Effective hematopoietic stem cell-based gene therapy in a murine model of hereditary pulmonary alveolar proteinosis.

Hereditary pulmonary alveolar proteinosis due to GM-CSF receptor deficiency (herPAP) constitutes a life-threatening lung disease characterized by alveolar deposition of surfactant protein secondary to defective alveolar macrophage function. As current therapeutic options are primarily symptomatic, we have explored the potential of hematopoietic stem cell-based gene therapy. Using Csf2rb-/- mice, a model closely reflecting the human herPAP disease phenotype, we here demonstrate robust pulmonary engraftment of an alveolar macrophage population following intravenous transplantation of lentivirally corrected hematopoietic stem and progenitor cells. Engraftment was associated with marked improvement of critical herPAP disease parameters, including bronchoalveolar fluid protein, cholesterol and cytokine levels, pulmonary density on computed tomography scans, pulmonary deposition of Periodic Acid-Schiff+ material as well as respiratory mechanics. These effects were stable for at least nine months. With respect to engraftment and alveolar macrophage differentiation kinetics, we demonstrate the rapid development of CD11c+/SiglecF+ cells in the lungs from a CD11c-/SiglecF+ progenitor population within four weeks after transplantation. Based on these data, we suggest hematopoietic stem cell-based gene therapy as an effective and cause-directed treatment approach for herPAP.

Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Nutrition- and life style-associated risk factors are increasingly prevalent. Metformin, the mainstay of type 2 diabetes mellitus (T2DM)-treatment, reduces the risk of hepatocarcinogenesis. However, its influence on the prognosis of patients with HCC has not been investigated on a large scale, yet. METHODS: Five thousand and ninety-three patients treated for HCC between 2000 and 2016 at three referral centres were included in this retrospective multicentre study. The aim of this study was to assess whether treatment with metformin for T2DM is associated with a prolonged overall survival (OS) in patients diagnosed with HCC. RESULTS: Among 5093 patients with HCC, 1917 patients (37.6%) were diagnosed with T2DM, of which 338 (17.6%) received treatment with metformin. Compared to diabetic patients not treated with metformin, patients on metformin had a significantly better hepatic function (Child-Pugh-Score A: 69.2% vs 47.4%, P < 0.001) and underwent significantly more often tumour resection (22.1% vs 16.5%, P = 0.024). Patients on metformin had a significantly longer median OS (mOS) compared to diabetic patients not treated with metformin (22 vs 15 months, P = 0.019). The prolongation of survival was most significant in patients treated with surgery. Using a propensity score match (PSM), patients were adjusted for hepatic function and initial therapy. In the matched cohorts, mOS remained significantly longer in metformin-treated patients (22 vs 16 months, P = 0.021). Co-treatment of metformin and sorafenib was associated with a survival disadvantage. CONCLUSION: Treatment with metformin was associated with an improved survival in patients with T2DM and HCC. This effect was most pronounced in patients at potentially curative tumour stages.

Retrograde portal vein flow and transarterial chemoembolization in patients with hepatocellular carcinoma - a case-control study.

BACKGROUND AND AIMS: Transarterial chemoembolization (TACE) is the most common treatment for hepatocellular carcinoma (HCC). In case of portal vein (PV) flow diversion, outcome may be compromised due to a decompensation of hepatic perfusion following arterial embolization. The aim of this study was to determine whether TACE in patients with retrograde PV flow results in a stronger deterioration of liver function and a poorer survival compared to patients with orthograde PV flow. METHODS: A database of 606 patients treated with TACE between 2000 and 2015 at Hannover Medical School was screened for Doppler ultrasound (US) findings on PV flow prior to TACE. A total of 407 patients were identified, among which 32 patients had retrograde PV flow. RESULTS: Patients with retrograde PV flow had significantly more often liver cirrhosis with advanced hepatic dysfunction (93.5% vs. 72.7%, p < .05). Median overall survival (OS) was 12 and 19 months in patients with retro- and orthograde PV flow, respectively (HR 1.27, p > .05). Patients with retrograde PV flow showed a trend for a shorter OS when matched for cirrhosis (12 vs. 21months, HR 1.51), Child-Pugh score/albumin-bilirubin grade (12 vs. 15 months). There was no difference in the deterioration of liver function after repeated treatments between both groups as assessed by increase of CP points and ALBI grade. CONCLUSIONS: Retrograde PV flow alone was not a significant prognostic marker, but patients with retrograde PV flow and advanced liver cirrhosis treated with TACE had a very short survival. Assessment of PV flow prior TACE may be helpful in borderline cases considered for TACE.

