Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis.

BACKGROUND: Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo-associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the 'comedo switch'. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG-associated skin disorders. RESULTS: In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin-like growth factor 1 receptors; peroxisome proliferator-activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. CONCLUSIONS: Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.

[Acceptance of medical apps and e­books among German radiologists]. / Akzeptanz von Medizin-Apps und E­Books unter deutschen Radiologen.

PURPOSE: Smartphones, tablet PCs, mobile applications (apps) and electronic book files (e-books) affect our lives in private and job-related settings. The aim of this study was to analyze the behavior of radiologists on smartphones, tablet PCs and e­books and to investigate its effect on their daily work. MATERIALS AND METHODS: An online survey containing of 23 questions was conducted using Survey Monkey© ( www.surveymonkey.com ). The invitation to the survey was done using the newsletter of the German Radiological Society (DRG). The acquired data was automatically stored by the software and then analyzed using descriptive statistics. RESULTS: In total, 104 radiologists (29% female) participated in the online survey. Of these, 93% and 96.5% owned a smartphone or a tablet PC, respectively, and 72% and 67% used medical apps and e­books, respectively. Through their use, 31% found moderate and 41% found enormous improvement in their daily work. A majority of participating radiologists would be willing to pay an increased user fee for optimized apps or e­books. CONCLUSION: With currently only moderate individual benefit of mobile medical apps and e­books, there is a widespread need for optimally configured apps and e­books with a correspondingly high market potential. KEY POINTS: (1) Radiologists use smartphones (93%) or tablet PCs (96.5%); (2) 72% of radiologists use a smartphone or tablet PC for medical material; (3) 53% of radiologists report significant assistance from or a high value of the mobile medical applications used; (4) There is a willingness to pay a license fee for optimized mobile applications or e­books.

Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice.

Integrins are heterodimeric transmembrane glycoproteins which are engaged in a variety of cellular functions, such as adhesion, migration and differentiation1. The integrin alpha 6 beta 4 is expressed on squamous epithelia, on subsets of endothelial cells, immature thymocytes and on Schwann cells and fibroblasts in the peripheral nervous system. In stratified epithelia, alpha 6 beta 4 is concentrated in specialised adhesion structures, called hemidesmosomes, which are implicated in the stable attachment of the basal cells to the underlying basement membrane by connecting the intermediate filaments with the extracellular matrix. The nature of the interactions between the various hemidesmosomal proteins, that lead to the formation of hemidesmosome is poorly understood. To study the contribution of the integrin alpha 6 beta 4 in hemidesmosome formation and their anchoring properties, we inactivated the beta 4 gene in mice by targeted gene disruption. Homozygous beta 4 null mice died shortly after birth and displayed extensive detachment of the epidermis and other squamous epithelia. The dramatically reduced adhesive properties of the skin was accompanied by the absence of hemidesmosomes at the basal surface of keratinocytes. No evidence was found for impaired T-cell development, nor for defects in myelination in the peripheral nervous system.

The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.

Cadherin cell-cell adhesion molecules form membrane-spanning molecular complexes that couple homophilic binding by the cadherin ectodomain to the actin cytoskeleton. A fundamental issue in cadherin biology is how this complex converts the weak intrinsic binding activity of the ectodomain into strong adhesion. Recently we demonstrated that cellular cadherins cluster in a ligand-dependent fashion when cells attached to substrata coated with the adhesive ectodomain of Xenopus C-cadherin (CEC1-5). Moreover, forced clustering of the ectodomain alone significantly strengthened adhesiveness (Yap, A.S., W.M. Brieher, M. Pruschy, and B.M. Gumbiner. Curr. Biol. 7:308-315). In this study we sought to identify the determinants of the cadherin cytoplasmic tail responsible for clustering activity. A deletion mutant of C-cadherin (CT669) that retained the juxtamembrane 94-amino acid region of the cytoplasmic tail, but not the beta-catenin-binding domain, clustered upon attachment to substrata coated with CEC1-5. Like wild-type C-cadherin, this clustering was ligand dependent. In contrast, mutant molecules lacking either the complete cytoplasmic tail or just the juxtamembrane region did not cluster. The juxtamembrane region was itself sufficient to induce clustering when fused to a heterologous membrane-anchored protein, albeit in a ligand-independent fashion. The CT669 cadherin mutant also displayed significant adhesive activity when tested in laminar flow detachment assays and aggregation assays. Purification of proteins binding to the juxtamembrane region revealed that the major associated protein is p120(ctn). These findings identify the juxtamembrane region of the cadherin cytoplasmic tail as a functionally active region supporting cadherin clustering and adhesive strength and raise the possibility that p120(ctn) is involved in clustering and cell adhesion.

