Lars Stelter

Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors.

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.

Preoperative evaluation of living kidney donors using multirow detector computed tomography: comparison with digital subtraction angiography and intraoperative findings

To assess the accuracy of multirow detector computed tomography (MDCT) for the evaluation of renal anatomy for preoperative donor assessment in living related kidney transplantation. MDCT‐scans (4‐ and 16‐slice‐CT) of 51 consecutive living kidney donors (age, 51.6 ± 9.7 years; range, 28–68 years) were analysed by three blinded observers and compared with digital subtraction angiography (DSA) and surgery. Contrast‐enhanced MDCT was performed with 1 mm slice thickness reconstruction interval during arterial and venous phases. Supernumerary renal arteries, veins, early branching of vessels and abnormalities of the ureters were documented. The overall accuracy of computed tomography angiography (CTA) for detection and classification of surgically relevant arterial variants was 97% (99/102). The interpretation of 16‐channel MDCT images was correct in all cases (accuracy, 100%), while the four‐channel CTA had three incorrect results regarding the differentiation of early branching vessels from double renal arteries (accuracy, 93%). The overall accuracy of DSA was 91%. Renal vein abnormalities were correctly diagnosed with MDCT in 100% compared with 89% correct findings with DSA. There were three kidneys with incomplete ureter duplication, detected both with MDCT and DSA. MDCT demonstrated superior accuracy compared with non‐selective DSA for the preoperative assessment of renal anatomy in living kidney donors; and for the distinction of supernumerary arteries versus early branching patterns, 16‐channel CTA data were better than those of the four‐channel system.

Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.

Minimum intensity projections of the biliary system using 16-channel multidetector computed tomography in patients with biliary obstruction: comparison with MRCP

The objective was the evaluation of minimum intensity projections (MinIP) of 16-channel multidetector computed tomography (MDCT) data for the visualization of biliary ducts with magnetic resonance cholangiopancreatography (MRCP) as reference method. Twenty-five patients with biliary obstruction who received MDCT of the abdomen and MRCP without subsequent interventions were analysed. Coronal and axial MinIP were reconstructed from the MDCT-data. The evaluation of image quality and the quantitative comparison to MRCP was performed by two observers in consensus. The additional diagnostic value of MinIP compared with conventionally visualised MDCT was assessed by three independent observers. With MRCP as the reference method, MinIP was superior to conventional MDCT concerning the visualization of the extent of bile duct dilatation (r, 1.000 vs 0.699) and the correlation of diameter measurement (r, 0.979 vs 0.942). Subsidiary to conventional MDCT, MinIP revealed an improvement of visualization of the biliary system in 73% of cases. Concerning the additional diagnostic value, MinIP allowed for a better definition of the obstruction site in 13% of patients, and in one patient a change of diagnosis was observed. Thus, MinIP can improve the diagnostic assessment of biliary obstructions in MDCT imaging.

Multislice computed tomography using a triple-phase contrast protocol for preoperative assessment of hepatic tumor load in patients with hepatocellular carcinoma before liver transplantation.

For evaluation of triple‐phase multislice computed tomography (CT) for assessment of hepatocellular carcinoma (HCC) before liver transplantation. All HCC patients who underwent liver transplantation at our institution between 2001 and 2006 and had contrast‐enhanced abdominal 4‐/16‐slice CT [unenhanced, arterial (20 s delay), portal venous (40 s), and venous (80 s) scan] within 100 days before transplantation were enrolled retrospectively. CT data were reviewed by two observers. Results were correlated to histopathologic findings by means of a lesion‐by‐lesion evaluation. Thirty‐two patients with 76 HCC‐lesions were included. The lesion‐based sensitivity of observer 1 and 2 was 78% (59/76) and 83% (63/76) (false positives, n = 6 and n = 10). The sensitivity of observer 1/2 was 89%/95% for lesions >20 mm (n = 37), 94% for lesions 11–20 mm (n = 18), and 43%/53% for lesions <10 mm (n = 21). The mean detection rates of unenhanced, arterial, portal venous, and venous phase scans were 30%, 74%, 59%, and 40%. All detected lesions were visible on arterial and/or portal venous scans (arterial only, 24%; portal venous only, 9%). Arterial and portal venous phase scans are the strongest contributors to the high detection rate of triple‐phase multislice‐CT in HCC. However, the detection of small HCC measuring <10 mm and false positive findings remains a challenge.

