Thomas J. Kroencke

Effect of Sildenafil on digital ulcers in systemic sclerosis – analysis from a single centre pilot study

Objective In this pilot study, the effect of sildenafil on digital ulcer (DU) healing and related clinical symptoms was analysed. Methods A total of 19 patients with systemic sclerosis (SSc) were treated with maximally tolerated sildenafil doses up to 6 months. Primary outcome was the healing of DUs. Changes in other clinical symptoms were also evaluated. Results In all, 49 DUs were present at baseline; this decreased to 17 ulcers (p<0.001) at the end of sildenafil treatment. Furthermore, the visual analogue scale (VAS) score for Raynauds phenomenon (RP), pain and activity improved (p=0.003, p=0.002 and p=0.05, respectively). A total of 9 patients developed 12 new DUs during sildenafil treatment. Conclusions This study indicates an effect of sildenafil on DU healing in patients with SSc and an improvement of RP and associated symptoms that should be validated in controlled studies.

Uterine artery embolization for leiomyomas: percentage of infarction predicts clinical outcome.

PURPOSE To determine the effect of partial versus complete leiomyoma infarction on relief of leiomyoma-related symptoms and freedom from invasive reinterventions and to assess if patient age, location of the dominant leiomyoma, number of leiomyomas, or baseline uterine and dominant leiomyoma volume were associated with clinical failure. MATERIALS AND METHODS Study protocol was approved by the institutional review board, and informed consent was obtained. One hundred fifteen consecutive women (median age, 42 years; range, 34-61 years) with symptomatic uterine leiomyomas underwent contrast material-enhanced magnetic resonance (MR) imaging at baseline and 24-72 hours after uterine artery embolization (UAE) to determine the percentage of infarction of leiomyoma tissue (complete = 100%, almost complete = 90%-99%, and partial = 0%-89%). Clinical outcome and frequency of reinterventions were compared for up to 36 months. RESULTS One hundred thirteen patients completed at least one clinical follow-up. Twenty-four months after UAE, 50% +/- 15.2 (standard error) of the patients with partial infarction and 80% +/- 13.4 (standard error) of patients with almost complete infarction had undergone no reintervention. No patient with complete infarction needed a second treatment (P < .001). The hazard ratios for reintervention between the complete infarction group and the almost complete and partial infarction groups were 15.88 (95% confidence interval [CI]: 1.22, 2225.54; P = .034) and 73.08 (95% CI: 8.33, 9636.35; P < .001), respectively. There were significant differences in hazard ratios between patients with partial and those with complete infarction for persistence or recurrence of menorrhagia (hazard ratio, 7.45; 95% CI: 2.08, 28.31; P = .002) and bulk-related symptoms (hazard ratio, 5.90; 95% CI: 1.66, 21.92; P = .007). There was no significant correlation between patient age, number of leiomyomas, location of the dominant leiomyoma, or baseline uterine and dominant leiomyoma volume and clinical failure. CONCLUSION Women with leiomyoma infarction above 90% on contrast-enhanced MR images after UAE show significantly better symptom control and fewer reinterventions than do patients with a lower infarction rate.

MR elastography of the liver and the spleen using a piezoelectric driver, single-shot wave-field acquisition, and multifrequency dual parameter reconstruction.

Viscoelastic properties of the liver are sensitive to fibrosis. This study proposes several modifications to existing magnetic resonance elastography (MRE) techniques to improve the accuracy of abdominal MRE.

Comparison of the iron oxide-based blood-pool contrast medium VSOP-C184 with gadopentetate dimeglumine for first-pass magnetic resonance angiography of the aorta and renal arteries in pigs.

