGROUND: Radiation-induced muscle pathology, characterized by muscle atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for muscle maintenance and regeneration, while in muscle pathology FAPs are precursors for exacerbated extracellular matrix deposition. However, the role of FAPs in radiation-induced muscle pathology has not previously been explored. METHODS: Four-week-old Male CBA or C57Bl/6J mice received a single dose (16 Gy) of irradiation (IR) to a single hindlimb with the shielded contralateral limb (CLTR) serving as a non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), and 56 days post-IR (long-term IR response). Changes in skeletal muscle morphology, myofibre composition, muscle niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, and metabolism and changes in progenitor cell fate where assessed. RESULTS: Juvenile radiation exposure resulted in smaller myofibre cross-sectional area, particularly in type I and IIA myofibres (P < 0.05) and reduced the proportion of type I myofibres (P < 0.05). Skeletal muscle fibrosis (P < 0.05) was evident at 56 days post-IR. The IR-limb had fewer endothelial cells (P < 0.05) and fibro-adipogenic progenitors (FAPs) (P < 0.05) at 56 days post-IR. Fewer muscle satellite (stem) cells were detected at 3 and 56 days in the IR-limb (P < 0.05). IR induced FAP senescence (P < 0.05), increased their fibrogenic differentiation (P < 0.01), and promoted their glycolytic metabolism. Further, IR altered the FAP secretome in a manner that impaired muscle satellite (stem) cell differentiation (P < 0.05) and fusion (P < 0.05). CONCLUSIONS: Our study suggests that following juvenile radiation exposure, FAPs contribute to long-term skeletal muscle atrophy and fibrosis. These findings provide rationale for investigating FAP-targeted therapies to ameliorate the negative late effects of radiation exposure in skeletal muscle.

Lung shunt fraction calculations before Y-90 transarterial radioembolization: Comparison of accuracy and clinical significance of planar scintigraphy and SPECT/CT.

PURPOSE: To determine the accuracy and clinical significance of planar scintigraphy lung shunt fraction (PLSF) and single-photon emission computerized tomography (SPECT) computed tomography (CT) lung shunt fraction (SLSF) before Y-90 transarterial radioembolization. MATERIALS AND METHODS: Seventy patients (46 men, 24 women; mean age, 64 ± 9.5 [SD] years) who underwent 83 treatments with Y-90 transarterial radioembolization for primary or secondary malignancies of the liver with a PLSF ≥ 7.5% were retrospectively evaluated. The patients mapping technetium 99 m (Tc-99 m) macroaggregated albumin (MAA) PLSF and SLSF were calculated and compared to the post Y-90 delivery SLSF. A model using modern dose thresholds was created to identify patients who would require dose reduction due to a lung dose ≥ 30 Gy, with patients who required >50% dose reduction considered to be delivery cancelations. RESULTS: A significant difference was found between mean PLSF (14.7 ± 11.6 [SD]%; range: 7.5-84.1%) and mean SLSF (8.7 ± 8.5 [SD]%; range: 1.7-73.5) (P < 0.001). The mean realized LSF (7.1 ± 3 [SD]%; range:1.5-17.6) was significantly less than the PLSF (P <0.001) but not the SLSF (P = 0.07). PLSF significantly overestimated the realized LSF by more than the SLSF (8.5 ± 5.3 [SD] % [range: -0.1-21.7] vs. 0.8 ± 3.6 [SD] % [range: -5-13.2], respectively) (P < 0.001). Based on the clinical significance model, 20 patients (20/83, 24.1%) would have required dose reduction or cancelation when using PLSF but would not require even a dose reduction when using the SLSF. Significantly more deliveries would have been be canceled if PLSF was used as compared to SLSF (22/83 [26.5%] vs. 6/83 [7.2%], respectively) (P < 0.001). CONCLUSION: SLSF is significantly more accurate at predicting realized LSF than PLSF and this difference is of clinical significance in a number of patients with a PLSF ≥ 7.5%.

Evaluation of Inflammatory Scores in Metastatic Colorectal Cancer Patients Undergoing Transarterial Radioembolization.

