http://repub.eur.nl/res/aut/5408/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34029/ 2011-09-01T00:00:00Z Background Self-expanding metal stents (SEMS) are known to have a significantly higher patency rate than plastic stents. We aimed to identify prognostic factors, besides stent type, for stent patency and to develop a score model that could further aid in guiding stent choice for the palliation of a malignant biliary stricture. Methods A retrospective multicenter study was conducted. Data on consecutive patients who had a stent placed between January 2002 and July 2009 were collected. Cumulative stent occlusion rates were analyzed by Kaplan-Meier curves and log rank testing, and prognostic factors were assessed by Cox regression analysis. Results A total of 690 stents (512 plastic stents, 174 SEMS) were endoscopically placed in 390 patients. At 8 weeks, stent occlusion had occurred in 32% of the plastic stents and 11% of the SEMS. Multivariate analysis indicated that plastic stents (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.9-3.5), a tight stricture requiring preceding dilation (HR 1.8, 95% CI 1.3-2.5), and a high initial bilirubin level (<50 μmol/L (HR 1.3, 95% CI 1.0-1.7) were independently associated with an increased risk of stent occlusion. A score model based on these 3 factors was able to distinguish between stent procedures with a relatively high and low risk of stent occlusion (median 14 vs. 26 weeks, respectively). Conclusion Besides plastic stents, stricture severity requiring preceding dilation, and initial higher bilirubin level were associated with a shorter period of stent patency. A simple score model based on these factors was able to predict stent occlusion and may aid in choosing the most appropriate stent type in individual patients. http://repub.eur.nl/res/pub/25930/ 2011-07-01T00:00:00Z Background: Gastrojejunostomy and stentplacement are the most commonly used treatments for malignant gastric outlet obstruction (GOO). The preference for either treatment largely depends on the expected survival. Our objective was to investigate predictors of survival in patients with malignant GOO and to develop a model that could aid in the decision for either gastrojejunostomy or stentplacement. Methods: Prognostic factors for survival were collected from a literature search and evaluated in our patient population, which included 95 retrospectively and 56 prospectively followed cases. All 151 patients were treated with gastrojejunostomy or stentplacement. Results: A higher WHO performance score was the only significant prognostic factor for survival in our multivariable analysis (HR 2.2 95%CI 1.7-2.9), whereas treatment for obstructive jaundice, gender, age, metastases, weight loss, level of obstruction and pancreatic cancer were not. A prognostic model that includes the WHO score was able to distinguish patients with a poor survival (WHO score 3-4, median survival: 31 days) from those with a relatively intermediate or good survival (WHO score 2, median survival: 69 and WHO score 0-1, median survival: 139 days, respectively). Conclusions: Only the WHO score is a significant predictor of survival in patients with malignant GOO. A simple prognostic model is able to guide the palliative treatment decision for either gastrojejunostomy (WHO score 0-1) or stentplacement (WHO 3-4) in patients with malignant GOO. http://repub.eur.nl/res/pub/33432/ 2011-06-01T00:00:00Z Objectives: Delayed hemorrhage is an infrequent, but serious complication of colonoscopic polypectomy. Large size is the only polyp-related factor that has been unequivocally proven to increase the risk of delayed bleeding. It has been suggested that location in the right hemi-colon is also a risk factor. The objective of this study was to determine whether polyp location is an independent risk factor for delayed post-polypectomy hemorrhage. Methods: A retrospective case-control study was conducted in two university hospitals and two community hospitals. Results: Thirty-nine cases and 117 controls were identified. In multivariate analysis, size and location were found to be independent polyp-related risk factors for delayed type hemorrhage. The risk increased by 13% for every 1 mm increase in polyp diameter (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.05-1.20, P0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P0.001) for delayed hemorrhage. Polyps in the cecum seemed to be especially at high risk in univariate analysis (OR 13.82, 95% CI 2.66-71.73), but this could not be assessed in multivariate analysis as the number of cases was too small. Polyp type (sessile or pedunculated) was not a risk factor. Conclusions: Polyp location in the right hemi-colon seems to be an independent and substantial risk factor for delayed post-polypectomy hemorrhage. A low threshold for preventive hemostatic measures is advised when removing polyps from this region. http://repub.eur.nl/res/pub/26469/ 2011-05-01T00:00:00Z Background: The natural behavior of flat low-grade (LGD) and indefinite dysplasia (IND) in patients with inflammatory bowel disease (IBD) remains uncertain and seems to be dependent on the interpretation of the pathologist. We