Transarterial Chemoebolization in Hepatocellular Carcinoma: A Binational Japanese-German Study.

Objective: The purpose of this study was to investigate outcomes of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) comparing the different approaches used in Germany and Japan. Methods: This binational IRB-approved retrospective dual-center study included a total of 94 HCC patients subdivided in a German and a Japanese cohort. For each patient, liver and tumor volumetry was performed using computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, a comprehensive risk profile, including body constitution and liver and kidney function was established. Primary endpoints were progression-free and overall survival (PFS/OS). Results: PFS in the German cohort was 168 vs 224d in the Japanese cohort (p=0.640). When subdivided by BCLC stage, no significant differences were reported (p=0.160-0.429). OS was significantly longer in the Japanese cohort with 856 vs. 303d (p<0.001). OS for BCLC A was significantly longer in the Japanese cohort (1960 vs. 428d; p<0.001), while survival rates did not differ significantly in BCLC B (785 vs 330d; p=0.067) and C-stages (208 vs 302d; p=0.186). Older age (p=0.034), poorer liver/kidney function (p=0.025-0-035), and a higher liver/tumor ratio (p<0.001) were found to correlate with shorter survival. ECOG scores were significantly higher in the German cohort (p=0.002). Conclusion: While OS is longer in TACE-treated patients in the Japanese cohort compared to the German cohort, the two approaches seem to be equally effective as PFS does not differ significantly. The different survival rates may be caused by the different clinical performance status of the selected collectives. In very early and early stage HCC, TACE in Japan seems to be an effective treatment option while in Germany for patients in those stages TACE remains a second-line option for patients not available for surgery or ablation.

Real-time CEUS-guided biopsy revealing a littoral cell angioma of the spleen after inconclusive CT and MRI findings.

The aim of this case report is to present real-time CEUS-guided biopsy for diagnosing rare benign splenic pathologies after inconclusive findings on cross-sectional imaging. We present the case of a 50-year-old male patient who received a contrast-enhanced computed tomography scan of the thorax during the evaluation for lung transplant due to lung fibrosis, with incidental finding of disseminated hypodense splenic lesions. During follow-up imaging, the patient did not tolerate a complete MRI examination, and two acquired pulse sequences did not confirm the final diagnosis. While CT-guided biopsy revealed no results, CEUS-guided target biopsy with repeated contrast injections showed a benign littoral cell angioma of the spleen. The use of real-time CEUS-guided target biopsy during lesion washout may be a useful tool to improve the accuracy of biopsy and accelerate the diagnosis in patients with parenchymal lesions after inconclusive cross-sectional imaging findings which may pose a challenge for CT-guided biopsy.

Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. METHODS: Two groups of patients (97 AAA and 100 controls), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. RESULTS: SRC (74% vs. 57%; p<0.016) and CKD (30% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. CONCLUSIONS: Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

Comorbidities Associated with Large Abdominal Aortic Aneurysms.

BACKGROUND: Abdominal aortic aneurysm has become increasingly important owing to demographic changes. Some other diseases, for example, cholecystolithiasis, chronic obstructive pulmonary disease, and hernias, seem to co-occur with abdominal aortic aneurysm. The aim of this retrospective analysis was to identify new comorbidities associated with abdominal aortic aneurysm. METHODS: We compared 100 patients with abdominal aortic aneurysms and 100 control patients. Their preoperative computed tomographic scans were examined by two investigators independently, for the presence of hernias, diverticulosis, and cholecystolithiasis. Medical records were also reviewed. Statistical analysis was performed using univariate analysis and multiple logistic regression analysis. RESULTS: The aneurysm group had a higher frequency of diverticulosis (p = 0.008). There was no significant difference in the occurrence of hernia (p = 0.073) or cholecystolithiasis (p = 1.00). Aneurysm patients had a significantly higher American Society of Anesthesiology score (2.84 vs. 2.63; p = 0.015) and were more likely to have coronary artery disease (p < 0.001), congestive heart failure (p < 0.001), or chronic obstructive pulmonary disease (p < 0.001). Aneurysm patients were more likely to be former (p = 0.034) or current (p = 0.006) smokers and had a significantly higher number of pack years (p < 0.001). Aneurysm patients also had a significantly poorer lung function. In multivariate analysis, the following factors were associated with aneurysms: chronic obstructive pulmonary disease (odds ratio, OR = 12.24; p = 0.002), current smoking (OR = 4.14; p = 0.002), and coronary artery disease (OR = 2.60; p = 0.020). CONCLUSIONS: Our comprehensive analysis identified several comorbidities associated with abdominal aortic aneurysms. These results could help to recognize aneurysms earlier by targeting individuals with these comorbidities for screening.