PURPOSE: To evaluate the correlation of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aspartate aminotransferase-to-lymphocyte ratio (ALRI), systemic inflammation index (SII), and lymphocyte count to oncologic outcomes in metastatic colorectal cancer (mCRC) patients undergoing transarterial radioembolization (TARE). MATERIALS AND METHODS: All patients undergoing TARE for mCRC were retrospectively reviewed at a single academic institution. A receiver operating characteristics (ROC) curve analysis was performed using a landmark survival point of 12 months, with an area under the curve (AUC) calculated. A cutoff point was determined by Youden's index and used to separate patients for OS and PFS analysis. Cox proportional-hazards models which included pertinent clinical factors were also created to evaluate PFS and OS. RESULTS: In total, 41 patients who underwent 66 TARE treatments were included. A correlation was seen between post-treatment ALRI < 45 (HR: 0.38 (95%CI: 0.17-0.86), p = 0.02) and PFS. Patients with a pretreatment ALRI score < 20 had a significantly longer OS (HR: 0.49 (95%CI: 0.19-0.88), p = 0.02) as did those with a post-treatment lymphocyte count > 1.1 109/L (HR: 0.27 (95%CI: 0.11-0.68), p = 0.005). In multivariate analysis of PFS, post-treatment lymphocyte count (HR: 8.46 (95%CI: 1.14-62.89), p = 0.044) was the only significantly associated inflammatory marker and presence of extrahepatic disease (HR:8.46 (95%CI: 1.14-62.89, p = 0.044) also correlated. Multivariate analysis of OS showed that pretreatment PLR (HR:1.01 (95%CI:1.-1.03), p = 0.02) and post-treatment NLR (HR:0.33 (95%CI:0.14-0.76), p = 0.009), PLR (HR:0.98 (95%CI:0.97-1), p = 0.046), SII (HR:1.04 (95%CI:1.01-1.08), p = 0.014), and lymphocyte count (HR:0.07 (95%CI:0.01-0.16), p = 0.003) were significantly associated. CONCLUSION: Inflammatory markers may be associated with OS and PFS in mCRC patients undergoing TARE.

Thermal Ablation in the Liver: Heat versus Cold-What Is the Role of Cryoablation?

Cryoablation is commonly used in the kidney, lung, breast, and soft tissue, but is an uncommon choice in the liver where radiofrequency ablation (RFA) and microwave ablation (MWA) predominate. This is in part for historical reasons due to serious complications that occurred with open hepatic cryoablation using early technology. More current technology combined with image-guided percutaneous approaches has ameliorated these issues and allowed cryoablation to become a safe and effective thermal ablation modality for treating liver tumors. Cryoablation has several advantages over RFA and MWA including the ability to visualize the ice ball, minimal procedural pain, and strong immunomodulatory effects. This article will review the current literature on cryoablation of primary and secondary liver tumors, with a focus on efficacy, safety, and immunogenic potential. Clinical scenarios when it may be more beneficial to use cryoablation over heat-based ablation in the liver, as well as directions for future research, will also be discussed.

Lung shunt fraction quantification methods in radioembolization: What you need to know.

In some patients undergoing radioembolization, lung toxicity is a limiting factor when calculating their dose. At the same time, it is known that the lung shunt fraction (LSF) is overestimated by the mapping exam. Furthermore, there are multiple methods to measure LSF. Planar measurement is both the most commonly utilized and easiest to perform, however new dosimetry software provides the ability to use more advanced 3D techniques. This paper reviews the different LSF calculation methods and elucidates the available data comparing the techniques, clinical relevance, and dose calculation.

Inflammatory Scores: Correlation with Clinical Outcomes in Hepatocellular Carcinoma Patients Undergoing Transarterial Radioembolization.

