Efficacy and Safety of Local Liver Radioablation in Hepatocellular Carcinoma Lesions within and beyond Limits of Thermal Ablation.

INTRODUCTION: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking. MATERIALS AND METHODS: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses. RESULTS: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS. CONCLUSION: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Clinical benefits of MRI-guided freehand biopsy of small focal liver lesions in comparison to CT guidance.

OBJECTIVES: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. METHODS: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. RESULTS: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). CONCLUSION: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. CLINICAL RELEVANCE STATEMENT: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. KEY POINTS: • Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. • MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. • Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.

Percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage: Technical and clinical outcomes.

The purpose of this study is to evaluate the technical and clinical outcome of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage. All patients who underwent ultrasound-assisted PTBD between January 2017 and December 2021 due to biliary leakage with nondilated biliary systems were retrospectively evaluated for periprocedural characteristics, medical indications, technical success (successful placement of drainage catheter), clinical success (resolved leak without additional procedures), fluoroscopy time, procedure duration, and clinical outcomes. 74 patients with a mean age of 64.1 ± 15.1 years were identified. Surgery was the most common etiology of biliary leak with 93.2% of the cases. PTBD had a 91.8% (68/74) technical success rate and an 80.8% clinical success rate. The mean procedure and fluoroscopy duration were 43.5 and 18.6 minutes. Age > 65 years (P = .027) and left-sided drainage (P = .034) were significant risk factors of clinical failure. Procedure-related major complications were 2 bleedings from the liver and 1 bleeding from an intercostal artery (major complication rate 4%). PTBD is a feasible, safe, and effective treatment option in patients with biliary leakage with low complication rates.

Image-Guided Embolotherapy of Arteriovenous Malformations of the Face.

PURPOSE: To evaluate the safety and outcome of image-guided embolotherapy of extracranial arteriovenous malformations (AVMs) primarily affecting the face. MATERIALS AND METHODS: A multicenter cohort of 28 patients presenting with AVMs primarily affecting the face was retrospectively investigated. Fifty image-guided embolotherapies were performed, mostly using ethylene-vinyl alcohol copolymer-based embolic agents. Clinical and imaging findings were assessed to evaluate response during follow-up (symptom-free, partial relief of symptoms, no improvement, and progression despite embolization), lesion devascularization (total, 100%; substantial, 76-99%; partial, 51-75%; failure, < 50%; and progression), and complication rates (classified according to the CIRSE guidelines). Sub-analyses regarding clinical outcome (n = 24) were performed comparing patients with (n = 12) or without (n = 12) subsequent surgical resection after embolotherapy. RESULTS: The median number of embolotherapy sessions was 2.0 (range, 1-4). Clinical outcome after a mean follow-up of 12.4 months (± 13.3; n = 24) revealed a therapy response in 21/24 patients (87.5%). Imaging showed total devascularization in 14/24 patients (58.3%), including the 12 patients with subsequent surgery and 2 additional patients with embolotherapy only. Substantial devascularization (76-99%) was assessed in 7/24 patients (29.2%), and partial devascularization (51-75%) in 3/24 patients (12.5%). Complications occurred during/after 12/50 procedures (24.0%), including 18.0% major complications. Patients with subsequent surgical resections were more often symptom-free at the last follow-up compared to the group having undergone embolotherapy only (p = 0.006). CONCLUSION: Image-guided embolotherapy is safe and effective for treating extracranial AVMs of the face. Subsequent surgical resections after embolization may substantially improve patients' clinical outcome, emphasizing the need for multimodal therapeutic concepts. LEVEL OF EVIDENCE: Level 4, Retrospective study.

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.

Stent-graft placement for hepatic arterial bleeding: assessment of technical efficacy and clinical outcome in a tertiary care center.

BACKGROUND: To evaluate technical and clinical results of stent-graft (SG) placement for bleeding from the hepatic artery (HA). METHODS: All patients intended and treated with SG deployment for bleeding from the HA at single center from January 2012 to May 2020 were retrospectively identified, and procedural details, risk factors for rebleeding, SG occlusion and mortality were analyzed. RESULTS: Twenty-seven patients (mean age 68.8 ± 10.1) were identified, and 25 patients underwent 26 SG procedures. Twenty-four patients had recent surgery. The technical success rate was 92.8%. Three patients (3/25) had rebleeding (88% clinical success). Intensive-care need before the procedure (p = 0.013) and smaller stent-graft size (≤4 mm, p = 0.032) were related to clinical failure. Twenty-two patients had follow-up imaging. The SG maintained patency in 10 (45.4%) patients at the most recent imaging. Only placement of SG distal to the HA bifurcation (p = 0.012) was related to occlusion. The 30-day and in-hospital mortality rate after SG was 8% and 24%. In-hospital mortality was associated with the intraabdominal septic source (p = 0.010) and revision surgery (p = 0.001). CONCLUSION: Stent-grafts are effective in the emergent treatment of HA bleeding. Mortality is mainly related to the general condition of the patient, and stent-grafts offer time to treat underlying medical problems sufficiently.

iRESCUE - Interventional embolization of Renal artEries after SurgiCal or traUmatic injury with hEmorrhage.