Experience from a real-life cohort: outcome of 606 patients with hepatocellular carcinoma following transarterial chemoembolization.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Transarterial chemoembolization (TACE) has been accepted as the standard care for intermediate stage disease. METHODS: In this study, we characterized 606 with HCC patients from Hannover Medical School treated with TACE. RESULTS: 606 with HCC patients treated with TACE were identified between 2000 and 2015. Most patients (59.8%) were at intermediate stage. Following TACE, most patients subsequently received systemic therapy or best supportive care (BSC), whereas 227 (37.5%) patients were bridged to potentially curative local treatments. Depending on subsequent therapies, median post-TACE survival ranged from 7 to 162 months. Ascites, cholinesterase, c-reactive and alpha-feto protein and tumor size were identified as prognostic factors. These factors as well as the HAP, mHAP-II and STATE score also determined post-TACE survival independent of subsequent therapies. Hepatic function progressively deteriorated with repeated TACE sessions. Despite that, post-TACE survival was not shortened in frequently treated patients (≥5 times) as compared to patients treated 4 times or less (p = not significant [n.s.]). Patients treated ≥5 times with TACE received significantly more often systemic therapy following TACE (37.3%) as compared to patients with 3-4 (30.1%), 2 (27.4%) and 1 (21.8%) sessions (p < .05). CONCLUSION: TACE is performed in a heterogeneous population as bridging therapy to other local treatments and palliative therapy. The long-term survival following TACE is determined by baseline tumor, patient-related factors and by subsequent therapies. Post-TACE survival is not shorter in patients with frequent treatments (≥5), and the rate of subsequent systemic treatments is higher compared to less frequently treated patients.

Patterns and challenges of treatment sequencing in patients with hepatocellular carcinoma: Experience from a German referral center.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers. Several local and systemic therapies are available for patients with HCC depending on the stage of the disease. In clinical practice, treatment decision-making, and sequencing may be very heterogeneous. METHODS: In this study, we retrospectively analyzed treatment algorithms in 2101 patients with HCC treated from 2000 to 2015 at Hannover Medical School, Germany. RESULTS: Transarterial chemoembolization was the most common initial treatment (n = 545; 25.9%), followed by resection (n = 435, 20.7%), local-ablative procedures (n = 283, 13.5%), systemic therapies (n = 275, 13.1%), and liver transplantation (n = 52; 2.5%). Most patients were treated only once (n = 960; 59.6%). A total of 433 (26.9%) and 160 (9.9%) patients received a second line and third line treatment after recurrent or progressive disease. Patients with more than one treatment line were diagnosed at significantly earlier disease stages (P < 0.001). Using binary logistic regression, AFP ≤ 200 µg/L, albumin > 36 g/L, and small tumor size (≤50 mm) were identified as predictors of achieving more than one treatment line. Subsequent treatment stage migration to a therapy suggested for the next advanced stage occurred only in 56.9%, whereas 43.1% received treatments suggested for earlier disease stages. Only 16% of all treated patients received systemic therapy in the salvage setting. CONCLUSION: Most patients were treated only once, and only a minority of patients received systemic treatment. The high dropout rate for subsequent therapies needs to be considered within therapy decision-making. There is an urgent need for prospective studies to define the best time point when to switch patients from local to systemic therapies.

Parametric response mapping of contrast-enhanced biphasic CT for evaluating tumour viability of hepatocellular carcinoma after TACE.

