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This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System). 321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p 0.001) and CEUS on-site (62.7 %; p 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site. This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms. Diese prospektive, multizentrische, DEGUM-geförderte Studie untersucht die diagnostische Genauigkeit standardisierter Algorithmen für die Kontrastmittelsonografie (CEUS-Algorithmen) in der nichtinvasiven Diagnostik des hepatozellulären Karzinoms (HCC) bei Hochrisikopatienten. HCC-Hochrisikopatienten mit histologisch gesicherter Leberläsion im B-Bild-Ultraschall wurden prospektiv multizentrisch eingeschlossen. Klinische Daten und Bildgebungsbefunde wurden über Online-Eingabemasken erfasst. Es erfolgte ein direkter Vergleich der diagnostischen Genauigkeiten für die konventionelle CEUS-Befundung zum Untersuchungszeitpunkt (CEUS-on-site) und die CEUS-Algorithmen ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) und CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System). 321 Patienten an 43 Zentren wurden eingeschlossen (93,1 % Leberzirrhose). Der histologische Befund ergab 256 HCCs und 23 intrahepatische cholangiozelluläre Karzinome (iCCA). Die höchste Sensitivität bei Zirrhose-Patienten (n = 299) erzielten der CEUS-Algorithmus ESCULAP (94,2 %) und CEUS-on-site (90,9 %), die geringste Sensitivität der CEUS LI-RADS-Algorithmus (64 %; p 0,001). Die Spezifität war höher für CEUS LI-RADS (78,9 %) versus ESCULAP (50,9 %) und CEUS on-site (64,9 %; p 0,001). Der negativ prädiktive Wert (NPW) war für CEUS LI-RADS niedriger als für ESCULAP (34,1 % vs. 67,4 %; p 0,001) und CEUS-on-site (62,7 %; p 0,001). Der positiv prädiktive Wert (PPW) war für alle Modalitäten hoch (rund 90 %). Dies ist die erste prospektive, multizentrische Studie zum Vergleich der standardisierten Kontrastmittelsonografie mit den kürzlich entwickelten CEUS-Algorithmen in histologisch gesicherten Leberläsionen bei Zirrhose-Patienten. Unsere Ergebnisse bestätigen die exzellente diagnostische Genauigkeit der Kontrastmittelsonografie in der nichtinvasiven HCC-Diagnostik bei Hochrisikopatienten. Die On-site-Diagnose eines erfahrenen Untersuchers erzielt dabei eine beinahe ebenso gute diagnostische Genauigkeit wie die CEUS-basierten Diagnosealgorithmen.

The aim of the study was to characterize SonoVue enhancement in hepatocellular carcinoma in correlation to both lesion diameter and histological differentiation of the lesion.In a prospective study 130 patients (72 male, 58 female, 62 +/- 10 years) with HCC lesions detected by B-mode sonography were examined. After injection of 1.2 - 2.4 ml SonoVue, HCC lesions were examined continuously for up to 5 min using "low MI" sonography.Arterial hypervascularization was found in 72 % of the HCC lesions without correlation to the lesion diameter or histological grading, when analyzed for the total group. However, the analysis of the G 1 subgroup showed significant correlation between lesion diameter and arterial hypervascularization. Arterial hypervascularization was found in 95 % of the G 1 lesions3 cm but in only 43 % of the G 1 lesions3 cm (p0.001). In contrast, analysis of the remaining HCC lesions (without G 1) showed arterial hypervascularization in 69 % of the lesions3 cm and in 72 % of the lesions3 cm (n. s.) without correlation to the diameter. In the late phase in the G 1 subgroup, hypoechoic demarcation was found in 95 % of the G 1 lesions3 cm, but in only 64 % of the G 1 lesions3 cm (p0.001). In contrast, in the less differentiated HCC lesions (without G 1), hypoechoic demarcation was found in 91 % (HCC3 cm) and in 82 % (HCC3 cm) of the lesions (n. s.).In well-differentiated HCCs (G1) hyperechoic enhancement in the arterial phase and hypoechoic demarcation in the late phase correlate to the diameter.

