Publications by authors named "Philipp M Paprottka"

45 Publications

[Imaging of intrahepatic cholangiocarcinoma : Reliable diagnosis according to the new S3 guideline].

Radiologe 2022 Jan 14. Epub 2022 Jan 14.

Interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, München, Deutschland.

The S3 guideline on hepatocellular carcinoma has been expanded to include malignant biliary carcinoma (synonym cholangiocarcinoma [CCA]). Magnetic resonance imaging (MRI) with additional magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice to evaluate local findings. Use of gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-based contrast agent increases its diagnostic value. Histologic confirmation is always required when diagnosing intrahepatic CCA (iCCA) because using imaging alone there is a risk of confusion with HCC subtypes.
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January 2022

Efficacy of ultrasound assisted catheter-directed thrombolysis compared to catheter-directed thrombolysis in vitro.

Acta Radiol 2021 Dec 6:2841851211061440. Epub 2021 Dec 6.

Department of Interventional Radiology, 9184Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany.

Background: Catheter-directed thrombolysis (CDT) is an effective and safe endovascular method used in critical limb ischemia and many other thromboembolic events. Ultrasound-assisted catheter-directed thrombolysis (US-CDT) is an emerging technique considered to accelerate thrombolysis and therefore is supposed to improve outcome.

Purpose: To evaluate the efficacy of US-CDT in comparison to standard CDT in vitro.

Material And Methods: A total of 69 sets of human venous blood were evaluated, each comprising a tube just treated with CDT, a tube treated with US-CDT, and a control tube. All tubes were kept under physiological conditions. Except for the controls, in all tubes 5 mg of tissue-type plasminogen activator was administered over the predetermined treatment interval. Thrombus mass was weighted at the end of the lysis intervals at 6 h or 24 h, respectively.

Results: CDT led to a mean thrombus reduction of 32% and ultrasound-assisted lysis led to a mean thrombus reduction of 41% ( < 0.001 for both). Thrombus reduction was significantly higher after US-CDT compared to CDT ( = 0.001). The better efficacy of US-CDT was mostly already apparent at early phases during thrombolysis and did further mildly increase over time (r = 0.24;  = 0.047).

Conclusion: In vitro US-CDT is significantly superior to standard CDT; this effect is apparent at an early timepoint of lysis and slightly further increases over time.
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December 2021

Outcome and Safety after 103 Radioembolizations with Yttrium-90 Resin Microspheres in 73 Patients with Unresectable Intrahepatic Cholangiocarcinoma-An Evaluation of Predictors.

Cancers (Basel) 2021 Oct 27;13(21). Epub 2021 Oct 27.

Department of Interventional Radiology, Technical University Munich, 81377 Munich, Germany.

Trans-arterial radioembolization (TARE) is increasingly evaluated for unresectable intrahepatic cholangiocarcinoma (ICC). Not all ICC patients benefit equally well from TARE. Therefore, we sought to evaluate variables predicting progression-free survival (PFS) and overall survival (OS). Patients with non-resectable ICC underwent TARE and were treated with 90Y resin microspheres. Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on PFS and OS. A total of 103 treatments were administered to 73 patients without major complications or toxicity. Mean OS was 18.9 months (95% confidence intervals (CI); 13.9-23.9 months). Mean and median PFS were 10.1 months (95% CI; 7.9-12.2) and 6.4 months (95% CI; 5.20-7.61), respectively. Median OS and PFS were significantly prolonged in patients with baseline cholinesterase (CHE) ≥ 4.62 kU/L (OS: 14.0 vs. 5.5 months; PFS: 6.9 vs. 3.2 months; < 0.001). Patients with a tumor burden ≤ 25% had a significantly longer OS (15.2 vs. 6.6 months; = 0.036). Median PFS was significantly longer for patients with multiple TARE cycles (24.4 vs. 5.8 months; = 0.04). TARE is a considerable and safe option for unresectable ICC. CA-19-9, CHE, and tumor burden have predictive value for survival in patients treated with TARE. Multiple TARE treatments might further improve survival; this has to be confirmed by further studies.
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October 2021

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

Eur J Nucl Med Mol Imaging 2021 05 12;48(5):1570-1584. Epub 2021 Jan 12.

Department of Nuclear Medicine, Jules Bordet Institute, Université Libre de Bruxelles, Rue Héger-Bordet 1, B-1000, Brussels, Belgium.

Purpose: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (Y)-resin microspheres.

Methods: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%).

Results: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and Tc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement).

Conclusion: Practitioners are encouraged to work towards adoption of these recommendations.
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May 2021

Association between objective response rate and overall survival in metastatic neuroendocrine tumors treated with radioembolization: a systematic literature review and regression analysis.

Expert Rev Anticancer Ther 2020 11 24;20(11):997-1009. Epub 2020 Oct 24.

Department of Interventional Radiology, Klinikum Rechts der Isar der Technischen Universität München , Munich, Germany.

Objectives: Neuroendocrine tumors (NETs) are a heterogeneous group of cancers arising from neuroendocrine cells. The aim was to evaluate objective response rate (ORR) as a predictor of overall survival (OS) in patients with metastatic NETs (mNETs) treated with radioembolization (RE).

Methods: Randomized controlled trials and observational studies of RE treatment of mNETs were identified by systematic literature review (SLR). Pooled ORR and OS estimates were calculated and a weighted generalized linear model (GLM) of ORR as a predictor of OS was derived, stratified by ORR assessment criteria and RE type (Yttrium-90 resin or glass microspheres).

Results: The SLR identified 32 observational studies. Mean ORR was 41% (95% confidence interval 38-45%). The Yttrium-90 resin and glass microsphere GLMs accounted for 59% and 57% of OS deviance, respectively. ORR was a significant predictor of OS in the resin microspheres model (p < 0.001), but not the glass microspheres model (p = 0.11).

