[A 59-year-old woman with upper abdominal pain and fever]. / 59-jährige Patientin mit Oberbauchschmerzen und Fieber.

A 59-year-old woman suffered from fever and upper abdominal pain. The computed tomography (CT) scan revealed a liver lesion. Conventional imaging techniques (CT, magnetic resonance imaging, contrast-enhanced ultrasonography) did not allow for a consistent diagnosis. Fine needle biopsy of the liver lesion was performed. Histologically, fibrotic inflammation was found and an inflammatory pseudotumor (IPT) diagnosed. Despite treatment with steroids and antibiotics, the size of the IPT increased; thus, surgical resection was necessary. In case of fever of unknown origin, IPT should be considered as a potential diagnosis.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Toxicity of ingested cadmium to the nematode Caenorhabditis elegans.

Benthic organisms ingest dissolved and particle-bound contaminants together with their food, whereas it is not clear which fraction of the ingested suspension causes the toxic effects. In the standard toxicity test using the nematode Caenorhabditis elegans, the organisms are fed with bacteria that bind contaminants, thus influencing the bioavailability of the contaminants for the organisms. To unravel the role of food bacteria in the toxicity of contaminants in C. elegans, suspensions with varying densities of bacteria were spiked with the toxic metal cadmium (Cd), either via the water or via the bacteria. The toxicity of Cd to C. elegans was clearly related to the uptake of bacteria in the nematode's gut. An increase in the bacterial density resulted in a significant decrease in the toxicity of Cd such that toxic effects better correlated with the aqueous than with the bacterial-bound or total Cd concentrations. The results suggested that the aqueous Cd that was ingested together with the food was the best available fraction and thereby mainly caused the observed toxicity on the reproduction of C. elegans.

Clinical signs in the diagnosis of deep vein thrombosis.

AIM: Deep vein thrombosis (DVT) is an insidious disease wherein more than 15 different clinical signs are described. The aim of this work was to focus on these clinical signs and to test them for their importance in making a diagnosis of DVT. METHODS: All patients treated with a tentative diagnosis of DVT in the emergency department were asked to take part in the study. Out of the 254 patients who were examined in order to exclude DVT, 204 patients agreed to participate in the study. The patients who agreed to take part were tested for fifteen clinical examination signs. The Wells score was then determined. RESULTS: Sixty-two were diagnosed with DVT. For 142 patients, DVT could be ruled out. The probability of DVT for 9 signs together is 88%, and for 3 signs is 78%. The negative predictive values are 91-95%. The combination of the clinical signs showed a specificity of 100%, independent if the patients were old, comorbid, and were diagnosed with the thrombosis in the lower limbs. The determination of the Wells score resulted in no convincing evidence for or against the diagnosis of DVT. CONCLUSION: We suggest a modified Wells score integrating missing clinical signs with more reliable predictive values. Even with the availability of ultrasound, clinical signs have not become superfluous. They are quick to carry out, safe, cheap and an important addition to the Wells score, particularly for multimorbid and elderly patients.

[Localisation of hepatic lesions to liver segments according to sonography (US), computed tomography (CT) and surgery (OP): a comparative study]. / Untersuchung der Segmentzugehörigkeit von Leberraumforderungen in Sonografie (US), Computertomografie (CT) und intraoperativ (OP): eine Vergleichsstudie.

INTRODUCTION: The localisation of focal liver lesions is usually performed according to the Couinaud classification system. The exact description of localisation and size of liver lesions is especially important for surgical procedures. The aim of this prospective study was the evaluation of differences and agreements in the localisation and size of hepatic lesions as found by ultrasound (US), computed tomography (CT) and according to the intraoperative status (OP). MATERIAL AND METHODS: 32 patients (21 male, 11 female) were enrolled in the study. The results obtained from sonography, computed tomography and surgery were classified into 5 categories for localisation and for size, respectively. RESULTS: According to the agreement between sonography and computed tomography, 25 % of all hepatic lesions were classified into category 1 (exact agreement), whereas 40.6 % were ranked into category 2 (almost exact agreement). Correlating sonography and intraoperative results, 31.3 % of the lesions were classified into category 1 and 46.9 % into category 2. In the comparison of CT with OP, 34.4 % of the lesions were found to be in category 1 and 43.8 % in category 2. Concerning the size of the lesions, almost half of the tumours (46.9 %) were classified into category 1 on the basis of the correlation between US and CT and 21.9 % on the basis of the correlation between US and OP. DISCUSSION: The localisation and description of the size of hepatic lesions is mainly similar or even identical on the basis of the different methods. Further improvements might be achieved by the introduction of a consistent nomenclature.

Irinotecan plus gemcitabine and 5-fluorouracil in advanced pancreatic cancer: a phase II study.