Purpose To evaluate the diagnostic benefit of contrast-enhanced ultrasound for the differential diagnosis of liver tumors in clinical practice. Materials and methods From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by contrast-enhanced ultrasound using a standardized protocol (pulse/phase inversion imaging, mechanical index 75% cases) or in some cases to CT or MRI. Results The final diagnosis of hepatic tumors included 573 benign hepatic tumors (hemangiomas n = 242, focal nodular hyperplasia n = 170, hepatocellular adenoma n = 19, other benign lesions n = 142) and 755 malignant hepatic tumors (metastases n = 383, hepatocellular carcinoma n = 279, other malignant lesions n= 93). The overall diagnostic accuracy of contrast-enhanced ultrasound in comparison to the correct final diagnosis based on the combined gold standard was 90.3%. Contrast-enhanced ultrasound was able to correctly assess 723/755 malignant lesions (sensitivity 95.8%) and 476/573 benign lesions (specificity 83.1%). The positive predictive value of contrast-enhanced ultrasound for the diagnosis of a malignant tumor was 95.4% and the negative predictive value of contrast-enhanced ultrasound was 95.7%. Conclusion Contrast-enhanced ultrasound clearly improves the differential diagnosis of hepatic tumors and is very helpful in clinical practice when B-scan or power Doppler morphological criteria are missing.

A 36-year-old man, with a history of recurrent respiratory infection, dermatomycosis, arthralgia and abnormal stools for 12 years, developed a febrile illness (up to 40 degrees C). A Serratia marcescens septicaemia responded to antibiotics. Four months later cervical and abdominal lymph-adenopathies were noticed. Cervical lymph node biopsy revealed lymphadenitis with epithelioid cell nests. Duodenoscopy with biopsy demonstrated Whipple's disease associated with lambliasis. Electron-microscopy showed rod-shaped bacteria typical of Whipple's disease, and Giardia lamblia. Using the polymerase chain reaction, Whipple-specific DNA fragments of 284 base pairs from the genome of the Whipple bacterium (Tropheryma whippelii) were demonstrated. Antibiotic treatment with Ampicillin (2 g three times daily) and ceftriaxone (2 g once daily) i.v. for 21 days, followed by oral ofloxacin (200 mg daily) and co-trimoxazole (three times daily 800 mg sulfamethoxazole and 160 mg trimethoprim), brought about remission of Whipple's disease. Long-term antibiotic treatment was continued with co-trimoxazole. Lambliasis recurred after 3 and 5 months, despite treatment with metronidazole, 250 mg three times daily for 7 days.

A large nonresectable upper-abdominal tumor in a 61-year-old woman was found to have been caused by inflammatory infiltration and mechanical obstruction of the mesenteric lymph nodes resulting in obstruction to lymphatic flow. Biopsy at the root of the mesentery and of abdominal lymph nodes raised the suspicion of Whipple's disease, a diagnosis confirmed by a small-intestine biopsy. Long-term antibiotic treatment was successful. Quantitative changes in the composition of the T-cell subpopulations at the time of the diagnosis reverted to normal in the course of treatment.

PURPOSE: SonoVue and Levovist (SH U 508A) are both ultrasound contrast agents, which are helpful in characterization and detection of malignant liver lesions. This study was performed to compare both contrast agents according to the capability to diagnose hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a prospective study, 65 patients with histologically proven hepatocellular carcinoma (HCC) were examined with both, Levovist and SonoVue. In all patients HCC lesions had been detected by B-mode sonography before the study start. After injection of 2.4 ml SonoVue i. v., the liver was examined continuously for up to three minutes using “low MI”-pulse inversion sonography. For the Levovist-examinations 2.5 g Levovist were injected i. v. After a delay of at least 2.5 minutes without scanning, the liver was examined with three different scans using “high-MI”-pulse-inversion sonography. RESULTS: The examination was technically sufficient in 98 % after SonoVue-injection and in 92 % after Levovist-injection (n. s.). Comparison of the results was performed for the 60/65 patients (61 lesions), in which both methods were technically sufficient. After SonoVue-injection contrast-enhancement in the arterial phase was found in 79 % (48/61) of the lesions. Demarcation of the HCC-lesion in the late phase was found in 89 % of the SonoVue-examinations and in 98 % of the Levovist-examinations (p < 0.05). Early SonoVue-enhancement and/or demarcation in SonoVue late-phase was found in 93 % of the HCC-lesions (n. s. compared to Levovist-late phase). CONCLUSION: Levovist-late phase has a higher sensitivity in predicting lesion dignity of HCC-lesions compared to SonoVue-late phase, but not compared to combination of SonoVue-early phase and late phase.