Conclusions: A weighted GLM showed a significant relationship between ORR and OS in patients with mNETs treated with Yttrium-90 resin microspheres. ORR could therefore potentially be an OS surrogate in future trials of Yttrium-90 resin microspheres. Further research is needed to confirm the relationship between ORR and OS and the difference between resin and glass microspheres.
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November 2020

[Comparison of radiation exposure in common hepatic interventions : A retrospective analysis of DeGIR registry data].

Radiologe 2021 Jan;61(1):80-86

Sektion für Interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, München, Deutschland.

Background: Transcatheter arterial chemoembolization (TACE) and biliary interventions are common procedures.

Objectives: In this retrospective study, the radiation exposure of patients undergoing hepatic intervention will be analyzed and compared depending on the type and objective of the intervention.

Materials And Methods: This is an analysis of 7003 data sets of performed TACEs and biliary interventions from the DeGIR registry for the years 2016, 2017, and 2018. The dose area product (DAP), fluoroscopy time (FT), type of intervention, and anatomically defined target were recorded.

Results: Data with documented radiation doses were available for 4985 TACEs and for 2018 biliary interventions. For biliary interventions the median DAP was 2594 (interquartile range [IQR] = 1174-5858) cGycm. For TACE, the median DAP was 11,632 [IQR = 5530-22,800] cGycm and significantly higher compared to biliary interventions (p < 0.0001). Biliary interventions with the highest DAP take place at the common hepatic duct; procedures with the longest FT were registered at the hepatic duct bifurcation.

Conclusions: The individual radiation exposure during liver interventions is less dependent of the complexity of the procedure or the fluoroscopy time, but rather on the type of intervention and the anatomic target. The presented data can help to approximately estimate the radiation exposure in advance when planning an intervention.
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January 2021

Availability of Transcatheter Vessel Occlusion Performed by Interventional Radiologists to Treat Bleeding in Germany in the Years 2016 and 2017 - An Analysis of the DeGIR Registry Data.

Rofo 2020 Oct 7;192(10):952-960. Epub 2020 Jul 7.

Klinikum rechts der Isar of the Technical University of Munich, Department of Interventional Radiology, Munich, DE.

Purpose:  Acute bleeding is a life-threatening condition that can be effectively treated minimally invasively by interventional radiologists using transcatheter vessel occlusion (TCVO). The purpose of this study was to evaluate the availability of TCVO performed by interventional radiologists in Germany based on the DeGIR registry.

Materials And Methods:  TCVO interventions from the years 2016 and 2017 were included (DeGIR module B). The number of interventions was assessed by state and region.

Results:  TCVO interventions were reported by 242 clinics in Germany. 16 763 module B interventions were reported in 2016 and 16 399 in 2017. DeGIR requirements for certification as a training center were fulfilled by 160 facilities in 2016 and by 162 facilities in 2017. Normalized to one million citizens, an average of 211 TCVO interventions were performed in 2016 and 200 in 2017 (standard deviation was 101 and 109); the median was 202 and 222, respectively. In all regions TCVO interventions were reported. Only a minimal number of small regions showed a lower number of clinics offering TCVO interventions.

Conclusion:  The results from the DeGIR registry indicate comprehensive nationwide availability of TCVO performed by interventional radiologists with the necessary experience in Germany on the state level for the treatment of acute bleeding. Furthermore, the distribution of facilities fulfilling the requirements of training centers allows for good educational possibilities for young interventional radiologists in Germany. Only the distribution of clinics offering TCVO in a few small regions might lead to increased transfer times in the case of acute bleeding.

Key Points: · As a treatment for life-threatening acute bleeding in Germany, transcatheter vessel occlusion led by interventional radiologists is readily available on the state level.. · Furthermore, the distribution of facilities fulfilling the requirements of training centers allows for good educational possibilities for young interventional radiologists in Germany.. · Due to the good training conditions in Germany, it might be possible to further improve the situation in smaller regions by training more interventional radiologists and employing them in regions with less coverage..

Citation Format: · Nadjiri J, Schachtner B, Bücker A et al. Availability of Transcatheter Vessel Occlusion Performed by Interventional Radiologists to Treat Bleeding in Germany in the Years 2016 and 2017 - An Analysis of the DeGIR Registry Data. Fortschr Röntgenstr 2020; 192: 952 - 960.
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October 2020

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization.

J Clin Med 2019 Dec 25;9(1). Epub 2019 Dec 25.

Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany.

Purpose: To evaluate factors associated with survival following transarterial Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC).

Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan-Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival.

Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29-88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1-12.9 months). Due to loss in follow-up, = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume ( = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, = 0.002). No case of radiation-induced liver disease was observed.

Discussion: Survival after Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
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December 2019

CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures.

Rofo 2020 Feb 28;192(2):163-170. Epub 2019 Aug 28.

Institute of Diagnostic and Interventional Neuroradiology Ludwig-Maximilian-University, Munich, Germany.

Purpose:  To observe the technical and clinical outcome as well as safety of CT fluoroscopy-guided drain placement in the multimodal clinical complication management of superinfected gastric leakage after sleeve gastrectomy.

Materials And Methods:  All consecutive patients who underwent CT fluoroscopy-guided drain placement to treat superinfected postoperative leakage after sleeve gastrectomy in our department between 2007 and 2014 were included in this retrospective study. All interventions were performed on a 16- or 128-row CT scanner under intermittent CT fluoroscopy guidance (15-25 mAs, 120 kV). The technical and clinical success rates as well as complications, additional therapies and patient radiation dose were analyzed.

Results:  14 patients (mean age: 43.8 ± 11.3 years, mean BMI: 52.9 ± 13.5, 7 women) who underwent a total of 31 CT fluoroscopy-guided drain placement procedures were included. 30 of 31 interventions (96.8 %) were technically successful. 7 patients underwent more than one intervention due to drain obstruction or secondary dislocation or as further treatment. During and after the intervention no procedure-associated complications occurred. In all patients, inflammation parameters decreased within days after the CT-guided intervention. The total interventional dose length product (DLP) was 1561 ± 1035 mGy*cm.