The mucin epiglycanin on TA3/Ha carcinoma cells prevents alpha 6 beta 4-mediated adhesion to laminin and kalinin and E-cadherin-mediated cell-cell interaction.

TA3/Ha murine mammary carcinoma cells grow in suspension, do not adhere to extracellular matrix molecules, but do adhere to hepatocytes and form liver metastases upon intraportal injection. Recently we showed that the integrin alpha 6 beta 4 on the TA3/Ha cells is involved in adhesion to hepatocytes. However, despite high cell surface levels of alpha 6 beta 4, TA3/Ha cells do not adhere to the alpha 6 beta 4 ligands laminin and kalinin. Here we show that this is due to the mucin epiglycanin that is highly expressed on TA3/Ha cells. Some monoclonal antibodies generated against epiglycanin induced capping of most of the epiglycanin molecules. TA3/Ha cells treated with these mAb did adhere to laminin and kalinin, and an epithelial monolayer was formed on kalinin, with alpha 6 beta 4 localized in HD1-containing hemidesmosome-like structures and E-cadherin at the cell-cell contact sites. Similar results were obtained after treatment of TA3/Ha cells with O-sialoglycoprotein endopeptidase which removes all epiglycanin. In addition, the enzyme induced E-cadherin-mediated cell-cell aggregation. Both treatments also enhanced the adhesion to hepatocytes, but given the potent antiadhesive effect of epiglycanin it is remarkable that nontreated TA3/Ha cells adhere to hepatocytes at all. We found that during this interaction, epiglycanin was redistributed. We conclude that epiglycanin can completely prevent both intercellular and matrix adhesion, but that this effect can be overcome in certain intercellular interactions because of the induced redistribution of the mucin.

Biochemical characterization and tissue distribution of the A and B variants of the integrin alpha 6 subunit.

Two cytoplasmic variants of the alpha 6 integrin, alpha 6A and alpha 6B, have been identified previously (Hogervorst, F., I. Kuikman, A. G. van Kessel, and A. Sonnenberg. 1991. Eur. J. Biochem. 199:425-433; Cooper, H. M., R. N. Tamura, and V. Quaranta. 1991. J. Cell Biol. 115:843-850). Using synthetic peptides, containing sequences of their cytoplasmic domains, we have produced mAbs specific for either of the variants. These antibodies reacted with a variety of different epithelial tissues. In some tissues (e.g., salivary gland) both variants could be detected while in others only one of the variants was found (e.g., alpha 6A in epidermis and alpha 6B in kidney). Among nonepithelial cells and tissues, perineural fibroblasts and Schwann cells in peripheral nerves and platelets reacted with anti-alpha 6A, while microvascular endothelia reacted with both anti-alpha 6A and anti-alpha 6B. From our immunohistochemical results there is not evidence that combination with beta 1 or beta 4 is restricted to one of the two variants of alpha 6. This was confirmed by immunoprecipitation studies which showed that both beta 1 and beta 4 were coprecipitated by both anti-alpha 6A or anti-alpha 6B antibodies from cells. Also, the distribution of alpha 6A and alpha 6B subunits associated with beta 1 on cells attached to laminin was similar: both were found in focal contacts colocalizing with vinculin. In contrast, the alpha 6A subunit, associated with beta 4 in cultures of a squamous cell carcinoma cell line, was found to codistribute with bullous pemphigoid antigen 230 in hemidesmosomal-like structures. The alpha 6A and alpha 6B variants, immunoprecipitated from various cell lines, exhibited slightly different electrophoretic mobilities. Analysis of the antigens under reducing conditions showed that the mobility of the light chains, but not of the heavy chains, is different. In addition, in some cells the light chains of alpha 6A and alpha 6B, each are of two different sizes. Treatment with N-glycanase showed that these two light chain variants of alpha 6A and alpha 6B are not due to differences in N-linked glycosylation, and may therefore represent alternative proteolytic products of the alpha 6 precursor. We further demonstrate that alpha 6A, but not alpha 6B, is a major target for PMA-induced phosphorylation. Phosphorylated alpha 6A contained phosphoserine and a small amount of phosphotyrosine. There are also two variants of the integrin alpha 3 subunit with different cytoplasmic domains, but in the cell lines examined only alpha 3A could be demonstrated by RT-PCR.(ABSTRACT TRUNCATED AT 400 WORDS)

The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit.