PURPOSE: To evaluate the ability of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aspartate aminotransferase-to-lymphocyte ratio (ALRI) and systemic-inflammation index (SII) to predict clinical outcomes in hepatocellular carcinoma (HCC) patients undergoing transarterial radioembolization (TARE). MATERIALS AND METHODS: One hundred forty-five patients who underwent treatment of 167 HCCs had their pretreatment and 1 month post treatment laboratory values evaluated. Overall survival (OS), progression-free survival (PFS) and local PFS models were performed with patients separated by median inflammatory scores. RESULTS: The median pretreatment NLR, PLR, ALRI and SII were 3.0 (range: 0.5-176), 104.4 (range: 25-830), 55.7 (range: 7.5-2090) and 360.2 (range: 51.1-7207.8), respectively. While the median post treatment NLR, PLR, ALRI and SII were 6.2 (range: 0.4-176), 180 (range: 35-2100), 125 (range: 15.9-5710) and 596.8 (range: 28.9-19,320), respectively. OS models showed significant differences when separating the groups by median post treatment NLR (p = 0.003) and SII (p = 0.003). Multivariate Cox regression models for OS with all pre and post treatment inflammatory markers (log-scale) as well as tumor size, AFP and Child-Pugh score showed significant pretreatment NLR [HR: 0.22 (95% CI:0.06-0.75), p = 0.016] and SII [3.52 (95% CI: 1.01-12.3), p = 0.048], as well as post treatment NLR [6.54 (95% CI: 1.57-27.2), p = 0.010] and SII [0.20 (95% CI: 0.05-0.82), p = 0.025] association. The post treatment ALRI (p = 0.010) correlated with PFS while, post treatment NLR (p < 0.001), ALRI (p = 0.024) and SII (p = 0.005) correlated with local PFS. CONCLUSION: Pretreatment and post treatment NLR and SII may be associated with OS and post treatment ALRI may be associated with both PFS and local PFS in HCC patients undergoing TARE.

Dynamic Lymphocyte Changes Following Transarterial Radioembolization: Association with Normal Liver Dose and Effect on Overall Survival.

OBJECTIVE: To evaluate the dynamic changes of lymphocytes following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) and their relationship to normal liver dose (NLD). MATERIALS AND METHODS: A total of 93 patients who underwent 102 treatments were retrospectively reviewed. Absolute lymphocyte counts pretreatment and at 1, 3, 6, and 12 months were evaluated. Kaplan-Meier, Spearman correlation, receiver operating characteristic (ROC) curve, and area under the curve (AUC) analyses were performed. RESULTS: The mean absolute lymphocyte count at baseline was 1.25 ± 0.79 103/µL which was significantly greater than 1 (0.71 ± 0.47 103/µL, p<0.0001), 3 (0.79 ± 0.77 103/µL, p=0.0003), and 6 (0.81 ± 0.44 103/µL, p=0.0001) months, but not significantly different than 12 (0.92 ± 0.8 103/µL, p=0.12) months post treatment. There was a modest negative correlation between NLD and lymphocyte count at 1 month (rho= -0.216, p=0.03), which strengthened at 3 months post treatment (rho= -0.342, p=0.008). AUC of ROC analysis between absolute lymphocyte count ≤1 103/µL or >1 103/µL at 1, 3, 6, and 12 months post treatment was 0.625, 0.676, 0.560, and 0.794, respectively. Univariate analysis of overall survival when separating patients by a lymphocyte count of ≤1 103/µL and >1 103/µL demonstrated a significant difference at 1 (HR: 0.56, 95% CI: 0.33-0.95, p=0.03), 3 (HR: 0.41, 95% CI: 0.18-0.94, p=0.035) and 6 (HR: 0.36, 95% CI: 0.17-0.77, p=0.008) months post treatment, but not pretreatment or at 12 months. CONCLUSION: NLD may correlate with lymphocyte depression at 1 and 3 months and lymphopenia may portend a worse overall survival in the post treatment setting.