Conclusion:  CT fluoroscopy-guided drain placement has been shown to be a safe minimally invasive procedure that rarely leads to complications for treating superinfected gastric leakage occurring after sleeve gastrectomy. We assume that operative revisions in a high-risk patient group can be avoided using this procedure.

Key Points:   · CT fluoroscopy-guided drain placement in obese - often medically highly complex - patients is a technically feasible procedure.. · Multimodal treatment (CT intervention, endoscopy and surgery) is required to successfully treat gastric leakage after bariatric surgery.. · High-risk surgery might be avoided by the CT-guided drain placement..

Citation Format: · Schwarz J, Strobl FF, Paprottka PM et al. CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures. Fortschr Röntgenstr 2020; 192: 163 - 170.
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February 2020

Retrospective outcome analysis of rates and types of complications after 8654 minimally invasive radiological port implantations via the subclavian vein without ultrasound guidance.

Radiol Med 2019 Sep 7;124(9):926-933. Epub 2019 Jun 7.

Department of Clinical Radiology, Institute of Clinical Radiology, University Hospitals Munich - Campus Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Purpose: To evaluate the rate and types of complications after minimally invasive radiological central vein port implantation without ultrasound guidance.

Materials And Methods: We retrospectively evaluated 8654 patients who underwent port implantations in the subclavian vein without ultrasound guidance in our institution from 1998 to 2014 with regard to types and rates of peri-, early and late post-interventional complications according to the common classification for complications published by the Society of Interventional Radiology (SIR). Additionally, the impact of the training level of the operators on the rate of complications was analyzed.

Results: Successful port implantations were performed in 99.8% (8636/8654 procedures). From 1998 to 2014, a total of 565 (6.52%) complications were recorded. The overall percentage of the peri-, early and late post-interventional complications according to the SIR criteria was 1.69, 0.15 and 4.68, respectively. Significant differences due to the training level of the performing physician could be seen for the rates of pneumothorax, arterial puncture and hematoma.

Conclusion: Minimally invasive radiological interventional port implantation is a safe treatment option with a low rate of complications even without ultrasound guidance.
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September 2019

The Munich-Transarterial Chemoembolisation Score Holds Superior Prognostic Capacities Compared to TACE-Tailored Modifications of 9 Established Staging Systems for Hepatocellular Carcinoma.

Digestion 2019 3;100(1):15-26. Epub 2018 Oct 3.

Department of Medicine II, Liver Center Munich, University Hospital, Munich, Germany.

Background/aims: The recently proposed Munich-transarterial chemoembolisation-score (M-TACE) was tailored to suit hepatocellular Carcinoma (HCC) patients evaluated for TACE. M-TACE outperformed the established HCC-staging-systems and successfully passed external validation. Modifications of staging-systems through the rearrangement of stages or by adding prognostic factors are methods of improving prognostic power. M-TACEs performance compared to scores modified this way should be tested.

Methods: Seven well-known HCC staging-systems (including Cancer of the Liver Italian Program-score [CLIP] and Barcelona Clinic liver cancer [BCLC]) and 2 TACE-specific scores (Selection for Transarterial Chemoembolisation Treatment [STATE] and Hepatoma Arterial embolisation Prognostic [HAP]) were rearranged in a cohort of 186 TACE-patients through score-point-analysis and subsequent linking of non-significant adjacent score-points. Additionally, a new score was constructed by combining the top established staging-system in TACE patients (CLIP-TACE) and the prognostic parameter with the highest hazard ratio for death in the TACE-cohort [C-reactive protein (CRP)]. Additionally, the TACE-tailored-scores were applied to an external TACE-cohort (n = 71). -Results: Rearrangement resulted in optimal stratification and monotonicity. CLIP-TACE demonstrated the best prognostic capability of all rearranged scores (c-index 0.668, AIC 1294) and the addition of CRP yielded further prognostic improvement (c-index 0.680, AIC 1289). However, superiority over M-TACE could not be achieved by any of the new scores in the internal and external cohort.

Conclusion: M-TACE outperforms TACE-tailored modifications of all relevant HCC-staging-systems. Prospective validation of M-TACE to promote its role as the preferred staging-system for TACE-patients is therefore justified.
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December 2019

CT fluoroscopy-guided percutaneous osteoplasty with or without radiofrequency ablation in the treatment of painful extraspinal and spinal bone metastases: technical outcome and complications in 29 patients.

Diagn Interv Radiol 2018 May-Jun;24(3):158-165

Institute for Clinical Radiology, University Hospitals Munich - Campus Großhadern, München, Germany.

Purpose: We aimed to assess the safety and technical outcome of computed tomography (CT) fluoroscopy-guided osteoplasty with or without prior percutaneous radiofrequency ablation (RFA) in patients with painful osteolyses.

Methods: We performed a retrospective analysis of 29 patients with painful extraspinal and spinal osteolyses (16 women, 13 men; 63.1±14.4 years) who underwent CT fluoroscopy-guided osteoplasty (10-20 mAs tube current) with or without RFA (26 and 14 lesions, respectively), in 33 consecutive procedures from 2002 to 2016. Technical success was defined as at least one complete RFA cycle and subsequent polymethyl metacrylate (PMMA) bone cement injection covering ≥75% of longest diameter of extraspinal osteolysis on axial plane or of distance between vertebral endplates. Procedure-related complications within 30 days and dose-length-product (DLP) were also evaluated.

Results: Osteolyses were located in the pelvis (acetabulum, n=10; iliac bone, n=4), spine (thoracic, n=6; lumbar, n=5; sacral, n=8), long bones (femur, n=3; tibia, n=1), sternum (n=2) and glenoid (n=1). Mean size of the treated osteolysis was 4.0±1.2 cm (range, 1.9-6.9 cm). Of 40 osteolyses, 31 (77.5%) abutted neighboring risk structures (spinal canal or neuroforamen, n=18; neighboring joint, n=11; other, n=8). Mean number of RFA electrode positions and complete ablation cycles was 1.5±0.9 and 2.1±1.7, respectively. Mean PMMA filling volume was 7.7±5.7 mL (range, 2-30 mL). Small asymptomatic PMMA leakages were observed in 15 lesions (37.5%). Mean total DLP was 850±653 mGy*cm. Six minor complications were observed, without any major complications.

