F Schmeel

Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC)

AbstractPurposenCytokine-induced killer (CIK) cells represent an exceptional T cell population uniting a T cell and natural killer cell like phenotype in their terminally differentiated CD3+CD56+ subset, which features non-MHC-restricted tumor-killing activity. CIK cells are expandable from peripheral blood mononuclear cells and mature following the addition of certain cytokines. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures.MethodsTherefore, we established the international registry on CIK cells in order to collect and evaluate data about clinical trials using CIK cells for the treatment of cancer patients. Moreover, our registry is expected to set new standards on the reporting of results from clinical trials using CIK cells. Clinical responses, overall survival (OS), adverse reactions and immunologic effects were analyzed in 45 studies present in our database. These studies investigated 22 different tumor entities altogether enrolling 2,729 patients.ResultsA mean response rate of 39xa0% and significantly increased OS, accompanied by an improved quality of life, were reported. Interestingly, side effects of CIK cell treatment were minor. Mild fevers, chills, headache and fatigue were, however, seen regularly after CIK cell infusion. Moreover, CIK cells revealed numerous immunologic effects such as changes in T cell subsets, tumor markers, cytokine secretion and HBV viral load.ConclusionDue to their easy availability and potent antitumor activity, CIK cells emerged as a promising immunotherapy approach in oncology and may gain major importance on the prognosis of cancer.

Comprehensive Cardiac Magnetic Resonance for Short‐Term Follow‐Up in Acute Myocarditis

Background Cardiac magnetic resonance (CMR) can detect inflammatory myocardial alterations in patients suspected of having acute myocarditis. There is limited information regarding the degree of normalization of CMR parameters during the course of the disease and the time window during which quantitative CMR should be most reasonably implemented for diagnostic work‐up. Methods and Results Twenty‐four patients with suspected acute myocarditis and 45 control subjects underwent CMR. Initial CMR was performed 2.6±1.9 days after admission. Myocarditis patients underwent CMR follow‐up after 2.4±0.6, 5.5±1.3, and 16.2±9.9 weeks. The CMR protocol included assessment of standard Lake Louise criteria, T1 relaxation times, extracellular volume fraction, and T2 relaxation times. Group differences between myocarditis patients and control subjects were highest in the acute stage of the disease (P<0.001 for all parameters). There was a significant and consistent decrease in all inflammatory CMR parameters over the course of the disease (P<0.01 for all parameters). Myocardial T1 and T2 relaxation times—indicative of myocardial edema—were the only single parameters showing significant differences between myocarditis patients and control subjects on 5.5±1.3‐week follow‐up (T1: 986.5±44.4 ms versus 965.1±28.1 ms, P=0.022; T2: 55.5±3.2 ms versus 52.6±2.6 ms; P=0.001). Conclusions In patients with acute myocarditis, CMR markers of myocardial inflammation demonstrated a rapid and continuous decrease over several follow‐up examinations. CMR diagnosis of myocarditis should therefore be attempted at an early stage of the disease. Myocardial T1 and T2 relaxation times were the only parameters of active inflammation/edema that could discriminate between myocarditis patients and control subjects even at a convalescent stage of the disease.

Feature-tracking myocardial strain analysis in acute myocarditis: diagnostic value and association with myocardial oedema

ObjectivesTo investigate the diagnostic value of cardiac magnetic resonance (CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected acute myocarditis and its association with myocardial oedema.MethodsForty-eight patients with suspected acute myocarditis and 35 control subjects underwent CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and radial strain (RS) was performed. Additionally, the protocol allowed for the assessment of T1 and T2 relaxation times.ResultsWhen compared with healthy controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS: -19.5u2009±u20094.4% vs. -23.6u2009±u20093.1%, CS: -23.0u2009±u20095.8% vs. -27.4u2009±u20093.4%, RS: 28.9u2009±u20098.5% vs. 32.4u2009±u20097.4%; Pu2009<u20090.05, respectively). LS (T1: ru2009=u20090.462, Pu2009<u20090.001; T2: ru2009=u20090.436, Pu2009<u20090.001) and CS (T1: ru2009=u20090.429, Pu2009<u20090.001; T2: ru2009=u20090.467, Pu2009<u20090.001) showed the strongest correlations with T1 and T2 relaxations times. Area under the curve of LS (0.79) was higher compared with those of CS (0.75; Pu2009=u20090.478) and RS (0.62; Pu2009=u20090.008).ConclusionsFT CMR myocardial strain analysis might serve as a new tool for assessment of myocardial dysfunction in the diagnostic work-up of patients suspected of having acute myocarditis. Especially, LS and CS show a sufficient diagnostic performance and were most closely correlated with CMR parameters of myocardial oedema.Key Points• Myocardial strain measures are considerably reduced in patients with suspected myocarditis.• Myocardial strain measures can sufficiently discriminate between diseased and healthy patients.• Myocardial strain measures show basic associations with the extent of myocardial oedema/inflammation.