Local recurrence following complete radiologic response in patients treated with transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: The purpose of this study was to determine the local progression rate and identify factors that may predict local progression, in patients who achieve a complete response (CR) radiologically after undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One-hundred-forty-seven patients, who achieved CR of 224 HCCs after TACE, were retrospectively reviewed. There were 109 men and 38 women with a mean age of 61.6 ± 6.8 (SD) years (range: 45.4-86.9 years). Logistic mixed-effects and Cox regression models were used to evaluate associations between clinical factors and local progression. RESULTS: A total of 75 patients (75/147; 51%) and 99 (99/224,44.2%) lesions showed local progression at a median of 289.5 days (Q1: 125, Q3: 452; range: 51-2245 days). Pre-treatment, international normalization ratio (INR) (1.17 ± 0.15 [SD] vs. 1.25 ± 0.16 [SD]; P <0.001), model for end-stage liver disease (9.4 ± 2.6 [SD] vs. 10.6 ± 3.2 [SD]; P = 0.010) and Child-Pugh score (6 ± 1 [SD] vs. 6.4 ± 1.3 [SD]; P = 0.012) were significantly lower while albumin serum level (3.4 ± 0.62 [SD] vs. 3.22 ± 0.52 [SD]; P = 0.033) was significantly greater in those who showed local progression as compared to those who did not. In terms of local-recurrence free survival, the number of TACE treatments (hazard ratio [HR]: 2.05 [95% CI: 1.57-2.67]; P<0.001), INR (HR: 0.13 [95% CI: 0.03-0.61]; P = 0.010) and type of TACE (P = 0.003) were significant. Patients with local progression on any tumor did not differ from those who did in terms of overall survival (P = 0.072), however, were less likely to be transplanted (20/75, 26.7%) than those who did not (33/72; 36.1%) (P = 0.016). CONCLUSION: A significant number of patients who achieve CR of HCC after TACE have local progression. This emphasizes the importance of long-term follow up.

Inflammatory Scores: Comparison and Utility in HCC Patients Undergoing Transarterial Chemoembolization in a North American Cohort.

BACKGROUND: The purpose of this study is to determine and compare the ability of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aspartate-aminotransferase-to-lymphocyte ratio (ALRI), systemic-inflammation index (SII) and lymphocyte count to predict oncologic outcomes in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: A single-center retrospective review of 296 patients who were treated for 457 HCCs was performed. Pre- and post-treatment laboratory and treatment outcome variables were collected. Objective radiologic response (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Patients were categorized into above and below median scores and compared. RESULTS: The median pretreatment NLR, PLR, ALRI, SII, and lymphocyte count were 2.7 (range: 0.4-55), 88.3 (range: 0.1-840), 71.8 (range: 0.1-910), 238.1 (range: 0.1-5150.8), and 1 (range: 0.1-5.2) 103/µL, respectively. Patients with above median ALRI scores were less likely to achieve an ORR as compared to those with below median ALRI values (132 (132/163, 81%) vs 150 (150/163, 92%), p = 0.004). On univariate analysis, patients with above median pretreatment NLR (HR 1.41, 95% CI: 1.09-1.83, p = 0.01) and below median lymphocyte count (HR 0.69, 95% CI: 0.53-0.92, p = 0.01) had significantly worse PFS. The relationship between PFS and NLR (p = 0.08) as well as lymphocytes (p = 0.20) no longer remained on multivariate analysis. On univariate analysis, below median pretreatment NLR (HR 1.72, 95% CI: 1.2-2.45, p = 0.003) and ALRI (HR 1.52, 95% CI: 1.05-2.2); p = 0.03) as well as above median lymphocyte count (HR 0.48, 95% CI: 0.34-0.7, p < 0.0001) were associated with improved OS. The significant relationship between lymphocytes and OS remained on multivariate analysis (HR 0.50, 95% CI: 0.28-0.9, p = 0.02), but the relationship with NLR (p = 0.94) did not persist. CONCLUSION: NLR is predictive of PFS and OS in patients with HCC undergoing TACE and may be superior to other inflammatory scores (PLR, ALRI, and SII) in this setting. However, lymphocyte count may be most predictive of OS.

Incidence and risk factors for sustained hepatic function toxicity 6 months after radioembolization: analysis of the radiation-emitting sir-spheres in non-resectable liver tumor (RESIN) registry.