Conclusion: CT fluoroscopy-guided percutaneous osteoplasty with or without concomitant RFA for the treatment of painful extraspinal and spinal osteolyses can be performed with a low complication rate and high technical success.
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October 2018

Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma.

Clin Nucl Med 2018 Jul;43(7):477-481

Departments of Nuclear Medicine and.

Aim: The aim of this study was to retrospectively analyze the prognostic value of combined Tc-macroaggregated albumin (MAA) SPECT/CT and [F]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma.

Methods: Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [F]FEC PET/CT scan as well as Tc-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied.

Results: All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (±51 days; range, 23-1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio; defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026; hazard ratio, 11.65; 95% confidence interval, 1.62-83.73; P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 ± 80 versus 585 ± 284 days (P = 0.015).

Conclusions: Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization.
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July 2018

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies.

Eur J Nucl Med Mol Imaging 2018 09 7;45(10):1721-1730. Epub 2018 Mar 7.

Nuclear Medicine, Istituto Tumori Pascale, Naples, Italy.

Purpose: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation.

Methods: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records.

Results: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976.

Conclusions: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.
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September 2018

Quantification of Adipose Tissue and Muscle Mass Based on Computed Tomography Scans: Comparison of Eight Planimetric and Diametric Techniques Including a Step-By-Step Guide.

Eur Surg Res 2018 23;59(1-2):23-34. Epub 2018 Jan 23.

Department of Anesthesiology, University Hospital Munich (LMU), Munich, Germany.

Background: Recent scientific work proved that knowledge about body composition beyond the body mass index is essential. Both adipose tissue and muscular status are determining risk factors of morbidity and mortality. Analysis of single cross-sectional computed tomography (CT) images, acquired during routine care only to prevent additional radiation exposure, provide a detailed insight into the body composition of chronically and critically ill patients.

Methods: This retrospective study included 490 trauma patients of whom a whole-body multiple detector CT scan was acquired at admission. From a single cross-sectional CT, we compared eight diametric and planimetric techniques for the assessment of core muscle mass as well as visceral and subcutaneous adipose tissue. Furthermore, we derived formulas for converting the measurement results of various techniques into each other.

Results: For intra- and interobserver reliability, we obtained intraclass correlation coefficients (ICCs) ranging from 0.947 to 0.997 (intraobserver reliability) and from 0.850 to 0.998 (interobserver reliability) for planimetric measurements. Diametric techniques conferred lower ICCs with 0.851-0.995 and 0.833-0.971, respectively. Overall, area-based measurements of abdominal adipose tissue yielded highly correlated results with diametric measures of obesity. For example, the Pearson correlation of visceral adipose tissue and sagittal abdominal diameter was 0.87 for male and 0.82 for female patients. Planimetric and diametric muscle measurements correlated best for lean psoas area and bilateral diametric measurement of the psoas with a Pearson correlation of 0.90 and 0.93 for male and female patients, respectively.

Conclusion: Planimetric measurements should remain the gold standard to describe fat and muscle compartments. Diametric measurements could however serve as a surrogate if planimetric techniques are not readily available or feasible as for example in large registries.
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November 2018

Transarterial chemoembolization for hepatocellular carcinoma: development and external validation of the Munich-TACE score.

Eur J Gastroenterol Hepatol 2018 Jan;30(1):44-53

Department of Medicine II.

Background: Allocation of patients with hepatocellular carcinoma (HCC) to the adequate therapy is determined by both tumor burden and liver function. The Barcelona Clinic Liver Cancer (BCLC) staging system and therapeutic algorithm recommends transarterial chemoembolization (TACE) based on the best evidence available to patients with intermediate-stage HCC (BCLC-B). However, many centers also treat subgroups of patients outside these recommendations and with more advanced disease by TACE. The purpose of this study was to identify prognostic factors in a TACE cohort, including BCLC-B patients, as well as patients treated outside of BCLC-B, to test the prognostic capabilities of published staging systems and to optimize prognostication for TACE patients.

Patients And Methods: A cohort of 186 first-line TACE patients was analyzed. Independent prognostic factors were identified and used to construct the Munich-TACE score (M-TACE). M-TACE was tested against established staging systems (including BCLC and two recently published TACE-specific scores) and a ranking using concordance index and Akaike Information Criterion was performed. Finally, an external validation in an independent TACE cohort (n=71) was conducted.

Results: Bilirubin, Quick/international normalized ratio, C-reactive protein, creatinine, α-feto protein, and tumor extension were identified as independent prognostic factors and used to construct M-TACE. M-TACE identifies three distinct subgroups (P<0.0001) with median survival times of 35.2, 16.9, and 8.6 months, respectively. Compared with established staging systems, M-TACE showed the best prognostic capabilities in both cohorts of patients (cohort 1: c-index, 0.71; Akaike Information Criterion: 1276; cohort 2: c-index, 0.754).

Conclusion: We identified independent risk factors for patients treated with TACE. The newly constructed M-TACE score is superior to established staging systems and might prove helpful to identify patients who are most suitable for TACE.
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January 2018

Evaluation of Visualization Using a 50/50 (Contrast Media/Glucose 5% Solution) Technique for Radioembolization as an Alternative to a Standard Sandwich Technique.

Cardiovasc Intervent Radiol 2017 Nov 5;40(11):1740-1747. Epub 2017 Jun 5.

Department of Clinical Radiology, LMU - University of Munich, Marchioninistrasse. 15, 81377, Munich, Germany.

Background: Radioembolization (RE) with yttrium (Y) resin microspheres generally employs a sandwich technique with separate sequential administration of contrast medium (CM), followed by vehicle (e.g., glucose 5% [G5] solution), then Y resin microspheres (in G5), then G5, and then CM again to avoid contact of CM and microspheres under fluoroscopic guidance. This study evaluates the visualization quality and safety of a modified sandwich technique with a 50/50-mixture of CM (Imeron 300) and G5 for administration of Y resin microspheres.