Rationale and Objectives:VSOP-C184 at a dose of 0.045 mmol Fe/kg has been shown to be an efficient blood pool contrast medium for equilibrium magnetic resonance angiography (MRA) that can be administered as a bolus. The present study was performed to determine whether VSOP-C184 is also suitable for first-pass MRA. Materials and Methods:Fifteen MRA examinations at 1.5 T were performed in minipigs using a fast 3D fast low-angle shot (FLASH) sequence (repetition time = 4.5 ms, echo time = 1.7 ms, excitation angle = 25°, matrix 256, body phased-array coil). The citrate-stabilized iron oxide preparation VSOP-C184 was investigated (total particle diameter: 7.0 ± 0.15 nm; core size: 4 nm) and compared with gadopentetate dimeglumine (Gd-DTPA). The following doses were tested: VSOP-C184: 0.015, 0.025, and 0.035 mmol Fe/kg; Gd-DTPA: 0.1 and 0.2 mmol Gd/kg; n = 3 examinations/dose. Data were analyzed quantitatively (signal enhancement (ENH) and vessel edge definition (VED)) and qualitatively. Results:First-pass MRA using the 3 doses of VSOP-C184 yielded the following ENH: aorta: 9.4 ± 2.6; 12.31 ± 1.2; 16.53 ± 1.7; renal arteries: 7.6 ± 2.2; 9.9 ± 1.0; 13.2 ± 0.5. The values for the 2 doses of Gd-DTPA were aorta: 12.9 ± 1.0; 16.8 ± 2.2; renal arteries: 11.2 ± 1.23; 11.3 ± 1.7. VED for the 3 doses of VSOP-C184 was aorta: 106.3 ± 31.0; 135.3 ± 58.8; 141.3 ± 71.0; renal arteries: 102.2 ± 24.3; 146.8 ± 63.0; 126.9 ± 37.6 and for the 2 doses of Gd-DTPA, aorta: 157.2 ± 47.8; 164.2 ± 36.8; renal arteries: 165.9 ± 30.4; 170.3 ± 38.2 respectively. The differences between VSOP-C184 and Gd-DTPA are clinically not relevant and statistically not significant (p ≥ .05). Qualitative evaluation of image quality, contrast, and delineation of vessels showed the results obtained with VSOP-C184 at doses of 0.025 and 0.035 mmol Fe/kg to be similar to those of Gd-DTPA at 0.1 and 0.2 mmol Gd/kg. Conclusion:VSOP-C184 is suitable for first-pass MRA at doses of 0.025 and 0.035 mmol Fe/kg and thus, in addition to its blood pool characteristics, allows for selective visualization of the arteries without interfering venous signal.

Uterine arterial embolization with tris-acryl gelatin microspheres : A histopathologic evaluation

Uterine artery embolization (UAE) as an alternative to surgery for the treatment of uterine fibroids and adenomyosis uteri became increasingly popular. While the clinical success of this new treatment strategy is without doubt, there is still considerable uncertainty with respect to the morphologic changes induced by UAE. In this study, a total of 173 women were treated with UAE using tris-acryl gelatin microspheres (TGMS), a new particulate spherical embolic agent, for either symptomatic adenomyosis or leiomyoma. Surgical specimens of 8 women who underwent subsequent myomectomy or hysterectomy were evaluated by conventional histology and immunohistochemistry. TGMS were readily apparent in both macroscopy and routine histology. In patients with fibroids, TGMS accumulated in medium-sized vessels in the direct tumor vicinity, a minor fraction of particles was detected in the outer half of the myometrium and within leiomyomata. In patients with adenomyosis, a random distribution of TGMS was noted throughout the outer half of the myometrium. Freshly infused particles occluded the respective arteries without a significant tissue reaction. In the course of time, a granulomatous foreign body reaction in the vicinity of particles occurred, eventually followed by complete vessel destruction. Leiomyoma treated with UAE showed either hyaline necrosis, coagulative necrosis, or no change at all. Foci of adenomyosis remained unaltered. In conclusion, after UAE with TGMS, particles were identified predominately but not exclusively at the periphery of fibroids. Pathologists must be aware of the morphologic changes induced by UAE in leiomyoma to avoid misinterpretation of induced tissue alterations as signs of malignant tumor growth.

Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans

BACKGROUND/AIMS Animal studies implicate a role of bile acids (BA) in thyroid-regulated energy expenditure (EE) via activation of the TGR-5/adenylate cyclase/deiodinase type 2 pathway. Here we investigated these possible associations in humans. METHODS EE, BA, and thyroid hormone status were assessed in 10 healthy subjects and eight patients with liver cirrhosis at baseline and after oral nutrition. In cirrhosis, blood was additionally sampled from the mesenteric vein and the radial artery. RESULTS At baseline, BA and EE related positively (r = 0.648, P = 0.048 in healthy subjects; r = 0.833, P = 0.010 in cirrhosis; r = 0.556, P =0.017 in all), with the highest correlation with deoxycholic acid levels. The respiratory quotient associated negatively to baseline BA (all, r = -0.639, P = 0.004). Postprandially, serum TSH decreased in both groups (P < 0.05 each). In cirrhosis, the decrease of TSH after 60 min correlated to the meal-stimulated BA increase (r = -0.762, P = 0.028). To assess the mechanism involved, we studied a single human TSHoma and TαT1 mouse thyrotrope cells. In TSHoma cells, TGR-5 was predominantly expressed cytoplasmically, and in vitro stimulation with BA did not substantially alter cAMP or deiodinase type 2. CONCLUSIONS Our data support a role of BA in human energy metabolism and in thyroid hormone control. Even though no convincing response to BA was demonstrated in TSHoma and TαT1 cells, the TSH decrease after a nutritional challenge suggests an interaction of BA on the set point of the thyroid axis.

