Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo.

Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors.

Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images-a voxel-based whole brain analysis.

OBJECTIVES: To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. METHODS: In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the "Diffeomorphic Anatomical Registration using Exponentiated Lie algebra" (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. RESULTS: Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. CONCLUSION: Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. KEY POINTS: • Repeated administration of gadobutrol does not lead to increased signal intensity. • Voxel-based whole-brain analysis allows assessment of subtle changes in signal intensity. • Macrocyclic contrast agents in a proven dosage are safe.

Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study.

OBJECTIVE: Serum lipase activities above the threefold upper reference limit indicate acute pancreatitis. We investigated whether high lipase activity-within the reference range and in the absence of pancreatitis-are associated with genetic single nucleotide polymorphisms (SNP), and whether these identified SNPs are also associated with clinical pancreatitis. METHODS: Genome-wide association studies (GWAS) on phenotypes 'serum lipase activity' and 'high serum lipase activity' were conducted including 3966 German volunteers from the population-based Study-of-Health-in-Pomerania (SHIP). Lead SNPs associated on a genome-wide significance level were replicated in two cohorts, 1444 blood donors and 1042 pancreatitis patients. RESULTS: Initial discovery GWAS detected SNPs within or near genes encoding the ABO blood group specifying transferases A/B (ABO), Fucosyltransferase-2 (FUT2), and Chymotrypsinogen-B2 (CTRB2), to be significantly associated with lipase activity levels in asymptomatic subjects. Replication analyses in blood donors confirmed the association of FUT-2 non-secretor status (OR=1.49; p=0.012) and ABO blood-type-B (OR=2.48; p=7.29×10(-8)) with high lipase activity levels. In pancreatitis patients, significant associations were found for FUT-2 non-secretor status (OR=1.53; p=8.56×10(-4)) and ABO-B (OR=1.69, p=1.0×10(-4)) with chronic pancreatitis, but not with acute pancreatitis. Conversely, carriers of blood group O were less frequently affected by chronic pancreatitis (OR=0.62; p=1.22×10(-05)) and less likely to have high lipase activity levels (OR=0.59; p=8.14×10(-05)). CONCLUSIONS: These are the first results indicating that ABO blood type-B as well as FUT2 non-secretor status are common population-wide risk factors for developing chronic pancreatitis. They also imply that, even within the reference range, elevated lipase activities may indicate subclinical pancreatic injury in asymptomatic subjects.

Acute inversion injury of the ankle without radiological abnormalities: assessment with high-field MR imaging and correlation of findings with clinical outcome.

BACKGROUND: Acute inversion injuries of the ankle are the most common sports accidents, accounting for approximately 10% of emergency room admissions. In up to 85%, an injury of the lateral collateral ligaments is observed. Classically, the assessment of these injuries has relied on clinical examination and radiographs, including stress views. The aim of our study was to correlate prospectively the findings of high-field 3 T MRI in acute ankle distortion with clinical outcome. METHODS: During a 6-month period, 38 patients were prospectively included. MRI was performed within 48 h of trauma and clinical examination using a protocol consisting of axial T2-weighted and coronal and sagittal T1-weighted images and a sagittal proton density (PDw) sequence. Each ligament injury was graded on a three-point scale. Functional outcome was evaluated using the AOFAS ankle-hindfoot scale. RESULTS: In 24/38 patients (63.12%), ligament injury was observed. In 22/24 cases, this was an injury of the lateral ligaments and in 2/24 cases of the medial ligaments. Injury of the syndesmosis occurred in three patients, a bone bruise in four, and an osteochondral lesion in three cases. Patients with an injury of two or more ligaments or a bone bruise had a lower AOFAS score and returned to sports activities and full weight-bearing later (P < 0.01). CONCLUSION: MR imaging at 3 Tesla is an independent predictor for clinical outcome. Therefore MRI may be beneficial in those cases where the findings influence further treatment.

Assessing early vascular changes and treatment response after laser-induced thermotherapy of pulmonary metastases with perfusion CT: initial experience.