AIMS: The aim of the present study was to evaluate the 6-month survival rate of patients with inoperable or metastatic pancreatic cancer treated with irinotecan and gemcitabine plus 5-fluorouracil. Secondary efficacy end points included response rate, time to progression (TTP), overall survival (OS) and toxicity. PATIENTS AND METHODS: 30 patients with histologically proven pancreatic carcinoma and at least one bidimensionally measurable lesion were enrolled. Of the patients, 83% had metastatic and 17% locally advanced disease. One cycle, lasting 21 days, comprised treatment on days 1 and 8 consisting of 75 mg/m(2) irinotecan i.v. for 90 min, 1,000 mg/m(2) gemcitabine i.v. for 30 min and 2,000 mg/m(2) fluorouracil (5-FU) for 24 h. A total of six cycles was planned for each patient. RESULTS: 28 patients competed at least one treatment cycle and were therefore assessable for efficacy, and 75% of them achieved the primary end point of the study (survival after 6 months). One-year survival was 25%. Stabilization (partial response and stable disease) was observed in 35.7% (10/28) and partial remission in 7.1% (2/28). The objective response rate was 7.1% (2/28) after completion of the six cycles. Median TTP was 3.4 months (1.2-11.5), and median OS was 8.3 months (2.1-36.2). Regarding severe hematological toxicities, only neutropenia was observed (grade 3 20.7%, 6/29, and grade 4 3.5%, 1/29). In spite of anti-emetic supportive care, nausea affected most of the patients: 79.3% (23/29). Grade 3 vomiting was observed in 4 of the 29 patients (13.8%) and grade 4 in 1 patient (3.5%). Only 1 patient experienced diarrhea grade 3 (3.5%) and 1 patient (3.5%) suffered from a grade 3 peroneal nerve enervation. CONCLUSIONS: A combination of irinotecan, gemcitabine and 5-FU is feasible and shows considerable efficacy in patients with inoperable or metastatic pancreatic cancer. Due to its low toxicity, this combination might be an interesting cytotoxic regimen in addition to targeted therapies.

Comparison of low and high frequency transducers in the detection of liver metastases.

BACKGROUND AND AIMS: To evaluate the benefit of the additional use of a high frequency ultrasound probe (7.5 MHz) in finding suspicious liver lesions compared to the examination using a 3.5-MHz transducer only. PATIENTS AND METHODS: One hundred and fifty-seven patients with underlying malignant disease were examined with both transducers using one of three ultrasound machines (Siemens Sonoline Elegra, GE Healthcare Logic 9, or Hitachi EUB-8500). Findings on hepatic lesions were collected on a standardised documentation sheet and evaluated by descriptive statistics. RESULTS: Ninety-three patients (59.2% of all patients) showed no evident liver lesion on conventional ultrasound with the 3.5 MHz probe. In 29 patients (18.5%) new suspicious liver lesions were found by using the high frequency transducer. Thirteen of these 29 patients (44.8%) were suspected to suffer from diffuse infiltration of the liver with malignant lesions or at least 10 additional visible lesions. In 14 patients, no liver lesion had been known before high frequency ultrasound examination. The size of newly described liver lesions ranged from 2 mm to 1.5 cm. Time needed for the additional examination with the high frequency transducer ranged between 1 and 15 min with an average of 4.0 min. CONCLUSION: The additional use of a high frequency transducer in patients with underlying malignant disease slightly extends the examination time, but reveals new, potentially malignant hepatic lesions in almost every fifth patient.

[Fatal outcome of varicella zoster sepsis in a 22-year old patient]. / Letaler Verlauf einer Varizella-Zoster-Sepsis bei einem 22-jährigen Patienten.

Infection with Varicella zoster virus (VZV) usually occurs in children up to 15 years with mild symptoms. We present a case of a 22-year old man with a fatal varicella zoster infection. He developed fulminant hepatitis with acute liver failure and an acute respiratory distress syndrom (ARDS). In this article the general aspects of VZV infection are discussed. Treatment options and previous publications are reviewed.

Barrett's esophagus: a discrepancy between macroscopic and histological diagnosis.

BACKGROUND AND STUDY AIMS: The diagnosis of Barrett's esophagus at present requires endoscopic and histological confirmation of specialized intestinal metaplasia. This study prospectively analyzed the endoscopic and histological prevalence of Barrett's esophagus and the risk factors for the presence of Barrett's esophagus among patients being treated in an endoscopy unit. PATIENTS AND METHODS: A total of 474 unselected patients (58% men; mean age 52 y) were included in the study. Two biopsy specimens each were taken from below and above the squamocolumnar junction and from the antrum and gastric body. Four-quadrant biopsies were taken every 1-2 cm to confirm a macroscopic suspicion of Barrett's esophagus. RESULTS: Barrett's esophagus was suspected at endoscopy in 109 patients (23%). Of the 109 patients with endoscopically suspected Barrett's esophagus, only 46 (42%) had the finding confirmed histologically. The sensitivity and specificity for the endoscopic diagnosis of Barrett's esophagus were 62% and 84%, respectively. A multivariate logistic regression analysis identified age (P = 0.0001; odds ratio per life-year 1.087; 95% CI, 1.046-1.139), male sex (P = 0.0020; OR 6.346; 95% CI, 2.094-22.314), and the number of biopsies (P = 0.0025; OR 1.661; 95% CI, 1.247-2.392) as factors associated with evidence of intestinal metaplasia on biopsy. CONCLUSION: The striking discrepancy between the endoscopic findings and the histological diagnosis may be due to the focal distribution of intestinal metaplasia. This emphasizes the importance of an adequate biopsy protocol. In addition, better methods of detecting focal islands of intestinal metaplasia that are not visible at conventional endoscopy are needed.