OBJECTIVES: To evaluate the efficacy and safety of urgent percutaneous embolization for the treatment of acute renal hemorrhage. MATERIALS AND METHODS: All patients undergoing endovascular embolization at our hospital for bleeding from renal artery branches between January 2010 and June 2020 were retrospectively evaluated. Periprocedural characteristics, technical details, clinical outcomes, and complications were documented. RESULTS: Seventy-six patients with a mean age of 67.3 ± 12.9 underwent 86 procedures. The most common cause of hemorrhage was iatrogenic (63/76), including 44 patients presenting after partial nephrectomy. Bleeding was successfully controlled in 80 of 86 procedures (92.8 % technical success), and clinical success (defined as control of bleeding with endovascular embolization) was achieved in 72 of 76 patients (94.5 %) with embolization, including seven patients undergoing re-intervention. In univariate analysis, risk factors for clinical failure were antiplatelet agents (p = 0.033), and technical failure (p < 0.001); and technical failure was the only significant risk factor in multivariate analysis. Only one patient (1.3 %) needed nephrectomy. AKI was seen after 16 (21 %) procedures, and preprocedural increased creatinine (≧1.8) and decreased GFR (<60) were risk factors for AKI (p = 0.022 and p = 0.020). In all patients except one, renal functions returned to baseline. One patient died because of pulmonary embolism (in-hospital mortality 1.3 %). CONCLUSION: Interventional embolization is feasible, safe, and effective in the treatment of renal hemorrhages. Among others, the complication management with minimally invasive procedures allows urologists to safely perform partial nephrectomy even in patients with central, large, and endophytic tumors, thereby preserving kidney function in these patients.

Advanced Fusion Imaging and Contrast-Enhanced Imaging (CT/MRI-CEUS) in Oncology.

Fusion imaging depicts an innovative technique that facilitates combining assets and reducing restrictions of advanced ultrasound and cross-sectional imaging. The purpose of the present retrospective study was to evaluate the role of fusion imaging for assessing hepatic and renal lesions. Between 02/2011-08/2020, 92 patients in total were included in the study, of which 32 patients had hepatic lesions, 60 patients had renal lesions. Fusion imaging was technically successful in all patients. No adverse side effects upon intravenous (i.v.) application of SonoVue® (Bracco, Milan, Italy) were registered. Fusion imaging could clarify all 11 (100%) initially as indeterminate described hepatic lesions by computed tomography/magnetic resonance imaging (CT/MRI). Moreover, 5/14 (36%) initially suspicious hepatic lesions could be validated by fusion imaging, whereas in 8/14 (57%), malignant morphology was disproved. Moreover, fusion imaging allowed for the clarification of 29/30 (97%) renal lesions initially characterized as suspicious by CT/MRI, of which 19/30 (63%) underwent renal surgery, histopathology revealed malignancy in 16/19 (84%), and benignity in 3/19 (16%). Indeterminate findings could be elucidated by fusion imaging in 20/20 (100%) renal lesions. Its accessibility and repeatability, even during pregnancy and in childhood, its cost-effectiveness, and its excellent safety profile, make fusion imaging a promising instrument for the thorough evaluation of hepatic and renal lesions in the future.

Neutrophils promote venular thrombosis by shaping the rheological environment for platelet aggregation.

In advanced inflammatory disease, microvascular thrombosis leads to the interruption of blood supply and provokes ischemic tissue injury. Recently, intravascularly adherent leukocytes have been reported to shape the blood flow in their immediate vascular environment. Whether these rheological effects are relevant for microvascular thrombogenesis remains elusive. Employing multi-channel in vivo microscopy, analyses in microfluidic devices, and computational modeling, we identified a previously unanticipated role of leukocytes for microvascular clot formation in inflamed tissue. For this purpose, neutrophils adhere at distinct sites in the microvasculature where these immune cells effectively promote thrombosis by shaping the rheological environment for platelet aggregation. In contrast to larger (lower-shear) vessels, this process in high-shear microvessels does not require fibrin generation or extracellular trap formation, but involves GPIbα-vWF and CD40-CD40L-dependent platelet interactions. Conversely, interference with these cellular interactions substantially compromises microvascular clotting. Thus, leukocytes shape the rheological environment in the inflamed venular microvasculature for platelet aggregation thereby effectively promoting the formation of blood clots. Targeting this specific crosstalk between the immune system and the hemostatic system might be instrumental for the prevention and treatment of microvascular thromboembolic pathologies, which are inaccessible to invasive revascularization strategies.

The added diagnostic value of complementary gadoxetic acid-enhanced MRI to 18F-DOPA-PET/CT for liver staging in medullary thyroid carcinoma.

