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M Rössle

Publications and source records attributed to M Rössle.

At least 19 recordsLinked to original sources

Platelet aggregation and platelet-derived growth factor inhibition for prevention of insufficiency of the transjugular intrahepatic portosystemic shunt: a randomized study comparing trapidil plus ticlopidine with heparin treatment.

Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phenomenon of stenting and the major cause of insufficiency of the transjugular intrahepatic portosystemic shunt (TIPS). For its prevention, a randomized study was performed comparing standard heparin treatment with a combination of trapidil, a drug with anti-platelet-derived growth factor (PDGF) activity, and ticlopidine, a platelet aggregation inhibitor. Ninety patients with cirrhosis who received a transjugular shunt were randomized, and 84 patients completed the trial. Group 1 (n = 42) received a bolus of heparin (12 to 24 U/kg) at shunt placement, followed by 1 week of intravenous and 4 weeks of subcutaneous heparin treatment. Group 2 (n = 42) received the same heparin bolus, followed by a 1-day intravenous heparin treatment and a 6-month treatment with trapidil (400 mg/d) and ticlopidine (250 mg/d). Shunt function was assessed by duplex-sonography and angiography. Stenoses were classified according to their location as type 1 (within the stent) and type 2 (in the draining hepatic vein). The estimated rate of overall stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving trapidil and ticlopidine (group 2) as compared with heparin (33 vs. 57%; P =.047). There was no difference in the estimated 1-year rate of type 1 stenoses between the two groups, but there was a significant reduction in type 2 stenoses (group 1: 58%, group 2: 19%; P =.016). The treatment effect continued after withdrawal of the drugs and was accompanied by a decreased incidence of rebleeding. The study demonstrates that the incidence of type 2 stenosis of the transjugular shunt can be reduced by combined inhibition of platelet aggregation and PDGF activity. The findings may be of relevance not only for the transjugular shunt, but also for other stent applications, e.g., vascular and biliary, as well as for bypass and shunt surgery.

Drug Therapy, Combination

Structural changes of the Escherichia coli GroEL-GroES chaperonins upon complex formation in solution: a neutron small angle scattering study.

We applied neutron scattering in conjunction with deuterium (D-) labeling in order to obtain information about the domain structure of GroEL and GroES isolated and in the complex. Each subunit of the heptameric GroES consists of two domains, a core domain (Met1 to Lys15 and Lys34 to Ala97) and an intervening loop region (Glu16 to Ala33). Neutron scattering shows that both regions change their conformation upon GroEL/GroES complex formation. The interdomain angle between the core regions of the heptameric GroES increases from 120 to 140 degrees, leading to a less dome-like shape of GroES, and the loop regions turn inwards by 75 degrees. The 23 C-terminal amino acids of the 14 GroEL subunits (Lys526 to Met548), which are unresolved in the crystal structure, are located either at the bottom of the cavity formed by the seven-membered GroEL ring or at the inner wall of the cavity. Upon complex formation the apical domains of GroEL move outwards, which facilitates binding of GroES at a Gro-EL-GroES center-to-center distance of (87 +/- 8) A. These structural changes may be important for the dissociation of the unfolded protein bound to the central cavity upon GroES binding. The overall structure determined by neutron scattering in solution tallies with the crystallographic model published after completion of this study. Differences in the conformation of GroES observed in the complex by the two methods support the view that the chaperonin complex is a flexible molecule which might switch in solution between different conformations.

Chaperonin 10

MDM-2 oncoprotein overexpression, p53 gene mutation, and VEGF up-regulation in angiosarcomas.