Arterial Versus Portal Venous Embolization for Induction of Hepatic Hypertrophy before Extended Right Hemihepatectomy in Hilar Cholangiocarcinomas: A Prospective Randomized Study

PURPOSE To assess the efficacy and safety of portal vein (PV) embolization versus hepatic artery embolization (HAE) for induction of hepatic hypertrophy before extended right hemihepatectomy in patients with hilar cholangiocarcinoma. MATERIALS AND METHODS Fifty patients (female, n = 15; male, n = 35; age range, 37-80 y) with hilar cholangiocarcinomas who were planned to undergo extended right hemihepatectomy were prospectively included in 2003-2006. In addition to biliary decompression of the left liver, patients were randomized to undergo embolization of the right hepatic artery (with transfemoral access and polyvinyl alcohol [PVA] particles plus coils) or right PV branches (with computed tomography [CT]-guided transhepatic access and PVA particles). CT was performed before and approximately 3 weeks after embolization for volumetric assessment of the liver. RESULTS In the HAE group, median growth of the left lateral segments was 40 mL (P < .01), with a median reduction of the whole liver of 10 mL (P = .41); adverse events were observed in two of 25 patients (8%), who each developed an abscess in the right liver lobe. In the PV embolization group, median growth of the left lateral segments was 110 mL (P < .01), with a median growth of the whole liver of 10 mL (P = .92); a subcapsular seroma occurred in one of 25 patients (4%). The median growth of the left lateral segments after PV embolization was significantly greater than after HAE (P = .004). CONCLUSIONS Compared with HAE, PV embolization was significantly superior regarding induction of hepatic hypertrophy of the left lateral segments.

Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography.

Transplantation of primary human hepatocytes is a promising approach in certain liver diseases. For the visualization of the hepa‐tocytes during and following cell application and the ability of a timely response to potential complications, a non‐invasive modality for imaging the transplanted cells has to be established. The aim of this study was to label primary human hepatocytes with micron‐sized iron oxide particles (MPIOs), enabling the detection of cells by clinical magnetic resonance imaging (MRI). Primary human hepatocytes isolated from 13 different donors were used for the labelling experiments. Following the dose‐finding studies, hepatocytes were incubated with 30 particles/cell for 4 hrs in an adhesion culture. Particle incorporation was investigated via light, fluorescence and electron microscopy, and labelled cells were fixed and analysed in an agarose suspension by a 3.0 Tesla MR scanner. The hepatocytes were enzymatically resuspended and analysed during a 5‐day reculture period for viability, total protein, enzyme leakage (aspartate aminotransferase [AST], lactate dehydrogenase [LDH]) and metabolic activity (urea, albumin). A mean uptake of 18 particles/cell could be observed, and the primary human hepatocytes were clearly detectable by MR instrumentation. The particle load was not affected by resuspension and showed no alternations during the culture period. Compared to control groups, labelling and resuspension had no adverse effects on the viability, enzyme leakage and metabolic activity of the human hepatocytes. The feasibility of preparing MPIO‐labelled primary human hepatocytes detectable by clinical MR equipment was shown in vitro. MPIO‐labelled cells could serve for basic research and quality control in the clinical setting of human hepatocyte transplantation.

