A Nonclassical Monocyte Phenotype in Peripheral Blood is Associated with Nonalcoholic Fatty Liver Disease: A Report from an EMIL Subcohort.

Nonalcoholic fatty liver disease (NAFLD) as the prototypic hepatic manifestation of metabolic syndrome is an independent risk factor for cardiovascular disease. Our study was designed to investigate the association between NAFLD and alteration in monocyte subsets as hallmark of cardiovascular disease. Seventy-three "Echinococcus Multilocularis and other medical diseases in Leutkirch" (EMIL) population-based cohort participants (mean observation period 11 years) were selected to study their monocyte phenotype by multiparameter flow cytometry. NAFLD was diagnosed using standard ultrasound based criteria excluding other causes of fatty liver disease. Three monocyte subsets ("classical" CD14++ CD16-, "intermediate" CD14++ CD16+, "nonclassical" CD14+CD16++ monocytes), and surface markers (CD36 and CD9) were determined. Classical risk markers covering inflammatory and dysmetabolic characters were also determined. Forty-three out of 73 subjects revealed a stable clinical phenotype, namely 17 subjects revealed NAFLD, whereas 26 subjects showed no fatty liver disease. Compared to the nonfatty liver group, the nonclassical monocyte fraction (p=0.049), total monocyte fraction and count were increased in NAFLD probands (p=0.028, and 0.035, respectively), while classical monocyte fraction (p=0.034) was decreased. Total monocyte fraction, nonclassical monocyte fraction, and waist circumstance were independent risk factors for NAFLD. The nonclassical monocyte fraction and classical monocyte fraction were significantly correlated with waist-to-hip ratio. This pilot long-term follow-up study suggests that nonclassical monocyte fraction and total monocyte fraction might have potential as a prognostic and modifiable biomarker in NFALD patients. This novel marker set might therefore be of interest to monitor druggable inflammatory pathways in individuals with hepatic manifestation of the metabolic syndrome.

Comparison of Two High-End Ultrasound Systems for Contrast-Enhanced Ultrasound Quantification of Mural Microvascularity in Crohn's Disease.

PURPOSE: To verify the reproducibility of contrast-enhanced ultrasound (CEUS) quantification results of two different high-end ultrasound systems and to evaluate the clinical utility of the method in patients with Crohn's disease (CD). MATERIALS AND METHODS: 18 patients with histologically confirmed CD (36.8 % women, 63.2 % men; mean age 43.7 ±â€Š14.1 years) and wall segments thicker than 5 mm were recruited. CEUS quantification and conventional ultrasound investigation were performed under standardized settings using Toshiba Aplio500 and Siemens Acuson S3000 high-end ultrasound systems. CEUS was performed at a low mechanical index of 0.1 after bolus application of 4.8 ml of SonoVue(®) contrast medium. The recorded DICOM clips were quantified using VueBox(®) (version 4.3) calculating 11 quantitative parameters. Subsequently, CEUS quantification and conventional ultrasound results were analyzed. RESULTS: Correlation of quantitative parameters between the Aplio500 and AcusonS3000 systems for peak enhancement (PE), rise time (RT), wash-in-rate (WiR) and quality of fit (QOF) yielded significance levels of p < 0.05 and p < 0.0001 for wash-in-wash-out area under the curve (WiWoAUC). Spearman rank test showed moderate levels of correlation for PE, RT, WiR and QOF (r = 0.5, 0.49, 0.49 and 0.5 respectively), and high correlation for WiWoAUC (r = 0.89) between the two ultrasound systems. CONCLUSION: Due to multiple uncontrollable affecting factors, the method of CEUS quantification by VueBox in the intestine cannot be recommended for device-independent multicenter studies. Therefore we suggest to use identical ultrasound systems and probes as well as to establish adequate reference ROIS, like a AIF-ROI.

Evaluation of Strain Elastography for Differentiation of Thyroid Nodules: Results of a Prospective DEGUM Multicenter Study.

PURPOSE: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. MATERIALS AND METHODS: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US. In addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. RESULTS: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21 %, 73 %, 86 %, 11 %, 0.8, respectively, for color Doppler US; 69 %, 75 %, 94 %, 30 %, 2.9, respectively, for SE-ES; 56 %, 81 %, 92 %, 32 %, 2.9, respectively, for SE-strain value; and 58 %, 78 %, 92 %, 30 %, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71 % for both strain value and strain ratio of nodules. CONCLUSION: SE as an additional ultrasound tool improves the value of ultrasound for the work-up of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future.