In-bore transrectal MRI-guided prostate biopsies: Are there risk factors for complications?

PURPOSEnTo systematically analyze risk factors for complications of in-bore transrectal MRI-guided prostate biopsies (MRGB).nnnMATERIALS AND METHODSn90 patients, who were scheduled for MRGB were included for this study. Exclusion criteria were coagulation disorders, therapy with anticoagulant drugs, and acute infections of the urinary and the lower gastrointestinal tract. Directly after, one week and one year after the biopsy, we assessed biopsy related complications (e.g. hemorrhages or signs of prostatitis). Differences between patients with and without complications were analyzed regarding possible risk factors: age, prostate volume, number of taken samples, biopsy duration, biopsy of more than one lesion, diabetes, arterial hypertension, hemorrhoids, benign prostate hyperplasia, carcinoma or prostatitis (according to histopathological analysis), and lesion localization. Complications were classified according to the Clavien-Dindo classification.nnnRESULTSnWe observed 15 grade I complications in 90 biopsies (16.7%) with slight hematuria in 9 cases (10%), minor vasovagal reactions in 4 cases (4.4%), and urinary retention and positioning-related facial dysesthesia in 1 case each (1.1%). One patient showed acute prostatitis requiring antibiotics as the only grade II complication (1.1%). There were no adverse events that occurred later than one week. Complications grade III or higher such as pelvic abscesses, urosepsis or severe hemorrhages were not seen. There were no significant associations between the assessed risk factors and biopsy-related complications.nnnCONCLUSIONnIn-bore transrectal MRI-guided prostate biopsies can be considered safe procedures in the diagnosis of prostate cancer with very low complication rates. There seem to be no risk factors for complications.

Quantitative liver MRI including extracellular volume fraction for non-invasive quantification of liver fibrosis: a prospective proof-of-concept study

We read with interest the recent reviews published in Gut , emphasising that even though the understanding of the pathobiology of liver fibrosis has been improved in the last three decades,1 novel and easy to implement diagnostic and therapeutic approaches are required.2 Indeed, fibrosis is the most important histological feature of patients with chronic liver disease (CLD), such as non-alcoholic fatty liver disease, and isxa0associated with long-term overall mortality, liver transplantation and liver-related events.3 Diagnostic and therapeutic approaches,2 therefore, require accurate measurements that ideally allow non-invasive fibrosis quantification, representing the whole liver free of bias and easily integrated in clinical routine.nnAxa0liver biopsy, still the reference standard, has substantial drawbacks (complications, intraobserver and interobserver variabilities).4 Transient elastographyxa0(TE), suggested for population-wide screens (eg, patients with diabetes),5 requires additional expensive devices and trained personnel. However, contrast-enhanced MRI is routinely performed and recommended in patients with CLD for exclusion of hepatocellular …

Prognostic value of pretreatment diffusion-weighted magnetic resonance imaging for outcome prediction of colorectal cancer liver metastases undergoing 90Y-microsphere radioembolization

