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Background and Study Aims: Biliary plastic stents are highly effective in the treatment of malignant biliary obstruction, but may become occluded over time, leading to jaundice and cholangitis. Stent occlusion is thought to be caused by bacterial adhesion and formation of biofilm. This study was carried out to assess whether treatment with ofloxacin in combination with ursodeoxycholic acid is superior to ursodeoxycholic acid alone in preventing stent occlusion., Patients and Methods: Patients with obstructive jaundice due to inoperable malignant disease underwent placement of a straight 11.5-Fr polyethylene stent. After stent insertion, the patients were randomly assigned to receive either ofloxacin (200 mg b.i.d.) with ursodeoxycholic acid (250 mg t.i.d.) or ursodeoxycholic acid alone. The end points of the study were the frequency of stent occlusions, the time to stent occlusion, and the safety of the two regimens., Results: Fifty-two patients were enrolled, of whom 26 were assigned to the combined therapy group and 26 to the control group. Thirty patients were suffering from pancreatic cancer, 13 from gallbladder or bile duct cancer, and nine had metastases from other malignant tumors. Eight stent occlusions (31%) occurred in the ofloxacin group and six (23 %) in the control group (P = 0.76). The mean times to stent occlusion were 95 +/- 9 days and 101 +/- 9 days, respectively (P = 0.91). No significant differences regarding survival time or safety were observed between the two groups., Conclusions: Ofloxacin in combination with ursodeoxycholic acid is not superior to ursodeoxycholic acid alone in preventing stent occlusion in patients with malignant obstructive jaundice.

Human hepatocytes cultured serum-free for up to 6 weeks were used to study expression and induction of enzymes and membrane transport proteins involved in drug metabolism. Phase I drug metabolizing enzymes cytochrome P450 (CYP)1A1, CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 were detected by Western blot analyses and, when appropriate, by enzymatic assays for ethoxyresorufin-O-deethylase(EROD)-activity and testosterone-6beta-hydroxylase(T6H)-activity. Expression of the membrane transporter multi-drug resistance protein (P-glycoprotein, MDR-1), multidrug resistance-associated protein (MRP-1), and lung-resistance protein (LRP) was maintained during the culture as detected by RT-PCR and Western blot analyses. Model inducers like rifampicin, phenobarbital, or 3-methylcholanthrene and beta-naphtoflavone were able to induce CYP1A or CYP3A4 as well as EROD or T6H activities for up to 30 days. CYP2C9, CYP2C19 and CYP2E1 expression was maintained but not inducible for 48 days. Also, rifampicin and phenobarbital were unable to increase MDR-1 and MRP-1 protein levels significantly., (Copyright 2000 Academic Press.)

Background/aims: Doppler sonography has been used to assess hepatic arterial perfusion in a number of published reports. However, adequate validation studies are available for neither the transcutaneous nor the intravascular Doppler approach. The aim of this comparative study was to assess hepatic arterial perfusion with both methods., Methods: In 15 patients the right hepatic artery was examined with intravascular and transcutaneous Doppler sonography after calibration of Doppler devices in vitro with a thread model. The measurements were performed simultaneously in five and separately within 24 h in 10 patients., Results: In vitro, the correlations between the velocities of the thread and the velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/-standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/-8.6 cm/s) were found with intravascular compared to transcutaneous Doppler sonography, significant correlations were demonstrable between results obtained by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07, transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were somewhat higher using the intravascular device, but correlated well with the numbers obtained by the transcutaneous approach., Conclusions: The data suggest that with use of different Doppler devices, systolic velocities are the most suitable parameter for Doppler assessment of hepatic arterial perfusion.

Since human hepatocytes are available only in limited number, the development of a serum-free culture system for long-term cultivation of differentiated and functional hepatocytes is of great importance. Here we describe the culture of human hepatocytes in a chemically defined serum-free medium for up to 5 weeks. Cell morphology was assayed by light and electron microscopy and revealed a well-preserved cellular morphology. Marker proteins for epithelial and bile duct cells, cytokeratin (CK) 18 and 19, and liver-specific proteins, like phosphoenolpyruvate carboxykinase-2 (PCK2) and serum proteins, were expressed. Liver-enriched transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and hepatocyte nuclear factor-4 (HNF-4), cytokine and mitogen activated factors (nuclear factor kappa B) NFkappaB, and activator protein-1 (AP-1) were maintained and active for several weeks in our cultures. In summary, our serum-free culture system allows the culture of differentiated human hepatocytes for several weeks. It may serve as a model system for metabolic, pharmacologic-toxicologic studies, and studies on human pathogens under defined chemical conditions., (Copyright 2000 Academic Press.)