Influence of plasma cortisol and other laboratory parameters on nonalcoholic Fatty liver disease.

The objective of the present study was to analyse the association between the plasma cortisol concentration and nonalcoholic fatty liver disease (NAFLD). A total of 1 326 subjects (age 18-65 years) were examined in the context of an epidemiological study of a population-based random sample. Medical history and anthropometric data of 662 women and 664 men were documented. In addition, laboratory examinations were performed and the fat concentration of the liver was estimated by ultrasound examination. Mean cortisol concentration in plasma was 260.4±156.8 nmol/l for women and 295.8±161.2 nmol/l for men. NAFLD was identified in 17.7% in women and 35.1% in men. Plasma cortisol concentration showed no association with the existence of NAFLD. NAFLD correlated positive with age, body-mass index (BMI), waist-to-hip-ratio (WHR), alanine aminotransferase (ALT), and triglycerides. The present study failed to establish any association of plasma cortisol concentrations and NAFLD.

Caliber of the common bile duct: effect of cholecystectomy and other factors in a ultrasonographic study of 8534 patients.

OBJECTIVE: The objective of the present study was to analyze the effects of different factors impacting the caliber of the common bile duct (CBD) and a comparison of maximum extrahepatic bile duct caliber in patients with and without a history of cholecystectomy. MATERIAL AND METHODS: A retrospective data analysis was undertaken of 8534 patients (4480 females; 4054 males; average age: 59.2±18.0 years) with sonographic documentation of bile duct caliber. Maximum intra- and extrahepatic bile duct diameters were studied. The normal maximum diameter of the extrahepatic bile duct was defined as 7 mm. In patients who had undergone prior cholecystectomy, a maximum bile duct diameter<10 mm was considered normal. RESULTS: The average maximum diameter of the CBD amounted to 5.3±3.0 mm for the overall collective. In patients who had undergone prior cholecystectomy, maximum CBD diameters in the normal range (<7 mm) were documented in 55%, while larger diameters (>7 mm) were observed in 45%. In the collective of patients without prior cholecystectomy, CBD diameters in the normal range (<7 mm) were found in 81%, with larger diameters observed in only 18.4% of patients. In both subgroups, there was a significant association between age and bile duct diameter (for those with prior cholecystectomy, p=0.0003; without prior cholecystectomy, p<0.0001). No statistically significant influence on CBD diameter was observed for either prior cholecystectomy (p=0.2116) or time interval since cholecystectomy (p=0.3537). Females, both with and without a history of prior cholecystectomy, showed a 1.4-1.5-fold higher risk of exhibiting a CBD diameter>7 mm (for those with prior cholecystectomy, p=0.0485; without prior cholecystectomy, p<0.001). CONCLUSIONS: Our data show a positive correlation between age and CBD diameter. There was no statistically significant relationship between CBD diameter and prior cholecystectomy, postoperative interval and BMI.

Associations of fatty liver disease and other factors affecting serum SHBG concentrations: a population based study on 1657 subjects.

Sex hormone binding globulin (SHBG) is a glycoprotein expressed predominantly in the hepatocytes. It regulates the transport of sex steroid hormones in the blood stream to their target tissues. The expression of the SHBG gene is subject to multifactorial regulation including hormonal, metabolic, and nutritional aspects. Against this background, we investigated the effect of fatty liver and metabolic syndrome, together with other parameters, on serum SHBG concentrations in a population-based cohort in Germany. This cross-sectional study included 870 women and 787 men (average age 42.3±12.8 years), who underwent ultrasound screening for fatty liver in addition to providing a complete medical history and undergoing physical and laboratory examination. Fatty liver was diagnosed on ultrasound criteria in 159 women (18.3%) and 287 men (36.5%). Fatty liver was shown to exert a significant influence on serum SHBG concentrations in men and in premenopausal women. Men with grade 1 fatty liver had a 1.96-fold increased risk (95%-confidence interval=1.28-3.02; p=0.0022) and postmenopausal women with grade 1 fatty liver a 2.4-fold risk (95%-confidence interval=1.11-5.27; p=0.0267) for low SHBG concentrations. Among metabolic parameters, HDL-C represented as affecting factor in men (p=0.0058) and premenopausal women (p=0.0002), while cholesterol only showed an association in premenopausal women (p=0.0439) and triglyceride in postmenopausal women (p=0.0436). No association of concentrations of SHBG and metabolic syndrome was observed. Age, BMI and waist-to-hip ratio also influence the SHBG concentration. Based on these findings, we conclude that fat accumulation in the liver influences SHBG concentrations in men and premenopausal women.