A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients.

BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability. CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance. TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.

Time-Harmonic Elastography of the Liver is Sensitive to Intrahepatic Pressure Gradient and Liver Decompression after Transjugular Intrahepatic Portosystemic Shunt (TIPS) Implantation.

We investigated the correlation between hepatic venous pressure gradient (HVPG) and liver shear wave speed (SWS) measured by multi-frequency time-harmonic ultrasound elastography (THE) before and after transjugular intrahepatic portosystemic shunt (TIPS) implantation. Ten patients with ascites, cirrhotic liver disease and portal hypertension were prospectively examined with invasive HVPG measurement and THE before and after TIPS implantation. HVPG and SWS decreased after TIPS placement from 20.4 ± 2.2 mmHg to 9.8 ± 4.1 mmHg (mean ± standard deviation) and from 3.87 ± 0.54 m/s to 3.27 ± 0.44 m/s. Mean reduction HVPG was -10.6 ± 3.7 mmHg, p < 0.001; mean reduction SWS was -0.60 ± 0.29 m/s, p < 0.001. A linear correlation was observed between HVPG and SWS (R = 0.59, p = 0.0061). THE-measured SWS is a first potential direct ultrasound marker for liver decompression following TIPS in ascites-associated cirrhotic liver disease and therefore might be suitable to non-invasively detect portal hypertension.

CT-guided corticosteroid injection of the sacroiliac joints: quality assurance and standardized prospective evaluation of long-term effectiveness over six months.

Steroid injection of the sacroiliac joints is widely used for the management of active sacroiliitis in patients with spondyloarthritis (SpA). The aims of this study were to prospectively investigate the effectiveness of corticosteroid injection of the sacroiliac joints and to identify factors determining positive and negative outcome. Twenty-nine patients (18 female, 11 male) suffering from sacroiliitis were treated by computed tomography (CT)-guided administration of 40 or 60 mg triamcinolone acetonide per joint. Clinical outcome of the intervention was determined using a visual analog scale from days 1 to 7 as well as after 1, 3, and 6 months. Patients were grouped according to intra-articular (n = 22) and peri-articular positions (n = 7) of the tip of the puncture needle. In patients with intra-articular needle position (76 %), the mean pain score decreased significantly from 7.3 (±1.9) to 3.9 (±3.4) at day 7 and to 3.9 (±3.4) after 1 month, 4.2 (±3.3) after 3 months, and 5.2 (±2.9) after 6 months. The group with peri-articular needle position (24 %) did not show a statistically significant pain reduction throughout the entire 6-month follow-up period. A substantial reduction of inflammatory back pain (reduction of at least 4 visual analog scale (VAS) points) was reported by 55 % of patients after 3 months and 45 % of patients after 6 months. Our results demonstrate that intra-articular CT-guided steroid instillation can achieve sufficient pain and symptom control for 6 months in patients suffering from active sacroiliitis. It is therefore recommended to perform this intervention under appropriate image guidance to ensure proper positioning of the needle tip.

In vivo abdominal magnetic resonance elastography for the assessment of portal hypertension before and after transjugular intrahepatic portosystemic shunt implantation.

OBJECTIVE: The objective of this study was to investigate the correlation between hepatic venous pressure gradient (HVPG) and in vivo viscoelasticity of the liver and spleen before and after transjugular intrahepatic portosystemic shunt (TIPS) implantation. MATERIALS AND METHODS: Ten patients with portal hypertension were examined twice by 3-dimensional multifrequency magnetic resonance elastography as well as prior and subsequent TIPS intervention; HVPG was also measured during TIPS placement. Five harmonic vibrations (25-60 Hz) were transferred to the abdominal region and recorded for the reconstruction of 2 viscoelastic constants, |G*| and φ, corresponding to the magnitude and the phase angle of the complex shear modulus G* of the liver and spleen. RESULTS: All patients had cirrhosis, yielding high |G*| values in the liver (8.34 ± 2.18 kPa) and spleen (8.44 ± 1.36 kPa). In both organs, a decrease of |G*| after TIPS placement was observed (liver: 8.34 ± 2.18 kPa vs 7.02 ± 1.46 kPa, P = 0.01; spleen: 8.44 ± 1.36 kPa vs 7.06 ± 1.32 kPa, P = 0.01), whereas φ was insensitive to TIPS. Relative changes in |G*| of the spleen were correlated with the relative change of HVPG (R² = 0.659, P = 0.013). CONCLUSIONS: The observed linear correlation between spleen viscoelasticity HVPG raises the prospect of an image-based noninvasive assessment of portal pressure by magnetic resonance elastography in the follow-up of TIPS placements.