OBJECTIVE: The objective of our study was to use perfusion CT to prospectively monitor early vascular changes in tumor perfusion of pulmonary metastases after laser-induced thermotherapy (LITT) and to determine whether any of the perfusion parameters would predict technical success after therapy. SUBJECTS AND METHODS: Twelve patients with histologically proven pulmonary metastases undergoing LITT were enrolled prospectively in this study. Perfusion CT was performed before treatment, 1 day after treatment, and 4-6 weeks after therapy, and tumor blood flow, tumor blood volume (TBV), mean transit time (MTT), and permeability of the capillary wall surface (capillary permeability-surface product) in 22 pulmonary metastases were calculated. Perfusion parameters at baseline and after LITT were compared. Measurement of tumor diameter on long-term follow-up CT was the gold standard with which perfusion CT results were compared for local control. RESULTS: Median tumor blood flow, TBV, and capillary permeability-surface product had decreased significantly from baseline by 43%, 61%, and 73%, respectively, 1 day after LITT. Perfusion parameters obtained 4-6 weeks after treatment had not changed significantly compared with those obtained 1 day after therapy. There seems to be a good correlation between changes in perfusion CT parameters 1 day after therapy and local outcome, according to the Response Evaluation Criteria in Solid Tumors (RECIST), 1 year after therapy. CONCLUSION: Perfusion CT of pulmonary metastases has potential in the assessment of early vascular changes that result from LITT and predicting technical success immediately after treatment. Tumors with perfusion measurements that had not changed after therapy indicated progressive disease.

Laser ablation of liver metastases from colorectal cancer with MR thermometry: 5-year survival.

PURPOSE: To determine technical success, technique effectiveness, complications, and survival after laser ablation of liver metastases from colorectal cancer. MATERIALS AND METHODS: Eighty-seven consecutive patients (65 men and 22 women; mean age, 62.8 years) with 180 liver metastases from colorectal carcinoma were included between 1998 and 2005. They underwent laser ablation with magnetic resonance (MR) thermometry in 170 sessions. Indications for laser ablation were locally unresectable tumors (16.1%), metastases in both liver lobes (34.5%), and refusal of surgery and/or general contraindications to surgery (49.4%). Technical success, technique effectiveness, and complication and survival rates were evaluated retrospectively. RESULTS: Technical success was achieved in 178 of 180 sessions (99%). Follow-up after 24-48 hours demonstrated an effectiveness rate of 85.6%. Local tumor progression rate was 10% after 6 months. Major complications included large pleural effusion, large subcapsular hematoma, abscess, large pneumothorax, pleuritis with fever, intrahepatic hemorrhage, and biloma. Mean survival from the time of diagnosis of the primary tumor was 50.6 months for all patients treated (95% CI, 44.9-56.3 months). Median survival time was 54 months and survival rates were 95.7% at 1 year, 86.2% at 2 years, 72.4% at 3 years, 50.1% at 4 years, and 33.4% at 5 years. The mean survival time after the first treatment was 31.1 months (95% CI, 26.9-35.3 months). CONCLUSIONS: Laser ablation of liver metastases of colorectal cancer with MR thermometry appears safe and efficacious. Although the results are encouraging, direct comparison with other ablative modalities in a prospective clinical trial would be necessary to definitely show one modality is superior.

Three-dimensional gradient-echo imaging for percutaneous MR-guided laser therapy of liver metastasis.

PURPOSE: To evaluate the use of three-dimensional (3D) gradient-echo (GRE) magnetic resonance imaging (MRI) for percutaneous MR-guided catheter placement for laser therapy of liver metastases. MATERIALS AND METHODS: Thirty-four patients were included. A total of 122 MR-guided percutaneous punctures of 67 liver metastases were performed on a 1.5T scanner (Symphony and Sonata; Siemens, Erlangen, Germany) using a 5.5F microcatheter system and titanium needle (Monocath; MeoMedical, Augsburg, Germany). In 88 of 122 procedures, a 2D fast low-angle shot (FLASH) T1-weighted GRE breath-hold sequence was acquired in the axial plane and if necessary in a second plane. Sequences were acquired and reviewed using the panel in the control room. In 34 of 122 procedures a 3D FLASH T1-weighted fat-saturated GRE (volume-interpolated breath-hold examination (VIBE)) sequence was acquired in the axial plane only. Acquisition and 3D review were controlled under sterile conditions with a panel inside the examination room (Syngo; Siemens). RESULTS: The 3D FLASH sequence significantly decreased the mean number of acquisitions needed to place the microcatheter with the titanium needle in the metastasis compared to interventions with the 2D FLASH sequence (2.9 +/- 0.83 vs. 4.4 +/- 1.63). With 2D FLASH imaging, acquisition in a second plane was necessary in 78 instances (20% of acquired 2D sequences) to ensure adequate positioning of the device during the procedure. The artifact caused by the titanium needle was smaller with the 3D FLASH sequence. The conspicuity of liver metastases and morphology (liver edge and vessels) was acceptable with both sequences. The 3D FLASH sequence improved differentiation when two to four titanium needles were inserted, due to smaller susceptibility artifacts caused by the needles. CONCLUSION: 3D GRE imaging with the capability to perform multiplanar reconstruction (MPR) shortens the procedure by reducing the number of sequences needed. Improved visibility of the titanium needles allows more precise insertion of multiple needles into the metastasis.