Materials And Methods: A retrospective analysis of 81 RE procedures in patients with primary or secondary liver tumors was performed. The quality of angiographic visualization of the hepatic vessels was assessed before the first injection and immediately before the whole dose has been injected. Visualization and flow rate were graded on a 5-point scale: 1 = very good to 5 = not visible/no antegrade flow. Univariate logistic regression models and multiple linear regression models were used to evaluate the prognostic variables associated with visualization and flow scores.

Results: Visualization quality was inversely related to flow rate, the lower the flow rate the better the grade of the visualization. Visualization quality was also inversely related to body-mass-index (BMI). Performing RE with the 50/50-CM/G5 mixture resulted in a mean injection time for 1 GBq of 15 min. No clinically significant adverse events, including radiation-induced liver disease were reported.

Conclusion: RE with a 50/50-mixture of CM and G5 for administration of Y resin microspheres in a modified sandwich technique is a safe administration alternative and provides good visualization of hepatic vessels, which is inversely dependent on flow rate and BMI. Injection time was reduced compared with our experience with the standard sandwich technique.
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November 2017

In vitro study of physical properties of various embolization particles regarding morphology before, during and after catheter passage.

Clin Hemorheol Microcirc 2016 ;64(4):887-898

Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Campus Grosshadern, Munich, Germany.

Objective: To evaluate various embolization particles on their physical properties with special regard on morphological variability and elasticity.

Methods: 8 embolization particles (EmboCept®, Contour SE® Microspheres, Embosphere® Micorspheres 400 μm, 500 μm, 1300 μm, Embozene® Microspheres, DC Beads®, Embozene Tandem®) were evaluated and graduated from 1-6 microscopically due to morphologic changes in vitro before, during and after their catheter passage by 4 blinded reviewers. To facilitate comparison, microscopic images were provided with a scale.

Results: All tested particles showed a homogenous shape and morphology before passage through the simulation catheter. During the passage all particles were elastically deformable, where necessary. After the catheter passage no loss of basic shape was seen. Changes in size were found in 5/8 particles. Grading of morphologic changes varied between mean value of 1.0 and 3.0. No complete destruction or loss of function was seen.

Conclusion: All tested embolization particles are, regarding their morphological properties in sense of homogenous shape and deformation after catheter passage, a safe treatment option. Tested in vitro no less of functionality regarding physical properties should be expected.
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March 2017

Safety, Efficacy, and Prognostic Factors After Radioembolization of Hepatic Metastases from Breast Cancer: A Large Single-Center Experience in 81 Patients.

J Nucl Med 2016 Apr 7;57(4):517-23. Epub 2016 Jan 7.

Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.

Unlabelled: The present study evaluated safety, efficacy, and prognostic factors for (90)Y-yttrium microsphere radioembolization of unresectable liver metastases from breast cancer.

Methods: Eighty-one patients were treated with radioembolization. Acute toxicity was monitored through daily physical examination and serum tests until 3 d after radioembolization; late toxicity was evaluated until 12 wk after radioembolization. Overall survival and response according to (18)F-FDG PET (>30% decrease of tracer uptake) and CA15-3 serum level (any decline) were recorded. Pretherapeutic characteristics, including pretreatment history, liver function tests, and PET/CT parameters, were assessed by univariate and subsequent multivariate Cox regression for predicting patient survival.

Results: A toxicity grade of 3 or more based on clinical symptoms, bilirubin, ulcer, pancreatitis, ascites, or radioembolization-induced liver disease occurred in 10% or less of patients. Two patients eventually died from radioembolization-induced liver disease. Sequential lobar treatment and absence of prior angiosuppressive therapy were both associated with a lower rate of serious adverse events. On the basis of PET/CA15-3 criteria, 52/61% of patients responded to treatment. Median overall survival after radioembolization was 35 wk (interquartile range, 41 wk). Pretherapeutic tumor burden of the liver greater than 50% or more (P< 0.001; hazard ratio, 5.67; 95% confidence interval, 2.41-13.34) and a transaminase toxicity grade of 2 or more (P= 0.009; hazard ratio, 2.15; 95% confidence interval, 1.21-3.80) independently predicted short survival.

Conclusion: Radioembolization for breast cancer liver metastases shows encouraging local response rates with low incidence of serious adverse events, especially in those patients with sequential lobar treatment or without prior angiosuppressive therapy. High hepatic tumor burden and liver transaminase levels at baseline indicate poor outcome.
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April 2016

CT fluoroscopy-guided closed-tip catheter placement before regional hyperthermia treatment of soft tissue sarcomas: 5-Year experience in 35 consecutive patients.

Int J Hyperthermia 2016 10;32(2):151-8. Epub 2015 Dec 10.

a Institute for Clinical Radiology, Ludwig Maximilians University Hospital , Munich and.

Purpose: This study was designed to assess technical success and complications in patients with high-risk soft tissue sarcomas undergoing CT fluoroscopy-guided closed-tip catheter placement before treatment with combined chemotherapy and regional hyperthermia.

Materials And Methods: This retrospective study comprised all patients referred for insertion of closed-tip catheters for the introduction of thermometry probes before regional hyperthermia treatment at a single university centre from 2010 to 2015. Catheter placements were performed under local anaesthesia and intermittent CT fluoroscopy guidance. Technical success, complication rate, duration of catheter insertion and dose-length product (DLP) were analysed. Technical success was defined as intratumoural catheter placement suitable for subsequent thermometry.

Results: A total of 35 procedures were performed on 35 patients (22 men, 13 women). In 34 out of 35 interventions catheters were inserted successfully; in one patient catheter placement was not feasible. No intra-interventional complications occurred. In six patients post-interventional complications were observed - two major (one abscess formation and one severe catheter dislocation) and four minor complications. Technical failure was observed in 11.4% of patients, especially catheter kinking. A total of 55 catheters were placed, with a mean number of 1.7 ± 0.7 per patient. Mean total DLP was 723.2 ± 355.9 mGy*cm.