[Sonographic controlled drainage of a fluid formation of the spleen in combination with pancreatitis]. / Sonographisch gesteuerte Punktion und Drainage einer Flüssigkeitsformation in der Milz bei Pankreasschwanzpankreatitis -- Milzhämatom oder in die Milz perforierte Pankreaspseudozyste?

With regard to acute or chronic pancreatitis various complications involving the spleen can occur, hematoma of the spleen being a rare complication. We describe the case of a patient in reduced general condition with elevated pancreatic enzymes and signs of inflammation. During multiple examinations, hematoma of the spleen, as well as hematomas close to the left adrenal gland and a larger hematoma close to the gastric wall were detected. In computed tomography and due to the laboratory parameters a pancreatitis was diagnosed. After CT-controlled puncture a communication between both formations was considered possible which was in retrospect CT-assisted not successful. Subsequently an ultrasound controlled drainage was performed, finally resulting in a restitutio ad integrum, thereby avoiding splenectomy. The described percutaneous puncture of a fluid formation in the splenic area represents a non-surgical option in the therapy of intrasplenic pancreatic fluid formations.

[Evaluation of intestinal hyperaemia in inflamed bowel by high resolution Contrast Harmonic Imaging (CHI)]. / Evaluation der Darmwandhyperämie entzündlicher Darmerkrankungen mittels hochauflösender echokontrastverstärkter Sonographie.

AIM: Intestinal hyperaemia is a sign of active disease in the inflamed intestine which can be detected by Doppler sonography. This technique, however, can be jeopardized by tissue motion artefacts (peristalsis), and intramural enteric vessel perfusion may be below the detection threshold. Visualisation of vessels by Contrast Harmonic Imaging (CHI) at a low Mechanical Index (low MI) is not restricted by the limitations mentioned above. Contrast Harmonic Imaging at low MI of the intestinal wall has not yet been described with high frequency probes. We therefore evaluated the validity of this method for detecting hyperaemia of the intestinal wall. METHODS: CHI at low MI was performed with a 7.5 MHz ultrasound probe in 12 patients with signs of an inflamed intestine. The contrast agent BR 1 (4.8 ml) was injected intravenously. Contrast enhancement was quantified by analysing gray scale values before and after injection of BR 1 in regions of interest within the submucosal layer. RESULTS: At about 15 sec. after injection of BR 1, arterial inflow of the contrast agent with visualisation of the feeding mesenteric vessels and intense contrast of the submucosal lamina could be observed. An increase of the gray scale values within the ROI after contrast enhancement was detected in all patients. CONCLUSION: We have shown that CHI at low MI is technically feasible for the demonstration of increased intestinal perfusion in inflammatory bowel disease by using a high resolution ultrasound probe. One possible method of quantifying the contrast enhancement is the gray scale analysis of pixels in defined regions of interest within the submucosal layer.

[Endoscopic mucosal resection for early esophageal cancer with esophageal varices]. / Endoskopische Mukosaresektion eines Osophagusfrühkarzinoms bei Leberzirrhose und Osophagusvarizen.

Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.

Contrast-enhanced ultrasound allows for interventions of hepatic lesions which are invisible on convential B-mode.

BACKGROUND AND AIMS: Contrast harmonic imaging significantly increases the detectability of liver lesions which are invisible on conventional B-mode sonography. With the introduction of contrast agents, which can be visualized at low mechanical index (low-MI), continuous real time observation of liver lesions under contrast conditions is possible. We addressed the question whether contrast-enhanced sonography allows for intervention of hepatic lesions impossible to detect on conventional B-mode imaging. PATIENTS AND METHODS: We evaluated twelve patients with hepatic tumors or abscesses, which could not be analyzed and punctured under fundamental B-mode guidance. The ultrasound contrast agent BRI was used for detection of the hepatic lesions under contrast harmonic imaging (CHI) conditions with phase inversion at low-MI. RESULTS: In eleven out of twelve patients interventions under CHI conditions were successful, as proven by histological, microbiological or tumor marker analysis. The puncture needles were visible in all cases. With an algorithm for optimizing the puncture conditions at low-MI CHI the biopsies can be performed in two steps. CONCLUSIONS: Our results show that biopsies of liver lesions under real-time continuous CHI at low-MI are feasible.

Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis.

BACKGROUND: In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC). METHODS: Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis. RESULTS: In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p<0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p<0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma. CONCLUSION: In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis.