13C-methacetin-breath test compared to also noninvasive biochemical blood tests in predicting hepatic fibrosis and cirrhosis in chronic hepatitis C.

BACKGROUND: The (13)C-methacetin-breath test and also several noninvasive blood tests comprising routine laboratory parameters have been proposed to predict fibrosis and cirrhosis in chronic hepatitis C. The aim of the study was to compare the diagnostic accuracy between these tests referring to hepatic histology as gold standard. METHODS: 96 patients with chronic hepatitis C virus infection underwent percutaneous liver biopsy and the (13)C-methacetin-breath test. The Fibroindex, the aspartate aminotransferase to platelet ratio index , and the aspartate aminotransferase to alanine aminotransferase ratio were used as parameters for the staging of fibrosis. The main endpoint was the area under the characteristic curves for the diagnosis of advanced fibrosis (F3-F4) and cirrhosis (F4) according to the Batts Ludwig criteria. RESULTS: ROC analysis revealed a cut-off <14.6 per thousand best with 92.6% sensitivity and 84.1% specificity for the (13)C-methacetin-breath test, for the Fibroindex >1.82 70.4% sensitivity and 91.3% specificity, for the aspartate aminotransferase to platelet ratio >1.0 a 66.7% sensitivity and 75.4% specificity, and for the aspartate aminotransferase to alanine aminotransferase ratio >1.0 63.0% sensitivity and 59.4% specificity in predicting liver cirrhosis. The areas under the curve for the breath test, the Fibroindex, aspartate aminotransferase to platelet ratio and the aspartate aminotransferase to alanine aminotransferase ratio were 0.958, 0.845, 0.799, and 0.688, respectively, when predicting cirrhosis. For identifying patients with advanced fibrosis, the areas under the curve were 0.827, 0.804, 0.779, and 0.561, respectively. Discordances between Fibroindex (21%), aspartate aminotransferase to platelet ratio (29%) or aspartate aminotransferase to alanine aminotransferase ratio (37.6%) and liver biopsy were significantly more frequent than between (13)C-breath test (11.6%) and liver biopsy (P<0.05). CONCLUSION: The (13)C-methacetin-breath test is more reliable in predicting advanced fibrosis and cirrhosis than simple biochemical parameters (aspartate aminotransferase to platelet ratio; aspartate aminotransferase to alanine aminotransferase ratio).

Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study.

BACKGROUND: Faecal occult blood testing is an established method of colorectal neoplasia screening. Guaiac-based tests are limited by poor patient compliance, low sensitivity, specificity and positive predictive value. Newer immunochemical-based tests, accurate but tedious, require a well-established laboratory set up. There is need for simpler immunochemical tests that can be performed at the out-patient clinic. AIM: To compare the performance characteristics of a new bedside immunological test strip device with a sensitive Guaiac-based and established immunochemical test for detection of faecal occult blood in patients undergoing colonoscopy. METHODS: A total of 389 consecutive patients from four centres who were referred for colonoscopy also provided the stool samples for detection of occult blood without dietary restrictions. Stool tests performed were (i) Guaiac-based, (ii) immunochemical enzyme-linked immunosorbent assay and (iii) bedside immunochemical strip test. RESULTS: At the optimal threshold level, the sensitivity and specificity of the beside immunochemical strip test for detection of significant colorectal neoplasia (adenomas >1.0 cm and carcinomas) were 60% and 95%, respectively. CONCLUSIONS: This bedside immunochemical strip test proved to be a simple, convenient, non-cumbersome and accurate tool with similar performance characteristics for detection of any bleeding lesion including colorectal neoplasia when compared with an established immunochemical faecal occult blood test.

Noninvasive assessment of liver steatosis, fibrosis and inflammation in chronic hepatitis C virus infection.

BACKGROUND: Duplex-Doppler ultrasound is a noninvasive method for the assessment of hepatic hemodynamics beyond conventional gray-scale imaging. The clinical value of the method for the grading and staging of chronic hepatitis C virus (HCV) infection and the prediction of hepatic steatosis still has to be determined. This study aimed to compare Duplex-Doppler and ultrasound with the histologic staging and the estimation of hepatic steatosis in chronic HCV infection. PATIENTS AND METHODS: One hundred and nineteen consecutive patients with chronic HCV infection underwent both liver biopsy and ultrasound with Duplex-Doppler. Maximum portal venous blood flow velocity, portal venous flow undulation, hepatic venous flow pattern and spleen size were assessed and compared with histologic findings. Histologic grading and staging was performed according to the modified HAI and hepatic steatosis was estimated. RESULTS: Doppler ultrasound was unable to discriminate between different degrees of fibrosis. Sensitivity/specificity of portal venous flow and undulations for the diagnosis of hepatic cirrhosis was 74.5%/53% and 76.5%/100%. The PPV and NPV of reduced undulations was 100% and 96.2%. Mono- or biphasic hepatic venous flow indicated advanced hepatic steatosis (sensitivity 88.2%, specificity 74.5%, PPV 36.6%, NPV 97.5%). Spleen size was significantly enlarged both in patients with cirrhosis and steatosis. CONCLUSIONS: Although Duplex-Doppler of the portal and hepatic veins is not a substitute for histologic grading and staging, portal vein undulations can predict liver cirrhosis with considerable accuracy. Moreover, triphasic patterns of hepatic venous flow virtually exclude significant fatty liver disease. Additional studies should perform intraindividual follow-up investigations to further define the role of Duplex-Doppler ultrasound in chronic HCV infection.