The endothelium is one of the largest cellular compartments of the human body and has a high proliferative potential. However, angiosarcomas are among the rarest malignancies. Despite this interesting contradiction, data on growth and angiogenesis control mechanisms of angiosarcomas are scarce. In this study of 19 angiosarcomas and 10 benign vascular control lesions we investigated the sequence and expression of the p53 tumor suppressor gene and the expression of the mdm-2 proto-oncogene, which is a negative regulator of p53 activity and of the vascular endothelial growth factor (VEGF), whose expression, among other factors, is regulated by the p53/MDM-2 pathway. Ten sarcomas (53%) exhibited clear nuclear p53 protein accumulation. Two of these cases revealed mutations in the sequence-specific DNA binding domain of the p53 gene. Thirteen angiosarcomas (68%) showed an increased amount of MDM-2 protein. Elevated expression of p53 and MDM-2 protein correlated with increased VEGF expression, which was found in nearly 80% of the angiosarcoma cases. Negative or clearly lower immunostaining was obtained in cases from the benign control collective. Only one case of a juvenile hemangioma reached the cutoff value of p53 positivity coincidentally with high VEGF expression. Our data suggest that the p53/ MDM-2 pathway is impaired in about two-thirds (14/ 19) of the angiosarcomas. This may be a key event in the pathogenesis of human angiosarcomas. The increased VEGF expression observed supports this hypothesis.

Adult

Risk factors and prevention of early infection after implantation or revision of transjugular intrahepatic portosystemic shunts: results of a randomized study.

The aim of this study was to evaluate the efficacy of a single dose of a second-generation cephalosporine to prevent postinterventional infection and to identify risk factors for postinterventional infection in patients receiving implantation or revision of a transjugular intrahepatic portosystemic shunt (TIPS). Eighty-four patients (105 transjugular interventions) were randomized receiving no antibiotic treatment (46 interventions) or 2 g cefotiam (56 interventions) given at the beginning of the procedure. Patients with overt infection or those receiving antibiotic treatment in the preceding two weeks were excluded. Groups were comparable with respect to biographic and medical data. Postinterventional infection was defined as an increase in WBC count (> or =15,000/microl), fever (> or =38.5 degrees C), or a positive blood culture. Infection occurred in 17% of the patients. Patients not receiving cefotiam had a slightly higher incidence of infection (20%) than patients treated with cefotiam (14%, NS). Multivariate analysis demonstrated prognostic relevance for multiple stenting and periprocedural use of a central venous line. The clinical outcome of the patients was unaffected by cefotiam treatment. In conclusion, a single dose of intrainterventional cefotiam does not prevent postinterventional infection. This may be due to the antimicrobial spectrum and short half-time of cefotiam. Strict adherence to aseptic conditions during intervention and early removal of central venous lines may reduce the rate of post interventional infection considerably. Antibiotic prophylaxis with cefotiam does not seem to be useful since it will not influence outcome and costs.

Antibiotic Prophylaxis

The first decade of the transjugular intrahepatic portosystemic shunt (TIPS): state of the art.

The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment resulting in decompression of the portal system by creation of a side-to-side portosystemic anastomosis. Since its introduction 10 years ago, more than 500 publications have appeared demonstrating rapid acceptance and increasing clinical use. This review summarizes the present knowledge of technical aspects and complications, follow-up of patients, and indications. With respect to the technique, the TIPS procedure is probably one of the most difficult interventions and, therefore, technical success and complications clearly depend on the skills of the operator. Thus, the number and kind of complications reported in this review do not necessarily relate to the procedural complications of an experienced center. The follow-up of the TIPS patient has to assess shunt patency, liver function and hepatic encephalopathy. Shunt patency can best be monitored by duplex-sonography. Routine radiological revision seems not to be helpful and does not improve results, i.e., rebleeding and survival. Short term patency may be improved by anticoagulation, while such a treatment does not influence long-term patency. With respect to the indications of TIPS, much is known about treatment of variceal bleeding. The nine randomized studies that are available to date show that survival is comparable between patients receiving TIPS or endoscopic treatment. The second group of patients is the group with refractory ascites and related complications, such as hepatorenal syndrome and hepatic hydrothorax. It has been demonstrated that TIPS improves these complications, but randomized studies are still lacking. In addition, TIPS has been applied successfully to patients with Budd-Chiari syndrome, portal vein thrombosis, before liver transplantation, and for the treatment of ectopic portal hypertensive bleeding.

Ascites

[Treatment of portal hypertension by portosystemic shunts].