Purpose The diagnosis of ischemic injury by B-mode-sonography is difficult in many cases. Aim of the pilot-study was to evaluate whether additional examination with the ultrasound contrast agent SonoVue could improve the sonographic diagnosis of ischemic injury. Materials and methods In a prospective study, intra-abdominal organs (n = 12) with ischemic lesions found by CT-scan were examined. All ischemic organs were examined by native B-mode-sonography and after injection of 1.2 ml SonoVue i. v. The SonoVue-examinations were performed using the CPS-software (Siemens, Erlangen). Results Native B-mode-sonography detected demarcation of ischemic lesions in only 7 of the 12 organs. In contrast, SonoVue-enhanced sonography diagnosed ischemic lesions in all organs. In one patient with renal infarction, however, the ischemic lesion found by SonoVue-enhanced sonography was smaller compared with the CT-scan. The diagnosis "compatible with ischemia" as cause for the abnormalities in B-mode sonography was described in only 3 out of 12 organs, and none of the organs were classified as "definite diagnosis of ischemia". In contrast, the diagnosis "definite diagnosis of ischemia" was made in 10 of the 12 organs when examined with SonoVue-enhanced sonography. In two further patients, the lesion was classified as "compatible with ischemia". In these patients, the diagnosis of ischemia was verified by CT-scan, due to the accompanying subtotal splenic infarction and a partial thrombosis of the coeliac trunc. Conclusion It became evident that SonoVue-enhanced sonography was more sensitive in the diagnosis of ischemic injury than native B-mode sonography.

Background: In patients with focal lesions which are isoechogenic to the spleen and which are located next to the spleen it is not easy to differentiate between lymph nodes and the accessory spleen. Therefore, the aim of this study was to evaluate if the color-SAE 1 technique performed after injection of Levovist is able to differentiate between accessory spleens and lymph nodes in patients with a mass in the hilus of the spleen. Methods: 12 patients with sonographic proof of a hypoechoic mass in the hilus of the spleen were examined (Sonoline-Elegra ultrasound system, Siemens, Erlangen, Germany). Color-SAE was performed 10 minutes after injection of 1 g of Levovist i. v. Results: All patients with accessory spleens (n= 7) showed a color-SAE mosaic pattern in the localization of the mass comparable to the color-SAE mosaic found in the spleen. In contrast, in none of the patients with lymph nodes next to the spleen (n = 5) was a color-mosaic pattern localized to the mass found, wheras the spleen showed regular color-SAE in all cases. Conclusion: Color-SAE with Levovist is a new diagnostic tool for the differentiation between accessory spleens and lymph nodes.

Whipple's disease is a chronic multisystem disorder caused by infection with the rod-shaped bacterium, Tropheryma whippelii. We report the case of a 65-year-old woman with intestinal Whipple's disease that had been refractory to monotherapy with a number of antibiotics over a 2-year period. The patient then presented with watery diarrhoea, cachexia (body mass index 18 kg/m (2)) and chronic anaemia (haemoglobin 7.6 g/dl). Wireless capsule endoscopy showed that the disease affected the entire small intestine. Focal occult areas of bleeding were observed in different parts of the jejunum. The capsule's transit time through the small intestine was 2 hours 43 minutes. Capsule endoscopy allows novel insights into the pathophysiology of Whipple's disease.

BACKGROUND In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. PATIENTS AND METHODS 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. RESULTS Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. CONCLUSION Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.

UNLABELLED Colour Doppler sonography (CDS) avoids misinterpretation of abdominal ultrasonography. Differential diagnosis of pathological structures found by grey-scale sonography can be difficult in many cases. AIM The present study aimed to determine how often additional colour Doppler sonography could be of benefit to avoid misinterpretation of grey-scale ultrasound images. METHODS 1350 abdominal sonograms were examined. The sonographic examination was performed using a Toshiba SSA-140 A-ultrasound machine (3.75 MHz and 2.5 MHz-transducer). Findings which could be misinterpreted in grey-scale images, e. g. structures suspicious of lymph nodes, small areas of ascites, hydronephrosis, cysts or cholestasis, were examined by additional colour Doppler sonography. RESULTS 327 findings (= 24 % of the cases) were classified as requiring additional examination by colour Doppler sonography. In 73 of these cases (= 22 % of cases having additional CDS), CDS identified blood flow in the pathological structure, which avoided misinterpretation of the grey-scale imaging. CONCLUSION Additional CDS avoids misinterpretation of grey-scale sonography especially in patients with portal hypertension.