Background & Aims: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection., Methods: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model., Results: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003)., Conclusions: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Background & Aims: In cirrhosis, liver blood flow becomes increasingly dependent on the hepatic artery. The aim of this study was to investigate hepatic arterial blood flow volume and resistance and hepatic arterial flow reserve in relation to liver function and systemic hemodynamic alterations in patients with cirrhosis., Methods: In 38 patients with cirrhosis, liver function, cardiac output, and systemic vascular resistance were studied, and hepatic arterial blood flow velocity, flow volume, and pulsatility index at baseline and during intra-arterial administration of adenosine (2-40 microg. min-1. kg body wt-1) were assessed by angiography combined with intravascular Doppler flowmetry., Results: Hepatic arterial flow velocity was 21 +/- 11, 31 +/- 17, and 41 +/- 27 cm/s; flow volume was 266 +/- 246, 342 +/- 289, and 417 +/- 220 mL/min; and pulsatility index was 2.2 +/- 0.7, 1.7 +/- 0.6, and 1.5 +/- 0.5 in Child-Pugh classes A, B, and C, respectively (differences not statistically significant). Adenosine-induced changes in these parameters were more marked in Child-Pugh class A (68 +/- 15 cm/s, 1246 +/- 486 mL/min, and -1.14 +/- 0.5) than in class C (45 +/- 23, P < 0.05; 704 +/- 492, P = 0.02; and -0.58 +/- 0.38, P < 0.05). Using analysis of variance, cardiac index, systemic vascular resistance, and ascites, but not Child-Pugh class, were related to baseline values and adenosine-induced changes., Conclusions: Adenosine is a potent dilator of the hepatic artery in humans. The data suggest that hepatic arterial blood flow and adenosine-dependent flow reserve in patients with cirrhosis are under systemic hemodynamic or neurohormonal control.

The aim of this prospective, nonrandomized study was to assess the short- and long-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic and systemic hemodynamics and on gastroesophageal collateral flow in patients with cirrhosis and failure of chronic sclerotherapy. Cardiac output (CO), free and wedged pulmonary artery pressure (FPAP and WPAP), systemic vascular resistance (SVR), azygos venous blood flow (AzVBF), and the relative (portal minus vena cava) pressure in the portal vein (rel.PP) were determined immediately before, 30 minutes, 1 week, 3 months, and 1 year after TIPS implantation in 21 patients with alcoholic and biliary cirrhosis with repeated bleeding from esophageal varices despite chronic sclerotherapy. TIPS was inserted when patients were in a stable hemodynamic condition. Palmaz stents were dilated to a 10-mm to 14-mm diameter until gastroesophageal collaterals were no longer visible on direct splenoportography. Relative portal pressure decreased from 21 +/- 5 mm Hg to 11 +/- 5 mm Hg 30 minutes after the procedure (P <.001). CO increased from 7.1 +/- 1.5 L/min at baseline to 8.9 +/- 2.0 L/min (P <.005) at 30 minutes, 8.2 +/- 2.0 L/min (P <. 01) at 1 week, and 8.0 +/- 2.0 L/min (P <.01) at 3 months after TIPS, and returned to 7.2 +/- 1.3 L/min (ns) after 1 year. Before TIPS, SVR was 990 +/- 285 dyne. sec. cm-5 and decreased to 856 +/- 252 dyne. sec. cm-5 (P <.05) and 866 +/- 267 dyne. sec. cm-5 (P <.05) at 30 minutes and 1 week after the procedure, and increased again to 903 +/- 208 dyne. sec. cm-5 (ns) and 1,016 +/- 260 dyne. sec. cm-5 (ns) at 3 months and 1 year, respectively. AzVBF continuously decreased from 474 +/- 138 mL/min before TIPS to 335 +/- 116 mL/min, 289 +/- 147 mL/min, 318 +/- 157 mL/min, and 250 +/- 104 mL/min (all P <.005) at 30 minutes, 1 week, 3 months, and 1 year after TIPS. Portal decompression after TIPS is associated with a significant increase of CO for at least 3 months, which is only partly explained by a transient decrease of SVR. After 1 year, CO had returned to baseline levels. Despite an immediate decrease in portal pressure, the reduction of blood flow through gastroesophageal collaterals is delayed and not complete before 1 year after TIPS. In contrast to previous short-term observations, TIPS does not seem to cause long-term aggravation of the hyperkinetic circulation in patients with cirrhosis.

