Combined CT-guided high-dose-rate brachytherapy (CT-HDRBT) and transarterial chemoembolization with irinotecan-loaded microspheres improve local tumor control and progression-free survival in patients with unresectable colorectal liver metastases compared with mono-CT-HDRBT.

Purpose: To compare the effectivity and toxicity of monotherapy with computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) vs. combination therapy of transarterial chemoembolization with irinotecan (irinotecan-TACE) and CT-HDRBT in patients with large unresectable colorectal liver metastases (CRLM) with a diameter of > 3 cm. Material and methods: Forty-four retrospectively matched patients with unresectable CRLM were treated either with mono-CT-HDRBT or with a combination of irinotecan-TACE and CT-HDRBT (n = 22 in each group). Matching parameters included treatment, disease, and baseline characteristics. National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) were used to evaluate treatment toxicity and the Society of Interventional Radiology classification was applied to analyze catheter-related adverse events. Statistical analysis involved Cox regression, Kaplan-Meier estimator, log-rank test, receiver operating characteristic curve analysis, Shapiro-Wilk test, Wilcoxon test, paired sample t-test, and McNemar test. P-values < 0.05 were deemed significant. Results: Combination therapy ensued longer median progression-free survival (PFS: 5/2 months, p = 0.002) and significantly lower local (23%/68%, p < 0.001) and intrahepatic (50%/95%, p < 0.001) progress rates compared with mono-CT-HDRBT after a median follow-up time of 10 months. Additionally, tendencies for longer local tumor control (LTC: 17/9 months, p = 0.052) were found in patients undergoing both interventions. After combination therapy, aspartate and alanine aminotransferase toxicity levels increased significantly, while total bilirubin toxicity levels showed significantly higher increases after monotherapy. No catheter-associated major or minor complications were identified in each cohort. Conclusions: Combining irinotecan-TACE with CT-HDRBT can improve LTC rates and PFS compared with mono-CT-HDRBT in patients with unresectable CRLM. The combination of irinotecan-TACE and CT-HDRBT shows satisfying safety profiles.

Spectral Computed Tomography-Derived Iodine Content and Tumor Response in the Follow-Up of Neuroendocrine Tumors-A Single-Center Experience.

Spectral computed tomography (SCT) allows iodine content (IC) calculation for characterization of hypervascularized neoplasms and thus might help in the staging of neuroendocrine tumors (NETs). This single-center prospective study analyzed the association between SCT-derived IC and tumor response in the follow-up of metastasized NETs. Twenty-six patients with a median age of 70 years (range 51-85) with histologically proven NETs and a total of 78 lesions underwent SCT for staging. Because NETS are rare, no primary NET types were excluded. Lesions and intralesional hotspots were measured in virtual images and iodine maps. Tumor response was classified as progressive or nonprogressive at study endpoint. Generalized estimating equations served to estimate associations between IC and tumor response, additionally stratified by lesion location. Most commonly affected sites were the lymph nodes, liver, pancreas, and bones. Median time between SCT and endpoint was 64 weeks (range 5-260). Despite statistical imprecision in the estimate, patients with higher IC in lymphonodular metastases had lower odds for disease progression (adjusted OR = 0.21, 95% CI: 0.02-2.02). Opposite tendencies were observed in hepatic and pancreatic metastases in unadjusted analyses, which vanished after adjusting for therapy and primary tumor grade.

MR Imaging Volumetric Response after Yttrium-90 Radioembolization for Colorectal Liver Metastases: Predictability at Baseline and Correlation with Survival.

PURPOSE: To prove the utility of magnetic resonance (MR) imaging response as a surrogate end point of treatment efficacy and survival after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CRLMs), and to investigate whether outcomes can be predicted at baseline using MR imaging or clinical variables. MATERIALS AND METHODS: A total of 50 (135) patients with TARE for CRLMs between August 2008 and January 2020 and peri-interventional MR imaging within defined timeframes were included for tumor segmentation. Pretreatment and posttreatment target tumor volumes were measured according to the volumetric Response Evaluation Criteria In Solid Tumors (vRECIST) and the quantitative European Association for the Study of the Liver (qEASL) criteria. Cox regression models were used to analyze the impact of MR morphologic response, vascularity at baseline, and clinical variables on patient survival. Logistic regression analyses were used to evaluate the predictors of MR morphologic response at baseline. RESULTS: The median survival was 337 days (95% confidence interval [CI], 243-431). As opposed to the vRECIST, the application of the qEASL criteria 3 months after the treatment allowed for a significant (P < .05) separation of the survival curves for partial response, stable disease, and progressive disease with a median survival of 412 days (95% CI, 57-767) in responders. High tumor burden and technetium-99m lung shunt significantly decreased the probability of survival. MR morphologic response was not predictable at baseline using imaging or clinical data. CONCLUSIONS: MR response according to the qEASL criteria outperformed the vRECIST in measuring the biologic impact of TARE and predicting patient survival. Baseline contrast enhancement did not predict MR response to treatment, which may reflect elevated dose requirements in tumors with a high proportion of viable tumor volume.

