Das insuläre Schilddrüsencarcinom ist ein niedrig differenzierter Carcinomtyp, der ca. 5 % aller Schilddrüsencarcinome repräsentiert. Es wird postuliert, daß sich das insuläre Schilddrüsencarcinom durch eine klinisch höhere Aggressivität auszeichnet. Unklar ist der Nutzen der Feinnadelbiopsie zur präoperativen Diagnostik dieser Carcinomform. Allgemein akzeptierte Kriterien zur histologischen Diagnose wurden von Carcangiu et al. vorgestellt. Wegen seiner Aggressivität wird eine radikale chirurgische Therapie empfohlen. Die Differentialdiagnose, insbesondere zum undifferenzierten und zum medullären Carcinom, ist von hoher Bedeutung, da Thyreoglobulin regelhaft synthetisiert wird und die Iodspeicherung eine Radioiodtherapie postoperativ und bei Rezidiv ermöglicht. Die Nachbeobachtung sollte analog zu gut differenzierten (papillären und folliculären) Formen des Schilddrüsencarcinoms erfolgen. Eine Serie von 8 Carcinomen wird vorgestellt. Alle Carcinome waren bei Diagnose fortgeschritten, allerdings wird ein aggressiver Krankheitsverlauf aus den Patientendaten ersichtlich.

BACKGROUND:In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal.AIMS:To characterise complete and incomplete responders.METHODS:Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years.RESULTS:In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only difference between the two groups before treatment was higher levels of alkaline phosphatase and gamma glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for gamma glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no differences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups.CONCLUSIONS:In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and gamma glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment.

BACKGROUND/AIMS:Some patients chronically infected with the hepatitis C virus (HCV) have persistently normal alanine aminotransferase (ALT) levels while progressive liver damage is observed histologically. In the present study, we compared the rate of proliferation, apoptosis, and necrosis in liver biopsy specimens of patients with persistently normal or elevated ALT levels. METHODS:Fourteen patients with persistently normal and 14 age- and sex-matched patients with elevated ALT levels were enrolled. Proliferation was detected using anti-Ki 67 in 10-microm liver biopsy specimens of the patients. Apoptosis was measured by TUNEL-assay and by monoclonal anti-M30 directed against caspase-cleaved cytokeratin 18 filaments. RESULTS:The mean number of anti-Ki 67 positive hepatocytes was lower in patients with persistently normal aminotransferases (3.1 +/- 2.8/10(3) vs 10.8 +/- 8.8/10(3) hepatocytes, p<0.0011) and was correlated with serum ALT (r=0.86, p<0.01) and aspartate aminotransferase levels (r=0.83, p<0.01). The rate of apoptosis detected by TUNEL assay was low and not different between patients with persistently normal and elevated aminotransferases. Staining with anti-M30 revealed a granular staining pattern and showed a trend towards higher cell death rates in patients with elevated aminotransferase levels (apoptotic hepatocytes with >75% staining: 3.97 +/- 6.24/10(3) hepatocytes vs 13.65 +/- 19.41/10(3) hepatocytes; p=0.08). CONCLUSIONS:Patients with chronic hepatitis C and normal aminotransferases have significantly lower hepatocyte proliferation rates and show a trend towards lower apoptosis rates compared with patients with elevated aminotransferases.

Insular carcinoma of the thyroid is a low differentiated type constituting about 5% of all thyroid cancers. Higher aggressiveness has been suggested as an important clinical feature. The value of preoperative fine-needle aspiration biopsy is not clearly proven for insular carcinoma. The criteria for histological diagnosis have been outlined by Carcangiu et al. Because of its aggressiveness, radical treatment at primary surgery appears advisable. Its clear distinction from undifferentiated (anaplastic) and medullary (C cell) cancers is important, as thyroglobulin is regularly synthesized by cancer cells. Enrichment of radioactive iodine makes such treatment feasible postoperatively and at relapse. Follow-up should be performed as in highly differentiated papillary and follicular thyroid cancer. A patient series of eight cases is presented. While all cancers were advanced at the initial diagnosis, the observed disease courses were in agreement with the assumption that insular carcinoma is a more aggressive form of differentiated thyroid cancer.