Variceal bleeding is still one of the key therapeutic problems inpatients with portal hypertension. Vasoactive drugs for the treatment of acute hemmorrhage as well as for the prevention of first and recurrent bleeding have been shown to be effective, in some situations as effective as endoscopic sclerotherapy. In recent years, endoscopic band ligation has replaced sclerotherapy for the prevention of rebleeding and become the new nonsurgical standard in this situation. Furthermore, the transjugular, intrahepatic, portosystemic stent shunt (TIPS) has gained widespread acceptance as a salvage procedure for acute bleeders unresponsive to other treatments as well as the second line approach to failures of chronic endoscopic or drug therapy for prevention of rebleeding. Primary prophylaxis is still the domain of beta-blockers or/and long-acting nitrates.

The antiinflammatory drug 5-aminosalicylic acid is available either as mesalamine in various slightly different galenic preparations or as a prodrug with 5-ASA bound to a carrier molecule as inert as possible, which releases 5-ASA via bacterial degradation in the ileocolon. Data from therapeutic trials in patients with Crohn's disease are only available for mesalamine and sulfasalazine. In active Crohn's disease, high-dose (> 3 g per day) mesalamine only is more effective than placebo, but inferior to systemic steroids. They may be used in patients refusing treatment with classical steroids or not tolerating them if this does not make a case for budesonide. The therapeutic gain of mesalamine over placebo for the prevention recurrence in patients who have reached remission by drug treatment is marginal. Thus, its use in this clinical situation is not appealing. Results for the maintenance of a surgically induced remission appear slightly better so that the use of > 3 g of mesalamine per day may be still justified in this scenario. It is an unresolved question whether the clinical efficacy of different galenic mesalamine prepations in maintaining postoperative remission varies with the preoperative disease location. Present data are not sufficient to support differential drug treatment based on this parameter.

Portal-hypertensive colopathy has attracted interest in recent years because such lesions can cause life-threatening hemorrhage. In contrast to upper gastrointestinal bleeding from varices, there is no established therapy for bleeding from angiodysplasia-like lesions. This case report describes the first successful use of transjugular intrahepatic portosystemic shunt (TIPS) for long-term control of bleeding from angiodysplasia-like colonic lesions in a patient with cirrhosis caused by chronic hepatitis B infection. During an 18-month course after TIPS, angiodysplasia-like lesions disappeared without any further evidence of recurrent hematochezia. TIPS may be helpful as second-line treatment in patients with recurrent portal-hypertensive bleeding from colonic angiodysplasia-like lesions who do not tolerate or are unresponsive to treatment with beta-adrenergic blockers.

The choice of methods for the treatment of acute variceal hemorrhage critically depends on the locally available expertise. Vasoactive drugs or balloon tamponade may bridge the time to more definitive measures such as sclerotherapy or band ligation. Drugs (nonselective beta-adrenergic blockers and long-acting nitrates) are almost equivalent to endoscopic sclerotherapy for the prevention of recurrent bleeding, while band ligation offers both increased efficacy (reduced rate of rebleeding and death) and decreased complication rates when compared to sclerotherapy. Thus, ligation will predominantly be used for the prevention of recurrent bleeding. Alternatively, drugs may be applied when acute bleeding was effectively stopped without the use of endoscopic means. Endoscopic sclerotherapy and surgery have no place in the primary prophylaxis of variceal hemorrhage in patients who have not bled before. Prevention of the first bleed is clearly the field for beta-blockers or nitrates. The role of banding ligation in this situation remains to be defined.