BACKGROUND: To quantify rates and risk factors for toxicity after hepatic radioembolization using resin yttrium-90 microspheres. METHODS: Radiation-Emitting SIR-Spheres in Non-resectable liver tumor (RESIN) registry enrollees were reviewed with 614 patients included. Mean patient age was 63.1±12.5 years. The majority of patients were male (n=375, 61%) and white (n=490, 80%). Common tumor types were hepatocellular (n=197, 32%), colorectal (n=187, 30%) and neuroendocrine (n=56, 9%). Hepatotoxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE v 5). Potential risk factors for hepatotoxicity were tested using the Kruskal-Wallis or Pearson Chi-squared tests, and multivariate linear regressions. RESULTS: At 6 months, 115 patients (18.7%) died (n=91, 14.8%), entered hospice (n=20, 3.3%) or sought treatment elsewhere (n=4, 4%). Seven (1.1%) deaths were from liver decompensation. Grade 3 toxicity rates were: bilirubin (n=85, 13.8%), albumin (n=28, 4.6%), ALT (n=26, 4.2%) and AST (n=37, 6.0%). For each of these liver function test components, baseline abnormal labs predicted Grade 3 toxicity at follow-up by Kruskal-Wallis test (P<0.001) and linear regression (all P<0.03). Other significant factors predicting toxicity at regression included elevated Body-Mass Index (albumin P=0.0056), whole liver treatment (bilirubin P=0.046), and lower tumor volume (ALT and INR, P<0.035 for both). CONCLUSIONS: Baseline liver function abnormalities prior to radioembolization is the strongest predictor of post-treatment Grade 3 toxicity with rates as high as 13.8%. Toxicity rates for specific lab values are affected by large volume treatments especially with low tumor volumes.

Weight loss with exercise improves muscle architecture and progenitor cell populations compared with weight loss alone in mice with preneoplastic colorectal lesions.

Weight loss and exercise reduce colorectal cancer (CRC) risk in persons with obesity. Whether weight loss and exercise effect myofiber characteristics and muscle stem/progenitor cell populations in mice with preneoplastic colorectal lesions, a model of CRC risk, is unknown. To address this gap, male C57Bl/6J mice were fed a high-fat diet (HFD) to induce obesity or a control (CON) diet prior to azoxymethane injection to induce preneoplastic colorectal lesions. The HFD group was then randomized to weight loss conditions that included (1) switching to the CON diet only (HFD-SED) or switching to the CON diet with treadmill exercise training (HFD-EX). Average myofiber cross-sectional area was not different between groups. There were more smaller-sized fibres in HFD-EX (p < 0.05 vs. CON), and more fibrosis in HFD-SED (p < 0.05 vs. HFD-EX and CON). There was a trend for more committed (Pax7+MyoD+) myoblasts (p = 0.059) and more fibro-adipogenic progenitors in HFD-EX (p < 0.05 vs. CON). Additionally, the canonical pro-inflammatory marker p-NF-κB was markedly reduced in the interstitium of HFD-EX (p < 0.05 vs. CON and HFD-SED). Our findings suggest that in mice with preneoplastic colorectal lesions, HFD followed by weight loss with exercise reduces muscle fibrosis and results in a higher content of muscle stem/progenitor cells. Novelty: Exercise improves muscle architecture in mice with preneoplastic colorectal lesion Exercise increases fibro/adipogenic progenitors and reduces inflammatory signaling in mice with preneoplastic colorectal lesions.

Surgical microwave ablation of otherwise non-resectable colorectal cancer liver metastases: Expanding opportunities for long term survival.

BACKGROUND: Colorectal liver metastases (CRLM) are the most common extra-lymphatic metastases in colorectal cancers, however, only 15-20% of these patients are candidates for resection. We reviewed our institutional experience with 135 surgical ablations for unresectable CRLM. METHODS: Retrospective review of surgically ablated CRLM from 2009 to 2018. Patient-specific variables were obtained from the medical record. Kaplan-Meier modeling was performed for survival analyses. RESULTS: We ablated 135 CRLM in 36 patients over 40 procedures. Median age was 52 years and 58% of patients were male. All patients received systemic chemotherapy. The ablation procedure was completed laparoscopically in 68% of procedures. Median number of ablated lesions per patient was 2 (range 1-15). Median maximum diameter of ablated lesions was 1.9 cm (range 0.5-12.2). Median follow up of the study was 28 months. In this time, median disease-free survival was not reached. Of the 135 lesions ablated, the per-lesion recurrence rate was 6/135 (4.4%). Median overall survival was 81 months. CONCLUSIONS: Surgical ablation of CRLM can provide excellent local control and long-term survival outcomes in patients who may otherwise not be candidates for other liver-directed therapies.