Image quality of noninvasive coronary angiography using multislice spiral computed tomography and electron-beam computed tomography: Intraindividual comparison in an animal model

Objective:Comparison of coronary artery visualization by multislice spiral CT (MSCT) and electron-beam CT (EBCT). Materials and Methods:Six minipigs underwent MSCT (collimation 4 × 1 mm, gantry rotation time 500 milliseconds, acquisition time per cardiac cycle 126 ± 30 milliseconds) and EBCT (slice thickness 1.5 mm, acquisition time per scan 100 milliseconds). Visualized vessel length and contour sharpness was measured, contrast-to-noise ratios were calculated, and the frequency of motion artifacts were evaluated. Results:MSCT depicted significantly longer segments of the coronary tree than EBCT (length: 248.8 vs. 222.8 mm; P < 0.05), delineated the vessel contours more sharply (slope of density curves: 219.2 vs. 160.2 ΔHU/mm; P < 0.05), and had a higher contrast-to-noise ratio (13.4 vs. 7.3; P < 0.05). The frequency of motion artifacts did not differ between both modalities (94.7% vs. 95.7% of visualized vessel length; P > 0.05). Conclusions:Because its higher spatial resolution and lower image noise, MSCT seems to be superior to EBCT in the visualization of the coronary arteries. Despite different temporal resolutions motion artifacts seem to be similar with both modalities.

Gadolinium-enhanced three-dimensional magnetic resonance angiography versus conventional digital subtraction angiography: Which modality is superior in evaluating living kidney donors?

This study evaluates the correlation of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) with the operative vessel findings in living kidney donors. The intraoperative vessel findings of 52 living renal donors were compared with the preoperative diagnoses of each imaging technique. Sixty-seven arteries were found during explantation. Forty kidneys showed a single arterial blood supply, and 12 kidneys showed a multiple arterial blood supply. No advantage of either imaging method was found for arterial imaging. There were 55 veins identified during organ harvesting. MRA could not determine the venous system in one donor (1.9%) and failed to detect one small pole vein in another. DSA did not yield a venous diagnosis in seven patients (13.5%) and yielded misdiagnoses in four patients. The correct diagnosis of renal donor veins differed significantly in favor of MRA (kappa 0.79 vs. 0.45; P=0.008). MRA is superior to DSA in assessing the renal vasculature in living kidney donors.

Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis

Transarterial chemoembolization (TACE) has gained wide acceptance as a bridge to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Aim of this analysis was to compare long‐term results with and without neoadjuvant TACE and to identify subgroups, which particularly benefit from TACE.

Acrylamido Polyvinyl Alcohol Microspheres for Uterine Artery Embolization: 12-month Clinical and MR Imaging Results

PURPOSE To report the 12-month clinical and magnetic resonance (MR) imaging results of an ongoing two-center registry involving acrylamido polyvinyl alcohol (PVA) microspheres for uterine artery embolization (UAE) for leiomyomas. MATERIALS AND METHODS A total of 69 patients underwent UAE with 500-700-microm, 700-900-microm, and 900-1,200-mum acrylamido PVA microspheres (BeadBlock). Thirty-three patients underwent UAE with a limited embolization (protocol A) and 36 patients underwent UAE with stasis as the angiographic endpoint (protocol B). Primary objectives were clinical efficacy measured by a leiomyoma-specific quality of life (QOL) questionnaire and infarction rate of leiomyomas on early contrast agent-enhanced MR imaging. Secondary objectives were in-hospital complications, patient satisfaction, and frequency of clinical failure. RESULTS Bilateral embolization was technically successful in 68 of 69 patients. A significant decrease (P < .001) in symptom severity and increase in health-related QOL was observed at 3 and 12 months with no significant differences between embolization protocols. However, contrast agent-enhanced MR imaging showed a significantly lower rate of completely infarcted leiomyomas in protocol A compared with protocol B (P < .05). Early clinical failures in patients treated according to protocol A were caused by incomplete tumor infarction. Minor complications occurred in five of 69 patients. Patient satisfaction was similar between protocols. CONCLUSIONS Acrylamido PVA microspheres are a clinically effective and safe embolic agent for UAE. The use of 500-700-microm spheres and a limited embolization results in an unacceptably high rate of failed tumor infarction. Superior imaging results and fewer repeat interventions can be achieved with use of 700-900-microm spheres and stasis as the angiographic endpoint.