OBJECTIVES: To determine the feasibility and role of parametric response mapping (PRM) for quantitative assessment of regional contrast-enhancement patterns in hepatocellular carcinoma (HCC). METHODS: Biphasic CT of 19 patients receiving repetitive conventional transarterial chemoembolisation (cTACE) for intermediate stage HCC were retrospectively analysed at baseline and follow-up at 3, 6, and 9 months. Voxel-based registration of arterial and porto-venous phases, with segmentation of the largest target lesion was performed. Frequency distribution plots of density-pairs of segmented voxels were generated. To differentiate necrotic, hypervascular and non-hypervascular tumour, and lipiodol/calcification, thresholds of 30, 100, and 300 HU were applied. Changes in density frequency plots over time were analysed and compared to response and assessment criteria (WHO, RECIST, EASL, mRECIST) and survival. RESULTS: PRM was feasible in all cases. Tumour volumes and hypervascular/non-hypervascular volume ratio showed significant longitudinal decrease (p < 0.05). Hypervascular volume at baseline was inversely correlated to survival (R = -0.57, p = 0.005). The only predictive parameter following cTACE to show significant survival difference was the change of the viable/non-viable ratio (p = 0.044), whereas common response assessment criteria showed no significant difference in survival. CONCLUSIONS: PRM allows a quantitative and more precise assessment of regional tumour vascularisation patterns and may be helpful for TACE treatment planning and response assessment. KEY POINTS: • PRM allows more precise assessment of tumour vascularisation compared to conventional evaluation • PRM is beneficial for cTACE treatment planning and response assessment • PRM allows a quantitative assessment of regional contrast enhancement patterns.

Two-Dimensional Perfusion Angiography of the Foot: Technical Considerations and Initial Analysis.

PURPOSE: To report the feasibility, technical considerations, and initial results of 2-dimensional (2D) perfusion angiography of the foot before and after endovascular interventions. METHODS: A retrospective single-center study involved 21 patients (mean age 73.4±10.5 years; 14 men) with severe peripheral vascular disease [Fontaine stage III (n=10) or IV (n=14)] who underwent lower limb digital subtraction angiography (DSA) prior to and following endovascular treatment of above- and/or below-knee lesions. A standardized contrast administration protocol (15 mL iodixanol 320 mg I/mL at 3 mL/s via a 5/6-F antegrade sheath) was applied during DSA using a 2D perfusion-enabled image intensifier. Representative hindfoot and forefoot regions of interest were analyzed, and representative numeric density values [time to peak (TTP), peak density value (PDV), and area under the (time-density) curve (AUC)] were calculated using 2D perfusion-enabled angiographic software to assess foot perfusion. Values were compared before and after angioplasty and by level of treatment (above or below knee). The parameters were correlated with disease severity (stenosis vs occlusion) and symptom level (Fontaine stage). RESULTS: A clinically significant improvement (29.4%) in the AUC was noted following angioplasty, reaching statistical significance within the hindfoot (p=0.03). No significant change in TTP or PDV was detected following angioplasty. Foot movement remained problematic when measuring time-density values. No statistical difference in perfusion values was appreciable between above- and below-knee angioplasty. CONCLUSION: Two-dimensional perfusion angiography of the foot allows quantitative evaluation using various density values with potential benefit for treatment planning and technical outcome analysis. Methodical restrictions currently remain, mainly regarding patient movement.

Transarterial chemoembolization (TACE) for colorectal liver metastases--current status and critical review.

BACKGROUND: Transarterial liver-directed therapies are currently not recommended as a standard treatment for colorectal liver metastases. Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The limited available data potentially reveals TACE as a valuable option for pre- and post-operative downsizing, minimizing time-to-surgery, and prolongation of overall survival after surgery in patients with colorectal liver only metastases. PURPOSE: In this overview, the current status of TACE for the treatment of liver-dominant colorectal liver metastases is presented. Critical comments on its rationale, technical success, complications, toxicity, and side effects as well as oncologic outcomes are discussed. The role of TACE as a valuable adjunct to surgery is addressed regarding pre- and post-operative downsizing, conversion to resectability as well as improvement of the recurrence rate after potentially curative liver resection. Additionally, the concept of TACE for liver-dominant metastatic disease with a focus on new embolization technologies is outlined. CONCLUSIONS: There is encouraging data with regard to technical success, safety, and oncologic efficacy of TACE for colorectal liver metastases. The majority of studies are non-randomized single-center series mostly after failure of systemic therapies in the 2nd line and beyond. Emerging techniques including embolization with calibrated microspheres, with or without additional cytotoxic drugs, degradable starch microspheres, and technical innovations, e.g., cone-beam computed tomography (CT) allow a new highly standardized TACE procedure. The real efficacy of TACE for colorectal liver metastases in a neoadjuvant, adjuvant, and palliative setting has now to be evaluated in prospective randomized controlled trials.

Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Imaging features of primary sarcomas of the great vessels in CT, MRI and PET/CT: a single-center experience.

BACKGROUND: To investigate the imaging features of primary sarcomas of the great vessels in CT, MRI and (18)F-FDG PET/CT. METHODS: Thirteen patients with a primary sarcoma of the great vessels were retrospectively evaluated. All available images studies including F-18 FDG PET(/CT) (n = 4), MDCT (n = 12) and MRI (n = 6) were evaluated and indicative image features of this rare tumor entity were identified. RESULTS: The median interval between the first imaging study and the final diagnosis was 11 weeks (0-12 weeks). The most frequently observed imaging findings suggestive of malignant disease in patients with sarcomas of the pulmonary arteries were a large filling defect with vascular distension, unilaterality and a lack of improvement despite effective anticoagulation. In patients with aortic sarcomas we most frequently observed a pedunculated appearance and an atypical location of the filling defect. The F-18 FDG PET(/CT) examinations demonstrated an unequivocal hypermetabolism of the lesion in all cases (4/4). MRI proved lesion vascularization in 5/6 cases. CONCLUSION: Intravascular unilateral or atypically located filling defects of the great vessels with vascular distension, a pedunculated shape and lack of improvement despite effective anticoagulation are suspicious for primary sarcoma on MDCT or MRI. MR perfusion techniques can add information on the nature of the lesion but the findings may be subtle and equivocal. F-18 FDG PET/CT may have a potential role in these patients and may be considered as part of the imaging workup.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

Phantom and cadaver measurements of dose and dose distribution in micro-CT of the chest in mice.

BACKGROUND: Micro-computed tomography (CT) allows high-resolution imaging of the chest in mice for small animal research with a significant radiation dose applied. PURPOSE: To report on measurement of the applied radiation dose using different scan protocols in micro-CT of the chest in mice. MATERIAL AND METHODS: Repetitive dose measurements were performed for four different micro-CT protocols (with/without respiratory gating) and for micro-CT fluoroscopy used for chest imaging. Measurements were carried out using thermoluminescence dosimeters (TLD) in mouse cadavers and in a PMMA phantom allowing measurement of the radiation dose in the direct path of rays and assessment of scattered radiation. RESULTS: The dose measured inside and outside the chests of the cadavers varied between 190 und 210 mGy, respectively. The expected mean doses in mice in the direct path of rays for the four examined micro-CT protocols varied between 170 and 280 mGy. The mean values for 1 and 5 minutes of fluoroscopy were 17 mGy and 105 mGy, respectively. CONCLUSION: The measured dose values are similar to the dose values for micro-CT of the chest reported so far. A relevant dose can be delivered by micro-CT of the chest, which could possibly interact with small animal studies. Therefore, the applied dose for a specific protocol should be known and adverse radiation effects be considered.

CIRSE Standards of Practice on Below-the-Knee Revascularisation.

The CIRSE Standards of Practice Committee established a writing group that was tasked with producing up-to-date recommendations for performing below-the-knee revascularisation, taking into account data on novel techniques, devices, and long-term outcomes that have emerged over the last decade. CIRSE Standards of Practice documents are not clinical practice guidelines or systematic reviews of the literature. This document is not intended to impose a standard of clinical patient care but recommends a reasonable approach to and best practices for performing below-the-knee revascularisation.

Modeling the Optimal Transportation for Acute Stroke Treatment : Impact of Diurnal Variations in Traffic Rate.