OBJECTIVEWe prospectively investigated the peri-hepatic lymph node volume in patients with primary biliary cirrhosis (PBC) and healthy controls to evaluate the correlation with histology, biochemical and immunological features.MATERIALS AND METHODSThe total peri-hepatic lymph node volume in the liver hilus was evaluated by high-resolution ultrasound in 67 consecutive patients with PBC and in 43 healthy controls. Stages I-IV of PBC were biochemically, immunologically and histologically proven in all patients.RESULTSAdequate visualization of the liver hilus was achieved in 59/67 patients (88%) with PBC and in 39/43 healthy controls (91%). Lymph nodes in the liver hilus were sonographically detected in all 59 patients with PBC and in 26/39 healthy controls (67%) with adequate visualization of the liver hilus. The mean peri-hepatic lymph node volumes were: stage I (n = 9): 0.8 +/- 0.5 ml; stage II (n = 28): 2.4 +/- 1.5 ml; stage III (n = 21): 4.2 +/- 2.3 ml; stage IV (n = 9): 3.2 +/- 1.0 ml. The peri-hepatic lymph node volume did not significantly correlate with cholestasis, liver function tests or the immunological status.CONCLUSIONSEnlarged lymph nodes in the liver hilus are sonographically detectable in almost all patients with PBC. The total peri-hepatic lymph node volume in patients with PBC reflects histological stage, i.e. larger lymph nodes are observed in more advanced disease.

Although several virus- and host-related predictive factors for the response to interferon alfa (IFN-alpha) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (deltaHCV RNA) in patients treated with 3 x 10(6) units of recombinant IFN-alpha2a (rIFN-alpha2a) three times per week subcutaneously and to compare deltaHCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (deltaHCV RNA < or = 1 log) within the first 4 weeks of IFN-alpha treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of < or = 10(6) copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of > 10(6) copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-alpha2a treatment. All patients with a virological sustained response had an initial deltaHCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial deltaHCV RNA was confirmed as the strongest predictor of virological sustained response (P < .0001). In conclusion, the data of the present study suggest that IFN-alpha treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of deltaHCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful IFN-alpha treatment.

Background: PBC without antimitochondrial antibodies (AMA) is called autoimmune cholangitis.PBC without or with AMA plus antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) and the histological features of PBC and chronic autoimmune hepatitis is called overlap syndrome.Patients and Methods: Because it has been shown that patients with AMA-positive OS respond differently to UDCA therapy from patients without OS, we investigated whether AMA-positive OS is different from PBC with respect to biochemical, serological and morphological criteria.Results: From a collective of 103 PBC-patients the data of 70 patients have been evaluated.45 (64%) had an AMA-positive overlap syndrome, 25 (36%) a PBC.There were no statistically significant differences between the two groups concerning stages of the disease, histological activity, AMA and AMA-subtypes, IgM, IgG, inflammation-indicating enzymes (GLDH, AST, ALT), cholestasis enzymes and the course of the disease.15/45 (33%) of the patients with OS and 7/25 (28%) with PBC responded rapidly to medical therapy, 30 patients (67%) and 18 (72%) responded but slowly.Conclusions: AMA-positive overlap syndrome is not different from primary biliary cirrhosis with respect to biochemical, serological and morphological data.Although there were no differences between patients with OS and PBC concerning response to medical therapy, this needs to be confirmed in a larger study.

In screening for hereditary non-polyposis colorectal cancer (HNPCC)-an autosomal dominant disorder characterised by mutations in mismatch repair genes-detection of microsatellite instability is an important diagnostic criterion. The mono- or dinucleotide repeat DNA sequences are usually amplified from formalin fixed, paraffin embedded tissue by polymerase chain reaction after numerous time consuming steps including deparaffinisation, DNA extraction, and purification. A rapid single step method for direct DNA analysis is described, based on preincubation of paraffin embedded tissue with Triton X-100 followed by DNA amplification with fluorescence labelled primers and electrophoresis in an automated sequencer. This procedure allows precise allele sizing and analysis of genetic instability, is more efficient and time saving, reduces the risk of contamination, and is therefore of particular interest in screening for HNPCC.