An infected esophageal duplication cyst in a patient with non-Hodgkin's lymphoma mimicking persistent disease.

Differentiation of mediastinal cysts appearing as soft-tissue attenuation masses on computed tomography (CT) scans from malignant mediastinal masses is difficult. We report a patient with non-Hodgkin's lymphoma, who was considered to have persistent disease in the posterior mediastinum based on CT scans. However, endoscopic ultrasound (EUS) demonstrated a paraesophageal, fluid-filled cyst with echodens inclusions and no evidence of any solid component. EUS-guided fine-needle aspiration (FNA) revealed mucous, epithelial and inflammatory cells, and additionally candida albicans was cultured. Based on these findings and constant size during follow-up, the diagnosis of an infected esophageal duplication cyst was made. Thus, this report further demonstrated the impact of EUS and EUS-FNA for management of posterior mediastinal cystic lesions in selected cases.

Does the liver ever age? Results of liver transplantation with donors above 80 years of age.

INTRODUCTION: Facing an increasing shortage of donor organs, donor criteria become more extended and so-called marginal organs are accepted for transplantation. For liver donation donor age above 70 years is accepted as a risk factor concerning primary dysfunction or nonfunction. Therefore, the aim of this study was to compare the early outcome of grafts older versus younger than 80 years of age. PATIENTS AND METHOD: Between August 2002 and February 2004, 40 adult liver transplants were performed using triple immunosuppression with tacrolimus, MMF, and low-dose corticosteroids. Recipients with HCC received low-dose rapamycin after postoperative day 14. The outcome of grafts from donors under 80 years of age (n=35) was compared with those from donors 80 years old or more (n=5). For statistical analysis Mann-Whitney-U-Test and Fisher's Exact Test were used with P < .05 considered statistically significant. RESULTS: The average donor age of our population was 54.4 +/- 17.3 years with five donors older than 80 years (80-83 years). These donors all had additional risk factors. The recipients of the latter grafts suffered from HCC and liver cirrhosis Child A (n=2) or from viral hepatitis (n=3). One recipient had advanced cirrhosis with severe complications. The outcomes of both groups were comparable concerning intraoperative and postoperative courses. All recipients of old liver grafts left the hospital with stable graft function. CONCLUSION: Liver grafts over 80 years can be transplanted with good results, especially if given to recipients with malignancy and otherwise stable liver function.

Characterization of the nuclear import of human MutLalpha.

DNA mismatch repair (MMR) is essential for the maintenance of replication fidelity. Its major task is to recognize mismatches as well as insertion/deletion loops of newly synthesized DNA strands. Although different players of human MMR have been identified, the regulation of essential steps of MMR is poorly understood. Because MMR is initiated in the nucleus, nuclear import might be a mechanism to regulate MMR. Nuclear targeting is accomplished by conserved signal sequences called nuclear localization signals (NLS), which represent clusters of positively charged amino acids (aa). hMLH1 contains two clusters of positively charged amino acids, which are candidate NLS sequences (aa 469-472 and 496-499), while hPMS2 contains one (aa 574-580). To study the effect of these clusters on nuclear import, NLS mutants of hMLH1 and hPMS2 were generated and expressed in 293T cells. The subcellular localization of the mutant constructs was monitored by confocal laser microscopy. We demonstrated that missense mutations of two signal sequences, one in hMLH1 and one in hPMS2, lead to impaired nuclear import, which was especially prominent for mutants of the hMLH1 residues K471 and R472; and hPMS2 residues K577 and R578.

13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection.