Conclusion: CT fluoroscopy-guided closed-tip catheter placement into high-risk soft tissue sarcomas was characterised by high technical success and relatively low complication rate. While major complications were rarely observed, catheter-kinking preventing successful thermometry represented the most frequent technical failure.
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January 2017

Use of PERCIST for Prediction of Progression-Free and Overall Survival After Radioembolization for Liver Metastases from Pancreatic Cancer.

J Nucl Med 2016 Mar 25;57(3):355-60. Epub 2015 Nov 25.

Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany

Unlabelled: We evaluated the prognostic accuracy of established PET response criteria in patients with liver metastases from pancreatic cancer after treatment with (90)Y microspheres.

Methods: Seventeen patients underwent (18)F-FDG PET/CT before and 3 mo after radioembolization for liver metastases from pancreatic cancer. Overall survival, progression-free survival, and time to intrahepatic progression were among other factors correlated with metabolic response as revealed by PERCIST 1.0-defined declining SUVpeak and total-lesion glycolysis.

Results: Metabolic response by change in SUVpeak (7/17) and change in total-lesion glycolysis (7/17) was a predictor for overall survival (P = 0.039; hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.06-0.93), progression-free survival (P = 0.016; HR, 0.15; 95% CI, 0.03-0.69), and time to intrahepatic progression (P = 0.010; HR, 0.16; 95% CI, 0.04-0.65). A summed baseline CT diameter of less than 8 cm for the 2 largest liver metastases predicted time to intrahepatic progression (P = 0.013; HR, 0.21; 95% CI, 0.06-0.72) but did not predict overall or progression-free survival. Patient outcome was not predicted by other parameters, including baseline SUVpeak, baseline total-lesion glycolysis, or change in serum level of carcinoembryonic antigen or carbohydrate antigen 19-9 from baseline to follow-up (each, P > 0.05).

Conclusion: Metabolic response by (18)F-FDG PET/CT predicts overall survival, progression-free survival, and time to intrahepatic progression after radioembolization for liver metastases from pancreatic cancer.
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March 2016

Evaluating Treatment Response of Radioembolization in Intermediate-Stage Hepatocellular Carcinoma Patients Using 18F-Fluoroethylcholine PET/CT.

J Nucl Med 2015 Nov 24;56(11):1661-6. Epub 2015 Sep 24.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany

Unlabelled: The aim of this study was to evaluate (18)F-fluoroethylcholine PET/CT as a metabolic imaging technique for the assessment of treatment response to (90)Y radioembolization in patients with locally advanced hepatocellular carcinoma (HCC).

Methods: Thirty-four HCC patients undergoing 78 (18)F-fluoroethylcholine PET/CT scans were identified for this study. Patients with initial or follow-up metastastic disease (n = 9) were excluded at the time point of the metastatic occurrence as well as patients with negative α-fetoprotein (AFP; n = 1), resulting in 24 patients and 57 scans that were eligible. All patients were scheduled for radioembolization and underwent 1 pretherapeutic and at least 1 posttherapeutic (18)F-fluoroethylcholine PET/CT scan. Volume-of-interest analysis and volume-of-interest subtractions were performed. Maximum, mean, and peak standardized uptake value (SUV) analysis was performed, and the total intrahepatic (18)F-fluoroethylcholine positive tumor volume (FEC-PTV) and tumor-to-background ratio were assessed. Statistical analysis was performed using a decreasing AFP of at least 20% as a standard of reference for therapy response including receiver-operating-characteristic analyses as well as descriptive and correlation analyses and multiple logistic regression.

Results: Fourteen follow-up examinations were categorized as responder and 19 follow-up examinations as nonresponder. Absolute AFP values did not correlate with SUV parameters (P = 0.055). In receiver-operating-characteristic analyses, the initial mean SUV, Δmaximum SUV, and Δtumor-to-background ratio demonstrated the highest area under the curve, 0.84 (P = 0.009), 0.83 (P = 0.011), and 0.83 (P = 0.012), respectively, resulting in a positive prediction of 82%, 83%, and 91% at the respective cutoff points. When multiple logistic regression analysis was applied, this resulted in an area under the curve of 0.90 (P = 0.001), with a positive prediction of 94% and a sensitivity of 94%. The FEC-PTV did not reach significance in the presented dataset.

Conclusion: (18)F-fluoroethylcholine PET/CT demonstrates a high potential for follow-up assessment in the context of radioembolization in patients with locally advanced, but nonmetastatic, HCC and initially elevated AFP, possibly enabling early therapy monitoring independent of morphology.
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November 2015

Comparative study of the corrosion behavior of peripheral stents in an accelerated corrosion model: experimental in vitro study of 28 metallic vascular endoprostheses.

Diagn Interv Radiol 2015 Sep-Oct;21(5):403-9

Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Munich, Germany.

Purpose: Clinical cases of stent-fractures show that corrosion behavior might play a role in these fractures. Implanted in vivo, especially in combination with other implanted foreign materials, these metallic products are exposed to special conditions, which can cause a process of corrosion. Here, we aimed to test the corrosion potential of stents made of different materials in an in vitro setting.

Methods: A total of 28 peripheral stents of different materials (nitinol, cobalt-chromium-nickel, tantalum, V4A) and surface treatments (electropolish, mechanical polish, no polish) were tested in vitro. Corrosion was accelerated by applying a constant voltage of 3.5 V and amperage of 1.16 mA in 0.9% NaCl.

Results: Nitinol stents showed the lowest susceptibility to corrosion and the longest period without damage. The Memotherm II® (BARD Angiomed®) was the only stent that showed neither macroscopic nor microscopic damages. The worst performing material was cobalt-chromium-nickel, which showed corrosion damages about ten times earlier compared to nitinol. Considering the reasons for termination of the test, nitinol stents primarily showed length deficits, while V4A and tantalum stents showed fractures. Cobalt-chromium-nickel stents had multiple fractures or a complete lysis in equal proportions. When placed in direct contact, nitinol stents showed best corrosion resistance, regardless of what material they were combined with. In terms of polishing treatments, electropolished stents performed the best, mechanical-polished stents and those without polishing treatment followed.