Prevalence of risk factors for liver disease in a random population sample in southern Germany.

BACKGROUND: Chronic liver disease leads to fibrosis and cirrhosis of the liver. This may, in turn, result in chronic liver failure or the development of hepatocellular carcinoma (HCC). Main risk factors for chronic liver disease are viral hepatitis and alcoholism. The present study assessed a randomly selected population in southern Germany for risk factors for chronic liver disease such as fatty liver disease, viral hepatis infection and life-style factors. In addition, the potential association with elevated liver enzymes was investigated. METHODS: A total of 2256 subjects (1182 females, 1074 males), aged 18 - 65 years, participated in the study. Each subject underwent a standardized ultrasound examination, and anthropometric and biochemical assessments. Test subjects were randomly selected from the general population of a town in southwestern Germany. Data were acquired from November to December 2002 without further follow-up. RESULTS: Several factors were found to be associated with chronic liver disease in the study population. Alcohol consumption >20 g/d was seen in 18.1% (n=409). Metabolic syndrome was diagnosed in 5.9% (n=132). The number of people with a BMI greater than 25 kg/m(2) was 45.1% (n=1017). The prevalence of subjects with chronic hepatitis B was 0.7% (n=15), that of anti-HCV positive patients, 0.6%(n=15). Elevated gGT was seen in 10.4% (n=14) of the patients. Prevalence of hepatic steatosis was 25.0% (n=564). CONCLUSIONS: Many cases of chronic liver disease could be prevented by healthy nutrition, optimized medical treatment of associated disorders, and prevention strategies such as routine vaccination, in particular, against hepatitis B virus (HBV).

Non-fatal and fatal liver failure associated with valproic acid.

Little is known about hepatotoxicity associated with valproic acid (VPA), a widely used substance in neuropsychiatry.All reported cases to the German Federal Institute for Drugs and Medical Devices between 1993 and 2009 of VPA-induced serious hepatic side effects were evaluated.A total of 132 cases of serious VPA-associated liver failure were identified. Approximately one third (34.8%) occurred under VPA monotherapy, while the majority was seen with VPA plus co-medication, most frequently antiepileptics (34.8%) and benzodiazepines (16.7%). A subgroup of 34 cases (25.8%) had a fatal outcome, the largest number reported to date. Of these, 32.4% were under VPA monotherapy and 67.6% under VPA plus concomitant medication. Within the study period a significant increase in the total number of reported cases and the subgroup of fatal cases was found.This first pharmacovigilance study of VPA-associated liver failure indicates a higher rate of non-fatal and fatal liver failure when VPA is given with co-medication as compared to monotherapy. However, co-medication per se does not increase the risk of fatalities.

[Ultrasonographically guided biopsy procedures: current practice in hospitals with established departments of gastroenterology]. / Aktuelle Praxis zur Durchführung ultraschallgesteuerter Punktionen an gastroenterologischen Abteilungen.

OBJECTIVE: Ultrasonographically guided adominal biopsies are a frequent daily procedure in German hospitals. There are, however, few guidelines or recommendations for these common procedures. The oive of the current study was to assess current practice with respect to ultrasonographically guided biopsy procedures in a survey of hospitals with established departments of gastroenterology or with over 500 beds. MATERIAL AND METHOD: A questionnaire addressing the preparation for, procedure during, and post-interventional monitoring following ultrasonographically guided biopsies was mailed to 349 German hospitals. The response rate was 51 % (n = 177). RESULTS: Establishment of an intravenous access is standard in 51.2 % (88/172) of the hospitals. Sedation analgesia is standard in 19.1 % (33/173) of the hospitals and is an option in a further 60.1 % (104/173). Local anesthesia is performed in 84.8 % (145/171) of the hospitals. A dedicated transducer for targeted biopsy is used in 40.6 % (81/176) of the hospitals, while 29.5 % (52/176) use a separate biopsy bracket attached to the probe. In 80.6 % (141/175) of the hospitals, a minimum platelet count of 50,000/µL is required. A minimum of 50 % is used as limit for quick in 86.5 % (147/170) of the hospitals. A value of 1 - 1.5 for the international normalized ratio (INR) is most commonly used in the hospitals. A partial thromboplastin time (PTT) between 28 and 50 sec. is used as the upper limit. Interruption of anticoagulants is handled in a very heterogeneous manner. Postinterventional monitoring following biopsy in ambulatory patients ranges from two to 24 hours. CONCLUSION: Our survey shows relevant differences in preparation, execution and postinterventional monitoring in ultrasonographically guided biopsy procedures as routinely performed in German hospitals. There seems to be a need for a guideline standardising ultrasonographically guided biopsy procedures.