Background and Study Aims: The value of transabdominal and endoscopic ultrasound (EUS) in detecting normal adrenal glands is not yet established. The aim of our study was to evaluate whether these techniques can be routinely used to visualize the adrenal glands in patients without suspected adrenal pathology.Patients and Methods: Transabdominal ultrasound was validated by examination of 10 corpses and was performed in 80 healthy volunteers (3.5 and 5 MHz). EUS of the left adrenal gland was performed in 154 consecutive patients referred for various other reasons. In 20 patients we attempted to visualize the right adrenal gland as well.Results: Both adrenal glands were correctly identified in all of the 10 corpses once they were opened. In healthy volunteers, the right adrenal gland was visualized by transabdominal ultrasound in 79/80 patients (99%) and the left adrenal gland in 55/80 patients (69%). EUS allowed detection of the left adrenal gland in 151/154 patients (98%). In three patients EUS failed because of grossly distorted anatomy. In 6/20 patients we were also able to detect the right adrenal gland by EUS, which was obvious in two cases because of incidentalomas.Conclusion: Visualization of the right adrenal gland is almost always possible by transabdominal ultrasound, while its detection by EUS is successful only in some cases. The left gland is more difficult to detect by transabdominal ultrasound, while it can nearly always be seen using EUS. Therefore, a combined transabdominal and endoscopic ultrasonographic approach is useful for visualization of the adrenal glands and may enable diagnosis of even small adrenal masses.

BACKGROUND AND OBJECTIVE:In patients with chronic inflammatory liver disease modern methods of ultrasound can visualize enlarged lymph nodes in the porta hepatis. Number, size and total volume of lymph nodes in the hepatoduodenal ligament in healthy subjects and in patients with chronic viral hepatitis without cirrhotic changes were investigated.PATIENTS AND METHODS:Sonographic localization of the perihepatic lymph nodes was validated at post-mortem and intraoperatively. Following this, 92 healthy persons (57 men, 35 women; average age 33 +/- 9 years) and 48 patients (30 men, 18 women; average age 35 +/- 8 years) with serologically and histologically confirmed chronic viral hepatitis (30 with hepatitis C, 18 with hepatitis B) were investigated by abdominal ultrasound (Acuson 128, 3.5 and 5 MHz). The hepatoduodenal ligament was assessed according to a standardized procedure with demonstration of the lymph node positions ventral to the portal vein and between the portal vein and the inferior vena cava.RESULTS:Satisfactory imaging of the hepatoduodenal ligament was achieved in 83 of the 92 healthy persons (90.2%) and in 44 of the 48 patients with chronic viral hepatitis (91.7%). Lymph nodes were demonstrated in 60 of the 83 healthy subjects (72.3%) and in 43 of 44 patients with chronic hepatitis (97.7%). The mean perihepatic lymph node volume was 2.8 +/- 2.6 cm3 (0-9.7 cm3) and was thus significantly smaller (P = 10(-9)) than in the patients with chronic viral hepatitis (19.8 +/- 15.7 cm3 [0-62.4 cm3]). There was no significant difference in lymph node volume between patients with hepatitis B and those with hepatitis C (23.1 +/- 14.9 cm3 vs 18.9 +/- 15.6 cm3; P = 0.16).CONCLUSIONS:With adequate ultrasound technique enlarged lymph nodes can be demonstrated in the porta hepatis of almost all patients with chronic hepatitis B or C. Lymph nodes of normal size can often be imaged also in healthy persons if their localization is known. The demonstration of lymph nodes in the hepatoduodenal ligament in the area of the porta hepatis and the determination of their volume can be helpful in the diagnosis of chronic inflammatory liver disease.