Flip angle modulations in late phase Gd-EOB-DTPA MRI improve the identification of the biliary system

OBJECTIVES To assess the improvement of bile duct visualization in Gd-EOB-DTPA enhanced MR-cholangiography (EOB-MRC) by using an increased flip angle. METHODS 35 patients underwent Gd-EOB-DTPA enhanced MRI of the liver including T2-weighted MRCP and hepatobiliary phase EOB-MRC using a flip angle of 10° (FA10) and of 35° (FA35), respectively. Images were evaluated regarding the delineation of biliary ducts, the order of branching and anatomic visualization of the biliary tree. ROI analysis was performed to estimate the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. RESULTS Applying the FA35 resulted in a significantly better SNR and CNR as compared to FA10. The overall image quality was rated as good for both, FA10 and FA35. The overall rating for regional delineation of the biliary system was rated significantly better for FA35 than for FA10 (p=0.02). Classification of bile duct anatomy variations, however, was equivalent in both techniques. CONCLUSIONS Increasing the flip angle of a T1-weighted 3D-sequence from 10° to 35° during the hepatobiliary phase of Gd-EOB enhanced MRI visually and quantitatively improved the visualization of the biliary ducts.

Novel Mechanistic Insights into Arginine Deiminase Pharmacology Suggest 18F-FDG Is Not Suitable to Evaluate Clinical Response in Melanoma

Because of deficiencies in l-arginine biosynthesis, some cancers are susceptible to therapeutic intervention with arginine deiminase (ADI), an enzyme responsible for consuming the dietary supply of l-arginine to deprive the disease of an essential nutrient. ADI is currently being evaluated in several clinical trials, and fully realizing the drugs potential will depend on invoking the appropriate metrics to judge clinical response. Without a clear biologic mandate, PET/CT with 18F-FDG is currently used to monitor patients treated with ADI. However, it is unclear if it can be expected that 18F-FDG responses will indicate (or predict) clinical benefit. Methods: 18F-FDG responses to ADI therapy were studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was also studied, with a particular emphasis on biologic pathways known to regulate 18F-FDG avidity. Results: Although proliferation of SK-MEL 28 was potently inhibited by ADI treatment in vitro and in vivo, no clear declines in 18F-FDG uptake were observed. Further investigation showed that ADI treatment induces the posttranslational degradation of phosphatase and tensin homolog and the activation of the PI3K signaling pathway, an event known to enhance glycolysis and 18F-FDG avidity. A more thorough mechanistic study showed that ADI triggered a complex mechanism of cell death, involving apoptosis via poly (ADP-ribose) polymerase cleavage—independent of caspase 3. Conclusion: These findings suggest that some unexpected pharmacologic properties of ADI preclude using 18F-FDG to evaluate clinical response in melanoma and, more generally, argue for further studies to explore the use of PET tracers that target apoptotic pathway activation or cell death.

Preoperative multidetector row computed tomography for evaluation and assessment of resection criteria in patients with pancreatic masses

Background: Preoperative assessment of pancreatic masses is still challenging as regards the characterization and assessment of irresectability. The opportunities of modern multidetector computed tomography (MDCT) with image postprocessing can be expected to enhance the diagnostic performance if accurate criteria are elaborated. Purpose: To estimate the accuracy of MDCT and multiplanar image reconstructions with the use of standardized imaging criteria for preoperative evaluation of pancreatic masses with respect to irresectability. Material and Methods: A total of 105 consecutive patients who underwent exploratory laparoscopy or pancreatic resection and had preoperative 3-phase MDCT (4–64 rows) were enrolled retrospectively. First, transverse sections and secondly additional 3Ds were reviewed by two independent blinded observers (O1/O2). Preoperative imaging findings were correlated with intraoperative and histopathologic results. Results: Among all 105 patients, 70 malignant pancreatic tumors and 35 benign pancreatic diseases were found (accuracy of 93% for O1 and 91% for O2). For arterial tumor invasion, receiver operator characteristic (ROC) analysis (values averaged from the results of O1 and O2) revealed an area under the curve (AUC) of 0.931 for transverse sections and 0.986 for 3Ds. Regarding irresectability, positive predictive values were 97% (with 3Ds, 97%) for O1/O2; negative predictive values were 84% (with 3Ds, 89%) for O1 and 86% (with 3Ds, 91%) for O2. Conclusion: MDCT with 3Ds was highly accurate for evaluation and assessment of irresectability criteria in patients with pancreatic masses. However, due to the limited specificity regarding arterial tumor infiltration, the indication for surgical exploration should be made generously in case of inconclusive findings.