Interventional Liver-Directed Therapy for Neuroendocrine Metastases: Current Status and Future Directions.

OPINION STATEMENT: Liver-directed therapy should be considered for patients with unresectable liver metastases from neuroendocrine tumor if symptomatic or progressing despite medical management. Our experience and current literature shows that the bland embolization, chemoembolization, and radioembolization are very effective in controlling symptoms and disease burden in the liver, and that these embolization modalities are similar in terms of efficacy and radiologic response. Their safety profiles differ, however, with recent studies suggesting an increase in biliary toxicity with drug-eluting bead chemoembolization over conventional chemoembolization, and a risk of long-term hepatotoxicity with radioembolization. For this reason, we tailor the type of embolotherapy to each patient according to their clinical status, symptoms, degree of tumor burden, histologic grade, and life expectancy. We do not recommend a "one-size-fits-all" approach. Our general strategy is to use bland embolization as first-line embolotherapy, and radioembolization for patients with high-grade tumors or who have failed other embolotherapy.

Successful Percutaneous Transcatheter Closure of a Common Femoral Artery Pseudoaneurysm With Use of MicroVascular Plug Despite Continued Catheter-Directed Thrombolysis.

Common femoral artery pseudoaneurysm is a known complication of percutaneous vascular access. Treatment options include surgical repair of the pseudoaneurysm or endovascular methods such as ultrasound-guided compression and direct thrombin injection into the pseudoaneurysm sac. Treatment of pseudoaneurysm is more challenging when a patient is undergoing concurrent catheter-directed or systemic thrombolytic therapy. This is a case report of endovascular treatment of an iatrogenic pseudoaneurysm of common femoral artery in a patient receiving concurrent catheter-directed thrombolytic therapy. This was performed successfully by precise deployment of a MicroVascular Plug into the pseudoaneurysm neck with immediate closure of pseudoaneurysm. Midterm follow-up confirmed sustained exclusion of the pseudoaneurysm sac with continued patency of the treated femoral artery.

The Late Effects of Radiation Therapy on Skeletal Muscle Morphology and Progenitor Cell Content are Influenced by Diet-Induced Obesity and Exercise Training in Male Mice.

Radiation exposure during muscle development induces long-term decrements to skeletal muscle health, which contribute to reduced quality of life in childhood cancer survivors. Whether the effects of radiation on skeletal muscle are influenced by relevant physiological factors, such as obesity and exercise training remains unknown. Using skeletal muscle from our previously published work examining the effects of obesity and exercise training on radiation-exposed bone marrow, we evaluated the influence of these physiological host factors on irradiated skeletal muscle morphology and cellular dynamics. Mice were divided into control and high fat diet groups with or without exercise training. All mice were then exposed to radiation and continued in their intervention group for an additional 4 weeks. Diet-induced obesity resulted in increased muscle fibrosis, while obesity and exercise training both increased muscle adiposity. Exercise training enhanced myofibre cross-sectional area and the number of satellite cells committed to the myogenic lineage. High fat groups demonstrated an increase in p-NFĸB expression, a trend for a decline in IL-6, and increase in TGFB1. These findings suggest exercise training improves muscle morphology and satellite cell dynamics compared to diet-induced obesity in irradiated muscle, and have implications for exercise interventions in cancer survivors.

Loss of the adipokine lipocalin-2 impairs satellite cell activation and skeletal muscle regeneration.