A prospective randomized controlled trial assessing the effect of music on patients' anxiety in venous catheter placement procedures.

The aim of the study was to assess the influence of music on anxiety levels compared to standard patient care in patients undergoing venous catheter placement procedures. This prospective randomized controlled trial included patients undergoing placement procedures for peripherally inserted central venous catheters (PICC), ports and central venous catheters (CVC). Patients were randomly assigned to a music intervention group (MIG) and a control group (CTRL). State and trait anxiety levels were assessed as primary outcome using the state-trait anxiety inventory (STAI) before and after the procedures. Secondary outcomes comprised averaged heart rate for all participants and time of radiological surveillance for port placement procedures exclusively. 72 participants were included into the final analysis (MIG n = 40; CTRL n = 32). All procedures were successful and no major complications were reported. Mean levels for post-interventional anxieties were significantly lower in the MIG compared to the CTRL (34.9 ± 8.9 vs. 44 ± 12.1; p < 0.001). Mean heart rate in the MIG was significantly lower than in the CTRL (76.1 ± 13.7 vs. 93 ± 8.9; p < 0.001). Procedure time for port implantation was significantly longer in the MIG by 3 min 45 s (p = 0.031). Music exposure during central venous catheter placement procedures highly significantly reduces anxiety and stress levels and can be used to improve patients' overall experience in the angio suite.

Yttrium-90 radioembolization for unresectable hepatocellular carcinoma: predictive modeling strategies to anticipate tumor response and improve patient selection.

OBJECTIVES: This study aims to better characterize potential responders of Y-90-radioembolization at baseline through analysis of clinical variables and contrast enhanced (CE) MRI tumor volumetry in order to adjust therapeutic regimens early on and to improve treatment outcomes. METHODS: Fifty-eight HCC patients who underwent Y-90-radioembolization at our center between 10/2008 and 02/2017 were retrospectively included. Pre- and post-treatment target lesion volumes were measured as total tumor volume (TTV) and enhancing tumor volume (ETV). Survival analysis was performed with Cox regression models to evaluate 65% ETV reduction as surrogate endpoint for treatment efficacy. Univariable and multivariable logistic regression analyses were used to evaluate the combination of baseline clinical variables and tumor volumetry as predictors of ≥ 65% ETV reduction. RESULTS: Mean patients' age was 66 (SD 8.7) years, and 12 were female (21%). Sixty-seven percent of patients suffered from liver cirrhosis. Median survival was 11 months. A threshold of ≥ 65% in ETV reduction allowed for a significant (p = 0.04) separation of the survival curves with a median survival of 11 months in non-responders and 17 months in responders. Administered activity per tumor volume did predict neither survival nor ETV reduction. A baseline ETV/TTV ratio greater than 50% was the most important predictor of arterial devascularization (odds ratio 6.3) in a statistically significant (p = 0.001) multivariable logistic regression model. The effect size was strong with a Cohen's f of 0.89. CONCLUSION: We present a novel approach to identify promising candidates for Y-90 radioembolization at pre-treatment baseline MRI using tumor volumetry and clinical baseline variables. KEY POINTS: • A decrease of 65% enhancing tumor volume (ETV) on follow-up imaging 2-3 months after Y-90 radioembolization of HCC enables the early prediction of significantly improved median overall survival (11 months vs. 17 months, p = 0.04). • Said decrease in vascularization is predictable at baseline: an ETV greater than 50% is the most important variable in a multivariable logistic regression model that predicts responders at a high level of significance (p = 0.001) with an area under the curve of 87%.

Evidence for a thromboembolic pathogenesis of lung cavitations in severely ill COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.

Tumor Seeding along the Puncture Tract in CT-Guided Interstitial High-Dose-Rate Brachytherapy.

PURPOSE: To quantify the occurrence of tumor seeding in computed tomography (CT)-guided high-dose-rate brachytherapy (HDRBT) and to identify potential risk factors. MATERIALS AND METHODS: CT-HDRBT is a minimally invasive therapeutic option for local ablation of unresectable tumors. The procedure involves CT-guided placement of an enclosed catheter and high-dose-rate brachytherapy using iridium-192. Transcutaneous puncture of a tumor with subsequent retraction of the applicator has the potential risk of tumor seeding along the puncture tract. A total of 1,765 consecutive CT-HDRBT procedures were performed at this center between 2006 and 2017 and were retrospectively analyzed. In addition, a distinction was made between whether the puncture tract was irradiated or not. Follow-up imaging datasets were evaluated for tumor seeding along the former puncture tracts. Descriptive and exploratory statistical analyses of the data were performed. RESULTS: Tumor seeding was observed in 25 cases (25 of 1,765 cases [1.5%]). A total of 0.008 cases occurred per person-age. Patient age was identified as a potential risk factor with an odds ratio of 1.046 (95% confidence interval, 1.003-1.091; P = .04). There were no differences between whether the puncture tract was irradiated or not (P = .552). CONCLUSIONS: Tumor seeding along the puncture tract can occur in CT-HDRBT but is rare.