Prevention of new osteitis on magnetic resonance imaging in patients with early axial spondyloarthritis during 3 years of continuous treatment with etanercept: data of the ESTHER trial.

OBJECTIVE: The aim of this study was to assess the degree of fluctuation of osteitis on MRI during long-term treatment with etanercept (ETN) in patients with early axial SpA (axSpA) with active inflammation (osteitis) on whole-body MRI in the spine and/or the SI joints at baseline. METHODS: We analysed MRI data from 328 SI joint quadrants and 943 spine vertebral units (VUs) in terms of osteitis in the pooled data set of 41 patients who were treated with ETN for 3 consecutive years. Scoring was performed by two blinded radiologists at baseline, year 2 and year 3. RESULTS: Through years 2 and 3, osteitis on MRI resolved completely in 56 of 144 (38.9%) SI joint quadrants and in 20 of 40 (50%) VUs affected at baseline, while persistent osteitis was found in 24 of 144 (16.7%) SI joint quadrants and in 8 of 40 (20.0%) spine VUs. The development of new osteitis in sites that were free of osteitis at baseline only occurred in 2 of 131 (1.5%) SI joint quadrants and in 3 of 862 (0.4%) spine VUs in both year 2 and year 3. CONCLUSION: There was a consistently small amount of osteitis on MRI in patients with early axSpA compared with baseline values, and only a very low rate of new-onset osteitis was found during 3 years of continuous treatment with ETN. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00844142.

Consistently Good clinical response in patients with early axial spondyloarthritis after 3 years of continuous treatment with etanercept: longterm data of the ESTHER trial.

OBJECTIVE: In patients with early active axial spondyloarthritis (axSpA) with a disease duration of < 5 years, the longterm efficacy of 3 years of continuous etanercept (ETN) treatment was assessed. METHODS: In a previously reported ESTHER trial, patients with axSpA were randomized to treatment with ETN (n = 40) versus sulfasalazine (SSZ; n = 36) in the first year. We analyzed the clinical, laboratory, and magnetic resonance imaging (MRI) response in the pooled dataset of patients (study population; n = 61), including patients with ankylosing spondylitis (AS, n = 31) and nonradiographic axSpA (nr-axSpA, n = 30) who were continuously treated with ETN for 3 consecutive years. Data were analyzed using the last observation carried forward and completer analysis. RESULTS: In the entire group of patients in the study population (n = 61), the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.7 (± 1.3) at baseline to 2.6 (± 2.4) at Year 3. The Ankylosing Spondylitis Disease Activity Score (ASDAS) decreased from 3.4 (± 0.8) to 1.5 (± 1.0). Also, mean values for MRI spine and sacroiliac joint scores showed a significant decrease. Response rates in the nr-axSpA group were similar and at least as good compared to the AS group for all outcome measures. When comparing remission stages, we found that ASDAS inactive disease correlated better with C-reactive protein and MRI remission than with Assessment of SpondyloArthritis international Society partial remission. CONCLUSION: There was a consistent and sustained clinical response in patients with early axSpA treated with ETN over 3 years. ClinicalTrials.gov registration number NCT00844142.

Erosions and fatty lesions of sacroiliac joints in patients with axial spondyloarthritis: evaluation of different MRI techniques and two scoring methods.

OBJECTIVE: Assessment of structural damage of sacroiliac joints (SIJ) in patients with axial spondyloarthritides (axSpA) has been discussed as a useful outcome measure in clinical trials. The aim of our study was to evaluate different magnetic resonance imaging (MRI) scoring methods and pulse sequences with a focus on fatty lesions and bony erosions. METHODS: Seventy-five patients with the diagnosis of axSpA underwent MRI at 3 timepoints as part of the ESTHER trial, which compared 2 groups of patients treated with etanercept or sulfasalazine. Two MRI sequences [unenhanced T1-weighted (T1w) turbo spin-echo (TSE) and unenhanced T1w opposed-phase gradient-echo sequences (opGRE)] and 2 different scoring systems (simple and comprehensive Berlin method) were used for the evaluation of fatty lesions and erosions of the SIJ. Differences between techniques and methods were evaluated by intraclass correlation coefficients (ICC) and standardized response means (SRM). RESULTS: Applying the simple Berlin method, mean fatty lesion scores for etanercept-treated patients were 4.59 and 5.19 at baseline and Week 48, respectively, while the comprehensive Berlin method revealed mean fatty lesion scores of 6.59 and 7.64, respectively. Corresponding SRM were 0.59 and 0.86 for simple and comprehensive methods, respectively, while ICC dropped from 0.76-0.77 to 0.59-0.62. Scoring of erosions on T1w opGRE images resulted in a higher interreader agreement (ICC of 0.65) compared to T1w TSE sequences (ICC of 0.18). CONCLUSION: Better characterization of fatty lesion changes within 1 year was achieved by the comprehensive Berlin scoring method; however, more reader variation has to be taken into account. The delineation of erosions is markedly improved when using T1w opGRE pulse sequences.

Intra-arterial ultra low iodine CT angiography of renal transplant arteries.

PURPOSE: This study was designed to evaluate the technical feasibility and the image quality of intra-arterial 320-row CT angiography (ia-CTA) in the detection of transplant renal artery stenosis (TRAS) using a very low dose of contrast agent. METHODS: Evaluation of ia-CTA using a 4F catheter in ten patients with impaired renal transplant function and suspected TRAS. Average amount of contrast agent applied was 10 ± 3.7 ml standard deviation (SD). Patient serum creatinine levels had been monitored for 72 h. TRAS was detected and graded (1: less than 20 %; 2: 20-49 %; 3: 50-74 %; 4: 75-99 %; 5: total occlusion) and presence of kinking was recorded. Attenuation and vessel delineation were parameters for image quality analysis of the renal arterial supply, divided into four segments. Subjective image quality. RESULTS: Ia-CTA of the renal transplant was technically successful in all patients, revealing relevant stenoses in 7 of 10 patients. Serum creatinine levels before and after ia-CTA were 2.71 ± 1.46 and 2.56 ± 1.39 mg/dl, respectively. None of the patients developed signs of contrast-induced nephropathy within 72 h. Subjective image quality was excellent in all four segments, rated by two separate readers. No segment was found to be nondiagnostic. Mean attenuation values in the arterial segments ranged between 754 and 987 Hounsfield units. CONCLUSIONS: Wide detector ia-CTA for the diagnosis of TRAS is feasible using very low doses of contrast agent and results in high image quality.

Active inflammation and structural change in early active axial spondyloarthritis as detected by whole-body MRI.

OBJECTIVE: To evaluate active inflammatory lesions (AIL) and structural changes (SC) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) compared with patients with ankylosing spondylitis (AS) on whole-body MRI (wb-MRI). METHOD: 75 patients with active disease and a symptom duration of <5 years (39 with AS and 36 with nr-axSpA) were investigated with a comprehensive wb-MRI protocol and scored for AIL and SC in the spine, sacroiliac joints (SIJs) and non-axial manifestations. RESULTS: 92% of patients with AS showed active inflammation in the SIJ, 53% in the spine and 94% and 39%, respectively, in the nr-axSpA group. There was a non-significant trend towards more inflammation in patients with AS compared with patients with nr-axSpA in SIJs and spine. Peripheral enthesitis/osteitis was more common in patients with AS (n=22) than in those with nr-axSpA (n=12) (p=0.05). SC were more common in patients with AS than in those with nr-axSpA, with significantly higher scores for SIJ fatty bone marrow deposition (FMD) in patients with AS (4.8±3.2) compared with those with nr-axSpA (2.4±2.7; p=0.001) and more frequent bone proliferation in the spine and the SIJ (p=0.02 and p=0.005, respectively). SIJ erosions were more common in AS (score 4.2±2.3) than in nr-axSpA (score 3.8±1.8) patients (not significant). CONCLUSIONS: Wb-MRI detects active inflammation and SC more frequently in the SIJs than in the spine. Half of the patients showed inflammation in non-axial sites. Active inflammatory and structural lesions were present both in patients with AS and those with nr-axSpA, being only slightly more common in patients with AS.

Similar response rates in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis after 1 year of treatment with etanercept: results from the ESTHER trial.

OBJECTIVE: We assessed whether there is a difference to etanercept (ETA) treatment in patients with ankylosing spondylitis (AS) compared with non-radiographic axial SpA (nr-axSpA) patients with a disease duration <5 years. METHOD: AS (n=20) and nr-axSpA (n=20) patients who were treated with ETA for 1 year were compared for differences in baseline data and treatment effect. Clinical, laboratory and MRI of sacroiliac joints (SI-joints) and spine were analysed. RESULTS: At baseline, there were no significant differences between the 20 AS and the 20 nr-axSpA patients regarding age, disease duration, gender, HLA-B27 and clinical disease activity in terms of Bath AS Disease Activity Index (BASDAI), C-reactive protein and MRI SI-joint and spine scores in the AS compared with the nr-axSpA group. After 1 year of treatment with ETA the treatment effect was similarly good in AS and nr-axSpA (reduction of BASDAI by 3.3 (95% CI 2.2 to 3.8) vs 3.6 (95% CI 2.8 to 4.4) and reduction of AS Disease Activity Score by 1.8 (95% CI 1.5 to 2.2) vs 1.8 (95% CI 1.5 to 2.1), respectively. CONCLUSIONS: The response rate to TNF-blockers does not differ between AS and nr-axSpA if the baseline data regarding symptom duration and disease activity are similar for the two groups.

Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial.

PURPOSE: The aims of this study were (1) to assess the frequency and duration of drug-free remission and efficacy of etanercept (ETA) treatment after flare in patients with early active axial spondyloarthritis who were treated with ETA (n=40) versus sulfasalazine (SSZ, n=36) for 48 weeks and (2) to analyse the efficacy of ETA treatment in patients in year 2 who did not reach remission at week 48. METHOD: At week 48, patients who reached study remission (Assessment of Spondyloarthritis international Society (ASAS) plus MRI remission) were followed up without active treatment up to 1 year. In case of a flare, patients were treated with ETA for another year. All patients who were not in ASAS plus MRI remission at week 48 were treated with ETA in year 2. RESULTS: ASAS plus MRI remission at week 48 was reached significantly more often in ETA-treated compared to SSZ-treated patients (33% vs 11%, p=0.03). However, the flare rate was not different between these two groups: 69% in the ETA group versus 75% in the SSZ group. Only 8% of patients initially treated with ETA versus 3% of those initially treated with SSZ reached permanent drug-free remission (not significant). After treatment with ETA over 1 year, patients with flare showed an improvement in all clinical and imaging variables. CONCLUSION: Patients with axial spondyloarthritis treated with ETA over 1 year did not reach drug-free remission in a higher percentage compared to patients from a control group treated with SSZ.

Formalin-fixed blood clots--additional histological findings on computed tomography-guided fine-needle aspiration biopsies in comparison with core biopsies.

OBJECTIVE: We investigated the diagnostic yield of histological examined formalin-fixed blood clots (FFBCs) in comparison with the established procedures of fine-needle aspiration biopsy (FNAB) and core biopsy (CB) obtained by percutaneous puncture under computed tomography (CT) guidance. METHODS: A total of 76 CT-guided punctures with removal of tissue by means of all 3 different techniques (FFBC, FNAB, and CB) were performed. Specimens were obtained from the lung (n=18), mediastinum (n=10), upper abdominal organs (n=32), pelvis (n=4), retroperitoneum (n=4), bones (n=7), and neck (n=1). All results were correlated with the clinical course of the patients (minimum, 6 months; mean period, 10 months). The results of each technique were compared. Results of a combined use of FFBC and FNAB were analyzed. RESULTS: The overall sensitivity (regardless of biopsy site) was 79% for FFBC, 83% for FNAB, and 95% for CB. In chest biopsies, FFBC reached a sensitivity of 92%, FNAB of 86%, and CB of 96%. In liver biopsies, the sensitivities were 47%, 70%, and 88% for FFBC, FNAB, and CB and, for the remaining biopsy sites, 90%, 90%, and 100%, respectively. The combination of FFBC and FNAB showed higher sensitivities than FFBC and FNAB alone. Overall sensitivity for the combination was 88%, with 92%, 72%, and 100% for thorax, liver, and other locations. A definitive diagnosis was made by FFBC in 87% of cases, by FNAB in 74%, and by CB in 88%. The combination of FFBC and FNAB showed a definite diagnosis in 90% of the cases. A tentative diagnosis has been established in 12%, 7%, 5%, and 4%, respectively. In 4 cases (5%), all 3 techniques failed to yield reliable diagnoses. CONCLUSIONS: The examination of FFBCs is a useful supplement to the established technique of CT biopsy. In combination with FNAB, FFBC has a comparable sensitivity as CB in chest punctures and other extrahepatic lesions.