Lipocalin-2 (LCN2) is an adipokine previously described for its contribution to numerous processes, including innate immunity and energy metabolism. LCN2 has also been demonstrated to be an extracellular matrix (ECM) regulator through its association with the ECM protease matrix metalloproteinase-9 (MMP-9). With the global rise in obesity and the associated comorbidities related to increasing adiposity, it is imperative to gain an understanding of the cross talk between adipose tissue and other metabolic tissues, such as skeletal muscle. Given the function of LCN2 on the ECM in other tissues and the importance of matrix remodeling in skeletal muscle regeneration, we examined the localization and expression of LCN2 in uninjured and regenerating wild-type skeletal muscle and assessed the impact of LCN2 deletion (LCN2-/-) on skeletal muscle repair following cardiotoxin injury. Though LCN2 was minimally present in uninjured skeletal muscle, its expression was increased significantly at 1 and 2 days postinjury, with expression present in Pax7-positive satellite cells. Although satellite cell content was unchanged, the ability of quiescent satellite cells to become activated was significantly impaired in LCN2-/- skeletal muscles. Skeletal muscle regeneration was also significantly compromised as evidenced by decreased embryonic myosin heavy chain expression and smaller regenerating myofiber areas. Consistent with a role for LCN2 in MMP-9 regulation, regenerating muscle also displayed a significant increase in fibrosis and lower ( P = 0.07) MMP-9 activity in LCN2-/- mice at 2 days postinjury. These data highlight a novel role for LCN2 in muscle regeneration and suggest that changes in adipokine expression can significantly impact skeletal muscle repair.

The NLRP3 inflammasome contributes to sarcopenia and lower muscle glycolytic potential in old mice.

The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. "Inflammaging," increased inflammation with advancing age, may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1-containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild-type (WT) and NLRP3-/- mice were aged to 10 (adult) and 24 mo (old). NLRP3-/- mice were protected from decreased muscle mass (relative to body mass) and decreased size of type IIB and IIA myofibers, which occurred between 10 and 24 mo of age in WT mice. Old NLRP3-/- mice also had increased relative muscle strength and endurance and were protected from age-related increases in the number of myopathic fibers. We found no evidence of age-related or NLRP3-dependent changes in markers of systemic inflammation. Increased caspase-1 activity was associated with GAPDH proteolysis and reduced GAPDH enzymatic activity in skeletal muscles from old WT mice. Aging did not alter caspase-1 activity, GAPDH proteolysis, or GAPDH activity in skeletal muscles of NLRP3-/- mice. Our results show that the NLRP3 inflammasome participates in age-related loss of muscle glycolytic potential. Deletion of NLRP3 mitigates both the decline in glycolytic myofiber size and the reduced activity of glycolytic enzymes in muscle during aging. We propose that the etiology of sarcopenia involves direct communication between immune responses and metabolic flux in skeletal muscle.

Is a Routine Chest X-ray Necessary in Every Patient After Percutaneous CT-Guided Lung Biopsy? A Retrospective Review of 278 Cases.

PURPOSE: To determine the rate, clinical significance, and predictors of delayed pneumothorax after CT-guided lung biopsy. METHODS: Medical and imaging records of all patients who underwent CT-guided lung biopsy between January 1, 2012, and January 9, 2015, were reviewed. "Early pneumothorax" was defined as one visualized on CT scan at the time of biopsy, "delayed pneumothorax" as one discovered on the first follow-up chest X-ray (CXR), and "clinically significant pneumothorax" as one requiring chest tube placement. RESULTS: Three hundred fifty-seven lung biopsies were performed; 79 patients did not have follow-up CXR and were excluded. Out of 278 cases included in the study, early pneumothorax occurred in 109 patients. Follow-up CXRs were available in the remaining 169 patients without early pneumothorax and were obtained 3.1 ± 2.9 h after biopsy. The rate of delayed pneumothorax was 8.6% (24/278). Clinically significant pneumothorax occurred in 10/24 (41.7%) patients with delayed pneumothorax, including one case of tension pneumothorax. Patients with delayed pneumothorax (n = 24) had smaller lesion long axial diameter (18.58 ± 9.84 vs 25.83 ± 17.69 mm, p = 0.005), longer intrapulmonary needle tract (23.45 ± 14.98 vs 14.17 ± 14.49, p = 0.004), and lower FEV1/FVC ratio (53.30 ± 22.47 vs 71.15 ± 13.77, p = 0.015), compared to those without delayed pneumothorax (n = 145). The length of intrapulmonary needle tract was the only independent predictor of delayed pneumothorax (p = 0.008) and symptomatic delayed pneumothorax (p = 0.019). CONCLUSION: Obtaining a routine follow-up CXR in all patients after CT-guided lung biopsy appears warranted, given the high rate of delayed pneumothorax and large percentage of patients who will require a chest tube. The only independent predictor of (symptomatic) delayed pneumothorax was the length of intrapulmonary needle tract.