The use of shunts for the treatment of portal hypertension has been revived after the introduction of the transjugular intrahepatic portosystemic shunt (TIPS) into clinical practice. This interventional procedure has mainly been used as rescue treatment for variceal bleeding resistant to endoscopic therapy and for ascites refractory to diuretic treatment and paracentesis. With respect to variceal bleeding TIPS has a low rate of "operative" mortality of < 1% and variceal rebleeding of 6 to 18%. In patients with refractory ascites the response to treatment is 50 to 92%. The major problems of the TIPS procedure are the increased incidence of hepatic encephalopathy and the high rate of shunt insufficiency of about 50%. Therefore, control of shunt function by duplex-sonography is essential to detect malfunction of the shunt. Radiological revision is then indicated if the clinical symptoms of portal hypertension (varices, ascites) reappear. The TIPS treatment has partially replaced the surgical shunting procedures. This decision is based on the potentially higher mortality of the surgical procedure. However, this has not been proven by randomized studies and, therefore, surgical shunts may also be indicated in selected patients with low operative mortality.

Humans

Randomised trial of transjugular-intrahepatic-portosystemic shunt versus endoscopy plus propranolol for prevention of variceal rebleeding.

BACKGROUND: The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension. The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding. METHODS: Between March, 1993, and March, 1996, 126 patients with variceal bleeding were randomly assigned either transjugular shunt (n = 61) or endoscopic treatment (n = 65). Patients were followed up for a median of 14 (IQR 8-25) months and 13 (8-25) months, respectively. In 31 (51%) of the shunted patients, simultaneous transjugular-variceal embolisation was done at the time of shunt placement. Endoscopic treatment consisted of sclerotherapy and/or banding ligation and was combined with propranolol medication. FINDINGS: Technical success was achieved in all patients assigned to the shunt group. During follow-up, the cumulative 1-year variceal rebleeding rates in the shunted and endoscopically treated patients were 15% and 41% and the 2-year rates were 21% and 52% (p = 0.001), respectively. In nine (12%) patients from the endoscopic group treatment failed and the patients received the transjugular-shunt treatment. A total of 19 bleeding episodes from any source occurred in 15 patients in the shunt group compared with 100 episodes in 33 patients in the endoscopic group. There was no difference in survival with estimated 1-year survival rates for shunted and endoscopically treated patients of 90% and 89%, and 2-year survival rates of 79% and 82%, respectively. The incidence of clinically significant hepatic encephalopathy after 1 year was higher in the shunt group (36% vs 18%, p = 0.011). INTERPRETATION: These results suggest, that the transjugular shunt is more effective than endoscopic treatment in prevention of variceal rebleeding but has a considerable risk of hepatic encephalopathy. Survival is similar in the two groups.

Adult

Acute hemoperitoneum after large-volume paracentesis.

Hemoperitoneum resulting from rupture of mesenteric varices is a rare complication of portal hypertension with a high mortality of up to 70%. This case report describes the symptoms, clinical course, and treatment of 4 patients with acute hemoperitoneum caused by mesenteric variceal bleeding after large-volume paracentesis. Abdominal pain and/or hemorrhagic shock developed in 4 patients (age, 48-68 years), admitted for refractory ascites, 3 hours to 4 days after 1-4 large-volume paracenteses (> 4000 mL). Duplex sonography, performed in 3 of the 4 patients before onset of bleeding, showed retrograde flow in the mesenteric veins, suggesting large-caliber mesenteric collateralization. Treatment consisted of surgical ligation followed by transjugular intrahepatic portosystemic shunt (TIPS) (2 patients) and emergency TIPS with embolization of the bleeding vessel (1 patient). One patient died before any intervention could be initiated. In these 4 patients, the concurrence of large-volume paracentesis and hemoperitoneum suggests their causal relationship. The mechanism may be a sudden reduction in intraperitoneal pressure increasing the pressure gradient across the wall of the mesenteric varices, resulting in rupture and bleeding. The awareness of this complication may accelerate the diagnostic process and treatment.

Acute Disease

Transjugular intrahepatic portosystemic shunt (TIPS). Thrombogenicity in stents and its effect on shunt patency.