Bullous pemphigoid antigen 180 (BP180) is a component of hemidesmosomes, i.e., cell-substrate adhesion complexes. To determine the function of specific sequences of BP180 to its incorporation in hemidesmosomes, we have transfected 804G cells with cDNA-constructs encoding wild-type and deletion mutant forms of human BP180. The results show that the cytoplasmic domain of BP180 contains sufficient information for the recruitment of the protein into hemidesmosomes because removal of the extracellular and transmembrane domains does not abolish targeting. Expression of chimeric proteins, which consist of the membrane targeting sequence of K-Ras fused to the cytoplasmic domain of BP180 with increasing internal deletions or lacking the NH2 terminus, indicates that the localization of BP180 in hemidesmosomes is mediated by a segment that spans 265 amino acids. This segment comprises two important regions located within the central part and at the NH2 terminus of the cytoplasmic domain of BP180. To investigate the effect of the alpha6beta4 integrin on the subcellular distribution of BP180, we have transfected COS-7 cells, which lack alpha6beta4 and BP180, with cDNAs for BP180 as well as for human alpha6A and beta4. We provide evidence that a mutant form of BP180 lacking the collagenous extracellular domain as well as a chimeric protein, which contains the entire cytoplasmic domain of BP180, are colocalized with alpha6beta4. In contrast, when cells were transfected with cDNAs for alpha6A and mutant forms of beta4, either lacking the cytoplasmic COOH-terminal half or carrying phenylalanine substitutions in the tyrosine activation motif of the cytoplasmic domain, the recombinant BP180 molecules were mostly not colocalized with alpha6beta4, but remained diffusely distributed at the cell surface. Moreover, in cells transfected with cDNAs for alpha6A and a beta4/beta1 chimera, in which the cytoplasmic domain of beta4 was replaced by that of the beta1 integrin subunit, BP180 was not colocalized with the alpha6beta4/beta1 chimera in focal adhesions, but remained again diffusely distributed. These results indicate that sequences within the cytoplasmic domain of beta4 determine the subcellular distribution of BP180.

Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180.

Hemidesmosomes (HDs) are stable anchoring structures that mediate the link between the intermediate filament cytoskeleton and the cell substratum. We investigated the contribution of various segments of the beta4 integrin cytoplasmic domain in the formation of HDs in transient transfection studies using immortalized keratinocytes derived from an epidermolysis bullosa patient deficient in beta4 expression. We found that the expression of wild-type beta4 restored the ability of the beta4-deficient cells to form HDs and that distinct domains in the NH2- and COOH-terminal regions of the beta4 cytoplasmic domain are required for the localization of HD1/plectin and the bullous pemphigoid antigens 180 (BP180) and 230 (BP230) in these HDs. The tyrosine activation motif located in the connecting segment (CS) of the beta4 cytoplasmic domain was dispensable for HD formation, although it may be involved in the efficient localization of BP180. Using the yeast two-hybrid system, we could demonstrate a direct interaction between beta4 and BP180 which involves sequences within the COOH-terminal part of the CS and the third fibronectin type III (FNIII) repeat. Immunoprecipitation studies using COS-7 cells transfected with cDNAs for alpha6 and beta4 and a mutant BP180 which lacks the collagenous extracellular domain confirmed the interaction of beta4 with BP180. Nevertheless, beta4 mutants which contained the BP180-binding region, but lacked sequences required for the localization of HD1/plectin, failed to localize BP180 in HDs. Additional yeast two- hybrid assays indicated that the 85 COOH-terminal residues of beta4 can interact with the first NH2-terminal pair of FNIII repeats and the CS, suggesting that the cytoplasmic domain of beta4 is folded back upon itself. Unfolding of the cytoplasmic domain may be part of a mechanism by which the interaction of beta4 with other hemidesmosomal components, e.g., BP180, is regulated.

Percutaneous irreversible electroporation of hepatocellular carcinoma: Contrast-enhanced ultrasound-findings during 1-year follow-up.

PURPOSE: To assess the postprocedure findings after percutaneous irreversible electroporation (IRE) of hepatocellular carcinoma (HCC) in contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Percutaneous IRE was performed in a total of 22 patients with 24 HCC tumours following interdisciplinary tumour board review. The lesions were documented using CEUS before, immediately and within 24 hours after IRE. During follow-up CEUS was performed at 6 weeks and 3, 9, and 12 months after ablation. Two experienced radiologists evaluated the acquired CEUS image date in a consensus reading. RESULTS: Median tumour size before treatment was 13.7±4.8 mm (short axis) and 16.0±5.2 mm (long axis). All HCC lesions showed arterial hyperenhancement in CEUS. Median size of the ablation defect after ablation was 29.3±5.2 mm (short axis) and 31.6±5.6 mm (long axis). After IRE all tumours showed complete devascularization. The size of the ablation defects showed significant shrinkage and reduced peripheral enhancement in the course of follow-up. At 12 months follow-up the ablation defect size decreased to 16.7±4.3 mm (short axis) and 18.3±4.1 mm (long axis). CONCLUSION: CEUS showed a complete devascularization of HCC tumours after IRE. Post-intervetional peripheral enhancement returned to normal during follow-up and may represent zones of reversible damage of cellular integrity through electroporation. A significant shrinkage of the ablation defects during 12 month of follow-up was seen in all cases.

Intestinal insulin/IGF1 signalling through FoxO1 regulates epithelial integrity and susceptibility to colon cancer.

Obesity promotes the development of insulin resistance and increases the incidence of colitis-associated cancer (CAC), but whether a blunted insulin action specifically in intestinal epithelial cells (IECs) affects CAC is unknown. Here, we show that obesity impairs insulin sensitivity in IECs and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibit enhanced CAC development as a consequence of impaired restoration of gut barrier function. Blunted insulin signalling retains the transcription factor FOXO1 in the nucleus to inhibit expression of Dsc3, thereby impairing desmosome formation and epithelial integrity. Both IEC-specific nuclear FoxO1ADA expression and IEC-specific Dsc3 inactivation recapitulate the impaired intestinal integrity and increased CAC burden. Spontaneous colonic tumour formation and compromised intestinal integrity are also observed upon IEC-specific coexpression of FoxO1ADA and a stable Myc variant, thus suggesting a molecular mechanism through which impaired insulin action and nuclear FOXO1 in IECs promotes CAC.

180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.

Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa characterized by universal alopecia and atrophy of the skin. We report a deficiency of the 180-kD bullous pemphigoid antigen in three patients with GABEB from unrelated families. We screened specimens of clinically normal skin from nine junctional epidermolysis bullosa patients (3 GABEB, 4 lethal, 1 cicatricial, 1 pretibial) by immunofluorescence using monoclonal antibodies to the 180-kD and 230-kD bullous pemphigoid antigens (BP180 and BP230). In the skin of the three GABEB patients there was no reactivity with antibodies to BP180, whereas staining for BP230 was normal. In the skin of the other six, non-GABEB patients, included in this study the expression of BP180 and BP230 was normal. Immunoblot analysis of cultured keratinocytes from one of the GABEB patients also failed to detect BP180 antigen, whereas BP230 was present in normal amounts. The deficient expression of BP180 is reflected in the RNA message, as in Northern blot analysis a reduced amount of BP180 transcripts, although of normal length, were detected. Interestingly, in another GABEB patient there were not-involved areas of skin, in which blistering could not be induced by rubbing. Biopsy material from these areas showed interrupted staining for BP180. There was no staining for BP180 in areas of clinically normal but involved skin of this patient. In conclusion, this study reveals that the BP180 antigen is deficient and the BP180 mRNA is reduced in generalized atrophic benign epidermolysis bullosa.

Integrin alpha 6 beta 4 forms a complex with the cytoskeletal protein HD1 and induces its redistribution in transfected COS-7 cells.

The integrin alpha 6 beta 4 is a major component of hemidesmosomes, in which it is linked to intermediate filaments. Its presence in these structures is dependent on the beta 4 cytoplasmic domain but it is not known whether beta 4 interacts directly with keratin filaments or by interaction with other proteins. In this study, we have investigated the interaction of GST-cyto beta 4A fusion proteins with cellular proteins and demonstrate that a fragment of beta 4A, consisting of the two pairs of fibronectin type III repeats, separated by the connecting segment, forms a specific complex containing a 500-kDa protein that comigrates with HD1, a hemidesmosomal plaque protein. A similar protein was also bound by a glutathione S-transferase fusion protein containing the cytoplasmic domain of a variant beta 4 subunit (beta 4B), in which a stretch of 53 amino acids is inserted in the connecting segment. Subsequent immunoblot analysis revealed that the 500-kDa protein is in fact HD1. In COS-7 cells, which do not express alpha 6 beta 4 or the hemidesmosomal components BP230 and BP180, HD1 is associated with the cytoskeleton, but after transfecting the cells with cDNAs for human alpha 6 and beta 4, it was, instead, colocalized with alpha 6 beta 4 at the basal side of the cells. The organization of the vimentin, keratin, actin, and tubulin cytoskeletal networks was not affected by the expression of alpha 6 beta 4 in COS-7 cells. The localization of HD1 at the basal side of the cells depends on the same region of beta 4 that forms a complex containing HD1 in vitro, since the expression of alpha 6 with a mutant beta 4 subunit that lacks the four fibronectin type III repeats and the connecting segment did not alter the distribution of HD1. The results indicate that for association of alpha 6 beta 4 with HD1, the cytoplasmic domain of beta 4 is essential. We suggest that this association may be crucial for hemidesmosome assembly.

Low Tube Voltage Liver MDCT with Sinogram-Affirmed Iterative Reconstructions for the Detection of Hepatocellular Carcinoma.

Aim of this study was to compare low tube voltage computed tomography (80 kV) of the liver using iterative image reconstruction (SAFIRE) with standard computed tomography (120 kV) using filtered back-projection (FBP) for the detection of hepatocellular carcinoma (HCC). 46 patients (43 men) with 93 HCC confirmed by 3 T MRI with Gd-EOB-DPTA, in inconclusive cases combined with contrast-enhanced ultrasound, underwent dual-energy CT. The raw data of the 80 kV tube was reconstructed using the iterative reconstruction algorithm SAFIRE with two strengths (I3 and I5). The virtual 120 kV image data set was reconstructed using FBP. The CT images were reviewed to determine the lesion-to-liver contrast (LLC), the lesion contrast-to-noise ratio (CNR) and the sensitivity. The LLC (57.1/54.3 [I3/I5] vs. 34.9 [FBP]; p ≤ 0.01), CNR (3.67/4.45 [I3/I5] vs. 2.48 [FBP]; p < 0.01) and sensitivity (91.4%/88.2% [I3/I5] vs. 72.0% [FBP]; p ≤ 0.01) were significantly higher in the low-voltage protocol using SAFIRE. Therefore, low tube voltage CT using SAFIRE results in an increased lesion-to-liver contrast as well as an improved lesion contrast-to-noise ratio compared to FBP at 120 kV which results in a higher sensitivity for the detection of HCC.

Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors.

Aim of this retrospective analysis was to evaluate the survival times after percutaneous irreversible electroporation (IRE) in inoperable liver tumors not amenable to thermal ablation. 71 patients (14 females, 57 males, median age 63.5 ± 10.8 years) with 103 liver tumors were treated in 83 interventions using IRE (NanoKnife® system). The median tumor short-axis diameter was 1.9 cm (minimum 0.4 cm, maximum 4.5 cm). 35 patients had primary liver tumors and 36 patients had liver metastases. The Kaplan-Meier method was employed to calculate the survival rates, and the different groups were compared using multivariate log-rank and Wilcoxon tests. The overall median survival time was 26.3 months; the median survival of patients with primary land secondary liver cancer did not significantly differ (26.8 vs. 19.9 months; p = 0.41). Patients with a tumor diameter >3 cm (p < 0.001) or more than 2 lesions (p < 0.005) died significantly earlier than patients with smaller or fewer tumors. Patients with hepatocellular carcinoma and Child-Pugh class B or C cirrhosis died significantly earlier than patients with Child-Pugh class A (p < 0.05). Patients with very early stage HCC survived significantly longer than patients with early stage HCC with a median survival of 22.3 vs. 13.7 months (p < 0.05).

Evaluation of a robotic system for irreversible electroporation (IRE) of malignant liver tumors: initial results.