Complications of Computed Tomography-Guided High-Dose-Rate Brachytherapy (CT-HDRBT) and Risk Factors: Results from More than 10 Years of Experience.

PURPOSE: For local ablation of unresectable tumors, computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) is a minimally invasive therapeutic option involving CT-guided catheter placement and high-dose-rate irradiation with iridium-192. Possible complications are related to transcutaneous puncture, retraction of the applicator, and delivery of brachytherapy. To classify CT-HDRBT in comparison with other minimally invasive therapeutic options, it is essential to know the probability of complications and their risk factors. This study therefore aimed at quantifying the occurrence of complications in CT-HDRBT and identifying potential risk factors. MATERIALS AND METHODS: Over a period of more than 10 years from 2006 to 2017, 1877 consecutive CT-HDRBTs were performed at our center and retrospectively analyzed. In 165 cases, CT-HDRBT was combined with transarterial (chemo-) embolization. Information on complications and potential risk factors was retrospectively retrieved from electronic documentation. Statistical analysis of the data was performed. RESULTS: No complications occurred in 85.6% of the interventions. The most common complications were bleeding (5.6%), infection (2.0%), and prolonged pain (1.5%). Summarized diameter (defined as sum of maximum diameters in axial orientation) of treated tumor lesions (odds ratio 1.008; p < 0.001), target lesion site (odds ratio 1.132; p = 0.033), combined treatment (odds ratio 1.233; p = 0.038), and the presence of biliodigestive anastomosis (BDA) (odds ratio 1.824; p = 0.025) were identified as risk factors. CONCLUSIONS: CT-HDRBT is a safe minimally invasive therapeutic option. Summarized diameter of treated tumor lesions, target lesion site, combined treatment, and presence of BDA are risk factors for complications.

Visibility of Hypovascularized Liver Tumors during Intra-Arterial Therapy Using Split-Bolus Single-Phase Cone Beam CT.

PURPOSE: To validate a split-bolus contrast injection protocol for single-phase CBCT in terms of detectability of hypovascular liver tumors compared to digital subtraction angiography (DSA). MATERIALS AND METHODS: In this retrospective, single-center study, 20 consecutive patients with in total 77 hypovascularized tumors referred for intra-arterial therapy received a split-bolus single-phase CBCT. Two readers rated the visibility of the target tumors scheduled for embolization in CBCT and DSA compared to the pre-interventional multiphasic CT or MRI used as reference on a 3-point scoring system (1 = optimal, 3 = not visible) and catheter-associated artifacts (1 = none, 3 = extended). SNR, CNR and contrast values were derived from 37 target tumors in CBCT and MRI. Statistical analysis included the kappa test to determine interrater reliability, the Friedman's test for the inter-modality comparison evaluating tumor visibility in DSA and CBCT as well as for quantitative assessment. Post hoc analysis included the Wilcoxon signed-rank test. p values < 0.05 were considered significant. RESULTS: Ninety percentage of target tumors were rated as visible in CBCT and 37.5% in DSA (p < 0.001). 70.1% of pre-interventionally detected hypovascularized tumors were depicted with CBCT and 31.2% by DSA (p < 0.001). 7.8% of known tumors were outside the FOV. Quantitative assessment showed higher image contrasts in CBCT (1.91 ± 7.01) compared to hepatobiliary-phase MRI (0.29 ± 0.14, p = 0.003) and to portal-venous (p.v.) MRI (0.31 ± 0.13, p < 0.001), but higher CNR for MRI (1.18 ± 0.80; 13.92 ± 15.82; 13.79 ± 6.65). CONCLUSION: In conclusion, the split-bolus single-phase CBCT detects significantly more hypovascularized liver tumors compared to DSA performed through the proper hepatic artery with high image contrasts. LEVEL OF EVIDENCE: Level III, diagnostic study.

Clinical Experience with Real-Time 3-D Guidance Based on C-Arm-Acquired Cone-Beam CT (CBCT) in Transjugular Intrahepatic Portosystemic Stent Shunt (TIPSS) Placement.