BACKGROUND: A high proportion of patients with advanced stages of medullary thyroid carcinoma (MTC) present with liver metastasis metastases. The aim of our study was to investigate the added diagnostic value of complementary gadoxetic acid-enhanced MRI to 18F-DOPA-PET/CT for liver staging in MTC. METHODS: Thirty-six patients (14 female, median age 55 years) with histologically confirmed MTC undergoing gadoxetic acid-enhanced liver MRI within 1 month of matching contrast-enhanced 18F-DOPA-PET/CT between 2010 and 2016 were selected for this IRB-approved retrospective study. 18F-DOPA-PET/CT and multiparametric MRI data sets were read consecutively and liver lesions were categorised on a 5-point Likert scale (1-definitely benign; 2-probably benign; 3-intermediate risk for metastasis; 4-probably metastasis; 5-definitely metastasis). It was noted if gadoxetic acid-enhanced MRI detected additional, 18F-DOPA-PET/CT-occult metastases (category 5) or if gadoxetic acid-enhanced MRI allowed for a definite classification (categories 1 and 5) of lesions for which 18F-DOPA-PET/CT remained inconclusive (categories 2-4). Follow-up PET/CT and MRI examinations were used as a reference standard. RESULTS: A total of 207 liver lesions (18F-DOPA-PET/CT 149, MRI 207; 152 metastases, 37 benign cysts, 18 hemangiomas) were analysed. Fifty-eight additional lesions were detected by MRI, of which 54 were metastases (median diameter 0.5 cm [interquartile range 0.4-0.7 cm]) occult on 18F-DOPA-PET/CT. MRI allowed for a definite lesion classification (categories 1 and 5) in 92% (190/207) whereas 18F-DOPA-PET/CT allowed for a definite lesion classification in 76% (113/149). MRI lead to a change in lesion categorisation in 14% (21/149). CONCLUSION: Gadoxetic acid-enhanced MRI allows for a more precise liver staging in MTC patients compared to 18F-DOPA-PET/CT alone, particularly for 18F-DOPA-negative metastases and lesions < 1 cm.

Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke.

Background and Purpose- Large vessel occlusion stroke leads to highly variable hyperacute infarction growth. Our aim was to identify clinical and imaging parameters associated with hyperacute infarction growth in patients with an large vessel occlusion stroke of the anterior circulation. Methods- Seven hundred twenty-two consecutive patients with acute stroke were prospectively included in our monocentric stroke registry between 2009 and 2017. We selected all patients with a large vessel occlusion stroke of the anterior circulation, documented times from symptom onset, and CT perfusion on admission for our analysis (N=178). Ischemic core volume was determined with CT perfusion using automated thresholds. Hyperacute infarction growth was defined as ischemic core volume divided by times from symptom onset, assuming linear progression during times from symptom onset to imaging on admission. For collateral assessment, the regional leptomeningeal collateral score (rLMC) was used. Clinical data included the National Institutes of Health Stroke Scale score on admission and cardiovascular risk factors. Regression analysis was performed to adjust for confounders. Results- Median ischemic core volume was 34.4 mL, and median hyperacute infarction growth was 0.27 mL/min. In regression analysis including age, sex, National Institutes of Health Stroke Scale, clot burden score, diabetes mellitus, smoking, hypercholesteremia, hypertension, Alberta Stroke Program Early CT Score, and rLMC scores, only the rLMC score had a significant, independent association with hyperacute infarction growth (adjusted ß=-0.35; P<0.001). Trichotomizing patients by rLMC scores yielded 65 patients with good (rLMC >15), 67 with intermediate (rLMC 11-15) and 46 with poor collaterals (rLMC <11) with an infarction growth of 0.17 mL/min, 0.26 mL/min, and 0.41 mL/min, respectively. Conclusions- Hyperacute infarction growth strongly depends on collaterals. In primary stroke centers, hyperacute infarction growth may be extrapolated to estimate the stroke progression during transfer times to thrombectomy centers and to support decisions on which patients to transfer.

Platelets Guide Leukocytes to Their Sites of Extravasation.

Effective immune responses require the directed migration of leukocytes from the vasculature to the site of injury or infection. How immune cells "find" their site of extravasation remains largely obscure. Here, we identified a previously unrecognized role of platelets as pathfinders guiding leukocytes to their exit points in the microvasculature: upon onset of inflammation, circulating platelets were found to immediately adhere at distinct sites in venular microvessels enabling these cellular blood components to capture neutrophils and, in turn, inflammatory monocytes via CD40-CD40L-dependent interactions. In this cellular crosstalk, ligation of PSGL-1 by P-selectin leads to ERK1/2 MAPK-dependent conformational changes of leukocyte integrins, which promote the successive extravasation of neutrophils and monocytes to the perivascular tissue. Conversely, blockade of this cellular partnership resulted in misguided, inefficient leukocyte responses. Our experimental data uncover a platelet-directed, spatiotemporally organized, multicellular crosstalk that is essential for effective trafficking of leukocytes to the site of inflammation.