OBJECTIVE: Comparison of conventional CT-guided manual irreversible electroporation (IRE) of malignant liver tumors and a robot-assisted approach regarding procedural accuracy, intervention time, dose, complications, and treatment success. METHODS: A retrospective single-center analysis of 40 cases of irreversible electroporation of malignant liver tumors in 35 patients (6 females, 29 males, average age 60.3 years). Nineteen of these ablation procedures were performed manually and 21 with robotic assistance. A follow-up (ultrasound, CT, and MRI) was performed after 6 weeks in all patients. RESULTS: The time from the planning CT scan to the start of the ablation as well as the dose-length product were significantly lower under robotic assistance (63.5 vs. 87.4 min, [Formula: see text]; 2132 vs. 4714 mGy cm, [Formula: see text]). The procedural accuracy, measured as the deviation of the IRE probes with respect to a defined reference probe, was significantly higher using robotic guidance (2.2 vs. 3.1 mm, [Formula: see text]). There were no complications. There was one incomplete ablation in the manual group. CONCLUSION: Robotic assistance for IRE of liver tumors allows for faster procedure times with higher accuracy while reducing radiation dose as compared to the manual placement of IRE probes.

Microwave ablation of large HCC lesions: Added value of CEUS examinations for ablation success control.

PURPOSE: To assess the value of dynamic contrast enhanced ultrasound (CEUS) for the detection of residual tumor tissue day 1 after microwave ablation (MWA) of large hepatocellular carcinoma (HCC) compared to MRI. MATERIAL AND METHODS: 30 consecutive patients (5 females, 25 males, mean age 64 years, age range 54-73 years) with an untreated HCC lesion larger than or equal to 3 cm underwent percutaneous MWA between 03/2014 and 04/2016. 1 patient was excluded because of an artificial pacemaker. All remaining 29 patients underwent 3-T MRI with liver-specific contrast agent and CEUS 1 day after ablation to detect residual tumor tissue. The 6-week follow-up including CEUS and MRI was defined as the reference standard. RESULTS: Complete ablation was achieved in 23 of 29 treated lesions (79%). The sensitivities and specificities for the detection of residual tumor tissue on day 1 were 100% and 83% for CEUS and 87% and 67% for MRI resp. without the differences being statistically significant. CONCLUSION: CEUS allows a reliable assessment of therapeutic success of percutaneous ablation of large HCC lesions one day after the ablation. Its ability to visualize reactive periablation perfusion changes in real-time might be of advantage in the depiction of residual tumor tissue when compared to MRI imaging alone.

Chronic liver disease: Quantitative MRI vs CEUS-based microperfusion.

PURPOSE: To compare the diagnostic performance of MRI-based T1 relaxometry with dynamic contrast-enhanced ultrasound (CEUS)-based liver microcirculation for evaluation of liver function. MATERIALS AND METHODS: 22 patients underwent Gd-EOB-DTPA-enhanced MRI with T1 relaxometry and previous or consecutive CEUS examinations. A transverse 3D VIBE sequence with an inline T1 calculation was acquired and the reduction rate of T1 relaxation time (rrT1) was evaluated. For CEUS measurements (1-6 MHz), a bolus injection of 1.4 ml sulfur hexafluoride microbubbles were administered and both cine loops and single images from arterial phase up to late phase were stored.Quantification of time to peak (TTP), rise time (RT), Wash- In Area Under the Curve (WiAUC), mean transit time (mTTI), the wash- in rate (WiR) and Wash-in perfusion index (WIPI)) was performed using a novel quantification software (VueBoxTM). To compare quantification parameters, patients were classified in patients representing a healthy population (rrT1 > 50%, n = 8) and those representing patients with liver disease (rrT1 < 50%, n = 14). RESULTS: Comparing perfusion parameters TTP, mTTI, and WiR were higher in patients without liver disease compared to patients with impaired liver function (p = 0.10-0.21). RT, WiAUC and WIPI were significantly lower in patients with impaired liver function (RT, 14.8±1.5 s; WiAUC, 17288±6179 a.u., WIPI, 1243±423) compared to patients without liver disease (RT, 21.2±2.6 s, p = 0.032; WiAUC, 71534±25600, p = 0.034; WIPI, 4286±1748, p = 0.04). In a simple linear regression model, none of the perfusion parameters correlated significantly with rrT1 (p = 0.08-0.63). CONCLUSION: Within the framework of this study, CEUS-based perfusion parameters were not able to assess severity of liver disease, however, WiAUC, RT and WIPI were significant perfusion parameters to make a rough assessment of liver function.