Conclusion: The analysis of corrosion behavior may be useful to select the right stent fulfilling the individual needs of the patient within a large number of different stents.
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December 2016

Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer.

Eur Radiol 2015 Sep 28;25(9):2693-700. Epub 2015 Feb 28.

Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany,

Objectives: Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC).

Methods: Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine.

Results: Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5× upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates.

Conclusions: The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT.

Key Points: • Four individual parameters predicted reduced survival following SIRT in CRC. • These parameters were combined into a nomogram of pre-therapeutic risk stratification. • The model provided good prediction of survival in two independent patient cohorts.
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September 2015

The effectiveness of selective internal radiation therapy in challenging cases of liver-predominant unresectable hepatocellular carcinoma.

Future Oncol 2014 Nov;10(15 Suppl):17-27

Department of Gastroenterology, Hepatology & Infectious Diseases, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.

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November 2014

Parallel-transmit-accelerated spatially-selective excitation MRI for reduced-FOV diffusion-weighted-imaging of the pancreas.

Eur J Radiol 2014 Oct 23;83(10):1709-14. Epub 2014 Jun 23.

Department of Clinical Radiology, Ludwig-Maximilians-University of Munich Hospitals, Munich, Germany; Department of Diagnostic and Interventional Radiology, University Hospital Tuebingen, Tuebingen, Germany.

Objectives: To find out whether the use of accelerated 2D-selective parallel-transmit excitation MRI for diffusion-weighted EPI (pTX-EPI) offers advantages over conventional single-shot EPI (c-EPI) with respect to different aspects of image quality in the MRI of the pancreas.

Materials And Methods: The MRI examinations of 33 consecutive patients were evaluated in this prospective and IRB-approved study. PTX-EPI was performed with a reduced (zoomed) FOV of 230 × 118 mm(2). The 2D-RF pulse of pTX-EPI was accelerated, i.e. shortened by a factor of 1.7 (pTX-acceleration factor). C-EPI used a full-FOV of 380 × 285 mm(2). In a qualitative analysis, two experienced readers evaluated 3 different aspects of image quality on 3- to 5-point Likert scales. Additionally, apparent diffusion coefficients (ADCs) were determined in both c-EPI and pTX-EPI in normal-appearing pancreatic tissue using regions of interests (ROIs). Mean ADC values and standard deviations were compared between the two techniques.

Results: The reduced-FOV pTX-EPI was superior to c-EPI with respect to overall image quality (p<0.0001) and identifiability of the pancreatic ducts (p<0.01). Artifacts were significantly less severe in pTX-EPI (p<0.01). The mean ADC values of c-EPI (1.29 ± 0.19 × 10(-3)mm(2)/s) and pTX-EPI (1.27 ± 0.17 × 10(-3)mm(2)/s) did not differ significantly between the two techniques (p=0.44). The variation within the ROIs as measured by the standard deviation was significantly lower in pTX-EPI (0.095 × 10(-3)mm(2)/s) than in c-EPI (0.135 × 10(-3)mm(2)/s), p<0.05.

Conclusions: PTX-accelerated EPI with spatially-selective excitation and reduced FOV leads to substantial improvements in DWI of the pancreas with respect to different aspects of image quality without significantly influencing the ADC values.
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October 2014

Technical and clinical outcome of percutaneous CT fluoroscopy-guided screw placement in unstable injuries of the posterior pelvic ring.

Skeletal Radiol 2014 Aug 10;43(8):1093-100. Epub 2014 May 10.

Institute for Clinical Radiology, Marchioninistr. 15, 81377, Munich, Germany,

Purpose: To evaluate technical success, complications, and effective dose in patients undergoing CT fluoroscopy-guided iliosacral screw placement for the fixation of unstable posterior pelvic ring injuries.

Materials And Methods: Our retrospective analysis includes all consecutive patients with vertical sacral fractures and/or injury of the iliosacral joint treated with CT fluoroscopy-guided screw placement in our department from 11/2005 to 03/2013. Interventions were carried out under general anesthesia and CT fluoroscopy (10-20 mAs; 120 kV; 16- or 128-row scanner, Siemens Healthcare, Erlangen, Germany). Technical outcome, major and minor complications, and effective patient dose were analyzed.

Results: We treated 99 consecutive patients (mean age 53.1 ± 21.7 years, 50 male, 49 female) with posterior pelvic ring instability with CT fluoroscopy-guided screw placement. Intervention was technically successful in all patients (n = 99). No major and one minor local complication occurred (1 %, secondary screw dislocation). General complications included three cases of death (3 %) due to pulmonary embolism (n = 1), hemorrhagic shock (n = 1), or cardiac event (n = 1) during a follow-up period of 30 days. General complications were not related to the intervention. Mean effective patient radiation dose per intervention was 12.28 mSv ± 7.25 mSv. Mean procedural time was 72.1 ± 37.4 min.

Conclusions: CT fluoroscopy-guided screw placement for the treatment of posterior pelvic ring instabilities can be performed with high technical success and a low complication rate. This method provides excellent intrainterventional visualization of iliac and sacral bones, as well as the sacral neuroforamina for precise screw placement by applying an acceptable effective patient dose.
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August 2014

DCE-MRI biomarkers for monitoring an anti-angiogenic triple combination therapy in experimental hypopharynx carcinoma xenografts with immunohistochemical validation.

Acta Radiol 2015 Mar 7;56(3):294-303. Epub 2014 Mar 7.

Department of Clinical Radiology, Laboratory of Experimental Radiology, University of Munich Hospitals, Ludwig-Maximilians-University Munich, Munich, Germany

Background: Novel anti-angiogenic treatments are increasingly complementing established cancer therapy strategies in head and neck tumors. Contrast-enhanced magnetic resonance imaging (MRI) can be applied for early and non-invasive therapy monitoring by non-invasive quantitative assessment of tumor microcirculation as in vivo imaging biomarkers of therapy response.