Background and objective: In patients with chronic inflammatory liver disease modern methods of ultrasound can visualize enlarged lymph nodes in the porta hepatis. Number, size and total volume of lymph nodes in the hepatoduodenal ligament in healthy subjects and in patients with chronic viral hepatitis without cirrhotic changes were investigated.Patients and methods: Sonographic localization of the perihepatic lymph nodes was validated at post-mortem and intraoperatively. Following this, 92 healthy persons (57 men, 35 women; average age 33 +/- 9 years) and 48 patients (30 men, 18 women; average age 35 +/- 8 years) with serologically and histologically confirmed chronic viral hepatitis (30 with hepatitis C, 18 with hepatitis B) were investigated by abdominal ultrasound (Acuson 128, 3.5 and 5 MHz). The hepatoduodenal ligament was assessed according to a standardized procedure with demonstration of the lymph node positions ventral to the portal vein and between the portal vein and the inferior vena cava.Results: Satisfactory imaging of the hepatoduodenal ligament was achieved in 83 of the 92 healthy persons (90.2 %) and in 44 of the 48 patients with chronic viral hepatitis (91.7 %). Lymph nodes were demonstrated in 60 of the 83 healthy subjects (72.3 %) and in 43 of 44 patients with chronic hepatitis (97.7 %). The mean perihepatic lymph node volume was 2.8 +/- 2.6 cm(3) (0-9.7 cm(3)) and was thus significantly smaller (P = 10(-9)) than in the patients with chronic viral hepatitis (19.8 +/- 15.7 cm(3) [0-62.4 cm(3)]). There was no significant difference in lymph node volume between patients with hepatitis B and those with hepatitis C (23.1 +/- 14.9 cm(3) vs 18.9 +/- 15.6 cm(3); P = 0.16).Conclusions: With adequate ultrasound technique enlarged lymph nodes can be demonstrated in the porta hepatis of almost all patients with chronic hepatitis B or C. Lymph nodes of normal size can often be imaged also in healthy persons if their localization is known. The demonstration of lymph nodes in the hepatoduodenal ligament in the area of the porta hepatis and the determination of their volume can be helpful in the diagnosis of chronic inflammatory liver disease.

Inflammatory processes in organs frequently lead to hyperplasia of regional lymph nodes. In the present study, we investigated whether lymph node enlargement within the hepatoduodenal ligament may reflect the inflammatory activity within the liver of patients chronically infected with the hepatitis C virus (HCV). In 114 patients with chronic hepatitis C and 49 healthy controls, the total lymph node volume within the hepatoduodenal ligament was prospectively investigated by ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the same occasion, and specimens were semiquantitatively evaluated by the histological activity index (HAI). Hepatitis C viremia was assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%) and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected in all patients with chronic hepatitis C and in 33 of 45 controls. The mean perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than in HCV-infected patients with mild to moderate inflammatory activity, severe inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4 mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P < 10(-6)). No correlation was found between the total lymph node volume within the hepatoduodenal ligament, HCV genotypes, and liver function test results. In conclusion, enlargement of perihepatic lymph nodes in patients with chronic hepatitis C is predictive for the presence of severe inflammatory activity. The mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown but appears to be related to viral replication within the liver and the immune-mediated inflammatory response of the host.