Robot-assisted microwave thermoablation of liver tumors: a single-center experience.

PURPOSE: To evaluate and compare the needle placement accuracy, patient dose, procedural time, complication rate and ablation success of microwave thermoablation using a novel robotic guidance approach and a manual approach. METHODS: We performed a retrospective single-center evaluation of 64 microwave thermoablations of liver tumors in 46 patients (10 female, 36 male, mean age 66 years) between June 2014 and February 2015. Thirty ablations were carried out with manual guidance, while 34 ablations were performed using robotic guidance. A 6-week follow-up (ultrasound, computed tomography and MRI) was performed on all patients. RESULTS: The total procedure time and dose-length product were significantly reduced under robotic guidance (18.3 vs. 21.7 min, [Formula: see text]; 2216 vs. 2881 mGy[Formula: see text]cm, [Formula: see text]). The position of the percutaneous needle was more accurate using robotic guidance (needle deviation 1.6 vs. 3.3 mm, [Formula: see text]). There was no significant difference between both groups regarding the complication rate and the ablation success. CONCLUSION: Robotic assistance for liver tumor ablation reduces patient dose and allows for fast positioning of the microwave applicator with high accuracy. The complication rate and ablation success of percutaneous microwave thermoablation of malignant liver tumors using either CT fluoroscopy or robotic guidance for needle positioning showed no significant differences in the 6-week follow-up.

Percutaneous irreversible electroporation (IRE) of prostate cancer: Contrast-enhanced ultrasound (CEUS) findings during follow up.

PURPOSE: Irreversible electroporation (IRE) is a focal non-thermal ablation technique that can be used to treat prostate cancer (Pca). The objective was to document the evolution of the volume of the prostate gland and the ablation zone after IRE of Pca. MATERIAL AND METHODS: A retrospective analysis of the image findings of CEUS 1 day, 6 weeks, 3 months and 6 months after IRE of 25 patients was conducted. The prostate gland volumes and the size of the ablation zones were documented. Changes in volume and size over time were calculated. RESULTS: There was a significant volume reduction of the prostate gland in the first 3 months after ablation. The mean percentage change after 6 weeks was 34.3% with another decrease of 35.0% after 3 months. Volume did not change between month 3 and 6. Size of ablation zone measured in short- and long-axis significantly diminished until 6 months after ablation. CONCLUSION: CEUS showed a significant involution of the prostate gland during the first 3 months and a significant decrease of the ablation zone during the first 6 months after IRE of prostate cancer.

Magnetic resonance imaging of the sacroiliac joints in patients with suspected spondyloarthritis - comparison of turbo spin-echo and gradient-echo sequences for the detection of structural alterations.

PURPOSE: Magnetic resonance imaging (MRI) is the method of choice for the evaluation of spondyloarthritis (SpA). According to the guidelines of the Assessment of Spondyloarthritis International Society (ASAS) and Outcome Measures in Rheumatology (OMERACT), MRI findings in SpA of the spine and the sacroiliac joints (SIJ) are classified as inflammatory and structural alterations. Modern gradient-echo sequences (GRE) are recommended for optimized detection of structural alterations of the SIJ. We assess the benefit of GRE in the detection of structural alterations of the SIJ in comparison to conventional turbo spin-echo sequences (TSE). MATERIAL AND METHODS: Retrospective study of 114 patients who received MRI of the SIJ for the evaluation of SpA. Structural alterations of the SIJ were assessed by two blinded readers separately for T1 TSE and T2* GRE. The findings were classified according to a previously published chronicity score separately for both sides and sequences. Interobserver reliability was calculated with Cohen's Kappa, and the significance of findings was assessed with the Wilcoxon test. P-values < 0.05 were required for statistical significance. RESULTS: 68 of 114 (60 %) patients showed SpA-typical findings of the SIJ. The average chronicity score for GRE (score 3.3) was significantly higher than for TSE (score 2.6), p = 0.001. The Kappa-values for the interobserver reliability were 0.86 - 0.90 without any statistically significant differences between both sides and sequences. CONCLUSION: Both T1 TSE and T2* GRE showed a high interobserver reliability in the detection of structural alterations in patients with SpA. However, T2* GRE detected significantly more structural alterations than T1 TSE and should be an integral part of a modern MRI protocol for the diagnostic workup of patients with suspected SpA.