History and Clinical Findings: A 39-year-old woman in good health suddenly developed painful paraesthesia and incomplete paresis of all four limbs. Furthermore, arterial hypertension and tachycardia were found. The patient reported a history of chronic allergic rhinitis for 10 years and asthma one year., Investigations: Laboratory data showed an increased leucocyte count with a substantial increase in eosinophils in peripheral blood as well as in bone marrow. Nonspecific inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, fibrinogen as well as eosinophil cationic protein (ECP) were also increased. Histological investigations of a skin-muscle biopsy of the quadriceps revealed necrotizing vasculitis with extravascular granulomata and histiocytic giant cells., Diagnosis, Treatment and Course: Based on the diagnosis of Churg-Strauss syndrome treatment with methylprednisolone (500 mg every second day) was started, but was found to be ineffective after 10 days. Symptoms responded well to a subsequent course of 150 mg cyclophosphamide combined with 50 mg prednisolone per day. Pareses and pain were significantly reduced and all qualitative nerve functions returned to normal within two weeks of treatment. Laboratory parameters, especially the ECP, were similarly normalized., Conclusion: Churg-Strauss syndrome should be considered in the differential diagnosis of unexplained polyneuropathy. Determination of ECP may not only help in the diagnosis but does also facilitate monitoring of treatment and of further course of the disease.

Patients and Methods: In a retrospective study, the results of percutaneous transhepatic therapy of bile duct stones under cholangioscopic control (PTCS) were evaluated in 32 patients in which a endoscopic retrograde stone removal was impossible or failed., Results: Previous gastric surgery was the most common reason for choosing the percutaneous route (22 cases). Five patients had biliodigestive anastomosis, two pyloric obstructions, and in three patients the retrograde stone removal failed. Complete stone removal was obtained after 3 to 11 (median 5) percutaneous procedures in all cases, in 28 patients by electrohydraulic lithotripsy, and in the remaining 5 cases by mechanical extraction alone. There was no complication due to cholangioscopy and lithotripsy themselves. Two cases had major complications which needed laparotomy (4%, one case had capsular bleeding from the liver, another one had catheter perforation of the duodenum). In addition, three cases (7%) had minor complications which required no therapy during the percutaneous fistula procedure. Two elderly multimorbid patients (4%) died during hospitalisation after successful stone removal not related to the performed procedure., Conclusion: The percutaneous transhepatic cholangioscopy (PTCS) and lithotripsy are highly effective techniques for endoscopic treatment of bile duct stones. Because of an increased rate of complications during the fistula procedures, both methods should be restricted to cases with difficult anatomic situation and high risk of surgery.

Background and Aim: Complications in chronic pancreatitis, such as duct occlusion due to stenosis or stones can be treated by interventional endoscopic procedures. The benefit of such procedures and the effect on the clinical course is still under debate. Therefore, it was the aim of this study to analyze the effect of endoscopic interventional procedures in more detail with respect to technical and clinical benefit., Patients and Methods: 100 patients with chronic pancreatitis (cP) were studied retrospectively. In 58 patients an indication for interventional endoscopic therapy was given (45 +/- 12 yrs; 46 M, 12 F; cP 1 degree: n = 1, cP II degree: n = 8, cP III degree: n = 49). The patients were allocated to three groups: stenosis (n = 18), pancreatic duct stones (n = 18) and stenosis and pancreatic duct stones (n = 20). In two patients no visualization of the main pancreatic duct was performed due to cholestasis that was treated primarily. In total, 295 endoscopic procedures were performed (EPT, duct dilatation, plastic endoprothesis, ESWL, mechanical lithotripsy). Technical success was 95%. All stenoses could be dilated or bridged by plastic stents. Fragmentation of main pancreatic duct stones was achieved in 92%. The overall complication rate of all 319 endoscopies (fever, bleeding, stent dislocation) was 15.8%. Five patients had to undergo surgery, however, not as a direct consequence of complications from or unability of endoscopic procedures. 86% of the patients reported complete pain relief after the endoscopic-interventional procedures and 62% during the follow-up interval (7.4 +/- 6.3 months). 59% of the patients with weight loss and 58% of the patients with initially stable weight experienced a weight gain following endoscopic-interventional therapy. Individual patients showed improvement of endocrine or exocrine pancreatic function. 82% of the patients did not require inhouse treatment or emergency admission to the hospital whereas three admissions on average were recorded prior to endoscopic interventional treatment. Therefore, we conclude that a subset of patients does benefit from endoscopic interventional therapy of complications of chronic pancreatitis. However, a controlled prospective study is still mandatory.