BACKGROUND: The 13C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. AIM: To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. METHODS: Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index-Knodell score. RESULTS: Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 +/- 9.2 per thousand vs. 24.1 +/- 5.7 per thousand; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 +/- 4.8% and in healthy controls 13.8 +/- 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 +/- 7.9 per thousand vs. 22.6 +/- 7.2 per thousand; P = 0.61) or cumulative recovery (13.6 +/- 3.7% vs. 13.2 +/- 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C-methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 +/- 4.9 per thousand; P < 0.005 and cumulative recovery after 30 min: 5.6 +/- 3.2%; P < 0.003). The 13C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. CONCLUSION: The non-invasive 13C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C.

The new DR-70 immunoassay detects cancer of the gastrointestinal tract: a validation study.

BACKGROUND: Malignant cells characteristically possess high levels of plasminogen activator, which induce local fibrinolysis. The DR-70 immunoassay is a newly developed test, which quantifies fibrin degradation products in serum by a proprietary antibody. AIM: To evaluate the DR-70 immunoassay as a detection assay for the presence of gastrointestinal cancers. METHODS: We prospectively collected blood sera of 85 patients with histologically proven tumour and 100 healthy blood donors. Ten microlitres of the sera was used for the DR-70 immunoassay. Nineteen patients had a hepatocellular and 10 cholangiocellular carcinoma, 13 cancer of the pancreas, 30 colorectal cancer, 10 stomach cancer and three cancer of the oesophagus. RESULTS: Receiver-operator curve analysis revealed <0.7 microg/mL as the best cut-off value to distinguish between patients with cancer and healthy controls. Using this cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 91% and a specificity of 93%. Patients with advanced tumour spread showed significantly higher DR-70 values than those with early-stage tumours (P < 0.0003). CONCLUSION: The DR-70 immunoassay reliably differs between cancer patients and healthy controls. Therefore, it promises to become a useful test for the detection of cancer in clinical practice.

[Lymphangioleiomyomatosis (LAM): a rare cause of ascites and pleural effusion]. / Lymphangioleiomyomatose (LAM): seltene Ursache von Aszites und Pleuraergüssen.

HISTORY AND CLINICAL FINDINGS: A 45 year old woman presented at our hospital for further evaluation of intermittent abdominal pain. The patient reported that she had suffered a spontaneous pneumothorax 8 years and a pleural effusion 3 years before. DIAGNOSTIC FINDINGS AND THERAPY: Abdominal ultrasound showed abdominal fluid which proved to be chylous ascites by diagnostic paracentesis. Radiologic (lymphangiography) findings were consistent with lymphangioleiomyomatosis (LAM). Remarkably, lymphangiography resulted in an immediate disappearance of the ascitic fluid. CONCLUSION: This report depicts a case of LAM which involved both pulmonary and intestinal symptoms. Previous pulmonary problems gave a hint towards the right diagnosis. Though lymphangiography is rarely performed in these days, the method was both diagnostic and therapeutic in the case presented.

[Acute lower gastrointestinal hemorrhage. Diagnosis and management]. / Akute untere Gastrointestinalblutung. Diagnostik und Management.

In most cases (80%), acute lower gastrointestinal bleeding stops spontaneously, but rebleeding is frequent (25%). The intensity and quality of the bleeding--hematochezia, melena, or occult bleeding--determines the diagnostic and therapeutic strategy (endoscopic evaluation of the upper and lower gastrointestinal tract, mesenteric angiography, scintigraphy, enteroscopy, capsule endoscopy) and its urgency. Acute lower gastrointestinal bleeding can mostly be treated conservatively or by endoscopic interventions (injection therapy, clip application, coagulation and ligation methods). Severe hemorrhage can render colonoscopy and the identification of the bleeding source technically difficult. Emergency operations are only indicated when patients with severe hemorrhage cannot be stabilized by interventional endoscopy or angiography with selective embolization.

[Diagnosis of colorectal carcinoma. An update]. / Diagnostik kolorektaler Karzinome. Aktueller Stand.

Colorectal cancer (CRC) is one of the most frequent tumors in western countries. More than 50% of all CRC are diagnosed at an advanced stage which precludes curative treatment. For this reason, early detection of CRC is mandatory to improve longterm outcome. Fecal occult blood testing (FOBT) once per year and subsequent colonoscopy (if the FOBT is positive) provides up to 30% decrease in mortality from CRC. Due to the fact that current data indicate a 60% reduction in CRC-associated mortality, colonoscopy has recently been approved for CRC screening by german public health insurance companies. Yet efforts in screening largely depend on patient compliance, particularly in view of cost-effectiveness. Introduction of new imaging techniques (CT-/MRI-colonography) may increase general acceptance, but clinical benefit and costs still remain to be determined in larger studies.

The value of routinely performed ultrasonography in patients with Crohn disease.