PurposeTo investigate the clinical potential of pretreatment apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DWI) for therapy response and outcome prediction in patients with liver-predominant metastatic colorectal cancer (CRC) undergoing radioembolization with 90Yttrium-microspheres (90Y-RE).MethodsForty-six consecutive patients with unresectable CRC liver metastases underwent standardized clinical DWI on a 1.5xa0T MR scanner prior to and 4–6 weeks after 90Y-RE. Pretreatment clinical parameters, ADC values derived from region-of-interest analysis, and the corresponding tumor sizes of three treated liver metastases per subject were recorded. Long-term tumor response to radioembolization was categorized into response (partial remission) and nonresponse (stable disease, progressive disease) according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) 3 months after treatment. Associations between long-term tumor response and the clinical and imaging parameters were evaluated. The impact of pretreatment clinical and imaging parameters on progression-free survival (PFS) and overall survival (OS) was further assessed by Kaplan–Meier and multivariate Cox-regression analyses.ResultsNonresponders had higher hepatic tumor burden (pu2009=u20090.021) and lower ADC values than patients responding to 90Y-RE, both pretreatment (986u2009±u2009215 vs. 1162u2009±u2009178; pu2009=u20090.036) and posttreatment (1180u2009±u2009350 vs. 1598u2009±u2009225; pu2009=u20090.002). ADC values higher than 935u2009×u200910−6 mm2 (5 vs. 3 months; pu2009=u20090.022) and hepatic tumor burdenu2009≤25% (6 vs. 3 months; pu2009=u20090.014) were associated with longer median PFS, whereas ADCu2009>935u2009×u200910−6 mm2 (14 vs. 6 months; pu2009=u20090.02), hepatic tumor burdenu2009≤25% (14 vs. 6 months; pu2009=u20090.048), size of the largest metastasisu2009<4.7xa0cm (18 vs. 7 months; pu2009=u20090.024), and Eastern Cooperative Oncology Group (ECOG) score <1 (8 vs. 5 months; pu2009=u20090.045) were associated with longer median OS. On multivariate analysis, ADCu2009>935u2009×u200910−6 mm2 and hepatic tumor burdenu2009≤25% remained prognostic factors for PFS, and ADCu2009>935u2009×u200910−6 mm2 and size of the largest metastasisu2009<4.7xa0cm were independent predictors of OS.ConclusionPretreatment ADC on DWI represents a valuable prognostic biomarker for predicting both the therapeutic efficacy and survival prognosis in CRC liver metastases treated by 90Y-RE, allowing risk stratification and potentially optimizing further treatment strategies.

Left and right ventricular strain in the course of acute myocarditis: a cardiovascular magnetic resonance study

PURPOSEnTo investigate the degree of impairment in left (LV) and right ventricular (RV) myocardial strain parameters over the course of acute myocarditis and to evaluate its value for the prediction of functional recovery upon follow-up.nnnMATERIALS AND METHODSn69 patients with acute myocarditis underwent cardiac magnetic resonance imaging during the acute stage (baseline) and after a mean 92.5u200a±u200a50.4 days follow-up.u200aStandard Lake Louise criteria (T2 signal intensity ratio, early gadolinium enhancement ratio and late gadolinium enhancement) and feature tracking derived LV and RV strain parameters were assessed. Logistic regression analysis was used to find predictors of functional recovery upon follow-up.nnnRESULTSnAll inflammatory parameters showed a considerable decrease over the course of the disease (Pu200a<u200a0.001 for all parameters). LV and RV function significantly improved on follow-up CMR (LV ejection fraction: 53.5u200a±u200a12.7u200a% vs. 61.3u200a±u200a9.5u200a%; Pu200a<u200a0.001, RV ejection fraction: 54.1u200a±u200a10.0u200a% vs. 59.4u200a±u200a6.3u200a%; Pu200a<u200a0.001). LV and RV myocardial strain (longitudinal, circumferential and radial strain) significantly improved from baseline to follow-up (Pu200a<u200a0.05 for all parameters). On multivariate analysis, LV global peak systolic longitudinal strain (OR: 0.303; Pu200a=u200a0.007) was the only independent predictor of functional recovery upon follow-up.u200a CONCLUSION: u2002Alterations in LV and RV functional strain parameters occur frequently during the acute stage of myocarditis. During the course of the disease, a significant improvement in LV and RV strain parameters can be observed. It further appears that initial LV longitudinal strain may serve as a new parameter for the prediction of functional recovery upon follow-up.nnnKEY POINTSn· Myocardial strain parameters significantly improve during the course of acute myocarditis.. · RV dysfunction can frequently be observed during the acute stage of myocarditis.. · LV longitudinal strain can independently predict functional recovery upon follow-up..nnnCITATION FORMATn· Luetkens JA, Petry P, Kuetting D etu200aal. Left and right ventricular strain in the course of acute myocarditis: axa0cardiovascular magnetic resonance study. Fortschr Röntgenstr 2018; 190: 722u200a-u200a732.