The hepatopulmonary syndrome (HPS) is a functional process and is characterized by the triad of liver cirrhosis, intrapulmonary vascular dilatations, and arterial hypoxemia in absence of detectable intrinsic disease of the lung and the heart. The pathophysiological fundament is the presence of a ventilation-perfusion (VA/Q) inequality based on marked vasodilatation of the pulmonary vessels at the precapillary level. Only in critically ill patients limitations of the diffusion of oxygen from the alveolar gas to the capillary blood and intrapulmonary arteriovenous communications will increasingly contribute to the hypoxemia. For diagnosis of the HPS the arterial blood gases (under condition of room air and 100% oxygen), the contrast echocardiography, the pulmonary angiography, and the multiple inert gas elimination technique will give important informations. Regarding recent studies liver transplantation is the treatment of choice in patients with severe HPS.

Background: There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day)., Methods: A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention. CDAI and an acute-phase protein (CRP) were used as criteria for a relapse., Results: The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo., Conclusions: Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet.

Background: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE., Aims: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease., Patients: 49 male and female adults without symptoms of severe bleeding and sepsis and who screened negative for benzodiazepine in both blood and urine, were included in the study., Methods: Patients were randomised to receive either three sequential bolus injections of flumazenil (0.4, 0.8, and 1 mg) or placebo at one minute intervals, followed by intravenous infusions of either flumazenil (1 mg/h) or placebo for three hours. Clinical PSE grading and vital signs were assessed hourly during baseline and post-treatment periods and half hourly during treatment. The main outcome measures were improvement in group average PSE score and reduction of two points in individual PSE score (clinically relevant improvement)., Results: The mean average improvement in the PSE score in the subjects treated with flumazenil was not statistically significantly different from placebo. However, for patients showing clinically relevant improvement, the difference between flumazenil and placebo was statistically significant (seven of 28 v none of 21; p = 0.015). Flumazenil was well tolerated., Conclusions: A subgroup of patients with PSE resulting from chronic liver disease may benefit from the administration of flumazenil.

This study investigated the relationship between urinary sodium excretion and liver function, as assessed by the aminopyrine breath test (ABT) and conventional parameters, in 62 patients with cirrhosis kept on a constant salt diet. Urinary sodium excretion was related non-linearly to the ABT (r = 0.76). Less significant correlations were observed to the Child-Pugh score (r = -0.65), cholinesterase (r = 0.58), bilirubin (r = -0.56), albumin (r = 0.51) and prothrombin time (r = 0.49). When patients were arbitrarily divided into 6 groups according to the ABT, sodium excretion balanced the sodium intake up to a 50% reduction in ABT. In groups with more than a 50% reduction sodium retention occurred. When patients were grouped according to the Child-Pugh score, urinary salt output was balanced in patients with scores of 5 and 6 and decreased in patients with scores greater six. However, the change in sodium output from normal salt excretion to sodium retention was less pronounced in patients grouped according to the Child-Pugh score than in patients grouped according to the ABT. The results suggest a non-linear relationship between the impairment in hepatic and renal function in cirrhosis. They are compatible with the concept of a threshold of hepatic function necessary to maintain normal renal function.