[Research activity in abdominal ultrasonography in German university departments of gastroenterology - comparison between 1999 and 2009]. / Forschungssituation in der Abdomensonografie in den gastroenterologischen Abteilungen der Universitätskliniken in der Bundesrepublik Deutschland - Vergleich 1999 - 2009.

AIM: The aim of this study was to generate an overview of the current research situation in abdominal ultrasonography conducted by gasteroenterology departments of German university hospitals and to compare this situation with data from 1999. METHODS: A survey was sent to all 36 German university hospitals encompassing information on research topics, number of research projects and publications, grants, and support by manufacturers of ultrasonography units. The response rate was 86 %. RESULTS: 74 % of gastroenterological departments had 113 ongoing research projects during the enquiry period - on average 3.6 projects per departement. Of these projects 43 % were clinical research, 11 % technical studies, 13 % various topics and 33 % studies with ultrasound contrast enhancers. Ten years ago 80 % of gastroenterological departments had research projects - on average 3.5 projects per department. There was no significant difference in the number of publications between the two enquiry periods. The percentage of publications in English had increased considerably from 57 % (1999) to 78 % (2009). Regarding scientific grants there was no relevant difference during the observed time spans. A total of 32 % (1999: 26 %) of departments receive external funding in addition to their regular budgets. Forty-five percent (1999: 31 %) receive support from manufacturers in the form of hard- and software for application studies. CONCLUSION: Regrettably the research situation in abdominal ultrasonography has not improved considerably during the observed time span. As already stated in 1999, the urgent need for improved research funding for what is the most widely applied image modality still remains an ongoing concern.

[Progress in undergraduate and postgraduate education in abdominal ultrasonography at German university hospitals in 1999-2009]. / Aus- und Weiterbildungssituation in der Abdomensonografie an deutschen Universitätskliniken--Vergleich 1999-2009.

AIM: The aim of this study was to assess the current state of undergraduate and postgraduate education in abdominal ultrasonography at German university hospitals and to compare these findings with data from 1999. METHODS: A survey, encompassing questions related to technical equipment, undergraduate education, graduate education and quality assurance, was conducted at all 36 gastroenterological departments of university hospitals in Germany. The response rate was 86 %. RESULTS: Currently, there is an average of four dedicated ultrasound units for abdominal ultrasonography per department. Two percent are basic units, 12 % are middle-class and 86 % are high-end units. Compared to 1999 there has been an improvement in the quality of ultrasound units but no increase in number; the percentage of high-end units has considerably increased. All departments offer undergraduate training in abdominal ultrasonography. On average, about 100 students per semester take part in training programmes. Ten years ago only 86 % of hospitals provided undergraduate training, for an average of 55 students per semester. Postgraduate training is offered full-time in 94 % of hospitals (1999: 77 %) over a mean time span of 6.1 months (1999: 4.3 months). In 2009a mean of 4.7 physicians per department underwent ultrasonography training, down from 5.6 physicians per department in 1999. CONCLUSION: Over the ten-year observation period, the quality of dedicated ultrasonography equipment for abdominal ultrasonography in the gastroenterological departments of German university hospitals has improved considerably, while the quality of postgraduate education has improved only slightly. In addition, there was improvement in undergraduate ultrasonography training.

[Gallbladder polyps: prevalence and risk factors]. / Gallenblasenpolypen: Prävalenz und Risikofaktoren.