OBJECTIVE:While diffuse deposition of fat may occur with corticosteroid (CS) administration both in the liver and in other organs, comparatively little is known about focal changes in the liver under corticosteroid medication. Therefore, we evaluated pattern and extent of focal hepatic steatosis by ultrasound (US) in patients receiving corticosteroids. SUBJECTS AND METHODS:93 patients with known inflammatory bowel disease (IBD) received corticosteroids during a period of at least six weeks prior to the ultrasound examination and 28 IBD-patients had no corticosteroids within the last three years. 13 additional patients received corticosteroids for other reasons than IBD for > 1 year. 80 healthy volunteers served as controls. Focal changes of the liver as assessed by high resolution ultrasound (Acuson 128, 3.5 and 5 MHz) were defined as areas of brighter echogenicity compared to the general aspect of the liver. The size of the hyperechoic areas was documented (photoprint). RESULTS:40/93 IBD-patients with corticosteroids (43%) had definite areas of brighter echos in the hilus region of the liver. In IBD-patients without corticosteroids only one patient showed a focal brighter echogenicity, whereas in the non-IBD group with corticosteroids 8/13 had focal lesions (62%). In the control group only four healthy subjects showed brighter areas (5%). CONCLUSION:Bright focal areas in the liver hilus occur in > 40% of IBD-patients during corticosteroid medication. This phenomenon occurs in IBD-patients as frequently and as intense as in other patients with longstanding corticosteroid therapy. There is a hilar area of the liver with typical size and location which reacts to corticosteroid administration with hyperechoic reflexes at ultrasound investigation. This is important to know when it comes to the differential diagnosis of focal changes.

Purpose: the detection by US (ín contrast to CT) of lymph nodes of any size in the mediastinum is usually considered to be a pathological finding. the aim of this study was to find out whether it was possible to detect normal lymph nodes by high-resolution mediastinal US Material and Methods: Six different mediastinal regions in 80 healthy asymptomatic volunteers and in 20 human cadavers were examined by means of US (with colour Doppler imaging) to assess US access to the respective regions and to demonstrate the number and size of detectable lymph nodes. All the cadaveric lymph nodes that were detected were examined histologically to exclude inflammatory or malignant infiltration Results: in almost all subjects, we obtained US access to the supra-aortic (100%), paratracheal (95%), prevascular (99%), and pencardial (98%) regions, and to the aorticopulmonary window (98%). US access to the subcarinal region was more difficult (75%). in the healthy subjects, lymph nodes were detected in the paratracheal region (in 35% of these subjects, mean lymph-node diameter 12×7 mm), in the aorticopulmonary window (45%, 14×8 mm), and in the subcarinal region (13%, 13×7 mm). in the cadavers, histologically normal lymph nodes were detected frequently in the paratracheal region (85%, mean size 11×6 mm) and in the aorticopulmonary window (90%, 11×5 mm) Conclusion: These results indicate that normal lymph nodes (and not only pathological lymph nodes) can be demonstrated by high-resolution mediastinal US

BACKGROUND/AIMS:Hepatitis G virus (HGV) and hepatitis GB virus-C (GBV-C) are recently identified non-A-E hepatitis-associated viruses. The prevalence of HGV/GBV-C in the general population is high (1.0-1.7%), but data on the clinical and histological manifestations of the new viruses are sparse. In the present study we investigated the prevalence and clinical and histological manifestation of HGV/GBV-C infections in patients with elevated aminotransferase levels of unknown etiology.METHODS:In 52 of 630 consecutive patients referred for evaluation of elevated aminotransferases the underlying liver disease remained unknown. Serum samples of these 52 patients with elevated aminotransferase levels of unknown etiology were tested for HGV/GBV-C RNA by reverse transcription-polymerase chain reaction (RT-PCR) using primers deduced from nonstructural regions. Cloned PCR products were sequenced and compared by phylogenetic analysis.RESULTS:HGV/GBV-C RNA was consistently detected in 7 of the 52 patients (13%). Sequence and phylogenetic analysis revealed the presence of only one subtype, with nucleotide sequence homologies between 86 and 91%. All seven patients had persistent viremia for at least 9 months. In six patients liver function test results normalized, and alanine aminotransferase levels remained persistently elevated in only one patient. Four HGV/GBV-C positive and ten HGV/GBV-C negative patients consented to a liver biopsy, which revealed similar results with minimal to mild chronic hepatitis and mild portal fibrosis.CONCLUSIONS:The prevalence of HGV/GBV-C infections in patients with elevated aminotransferases of unknown etiology is low. Since clinical, biochemical and histomorphologic features of patients with elevated aminotransferases of unknown etiology with and without HGV/GBV-C infection are indistinguishable, the role of HGV/GBV-C in the pathogenesis of chronic liver disease appears insignificant.