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584 result(s) for "Vogl, Thomas"
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The Role of Conventional TACE (cTACE) and DEBIRI-TACE in Colorectal Cancer Liver Metastases
Colorectal cancer (CRC) is one of the most common tumor entities worldwide and a common cause of cancer-associated death. Colorectal cancer liver metastases (CRLM) thereby constitute a severe life-limiting factor. The therapy of CRLM presents a major challenge and surgical resection as well as systemic chemotherapy remain the first-line treatment options. Over the years several locoregional, vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. Among such options is the conventional/traditional transarterial chemoembolization (cTACE) by local injection of a combination of chemotherapeutic- and embolic-agents. A similar treatment is the more recent irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE), which are administered using the same approach. Numerous studies have shown that these different types of chemoembolization can be applied in different clinical settings safely. Furthermore, such treatments can also be combined with other local or systemic therapies. Unfortunately, due to the incoherent patient populations of studies investigating TACE in CRLM, critics state that the definite evidence supporting positive patient outcomes is still lacking. In the following article we review studies on conventional and DEBIRI-TACE. Although highly dependent on the clinical setting, prior therapies and generally the study population, cTACE and DEBIRI-TACE show comparable results. We present the most representative studies on the different chemoembolization procedures and compare the results. Although there is compelling evidence for both approaches, further studies are necessary to determine which patients profit most from these therapies. In conclusion, we determine TACE to be a viable option in CRLM in different clinical settings. Nevertheless, a multidisciplinary approach is desired to offer patients the best possible care.
Long-term cardiac pathology in individuals with mild initial COVID-19 illness
Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77–177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274–383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness. In individuals with long-term cardiac symptoms after an initially mild course of COVID-19 illness, magnetic resonance imaging and measurement of cardiac injury biomarkers commonly detected ongoing cardiac inflammation but not structural heart disease.
Combination Therapy of Bland Transarterial Embolization and Microwave Ablation for Hepatocellular Carcinoma within the Milan Criteria Leads to Significantly Higher Overall Survival
A comparison of the combination therapy consisting of microwave ablation (MWA) after bland lipiodol-based transarterial embolization (TAE) with MWA alone in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Forty-nine patients in the TAE-MWA group (12 women and 37 men; mean age: 63.3 ± 9.6 years) with 55 tumors and 63 patients in the MWA group (18 women and 45 men; mean age: 65.9 ± 10.5 years) with 67 tumors were retrospectively enrolled in this study. For the investigation of treatment protocols based upon both safety and efficacy, patients’ cases were analyzed with regard to complications, local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS). There were no cases of major complications in either group. The LTP rate was 5.5% in the MWA-TAE group and 7.5% in the MWA group (p = 0.73). The rate of IDR was 42.9% in the MWA-TAE group and 52.4% in the MWA group (p = 0.42). The 12-, 24-, and 36-month OS rates starting at the date of tumor diagnosis were 97.7%, 85.1%, and 78.8% in the TAE-MWA group, and 91.9%, 71.4%, and 59.8% in the MWA group, respectively (p = 0.004). The 6-, 12-, and 24-month PFS rates were 76.5%, 55%, and 44.6% in the TAE-MWA group, and 74.6%, 49.2%, and 29.6% in the MWA group, respectively (p = 0.18). The combination therapy of TAE-MWA was significantly superior to MWA monotherapy according to OS in treating HCC within the Milan criteria.
Selective targeting of tumor associated macrophages in different tumor models
Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).