Objectives: The clinical feasibility of self-expanding metal stents with respect to the technical success, complications, and reintervention rate should be tested., Methods: Five coated and 26 uncoated prototype Wallstents, especially designed for stenosis of the upper GI tract, were implanted in 23 patients. All patients with dysphagia suffered from inoperable tumor stenosis of the esophagus or the cardia. Stent implantation was performed under slight i.v. sedoanalgesia., Results: Technical success was achieved in all 31 implanted stents. Forty-eight hr after implantation, dysphagia was improved in 21/23 patients. Acute problems observed within 1 wk were stent migration (1 patient, uncoated stent), oblique position of the stent (3 patients), epigastric or retrosternal pain (9 patients), insufficient stent expansion (4 patients), and pouch formation at the upper rim of the stent (4 patients). An uncomplicated follow-up (median 66 days, range 10-139 days) was seen in 12 patients (52%). Major problems in the follow-up period were stent migration in three patients (three coated stents, two stent migrations in one patient) and stent obstruction by tumor ingrowth/overgrowth and/or food impaction in eight patients (35%). Most of these problems could be successfully resolved by implantation of a second stent or electrocoagulation of overgrowing tumor tissue. By the 1st of March, 1994, three patients were still alive with a follow-up period of 530 days (median range, 336-880 days); 20 patients were decreased with a follow-up period of 70 days (median range, 3-374 days)., Conclusions: Implantation of esophageal Wallstents is safe and has a low risk of acute complications and mortality for the patient. Early complications such as perforation and bleeding did not occur. Tumor ingrowth/overgrowth are the major reasons for the high reintervention rate in the follow-up period. Coated stents can resolve this problem, provided that stent migration can be avoided by improvement of the coating technology.

The dynamics of cognitive brain functions of 104 patients with both chronic non-cirrhotic (NC) and cirrhotic liver disease (C: C1, non-encephalopathic; C2, encephalopathic) were investigated by means of visual P300 potentials elicited in both the paradigms of transient (PI) and selective attention (PII). Conventional PVEPs, psychometric tests and quantitative liver function tests were also performed. As compared to both an age-matched control group (N) and the non-cirrhotic patients (NC), the N250 and P300 latencies of the cirrhotics (C) were equally prolonged in both P300 paradigms (P = 0.0001). By contrast, the P300 amplitudes were not different between the patient groups in either P300 paradigm. In the cirrhotics, however, the P300 amplitude differences between PII and PI (+ 3.7 +/- 2.8 muV, mean +/- 1 S.D.) were significantly (P < 0.01) smaller than in the non-cirrhotics (+ 7.5 +/- 5.2 muV) reflecting disturbances in the dynamics of visual attention. Interestingly, these P300 amplitude differences between both paradigms were positively correlated (r = 0.35; P = 0.005) with hepatic metabolic capacity, but not with liver blood flow (r = 0.23; P > 0.05). The diagnostic efficacy of the visual P300 in PI (sensitivity, 48%; specificity, 100%) was lower than that of the visual P300 in PII (79%; 100%) and that of the psychometric tests (63%; 94%), but it remained superior to that of the PVEPs (29%; 97%). It is concluded that in patients with cirrhotic liver disease visual P300 potentials can even reveal the dynamics of minor cognitive brain dysfunction and may also provide interesting pathophysiological information.

This report describes the initial clinical implementation of a new laser lithotripter system capable of effective fragmentation of common bile duct stones with a high degree of safety provided by an integrated stone-tissue detection system. This system automatically terminates laser pulse transmission if tissue contact is sensed. Eighteen patients with giant or impacted common bile duct stones refractory to standard treatment techniques were treated via the endoscopic retrograde route using a rhodamine-6G dye laser with an integrated stone-tissue detection system. In the event of tissue contact, the stone-tissue detection system cuts off the laser pulse after 190 ns (after transmission of 5% to 8% of the total pulse energy). Nine patients were treated under cholangioscopic control, and nine patients were treated blindly under fluoroscopic control using only standard duodenoscopes with either a 6F standard endoscopic retrograde cholangiopancreatography catheter (4 patients), a 6.8F balloon catheter (3 patients), or a laser lithotriptor basket (2 patients). Laser-induced fragmentation was achieved in all 18 patients (100%). Sixteen of 18 patients (89%) became completely stone-free after completion of the treatment, including additional intracorporeal shock wave lithotripsy in five patients. The only major complications occurred in one fully anticoagulated patient with a prosthetic heart valve who developed significant hemobilia and transient cholangitis but recovered after conservative treatment. Laser lithotripsy using the rhodamine-6G dye laser plus stone-tissue detection system appears safe and effective and allows "blind" fragmentation of difficult common bile duct stones to be performed under radiologic control.