PURPOSE: To compare the thrombogenicity and patency of the Palmaz stent and the Wallstent, and to evaluate the effect of periprocedural heparin therapy in cirrhotic patients with maintained coagulation capacity who receive a transjugular intrahepatic portosystemic shunt (TIPS). MATERIAL AND METHODS: Twenty-four patients were randomized into 4 groups of 6 patients. Each received a Palmaz-stent or Wallstent TIPS with or without periprocedural heparin therapy. The groups receiving periprocedural heparin were given 24 U/kg b.w. just before stent placement, followed by 24 h therapeutic i.v. heparin. After 24 hours, all patients received i.v. heparin for 1 week followed by subcutaneous treatment with low-molecular-weight heparin (0.3 ml/day) for another 4 weeks. Stent thrombogenicity was determined scintigraphically after i.v. injection of 120-290 mBq of 99mTc-labeled platelets at the time of stent placement and expressed as the stent/heart ratio. Shunt patency was assessed by duplex sonography and confirmed radiologically. RESULTS: The aggregation ratio was highest 90 min after stent implantation. Wallstents showed a significantly higher ratio than Palmaz stents. Heparin reduced the ratio in patients with a Wallstent (-41%) but had no effect on Palmaz stents. Patients with a Wallstent without heparin had a higher rate of early shunt insufficiency (66.6%) than the other patients (0-16.6%). Primary assisted long-term patency was similar in the 4 groups. CONCLUSION: Wallstents were more thrombogenic than Palmaz stents and gave a significantly higher risk of early shunt insufficiency in cirrhotic patients with maintained coagulation capacity. Periprocedural heparin was effective in the prevention of shunt insufficiency and is therefore indicated in such patients.

Anticoagulants

[Transjugular intrahepatic portasystemic shunt (TIPS)--indications and outcome].

The use of the use of the transjugular intrahepatic portosystemic shunt (TIPS) and its indication for treatment of the various symptoms of portal hypertension is till under debate. This paper presents guidelines for its application based on randomized studies, case reports, and own experience. TIPS is indicated in acute variceal bleeding not responding to endoscopic treatment and medication. In this emergency situation TIPS has probably a lower early mortality rate than surgical shunts. The prophylactic treatment of first variceal bleeding is a domain for medical therapy. Due to its increased incidence of hepatic encephalopathy TIPS may only be indicated in very selected cases with a high risk of bleeding and associated severe complications. Five randomized trials including 402 patients exist comparing endoscopic treatment and TIPS. Except one study the results are conclusive demonstrating comparable survival of the groups. Despite these results, in view of the high rate of shunt-induced encephalopathy with its negative effect on life quality, TIPS may better be a secondary treatment as long as studies on life quality are lacking. However, im many patients additional complications, e.g., accompanying ascites or intolerance to bleedings, may justify the primary use of TIPS. TIPS is also effective in the treatment of refractory ascites. Conclusive randomized studies are not available, therefore, TIPS should be restricted to patients who are intolerant to or who fail paracentesis. In addition to the leading indications mentioned, rare indications for TIPS and the role of surgical shunts are discussed.

Esophageal and Gastric Varices

The transjugular intrahepatic portosystemic stent-shunt: a review of the literature and own experiences.

The transjugular intrahepatic portosystemic stent-shunt (TIPS) technique consists of a transhepatic puncture of the portal vein and stenting of the parenchymal tract between the hepatic and portal veins. Complications of both puncture and stenting are observed in approximately 5% of procedures. Most of the complications are without clinical consequences and the procedural mortality is very low in experienced hands (1%). During a 1 year follow up, 35% of patients were seen to develop stenosis and 15% developed occlusion of the stent-shunt. However, in spite of the considerable incidence of stenosis/occlusion, the rate of variceal rebleeding is rare when patients are followed up carefully by duplex sonography, which allows accurate and early detection of shunt insufficiency. One of the major long-term clinical problems of TIPS is the induction or worsening of hepatic encephalopathy. Although most patients respond to medical treatment, some develop debilitating encephalopathy or progressive liver failure. In these patients, reduction of shunt flow by the implantation of a reducing stent, or its occlusion with a balloon catheter, may be indicated. In conclusion, in spite of many complications, TIPS is relatively safe and efficient and hepatic encephalopathy is manageable in most cases.

Contraindications

Transjugular intrahepatic portosystemic shunt and hepatic encephalopathy.