PURPOSE: The aim of this study was to evaluate the feasibility of cone-beam computed tomography (CBCT)-based real-time 3-D guidance of TIPSS placement and its positioning compared to standard guiding methods. MATERIALS AND METHODS: In a prospective, randomized, consecutive study design from 2015 to 2017, we included 21 patients in the CBCT guided group and 15 patients in the ultrasound (US) guided group. The prospective groups were compared in terms of success rate of intervention, portal vein puncture/procedure time, number of puncture attempts and applied dose. We furthermore retrospectively analyzed the last 23 consecutive cases with fluoroscopic guided portal vein puncture in terms of success rate, procedure time and applied dose, as it has been the standard method before US guidance. RESULTS: The median number of puncture attempts (CBCT: n = 2, US: n = 4, p = 0.249) and the mean puncture time (CBCT: 32 ± 45 min, US: 36 ± 45 min, p = 0.515) were not significantly different. There were furthermore no significant differences in the mean time needed for the total TIPSS procedure (CBCT: 115 ± 52 min, US: 112 ± 41 min, fluoroscopy: 110 ± 33 min, p = 0.996). The mean applied dose of the complete procedure also showed no statistically significant differences (CBCT: 563 ± 289 Gy·cm2, US: 322 ± 186 Gy·cm2, fluoroscopy: 469 ± 352 Gy·cm2, p = 0.069). There were no image guidance related complications. CONCLUSION: Real-time 3-D needle guidance based on CBCT is feasible for TIPSS placement. In terms of puncture attempts, duration and dose, CBCT guidance was not inferior to the control groups and may be a valuable support for interventionists in TIPSS procedures.

C-Arm Cone Beam CT for Intraprocedural Image Fusion and 3D Guidance in Portal Vein Embolization (PVE).

PURPOSE: Portal vein embolization (PVE) is applied in patients with extended oncologic liver disease to induce hyperplasia of the future liver remnant and make resection feasible. Ultrasound (US) guidance is the gold standard for percutaneous portal vein access. This study evaluated feasibility and safety of C-arm cone beam computed tomography (CBCT) for needle guidance. MATERIALS AND METHODS: In 10 patients, puncture was performed under 3D needle guidance in a CBCT data set. Contrast-enhanced (CE) CBCT was generated (n = 7), or native CBCT was registered to pre-examination CE-CT via image fusion (n = 3). Technical success, number of punctures, puncture time (time between CBCT acquisition and successful portal vein access), dose parameters and safety were evaluated. For comparison, 10 patients with PVE under US guidance were analyzed retrospectively. Study and control group were matched for age, BMI, INR, platelets, portal vein anatomy. RESULTS: All interventions were technically successful without intervention-related complications. In the study group, the mean number of puncture attempts was 3.1 ± 2.5. Mean puncture time was 12 min (±10). Mean total dose area product (DAP) was 288 Gy cm2 (±154). The mean relative share of CBCT-related radiation exposure was 6% (±3). Intervention times and DAP were slightly higher compared to the control group without reaching significance. CONCLUSION: CBCT-guided PVE is feasible and safe. The relative dose of CBCT is low compared to the overall dose of the intervention. This technique may be a promising approach for difficult anatomic situations that limit the use of US for needle guidance.

TNF Signaling in Peritoneal Mesothelial Cells: Pivotal Role of cFLIPL.

♦ BACKGROUND: Peritoneal dialysis (PD) coincides with high concentrations of proinflammatory cytokines, such as tumor necrosis factor (TNF), in the peritoneal cavity. During treatment, chronic inflammatory processes lead to damage of the peritoneal membrane and a subsequent ultrafiltration failure. Human peritoneal mesothelial cells (HPMCs) play a central role as mediators and targets of PD-related inflammatory changes. Although TNF Receptor 1 (TNFR1) is expressed in high numbers on the cells, TNF-induced apoptosis is inhibited. Here, the underlying molecular mechanisms of TNFR1 signaling in HPMCs are investigated. ♦ METHODS: Human peritoneal mesothelial cells were isolated from the omentum of healthy donors and the dialysis solution of PD patients. Flow cytometry was applied to determine cell surface expression of TNFR1 on HPMCS from healthy donors in absence or presence of TNF or PD fluid (PDF) and were compared to TNFR1 expression on cells from PD patients. To investigate TNFR1-mediated signaling, HPMCs were treated with PDF or TNF, and expression patterns of proteins involved in the TNFR1 signaling pathway were assessed by western blot. ♦ RESULTS: Incubation with PDF led to a significant up-regulation of TNFR1 on the cell surface correlating with elevated TNFR1 numbers on HPMCs from PD patients. Investigations of underlying molecular mechanisms of TNFR1 signaling showed that PDF affects TNFR1 signaling at the proapoptotic signaling pathway by upregulation of IκBα and downregulation of cFLIPL. In contrast, TNF exclusively induces the activation of NFκB by an increase of phosphorylated IκBα. ♦ CONCLUSIONS: Novel and relevant insights into the mechanisms of TNFR1-mediated signaling in HPMCs with an impact on our understanding of PD-associated damage of the peritoneal membrane are shown.