PURPOSE: The objective of the present study was to investigate the prevalence of gallbladder polyps and possible risk factors in a random population sample of an urban population. MATERIAL AND METHODS: A total of 2099 subjects (1072 women, 1027 men; aged 19 - 65 years, mean age 42.1 (SD ± 12.8 years) were prospectively examined using ultrasound, a standardized questionnaire and laboratory studies. RESULTS: Gallbladder polyps were identified in 6.1 % (128 / 2099) of all subjects (women: 6.1 % [63 / 1027]); men: 6.1 % [65 / 1072]). Solitary polyps were found in 52.4 % (65 / 124), two polyps in 16.1 % (20 / 124), three polyps in 6.5 % (8 / 124), several polyps in 22.6 % (28 / 124) and multiple polyps in 2.4 % (3 / 124) of subjects. The mean polyp diameter was 4.7 mm (SD ± 2.2; range 2 - 20 mm). The polyp diameter was ≤ 7 mm in 94.5 % of subjects. The polyps were described as pedunculate in 82.3 % (102 / 124). The polyps were broad-based in 11.3 % of subjects (14 / 124; men: 18 % women: 4.8 %). The polyps were homogeneously echogenic in 100 % of cases and with irregular contours in only one male subject. Multiple logistic regression failed to demonstrate an influence on the increased occurrence of gallbladder polyps for the risk factors of male sex, age, body-mass index (BMI), alcohol, nicotine or caffeine consumption or diabetes mellitus. CONCLUSION: The prevalence of gallbladder polyps reported in the present study (6.1 %) is higher than figures previously published for populations in Germany or Europe. The majority of polyps were pedunculate and solitary. A typical risk factor profile for gallbladder polyps could not be identified in the present population sample.

Gallstone prevalence and risk factors for gallstone disease in an urban population of children and adolescents.

BACKGROUND: At present only a few sonography-based studies have assessed gallstone prevalence and associated risk factors in children and adolescents in randomly selected urban population samples. The aim of the present study was to analyze the prevalence of cholecystolithiasis and associated risk factors in children and adolescents. METHODS: From a randomly selected urban population sample a total of 307 children and adolescents (157 girls, 150 boys; age 12 - 18 years, mean age 15.1 +/- 2.0 years) were studied using ultrasonography, standardized questionnaires and blood samples. RESULTS: Three adolescents (one girl, two boys), corresponding to a prevalence of 1.0 %, showed gallstones. One 14-year-old girl and one 17-year-old boy were overweight using Cole's classification. A positive family history and female gender could not be confirmed as risk factors. CONCLUSION: Obesity appears to be a risk factor in the development of gallstones in childhood and adolescence.

Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions in clinical practice (DEGUM Multicenter Trial): CEUS vs. MRI--a prospective comparison in 269 patients.

PURPOSE: The aim of this prospective multicenter study was to assess the diagnostic role of CEUS in the diagnosis of newly discovered focal liver lesions in clinical practice. One important aspect is the comparison of CEUS with magnetic resonance imaging (MRI). MATERIALS AND METHODS: From 05 / 2004 to 12 / 2006, standardized CEUS was performed prospectively on 1349 patients with focal liver lesions that had been newly detected by fundamental ultrasound in order to determine tumor differentiation and tumor entity. 269 patients had a standardized MRI after CEUS. In typical liver hemangioma and focal nodular hyperplasia (FNH), the definitive diagnosis was based on the MRI as the "diagnostic gold standard" and on clinical evidence and additional follow-up (subgroup A) or on histology (subgroup B). 262 patients met the diagnostic standard that had been set. RESULTS: In the subcollective (n = 262), the tumor differentiation (malignant or benign) of CEUS and MRI was concordant in 225 cases (85.9%), and the assessment of tumor entity in 204 cases (77.9%). In subgroup A (n = 180), concordant results for tumor differentiation were obtained in 169 (93.2%) and for tumor entity in 160 (88.9%) cases. Liver hemangiomas (n = 122) and FNH (n = 43) were most frequent. Subgroup B (n = 82) comprised mainly malignant liver lesions (n = 55), with only a few of hemangiomas (n = 8) or FNH (n = 5). Tumor differentiation was concordant in 56 (68.3%) and tumor entity in 44 cases (53.7%). There were no statistically proven differences between CEUS and MRI. CONCLUSION: CEUS and MRI are of equal value for the differentiation and specification of newly discovered liver tumors in clinical practice. CEUS and MRI are extremely reliable for the differentiation of benign and malignant lesions, the diagnosis of liver hemangiomas and FNH. The characterization of metastases and HCC is also very reliable.

Comparison of panorama ultrasonography, conventional B-mode ultrasonography, and computed tomography for measuring liver size.