Purpose: To monitor the anti-angiogenic effects of a novel combination therapy on experimental head and neck squamous cell carcinomas (HNSCC) with dynamic contrast-enhanced (DCE)-MRI.

Material And Methods: Athymic rats (n = 18) with subcutaneous HNSCC xenografts were investigated by DCE-MRI before and after 7 days of a daily triple therapy regimen combining the COX-II-inhibitor celecoxib, the matrix-metalloproteinase-inhibitor GM6001, and the uPA-inhibitor upamostat. Quantitative measurements of tumor blood flow (tBF), tumor blood volume (tBV), and permeability-surface area product (PS) were calculated and validated by immunohistochemistry.

Results: Mean tBF and tBV in triple-therapy animals decreased significantly from day 0 to day 7 (tBF, 41.0 ± 14.2 to 20.4 ± 5.7 mL/100 mL/min; P < 0.01; tBV, 17.7 ± 3.9 to 7.5 ± 3.3%; P < 0.01). No significant effects on PS were observed in either group (P > 0.05). Immunohistochemical analysis showed a significantly lower tumor vascularity in the therapy group than in the control group (CD31), significantly fewer Ki-67+ proliferating tumor cells and significantly more Capase-3+ apoptotic tumor cells (P < 0.05). Significant (P < 0.05) correlations were observed between tBF/tBV and CD31 (tBF, r = 0.84; tBV, r = 0.70), tBV and Ki-67 (r = 0.62), as well as tBF and caspase-3 (r = -0.64).

Conclusion: DCE-MRI may be a suitable tool for the non-invasive monitoring of the anti-vascular effects of this innovative triple therapy regimen with potential for clinical translation.
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March 2015

CT fluoroscopy-guided percutaneous fiducial marker placement for CyberKnife stereotactic radiosurgery: technical results and complications in 222 consecutive procedures.

J Vasc Interv Radiol 2014 May 12;25(5):760-8. Epub 2014 Feb 12.

Department and Policlinics of Diagnostic Radiology, Carl Gustav Carus University Dresden, Dresden, Germany.

Purpose: To evaluate technical outcome and safety of computed tomographic (CT) fluoroscopy-guided percutaneous fiducial marker placement before CyberKnife stereotactic radiosurgery.

Materials And Methods: Retrospective analysis was performed of 196 patients (106 men) undergoing CT fluoroscopy-guided fiducial marker placement in 222 consecutive procedures under local anesthesia from March 2006 to February 2012. Technical success was defined as fiducial marker location in the tumor or vicinity suitable for CyberKnife radiosurgery evaluated on postinterventional planning CT. Complications were classified per Society of Interventional Radiology (SIR).

Results: One hundred ninety-six patients (age, 61.5 y ± 13.1) underwent percutaneous placement of 321 fiducial markers (mean per tumor, 1.2 ± 0.5; range, 1-4) in 37 primary tumors and 227 metastases in the thorax (n = 121), abdomen (n = 122), and bone (n = 21). Fiducial marker placement was technically successful in all procedures: intratumoral localization in 193 (60.1%), at tumor margin in 50 (15.6%), and outside of tumor in 78 cases (24.3%; mean distance to marker, 0.4 cm ± 0.6; range, 0-2.9 cm). Complications were observed in 63 placement procedures (28.4%), including minor self-limiting pneumothorax (n = 21; SIR class B) and self-limiting pulmonary hemorrhage (n = 35; SIR class A), and major pneumothorax requiring thoracostomy/drainage insertion (n = 14; SIR class D) and systemic toxicity of local anesthetic drug (n = 1; SIR class D).

Conclusions: CT fluoroscopy-guided percutaneous fiducial marker placement can be performed with high technical success under local anesthesia in various anatomic regions. Although self-limiting in most cases, pneumothorax and pulmonary hemorrhage are frequently observed during fiducial marker implantation into lung tumors.
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May 2014

Towards new response criteria in neuroendocrine tumors: which changes in MRI parameters are associated with longer progression-free survival after radioembolization of liver metastases?

J Magn Reson Imaging 2015 Feb 21;41(2):361-8. Epub 2014 Jan 21.

Department of Clinical Radiology, University Hospitals-Grosshadern, Ludwig-Maximilians University, Munich, Germany; Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), University Hospitals-Grosshadern, Ludwig-Maximilians University, Munich, Germany.

Purpose: To evaluate the association of therapy-related changes in imaging parameters with progression-free survival (PFS) of patients with unresectable liver metastases from neuroendocrine tumors (NETLMs).

Materials And Methods: Forty-five radioembolized patients (median age: 62 years; range: 43-75) received a pre- and 3 months posttherapeutic magnetic resonance imaging (MRI) examination. The latter were evaluated for tumor size, arterial enhancement, and necrosis pattern. Influences of therapy-related changes on PFS were analyzed. Statistical analysis included Student's t-test, Wilcoxon test, Cox regression analysis, and Kaplan-Meier curves.

Results: The median percentage decrease in sum of diameters was 9.7% (range: 43.9% decrease to 15.4% increase). Twenty-one patients (47%) showed increased necrosis. Three parameters were associated with significantly longer PFS: a decrease of diameter (hazard ratio [HR]: 0.206; 95% confidence interval [CI]: 0.058-0.725; P = 0.0139), a decrease in tumor arterial enhancement (HR: 0.143; 95% CI: 0.029-0.696; P = 0.0160), and an increase in necrosis after 3 months (HR: 0.321; 95% CI: 0.104-0.990; P = 0.0480). Multivariate analysis revealed that changes in diameter and arterial enhancement have complementary information and are associated independently with long PFS.

Conclusion: A decrease both in sum of diameters and arterial enhancement of metastases, as well as an increase in necrosis, are associated with significantly longer PFS after radioembolization.
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February 2015