Early dynamic changes in circulating tumor cells and prognostic relevance following interventional radiological treatments in patients with hepatocellular carcinoma
The aim of this study was to investigate the dynamic changes of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC) before and immediately after conducting a microwave ablation (MWA) and conventional transarterial chemoembolization (C-TACE). Additionally, the CTCs short-term dynamics were compared with the clinical course of the HCC-patients. Blood samples from 17 patients with HCC who underwent MWA (n = 10) or C-TACE (n = 7) were analyzed. Venous blood was taken before and immediately after the radiological interventions to isolate and quantify CTCs using flow cytometry. CTCs were identified as CD45- and positive for the markers ASGPR, CD146 and CD274 (PD-L1). Patients were followed of up to 2.2 years after the radiological intervention. CTCs were detected in 13 HCC patients (76%) prior to the radiological interventions. The rate of CTCs was significantly decreased after the intervention in patients treated with MWA (0.4 CTCs/mL of blood, p = 0.031). However, no significant differences were observed in patients who received C-TACE (0.3 CTCs/mL of blood, p = 0.300). Overall, no correlation was found between the CTCs rate before and after the radiological intervention and recurrence rate of HCC. This preliminary data could confirm the tumoricidal effects of MWA in patients with HCC by significantly decreasing CTCs rate. In our study, we were able to detect CTCs in HCC patients using 3 different tumor markers. This preliminary data shows significant lower CTCs detected in response to MWA. However, large-scale randomized clinical trials are needed to determine the future role and the prognostic relevance of CTCs following this treatment.
Radiation exposure and estimated risk of radiation-induced cancer from thoracic and abdominal radiographs in 1307 neonates
Objective This study examined radiation exposure and the possible risk of radiation-induced cancer in a large sample of newborn and premature patients. Material and methods In this retrospective study, we included all hospitalised neonates treated at our university hospital who received at least one X-ray examination from 1 January 2013 to 31 December 2018. We evaluated the dose area product (DAP), effective dose (ED), and estimated risk. The International Commission on Radiological Protection Publication 60 defines values (2.8–13 × 10 −2  Sv −1 ) to calculate the estimated risk in relation to the ED. Results Of the 3843 patients (aged 241.1 ± 35.45 days) treated in the neonatal care unit, 1307 (34%) received at least one X-ray. The mean number of X-ray examinations per patient was 3.19 and correlated negatively with birth weight. The mean cumulative DAP was 5.9 mGy*cm 2 , and the cumulative ED was 23.7 µSv per hospital stay. Patients with a birth weight of < 1000 g showed the highest cumulative ED and DAP ( p  < 0.001). Patients with a birth weight of < 2500 g had the highest ED and DAP per image ( p  < 0.001). The highest radiation exposure (ED/DAP) occurred for thoracic/abdominal examinations, especially for neonates < 500 g ( p  < 0.001). Conclusion There is a strong correlation between immaturity, the number of X-ray examinations, and radiation exposure. The total exposure was minimal, and the number of X-rays per patient has been decreasing in recent years. Clinical relevance Possible risks to newborns and premature infants caused by ionising X-rays are often the subject of scientific and clinical discussion. Nevertheless, conventional X-ray imaging remains a frequently used tool, and total exposure remains at a very low level. Key Points The number of X-rays per patient has been decreasing in a large university hospital . Half of all patients received only one X-ray; most had a birth weight over 1500   g . This radiation risk can be classified as ‘minimal’ for patients with a birth weight of <   500   g and as ‘negligible’ for others .
Advanced image-based virtual monoenergetic dual-energy CT angiography of the abdomen: optimization of kiloelectron volt settings to improve image contrast
Objectives To compare quantitative image quality parameters in abdominal dual-energy computed tomography angiography (DE-CTA) using an advanced image-based (Mono+) reconstruction algorithm for virtual monoenergetic imaging and standard DE-CTA. Methods Fifty-five patients (36 men; mean age, 64.2 ± 12.7 years) who underwent abdominal DE-CTA were retrospectively included. Mono + images were reconstructed at 40, 50, 60, 70, 80, 90 and 100 keV levels and as standard linearly blended M_0.6 images (60 % 100 kV, 40 % 140 kV). The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of the common hepatic (CHA), splenic (SA), superior mesenteric (SMA) and left renal arteries (LRA) were objectively measured. Results Mono+ DE-CTA series showed a statistically superior CNR for 40, 50, 60, 70 and 80 keV ( P  < 0.031) compared to M_0.6 images for all investigated arteries except SMA at 80 keV ( P  = 0.08). CNR at 40 keV revealed a mean relative increase of 287.7 % compared to linearly blended images among all assessed arteries ( P  < 0.001). SNR of Mono+ images was consistently significantly higher at 40, 50, 60 and 70 keV compared to M_0.6 for CHA and SA ( P  < 0.009). Conclusions Compared to linearly blended images, Mono+ reconstructions at low keV levels of abdominal DE-CTA datasets significantly improve quantitative image quality. Key Points • Mono+ combines increased attenuation with reduced image noise compared to standard DE-CTA. • Mono+ shows superior contrast-to-noise ratios at low keV compared to linearly-blended images. • Contrast-to-noise ratio in monoenergetic DE-CTA peaks at 40 keV. • Mono+ reconstructions significantly improve quantitative image quality at low keV levels.
Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation
Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation. Combining protease degradation, pull-down assays, mass spectrometry, and targeted mutations, we identified specific peptide sequences within the second calcium-binding EF-hands triggering TLR4/MD2-dependent inflammation. These binding sites are free when S100A8/S100A9 heterodimers are released at sites of inflammation. Subsequently, S100A8/S100A9 activities are locally restricted by calcium-induced (S100A8/S100A9)2 tetramer formation hiding the TLR4/MD2-binding site within the tetramer interphase, thus preventing undesirable systemic effects. Loss of this autoinhibitory mechanism in vivo results in TNF-α-driven fatal inflammation, as shown by lack of tetramer formation in crossing S100A9-/- mice with 2 independent TNF-α-transgene mouse strains. Since S100A8/S100A9 is the most abundant DAMP in many inflammatory diseases, specifically blocking the TLR4-binding site of active S100 dimers may represent a promising approach for local suppression of inflammatory diseases, avoiding systemic side effects.
Assessment of an Advanced Monoenergetic Reconstruction Technique in Dual-Energy Computed Tomography of Head and Neck Cancer
Objectives To define optimal keV settings for advanced monoenergetic (Mono+) dual-energy computed tomography (DECT) in patients with head and neck squamous cell carcinoma (SCC). Methods DECT data of 44 patients (34 men, mean age 55.5 ± 16.0 years) with histopathologically confirmed SCC were reconstructed as 40, 55, 70 keV Mono + and M_0.3 (30 % 80 kV) linearly blended series. Attenuation of tumour, sternocleidomastoid muscle, internal jugular vein, submandibular gland, and noise were measured. Three radiologists with >3 years of experience subjectively assessed image quality, lesion delineation, image sharpness, and noise. Results The highest lesion attenuation was shown for 40 keV series (248.1 ± 94.1 HU), followed by 55 keV (150.2 ± 55.5 HU; P  = 0.001). Contrast-to-noise ratio (CNR) at 40 keV (19.09 ± 13.84) was significantly superior to all other reconstructions (55 keV, 10.25 ± 9.11; 70 keV, 7.68 ± 6.31; M_0.3, 5.49 ± 3.28; all P  < 0.005). Subjective image quality was highest for 55 keV images (4.53; κ = 0.38, P  = 0.003), followed by 40 keV (4.14; κ = 0.43, P  < 0.001) and 70 keV reconstructions (4.06; κ = 0.32, P  = 0.005), all superior ( P  < 0.004) to linear blending M_0.3 (3.81; κ = 0.280, P  = 0.056). Conclusions Mono + DECT at low keV levels significantly improves CNR and subjective image quality in patients with head and neck SCC, as tumour CNR peaks at 40 keV, and 55 keV images are preferred by observers. Key Points • Mono + DECT combines increased contrast with reduced image noise, unlike linearly blended images. • Mono + DECT imaging allows for superior CNR and subjective image quality. • Head and neck tumour contrast-to-noise ratio peaks at 40 keV. • 55 keV images are preferred over all other series by observers.