PURPOSE: The objective of the present study is to compare the utility of extended field-of-view ultrasonography and conventional B-mode ultrasonography for determining liver size. MATERIALS AND METHODS: The liver size in the medioclavicular line (MCL) was determined in 104 inpatients (females: n = 47; males: n = 57) using both ultrasound methods (Philips HDI 5000). The liver size measured in computed tomography (CT; MX 8000 IDT, Philips) served as the gold standard. The body mass index (BMI), ultrasound scanning conditions, and hepatomegaly identified by CT were evaluated as possible factors affecting the measurement accuracy of the sonographic methods. RESULTS: The standard deviation of the differences between the measured pairs of values shows less dispersion in B-mode ultrasonography (18.7 mm) than panorama ultrasonography (20.8 mm). The mean value of differences between the measured pairs (bias) in the ultrasonographic methods compared to CT is considerably higher in panorama sonography (15.3 mm; SD = 20.8) than in B-mode ultrasonography (0.27 mm; SD = 18.7). A paired t-test of the mean values shows a significant difference between the ultrasonographic methods (p < 0.0001). In diagnosing or excluding hepatomegaly, B-mode sonography is consistent with CT findings in 84 (80.8 %) of 104 patients and panorama ultrasonography is consistent with CT findings in 77 (74.0 %) of 104 patients. Ultrasonographic methods show moderate agreement with each other (Kappa = 0.4265). Higher BMI and limited scanning conditions lead to an increase in the mean difference of measured pairs of values (bias) as well as to an increase in standard deviation of the differences (dispersion). CONCLUSION: The determination of liver size in the medioclavicular line using panorama ultrasonography often leads to the false-positive diagnosis of hepatomegaly. Therefore, the method should not be recommended for routine diagnostic scans. In cases of significant hepatomegaly, however, panorama ultrasonography offers superior visualization compared to conventional B-mode ultrasonography.

Prevalence and risk factors of focal sparing in hepatic steatosis.

PURPOSE: The prevalence, localization and potential risk factors for focal sparing were prospectively assessed in subjects with sonographically detectable hepatic steatosis as part of a population-based cross-sectional study. MATERIALS AND METHODS: A total of 1,624 persons (n = 906 women; n = 718 men) were evaluated using ultrasonography, laboratory testing and a standardized questionnaire. The following were excluded from the analysis: subjects with reported alcohol consumption > 40 g/day (males) or > 20 g/day (females), those with known chronic hepatitis B or C infection, elevated serum transaminases (AST: m > 44 U/l, f > 33 U/l; ALT: m > 45 U/l, f > 35 U/l) and prior right nephrectomy. RESULTS: The prevalence of focal sparing in patients with hepatic steatosis (grade I) was 25.6 % for men and 13.0 % for women. In patients with grade II/III disease, the prevalence was 70.9 % for men and 77.6 % for women. The most common site of focal sparing was in segment IV. The average diameter was 22.3 mm (range 7 - 84 mm). No correlation was found for postulated risk "age" (p = 0.09) or "status post cholecystectomy" (p = 0.09). Male sex (p = 0.02) and metabolic syndrome (odds ratio, 2.1; 95 % confidence interval, 1.1 - 4.1; p = 0.02) were confirmed as risk factors. CONCLUSION: Sonographic evidence of focal sparing in subjects with hepatic steatosis is associated with an increased risk for metabolic syndrome and may be an easily obtained diagnostic criterion in routine clinical settings.

[The role of ceruloplasmin in the differential diagnosis of neuropsychiatric disorders]. / Die Bedeutung des Coeruloplasmins für die Differenzialdiagnose neuropsychiatrischer Störungen.

The blue copper protein ceruloplasmin has been of interest to psychiatrists for decades following Heilmeyer's observation of elevated serum copper levels in schizophrenic patients. Immunoturbidimetry, however, does not yield elevated serum ceruloplasmin concentrations in schizophrenia while ceruloplasmin-related oxidase activity appears to be elevated in patients with schizophrenia and reduced in patients with Alzheimer's disease. Low serum concentrations of immuno-turbidimetrically measured ceruloplasmin, and of oxidase activity, are typical of Wilson's disease, Menkes' disease, and aceruloplasminemia, three familial neurodegenerative disorders of pronounced variability, with regard to both genotype and phenotype. Especially patients with Wilson's disease may exhibit behavioural symptoms only over a long period. Heterozygous carriers of Wilson's disease and aceruloplasminaemia may have low serum ceruloplasmin concentrations; they will not develop somatic symptoms, but the significance of these carrier states, or of "hypoceruloplasminaemia", with regard to mental disorders is unknown.