BACKGROUND: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. METHODS: 255 consecutive patients with chronic CD (117 M, 138 F, mean age (+/-s) 38 +/- 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. RESULTS: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI > 150) and 17/46 (37%) as inactive disease (CDAI < or = 150). Of the 17 patients with a TMR and CDAI < or = 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. CONCLUSION: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation.

BACKGROUND: Deoxycholic acid has long been attributed as a tumour promoter in the colon. It exerts its growth-related actions in a phorbol ester-like manner, by stimulating protein kinase C. The aim of this study was to investigate the effect of deoxycholic acid on proliferation and apoptosis in the colon, by exposing colon cancer cells to it in increasing concentrations. METHODS: Human colon cancer cells (Caco-2 and HT-29) were treated with deoxycholate or its two structural isomers, 3-beta-12-alpha-dihydroxy-5-beta-cholan-24-oic acid and 3-alpha-12-beta-dihydroxy-5-beta-cholan-24-oic acid. Proliferation was evaluated by cell counting, and apoptosis by estimating percentage cell survival and assessment of nuclear morphology. RESULTS: Within the concentration range of up to 20 microM, deoxycholate stimulated growth of both human colon cancer cell lines. Its growth-promoting effect was abolished after inhibition of protein kinase C. At concentrations above 100 microM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth. CONCLUSION: Low-dose deoxycholate stimulates colon cancer cell proliferation while > 100 micromol L(-1) of this secondary bile acid induces apoptosis in colon cancer cells. Deoxycholate might promote the likelihood of malignant transformation by increasing epithelial cell turnover in the colon.

[Hypertransaminasaemia and impaired liver function in a patient with oligosymptomatic celiac disease]. / Leberfunktionsstörung als Leitsymptom einer einheimischen Sprue.

Hypertransaminasaemia and impaired liver function in a patient with oligosymptomatic celiac disease. We describe the case of a 45-year-old man who was referred for evaluation of elevated aminotransferases. One year before referral the patient developed an ischemic stroke followed by a subdural hematoma three months later. In our outpatient clinic the patient presented with a malabsorption syndrome including diminished vitamin-K-dependent clotting factors. Serologic testing was positive for IgA antigliadin antibodies and IgA antiendomysial antibodies. Celiac disease was confirmed by an upper endoscopy examination and biopsies obtained from the distal duodenum. Histological examination showed villous atrophy, crypt hyperplasia and an increase in intraepithelial lymphocyte count consistent with celiac disease. After initiation of a gluten-free diet the malabsorption syndrome as well as liver dysfunction improved. Serum aminotransferase levels normalized within 6 months. The clinical course demonstrates involvement of the liver in patients with celiac disease.

Deoxycholic acid stimulates migration in colon cancer cells.

BACKGROUND: Deoxycholic acid and other secondary bile acids have long been considered tumour promoters in the colon. However, their effect on cell migration, known to play an important role in colon carcinogenesis, has not been studied so far. OBJECTIVE: To investigate the possible effects of deoxycholic acid on colon cancer-cell migration in culture. METHODS: Human colon carcinoma cells (Caco-2) were seeded on basement membrane matrix. To evaluate replication-blocked cell migration, we wounded confluent monolayers of cells with a sterile scalpel, and inhibited cell replication with mitomycin C. Immediately after wounding, the cells were exposed to 0-100 micromol/l deoxycholic acid. Migration over 72 h was monitored using a phase contrast microscope. RESULTS: Replication-blocked migration was stimulated by deoxycholic acid in a dose-dependent manner, with the maximum effect at 20 micromol/l deoxycholic acid. Enhancement of migration rate was unaffected by immunoneutralization of transforming growth factor beta (a known migration-promoting peptide). However, specific inhibition of protein kinase C markedly inhibited deoxycholic acid-induced Caco-2 cell migration. CONCLUSION: In addition to its well-established role in the enhancement of proliferation, deoxycholic acid also stimulates colon cancer-cell migration along the basement membrane matrix. The mechanism of this stimulation is likely to involve protein kinase C. Deoxycholic acid-stimulated migration might additionally contribute to the tumour-promoting effects of secondary bile acids in the colon.

[Diagnosis related groups (DRG)--current significance in gastroenterology]. / Diagnosis Related Groups (DRG)--aktuelle Bedeutung in der Gastroenterologie.

Prospective payment systems using the diagnosis related groups (DRG) payment mechanism have been introduced in many countries all over the world. In June 2000 the Australian Refined Diagnosis Related Groups System (AR-DRG) was chosen as the model which will be introduced in 2003 as the control instrument for the hospital dependent public health system in Germany. Background and possible implications for gastroenterologists and hepatologists are discussed.