PURPOSE: Prolonged transfer times between the primary stroke center (PSC) and the comprehensive stroke center (CSC) are one of the major causes of treatment delay for endovascular stroke treatment. We aimed to analyze the effect of the diurnal variations in traffic rates at weekdays and weekends on the catchment area size of three transportation paradigms, i.e. mothership, drip-and-ship (DS) and drip-and-drive (DD). METHODS: A conditional probability model that predicts the probability of good outcome for patients with suspected large vessel occlusion was used to analyze the prehospital stroke triage in northwest Germany and produce catchment area maps. Transportation times were calculated during each hour of a weekday and a Sunday using Google Maps. For comparison, real DD transportation times from our CSC in Hamburg-Eppendorf (blinded for review) to a PSC in Lüneburg were prospectively recorded. RESULT: On weekdays, the mothership catchment area was the largest (≥40,000 km2, 63%) except for a decrease during morning rush hours, when the DD catchment area was highest (30,879 km2, 48%). The DS catchment area was higher than the DD catchment area during the afternoon rush hours both during the week as well as on Sundays. CONCLUSION: Our study showed a considerable impact of the diurnal variations in traffic rate and direction of travel on optimal stroke transportation. Stroke systems of care should take real time traffic information into account.

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-ß1.

BACKGROUND: Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. METHODS: Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. RESULTS: We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. CONCLUSIONS: Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

Transarterial chemoembolization for hepatocellular carcinoma: quality of life, tumour response, safety and survival comparing two types of drug-eluting beads.

PURPOSE: To compare two different types of drug-eluting microspheres with regard to impact on HRQoL after first TACE, tumour response, peri-procedural complications, adverse events and 1-year survival in patients suffering from unresectable hepatocellular carcinoma (HCC). METHODS: HRQoL was prospectively assessed with validated questionnaires (EORTC QLQ-C30 and -HCC18) before and 2 weeks after treatment with their first drug-eluting beads (DEB-)TACE with either acrylamido-polyvinylalcohol-AMPS hydrogel microspheres (groupDCB; 20 patients) or polyvinyl alcohol-co-acrylic acid microspheres (groupHS; 16 patients). Baseline characteristics, peri-procedural complications, treatment-related adverse events and 1-year survival were compared between both types of microspheres. Treatment response and objective response rates (ORR) were analysed using established tumour response criteria. Subgroup analysis for pooled groups with small (groupSMALL; 21 patients) versus large particles (groupLARGE; 15 patients) was performed. RESULTS: At baseline, there were no significant differences between the treated microsphere groups. No significant differences were found in absolute HRQoL changes after first DEB-TACE between the different types of microspheres. Response rates and survival were comparable between the investigated microsphere groups. For groupSMALL, we found a significant difference in post-interventional deterioration of physical function (- 19.4%) compared to groupLARGE (- 8%; p = 0.025). Tumour response and ORR according to mRECIST were significantly higher in groupSMALL (p = 0.008; p = 0.009). CONCLUSION: DEB-TACE is generally well tolerated and effective, with comparable changes in HRQoL for both types of drug-eluting microspheres. Tumour response is better with small microspheres. A relevant deterioration of physical function underlines that an aggressive TACE using small beads should be well deliberated.

Correlation between SACE (Subjective Angiographic Chemoembolization Endpoint) score and tumor response and its impact on survival after DEB-TACE in patients with hepatocellular carcinoma.

PURPOSE: To asses angiographic and computed tomographic success criteria during and after transcatheter arterial drug-eluting bead chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC) and its impact on progression-free survival (PFS) and overall survival (OS). METHODS: In this retrospective single-center study, 50 patients with unresectable HCC having undergone DEB-TACE from January 2010 to July 2015 were assessed. The angiographic endpoint was classified by Subjective Angiographic Chemoembolization Endpoint (SACE) scale. Relative tumor density in arterial (DArt) and portal venous phase (DPV) computed tomography post- versus pre-DEB-TACE were calculated, respectively. Tumor response according to modified Response Criteria in Solid Tumors (mRECIST) was assessed. Univariate Kaplan-Meier and Cox regression analysis were carried out. RESULTS: SACE scores I, II, III, and IV were found in 1 (2%), 20 (40%), 15 (30%), and 14 (28%) patients, respectively. Median OS and PFS were 14.2 and 5.5 months, respectively. Death rates at 6 months, 1 year and 2 years were 24%, 38%, and 52%, respectively. SACE score during DEB-TACE significantly correlated with local and overall mRECIST results (local: p < 0.001, r = 0.49, overall: p = 0.042, r = 0.29) and inversely correlated with DPV (p = 0.005, r = - 0.40). In univariate analysis, progressive disease (PD) according to mRECIST and increase of DArt and DPV were associated with significantly shorter PFS. Modified RECIST independently predicted OS (hazard ratio for complete remission vs. PD = 0.15, 95% confidence interval 0.03-0.68, p = 0.014). CONCLUSIONS: A direct impact of SACE on PFS or OS could not be shown. However, SACE significantly correlated with local and overall mRECIST tumor response that again significantly predicted OS. We therefore postulate an indirect impact of SACE on OS. Consequently, complete embolization should be attempted.

Comparison of health-related quality of life after transarterial chemoembolization and transarterial radioembolization in patients with unresectable hepatocellular carcinoma.

PURPOSE: The purpose of this study was to compare quality of life (QoL) after two different transarterial therapies [transarterial chemoembolization (TACE) and transarterial radioembolization (TARE)] for patients with unresectable hepatocellular carcinoma (HCC) to assess tumor therapy in palliative situation additional to traditional aims like survival or image response. MATERIAL AND METHODS: QoL was evaluated with two validated questionnaires (EORTC QLQ-30 and EORTC HCC18) before and 14d after treatment in 94 initial therapies (TACE n = 67; TARE n = 27). QoL changes after treatment were analyzed. Tumor response was evaluated using RECIST/WHO/mRECIST/EASL criteria. A multivariate linear regression was undertaken to identify potential influence factors on change of QoL. RESULTS: Mean return rate of questionnaires was 71.3% allowing analysis of 67 therapies (TACE n = 46; TARE n = 21). Initial global health status/QoL was significantly higher in TACE (62.5%) compared to TARE with 50.8%. Absolute global health decrease was higher in TACE (- 10.5%) compared to TARE (- 4.8%, p = 0.396). Also relative global health decrease was higher in TACE (- 16.82%) compared to TARE (- 9.37%). Findings for other items were corresponding, as less impairment was found for TARE compared to TACE for physical/social functioning, fatigue and pain. Objective mRECIST response rate was 22.8% in TACE and 21.1% in TARE. CONCLUSION: Neither TACE nor TARE showed a major decrease in QoL after first treatment. TACE showed a slightly but not significantly higher decrease, so this study is not clearly in favor for one treatment. But with the addition that TARE showed less decrease even in patients with higher tumor burden and lower baseline.

Shear wave elastography prior to transjugular intrahepatic portosystemic shunt may predict the decrease in hepatic vein pressure gradient.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to treat portal hypertension complications. Our aim was to evaluate liver and spleen stiffness measurement (LSM and SSM, respectively) changes using acoustic radiation force impulse imaging (ARFI) in comparison to Child-Pugh scores for predicting hepatic venous pressure gradient (HVPG) decreases after TIPS implantation. METHODS: This prospective study included 31 consecutive clinically significant portal hypertension patients with TIPS indication. All patients received LSM and SSM before TIPS, at baseline, 2 days (follow-up 1) and 6 weeks (follow-up 2) post-implantation. HVPG was performed during the TIPS procedure. RESULTS: The mean decrease in HVPG after TIPS was 63%. LSM and SSM decreased significantly between baseline and follow-up 2 (p < 0.001 and p < 0.001, respectively). At baseline, follow-up 1 and follow-up 2, significant correlations were detected between mean SSM and mean HVPG (p = 0.026; p = 0.018; p = 0.002, respectively). HVPG decreased to ≤ 10 mmHg in 61% of patients for which LSM, SSM, and Child-Pugh score were predictors (p = 0.033, p = 0.002 and p = 0.030, respectively). The area under the curve (AUC) for LSM, SSM, and Child-Pugh was 0.88, 0.90, and 0.84, respectively, with close sensitivity and specificity. SSM had the highest diagnostic accuracy for predicting an HVPG decrease to ≤ 10 mmHg in comparison to LSM and Child-Pugh score. CONCLUSION: Spleen stiffness is superior to liver stiffness and Child-Pugh score as a non-invasive surveillance tool for evaluating patients with clinically significant portal hypertension (HVPG ≥ 10 mmHg) prior to TIPS.