Hepatic encephalopathy (HE) is a frequent complication of portosystemic shunts with an incidence of about 25%. In side-to-side shunts, such as the transjugular intrahepatic portosystemic shunt (TIPS), there is relation between the incidence of postshunt HE and the diameter of the shunt. A smaller shunt with a diameter of < 8 mm has a lower risk of HE by maintaining some prograde portal perfusion in most patients and preventing arterioportal blood flow which may be of disadvantage in most conditions. On the other hand, a smaller shunt diameter limits the reduction in the portal-systemic pressure gradient and, therefore, may have a higher risk of rebleeding. The size of the shunt must be based on these risks which may be estimated by factors such as age, Child class, previous episodes of HE, size of varices and severity of previous bleedings. In retrospect, the decision for a specific diameter, i.e. pressure reduction, was right if the patient's liver function remained stable after TIPS, no HE occurred, and the varices disappeared. If this is not the case, the shunt diameter needs fine tuning with reduction in case of HE or functional deterioration, or enlargement if rebleeding occurred or the varices show a higher risk of such an event. This potential of fine tuning at any time is the major advantage of TIPS over the surgical shunting procedures.

Age Factors

[Recurrent bleeding from colonic varices in portal hypertension. The successful prevention of recurrence by the implantation of a transjugular intrahepatic stent-shunt (TIPS)].

HISTORY AND CLINICAL FINDINGS: Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent bleeding from oesophageal varices. Half a year later he again was admitted to hospital because of recurrent passage of bloody stools. The cardiovascular status was stable; the liver was enlarged by 15 cm in the medioclavicular line. INVESTIGATIONS: Endoscopy revealed several varices in the colon near the right flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed portal hypertension with cirrhosis of the liver and partial thrombosis of the main trunk of the portal vein without any sign of cavernous transformation. TREATMENT AND COURSE: Because of the partial portal vein thrombosis it was decided to insert a transjugular intrahepatic portosystemic stent shunt. This obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%. With the shunt functioning well there were no further bleedings in the subsequent year. CONCLUSION: The only slightly invasive TIPS implantation is an effective therapeutic procedure for bleeding from colon varices caused by portal hypertension.

Colon

[Septic portal vein thrombosis. Its successful therapy by local fibrinolysis and a transjugular portasystemic stent-shunt (TIPS)].

HISTORY AND FINDINGS: A 68-year-old man, without any preceding hepatic or abdominal disease, suddenly developed a severe septic illness with consumptive coagulopathy and upper abdominal pain. B-mode and duplex ultrasonography revealed fresh portal vein thrombosis. Despite extensive conservative measures there was no significant improvement after one week and further thrombus extension with threatened acute mesenteric vein occlusion. TREATMENT AND COURSE: Local fibrinolysis with recombinant plasminogen activator and urokinase via percutaneous transjugular intrahepatic catheterization of the portal vein achieved almost complete dissolution of the thrombus within 3 days. Subsequently the portal vein catheter was changed into a transjugular portosystemic stent shunt (TIPS). CONCLUSIONS: While local or systemic fibrinolysis has been practised in previously reported cases of acute portal vein thrombosis, the described use of TIPS introduces a new element. The shunt between hepatic and portal veins assures therapeutic access to the portal venous bed. It lowers portal vein pressure and can diminish the danger of recurrent thrombosis by raising portal flow. This minimally invasive procedure may be a nearly ideal treatment even in the course of portal vein thrombosis which has a high complication rate.

Aged

The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites.

BACKGROUND: Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. METHODS: Fifty of 62 consecutive patients with cirrhosis and refractory ascites (18 with Child-Pugh class B liver disease and 32 with class C) were treated with the stent shunt--an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (+/- SD) of 426 +/- 333 days. Those with advanced cancer, severe heart failure, or severe liver failure were excluded. RESULTS: The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses (ascites detected by ultrasound but with no need for paracentesis). Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 +/- 0.09 mg per deciliter (133 +/- 8 mumol per liter) before placement of the stent shunt, 1.5 +/- 1.6 mg per deciliter (133 +/- 141 mumol per liter) one week after the procedure, and 0.9 +/- 0.3 mg per deciliter (80 +/- 27 mumol per liter) after six months (P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients, including intraabdominal bleeding requiring blood transfusions in 2 patients. Thrombotic occlusion of the stent shunt occurred within two weeks in 5 patients, and later insufficiency of the shunt occurred in 16 patients, including 12 with recurrence of ascites after complete remission. During followup, an additional 29 patients died--10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patient's being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response. CONCLUSIONS: Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial.

Ascites