Quantification of Liver Fibrosis at T1 and T2 Mapping with Extracellular Volume Fraction MRI: Preclinical Results

Purpose To evaluate MRI T1 and T2 mapping with calculation of extracellular volume (ECV) for diagnosis and grading of liver fibrosis. Materials and Methods Different grades of fibrosis were induced in 60 male Sprague-Dawley rats by bile duct ligation (BDL) and carbon-tetrachloride (CCl4) intoxication. Portal pressure was measured invasively, whereas hepatic fibrosis was quantified by hydroxyproline content, Sirius red staining, and α smooth muscle actin staining. T1 values, T2 values, and ECV were assessed by using quantitative MRI mapping techniques. Results T1 values in animals 4 weeks after BDL were greater than in control animals (718 msec ± 74 vs 578 msec ± 33, respectively; P < .001). T2 values at 4 weeks were also greater in animals that underwent BDL than in control animals (46 msec ± 6 vs 29 msec ± 2, respectively; P < .001). Similar T1 and T2 findings were observed after CCl4 intoxication. ECV was greater in animals 4 weeks after BDL compared with control animals (31.3% ± 1.3 vs 18.2% ± 3.5, respectively; P < .001), with similar results after CCl4 intoxication. High correlations were found between ECV and hepatic hydroxyproline content (BDL: r = 0.68, P < .001; CCl4: r = 0.65, P < .001), Sirius red staining (BDL: r = 0.88, P < .001; CCl4: r = 0.82, P < .001), α smooth muscle actin staining (BDL: r = 0.70, P < .001; CCl4: r = 0.73, P < .001), and portal pressure (BDL: r = 0.54, P = .003; CCl4: r = 0.39, P = .043). Conclusion Elevation of T1 and T2 values and ECV was associated with severity of liver fibrosis and portal hypertension in an experimental animal model.

Frühzeitige Überlebenszeitstratifikation durch Diffusionsbildgebung nach SIRT bei kolorektalen Lebermetastasen

Zielsetzung: Grosenbasierte Verfahren zur Therapieerfolgsmessung lokal interventioneller Therapieverfahren, z.B. RECIST, konnen ein fruhes Therapieansprechen haufig nur unzureichend erfassen. Aktuelle Studienergebnisse weisen darauf hin, dass die MRT-Diffusionsbildgebung (DWI) ein Therapieansprechen bereits vor morphologisch fassbaren Anderungen aufzeigt. Ziel dieser Studie war es daher zu prufen, ob sich die DWI mittels quantitativer Analyse des Diffusionskoeffizienten (ADC) zur fruhen Vorhersage des Gesamtuberlebens (OS) von Patienten mit hepatisch metastasiertem kolorektalem Karzinom nach selektiver interner Radiotherapie (SIRT) eignet. Material und Methodik: 41 Patienten erhielten 19 ± 16 Tage vor und 36 ± 10 Tage nach SIRT mit 90Y-Mikrospharen eine MRT Untersuchung mit DWI (1.5T, Philips Intera). Pra- und posttherapeutische Minimum ADC-Werte (b = 0, 50, 800) wurden in den 3 grosten Lebermetastasen im Behandlungsareal gemessen, gemittelt und verglichen. Mittels Kaplan-Meier-(log-rank-Test) und multivariater Cox-Regressionsanalyse wurde untersucht, ob ein posttherapeutischer ADC-Anstieg prognostische Aussagekraft fur das OS besitzt. Weitere untersuchte Einflussfaktoren auf das OS waren Alter, Geschlecht, Karnofsky-Score, Bilirubin, hepatische Tumorlast und das Vorhandensein extrahepatischer Metastasen. Ergebnisse: Das mediane OS nach Therapie betrug 8 Monate. Patienten mit ADC-Anstieg ≥0% nach SIRT wiesen ein deutlich verlangertes medianes OS als Patienten mit ADC-Reduktion auf (18 vs. 4 Monate; p < 0.001). Weiterhin hatten hepatische Tumorlast ≥50% (6 vs. 8 Monate; p = 0.025) und die applizierte Dosis ≥2 Gy (5 vs. 10 Monate; p = 0.048) einen signifikanten Einfluss auf das OS. In der multivariaten Analyse verblieb das Nichtvorhandensein eines posttherapeutischen ADC-Anstiegs ≥0% als einziger signifikanter und unabhangiger Risikofaktor zur Pradiktion des OS (p < 0.001). Schlussfolgerungen: Die DWI erlaubt eine Einschatzung des Therapieansprechens bereits wenige Wochen nach SIRT und ermoglicht damit eine fruhzeitige Uberlebenszeitstratifikation.