Important improvements and technical developments in ultrasonography during the last years have been made. The aim of this article is to describe the new techniques in ultrasonography, such as SieScape, Color-SieScape, 3-D-power-Doppler, tissue harmonic imaging, second harmonic imaging, phase inversion ultrasonography and contrast media to demonstrate their clinical implications.

Hintergrund: Colorectale Carcinome sind gut bekanntermasen eine mogliche langfristige Konsequenz einer Colitis ulcerosa (CU). Sie entstesthen bei etwa 10–15% der CU Patienten. Das Risiko fur ein CU associziiertes Carcinom im Ileum, entweder im terminalen Ileum oder einem Ileum-Pouch, ist weit weniger gut charakterisiert. Methoden und Patienten: Wir analysierten eine Serie von 652 konsekutiven CU Patienten, welche zwischen 1984 und 2005 operiert wurden. Deren Operationsprarate des Dickdarms und Ileums wurden umfangreich histopathologisch untersucht (Median: 18 Paraffinblocke je Colectomie), speziell im Hinblick auf Dysplasien und Carcinome. Ergebnisse: Bei insgesamt 69 CU Patienten wurde ein colorektales Adenocarcinom diagnostiziert (Pravalenz in unserer Serie: 11%). Bei vier CU Patienten (2Manner, 2 frauen; Alter 28–49 Jahre) lag ein Adenocarcinom des Ileums vor (Pravalenz: 0,6%). Ein Patient (#1) hatte ein primares Carcinoma im terminalen Ileum als Komplikation seiner CU mit retrograder Anschlussileitis; synchron hatte er multifokale Dysplasien in Colon, dort jedoch kein Carcinom. Bei drei Patienten (#2, #3, #4) entstand ein Carcinom in einem Ileum-Pouch. Zwei von ihnen hatten eine Anamnese von fruherer Dysplasie im Rektum, bei beiden trat das Carcinom 3–4 Jahre nach restaurativer Proktocolektomie an der Ileum-Pouch-Analen Anastomose auf, und einer (#3) hatte ein weiteres Carcinom im Corpus des J Pouch. Ein Patient (#4) hatte ein Adenocarcinom an der Anastomose eines omega-formigen Ileumpouches zu einem kurzen Rest des Rektums, 10 Jahre nach seiner restaurativen Colektomie. Diskussion: Das Risiko fur ein CU assoziiertes intestinales Carcinom reicht uber das Colon und Rektum hinaus – auch in das Ileum hinein. Disponierend ist dafur ist eine Retrograde Anschlussilieits. Das Vorliegen eines Dysplasie im Rektum scheint ein Risikoindikator fur die spatere Entwicklung eines Ileumcarcinoms im Pouch zu sein.

This study was performed to assess the role of additional diagnostic laparoscopy in the preoperative staging of patients with gastric cancer and pancreatic cancer prior to intended curative surgery. Furthermore patients with ascites of unknown origin were evaluated. 127 patients with primary solid abdominal tumors were eligible for evaluation; of those 66 patients had a gastric cancer and 61 a pancreatic cancer. Patients without histologically proven metastases proceeded to laparotomy. Ascites of unknown origin was the indication for performing a diagnostic laparoscopy in 23 patients. Metastases were detectable laparoscopically in 13 of 66 patients (20%) with gastric cancer. Intraoperatively metastases were evident in further 7 cases. In 14 of 61 patients (23%) with pancreatic cancer metastases were detected by laparoscopy and in further 5 patients intraoperatively. A peritoneal carcinosis was diagnosed laparoscopically in 17 of 23 patients with ascites of unknown origin. Preoperative staging by additional diagnostic laparoscopy proved effective in patients with gastric- and pancreatic cancer.