Comparison of sonographically measured bowel wall vascularity, histology, and disease activity in Crohn's disease.

The purposes of this study was to provide a retrospective comparison of semiquantitatively measured bowel wall vascularity by power Doppler sonography, endoscopic-histopathological biopsy findings, and disease activity in patients with confirmed Crohn's disease. Thirty-two out of 1,332 patients with histologically confirmed Crohn's disease (18 female, 14 male; mean age 38.8 years) met the inclusion criteria: ileocolonoscopy with biopsy and power Doppler sonographic determination of bowel wall vascularity with assessment of disease activity within a period of 5 days. Sonographic determination of bowel wall vascularity was based on a semiquantitative score. Endoscopic bowel wall biopsy specimens were assessed using a self-developed inflammation score and the disease activity was calculated using Crohn's disease activity index (CDAI). A significant association (p < 0.05) was shown for results of histology and bowel wall vascularity in the terminal ileum (kappa = 0.66; sensitivity 95%; specificity 69%). There was no observed association between CDAI and histology, although there was an association between CDAI and bowel wall vascularity (sensitivity 82%). Increased bowel wall vascularity in the terminal ileum measured by power Doppler ultrasound reflects inflammatory activity in histologically examined bowel wall. Power Doppler ultrasound may be able to monitor activity changes of the bowel wall determined by pharmaceutical treatment.

Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions - prospective comparison in clinical practice: CEUS vs. CT (DEGUM multicenter trial). Parts of this manuscript were presented at the Ultrasound Dreiländertreffen 2008, Davos.

AIM: The aim of our study was to evaluate the diagnostic value of Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions in a prospective multi-center study in clinical practice. For this purpose CEUS was compared with the spiral-CT (SCT), the standard radiological method. MATERIAL AND METHODS: 1349 patients with unclear liver lesions after fundamental ultrasound diagnostics including color doppler analysis were examined with standardized CEUS (pulse inversion method, mechanical index < 0.4) from May 2004 to December 2006 in 14 hospitals in a prospective study. The enhancement of contrast medium in the liver tumors was analyzed according to known tumor-specific vascular patterns, using standardized documentation and analysis methods for the differentiation of tumor differentiation (malign or benign) and tumor specification (entity). A subcollective of 267 patients was additionally examined by standardized SCT method. Final diagnosis was based on histology, SCT or MRI in typical findings of liver hemangioma and FNH and on proved clinical data and additional follow up. RESULTS: The subcollective of 267 patients was divided in two subgroups. In 109 of these patients (subgroup A) there was no histological verification, diagnoses based on clear SCT-findings in 79 cases of hemangioma or FNH, as well as in 20 cases with a clear clinical diagnosis. 6 cases (5.5 %) remained unclear. In this subgroup the assessment of tumor differentiation was concordant with CEUS in 90 cases, discordant in 19 cases and the assessment of tumor specification was concordant in 82 and and discordant in 27 cases. In 158 patients (subgroup B) a histological finding was also present, only in 4 cases no definitive tumor diagnosis was achieved. In this subgroup assessment of tumor differentiation with CEUS and SCT was concordant in 124 cases and discordant in 30 cases (CEUS/SCT: sensitivity 94.0 / 90.7 %, specificity 83.0 / 81.5 %, PPV 91.6 / 91.5 %, NPV 87.5 / 80.0 %, accuracy 90.3 / 87.8 %). Tumor specification matched in 103cases and were different in 51 cases (CEUS/SCT: sensitivity 95.3 / 90.6 %, specificity 83.7 / 81.6 %, PPV 92.7 / 91.4 %, NPV 89.1 / 80.0 %, accuracy 91.6 / 87.7 %). A statistically significant difference could not be established. The analysis of particular tumor specification showed a statistically non significant slight advantage in tumor differentiation for CEUS in the case of hemangioma, FNH, HCC and metastases. CONCLUSION: In a multi-center approach under routine clinical conditions, this prospective study demonstrates CEUS to be of equal rank to the CT-scan in regard to the assessment of tumor differentiation and specification. No statistically significant differences could be established. CEUS should be employed before computed tomography is performed for the differentiation of liver tumors, because radiation exposure and invasive biopsies can be avoided in veritable numbers of cases, when precise clinical evaluation of the findings is implemented.