The case of a 56-yr-old patient with polycythemia vera who was initially seen with jaundice is reported. Compression of the common bile duct by choledochal varices was found to be the cause of the obstructive jaundice. This compression was successfully treated with placement of a plastic endoprosthesis across the stenosis during endoscopic retrograde cholangiopancreatography. The significance of choledochal varices in the evaluation of obstructive jaundice is emphasized.

Visual event-related P300 potentials, conventional visual evoked potentials, and psychometric tests were applied to patients with noncirrhotic chronic liver disease and to clinically nonencephalopathic and encephalopathic cirrhotics to compare their diagnostic efficacy in detecting early portosystemic encephalopathy (PSE). Sixty-four investigations were performed in 58 patients. The latencies of the P300 parameters were significantly longer in both the encephalopathic and nonencephalopathic cirrhotics than in the noncirrhotics, indicating distinctly abnormal cortical processing of visual stimuli in cirrhotic patients. The visual P300 potentials showed the highest sensitivity and specificity for grade I PSE. Abnormal P300 test results were also found in 78% of the clinically nonencephalopathic cirrhotics, while psychometric tests showed abnormalities in only 41%. The P300 latencies were similar in alcoholic and nonalcoholic cirrhotics. Significant inverse correlations were found between the P300 latencies and measures of quantitative liver function such as galactose-elimination capacity and aminopyrine breath test. It is concluded that visual event-related P300 potentials are a sensitive index of subclinical and grade I PSE. Furthermore, the degree of cognitive dysfunction detected by this method in patients with liver cirrhosis appears to be related to the reduction in hepatic metabolic capacity.

The method of Pattern Flash elicited P300 (PFP300) has been applied to evaluate the dynamic alterations in cognitive function of a 58 year old woman (H. C.) presenting with hepatic failure due to fulminant hepatitis Non-A-Non-B. At the time of the first investigation she complained about slight memory deficits and revealed signs of hepatic encephalopathy grade I according to Parson-Smith et al. (bilirubin 26.0 mg/dl, NH3 102 micrograms/dl, electrolytes and blood sugar normal). Psychometric tests: Number connection test (NCT): 54 s (28-53 s, greater than 2sd); Syndrom-Kurz-Test (SKT): total score = 9 (0-4), compatible with a slight "organic brain syndrome". PFP300: N250 latency 343.5 ms (276.4 +/- 14.7 ms, greater than 4sd); PFP300-latency: 442.5 ms (326.9 +/- 14.7, greater than 7sd); PFP300 amplitudes: 16.0 microV (14.4 +/- 8.4, +/- 1sd), indicating severe disturbance in visual discrimination without visual attention deficits. Due to progressive deterioration of liver function the patient had to undergo orthotopic liver transplantation. The patient was reinvestigated four weeks later. The clinical and laboratory status were normal and no signs of hepatic encephalopathy could be detected clinically or by means of the psychometric tests. The parameters of the PFP300 complex had also completely returned to normal: N250-latency: 273.0 ms (less than 1sd); PFP300-latency: 348.0 ms (less than 1sd). This observation suggests that the analysis of P300 can help to detect and follow minor cognitive deficits in cases of acute hepatic encephalopathy. It further underscores the hepatic etiology as well as the potential reversibility of this type of encephalopathy.

This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease.

In a controlled study patients with Crohn's disease received an exclusion diet or an diet low in refined carbohydrates and rich in fiber. A total of 26 patients was observed for 1 year. The exclusion diet was not significantly superior to the standard diet with respect to the clinical course (Crohn's disease activity index according to Best or van Hees) or laboratory parameters of inflammatory activity. During dietary counselling relapses were infrequent and symptoms improved in both dietary groups.

The effects of chloroquine and hepatic stimulator substance (HSS) on cellular accumulation and nuclear binding of 125I-epidermal growth factor (EGF) were examined in primary culture of adult rat hepatocytes. When intact hepatocytes were incubated at 37 degrees C with 125I-EGF, the cellular accumulation and the nuclear binding reached a peak at 1 h and declined thereafter, where the nuclear binding was 2.49% at 1 h and 2.53% at 2 h. Chloroquine resulted in a time-dependent increase in the cellular accumulation and the nuclear binding was 3.37% at 1 h and 3.72% at 2 h. In contrast, HSS produced no change in each value, suggesting that HSS does not modulate EGF receptors in plasma membrane and nucleus.