studied the progression rate of flat LGD and IND to advanced neoplasia (high-grade dysplasia [HGD] or colorectal cancer [CRC]) before and after histopathological review by a panel of gastrointestinal expert pathologists. Methods: A nationwide pathology database was used to identify IBD patients with dysplasia in six Dutch university medical centers between 1990 and 2006. Medical charts of patients with recorded flat LGD or IND were reviewed. Histological slides from three university medical centers were reviewed by a panel of three expert gastrointestinal pathologists. Results: We identified 113 flat LGD patients and 26 flat IND patients. Advanced neoplasia was found in 18 flat LGD patients (16%) after a median follow-up of 48 months, resulting in a 5-year progression rate of 12%. Five IND patients (19%) developed advanced neoplasia after a median follow-up of 24 months, resulting in a 5-year progression rate of 21%. Review of 1547 histological slides from 87 patients resulted in an increase of the 5-year progression rate of flat LGD to advanced neoplasia to 37%, whereas the progression rate of IND decreased to 5%. Conclusions: A diagnosis of flat LGD that is confirmed by a panel of expert gastrointestinal pathologists is associated with a substantial risk of progression to advanced neoplasia, while confirmed IND is associated with a low risk of progression. (Inflamm Bowel Dis 2010;) http://repub.eur.nl/res/pub/18681/ 2010-03-01T00:00:00Z Background: Fully covered stents are designed to resist tissue ingrowth that is often seen with partially covered stents. An issue with fully covered stents is the risk of migration. Objective: We aimed to determine efficacy, recurrent dysphagia, and complications of the SX-ELLA stent Esophageal HV, which is fully covered to resist tissue ingrowth and has an antimigration ring to withstand migration. Design: Prospective cohort study. Setting: Two tertiary referral centers. Patients: Forty-four patients with malignant esophageal strictures from inoperable or metastatic esophageal or gastric cardia cancer (n = 42) or lung cancer (n = 2). Interventions: Placement of an SX-ELLA stent. Main outcome measures: Functional outcome, recurrent dysphagia, complications, and survival. Results: Dysphagia improved from a median score of 3 (liquids only) before stent placement to 1 (ability to eat some solid food) 4 weeks later (P < .001). Twelve of 44 (Kaplan Meier analysis = 40%) patients developed 18 episodes of recurrent dysphagia of which 6 were caused by stent migration and 2 by tissue overgrowth. In total, 14 episodes of major complications developed in 10 of 44 (Kaplan Meier analysis = 29%) patients, 8 of which were caused by hemorrhage. After a median follow-up of 15 months, 39 patients had died (median survival 110 days), 5 (11%) from hemorrhage. Limitations: Nonrandomized study design. Conclusions: Dysphagia caused by esophageal cancer can be successfully palliated by placement of a new, fully covered esophageal stent (SX-ELLA). Although this single-wire braided stent with an antimigration ring is supposed to be less traumatic and to reduce migration, this was not substantiated in this study. Further improvements of stent features are needed to achieve the goals set for this study. http://repub.eur.nl/res/pub/19220/ 2010-03-01T00:00:00Z Background: Both gastrojejunostomy (GJJ) and stent placement are commonly used palliative treatments of obstructive symptoms caused by malignant gastric outlet obstruction (GOO). Objective: Compare GJJ and stent placement. Design: Multicenter, randomized trial. Setting: Twenty-one centers in The Netherlands. Patients: Patients with GOO. Interventions: GJJ and stent placement. Main Outcome Measurements: Outcomes were medical effects, quality of life, and costs. Analysis was by intent to treat. Results: Eighteen patients were randomized to GJJ and 21 to stent placement. Food intake improved more rapidly after stent placement than after GJJ (GOO Scoring System score ≥2: median 5 vs 8 days, respectively; P < .01) but long-term relief was better after GJJ, with more patients living more days with a GOO Scoring System score of 2 or more than after stent placement (72 vs 50 days, respectively; P = .05). More major complications (stent: 6 in 4 patients vs GJJ: 0; P = .02), recurrent obstructive symptoms (stent: 8 in 5 patients vs GJJ: 1 in 1 patient; P = .02), and reinterventions (stent: 10 in 7 patients vs GJJ: 2 in 2 patients; P < .01) were observed after stent placement compared with GJJ. When stent obstruction was not regarded as a major complication, no differences in complications were found (P = .4). There were also no differences in median survival (stent: 56 days vs GJJ: 78 days) and quality of life. Mean total costs of GJJ were higher compared with stent placement ($16,535 vs $11,720, respectively; P = .049 [comparing medians]). Because of the small study population, only initial hospital costs would have been statistically significant if the Bonferroni correction for multiple testing had been applied. Limitations: Relatively small patient population. Conclusions: Despite slow initial symptom improvement, GJJ was associated with better long-term results and is therefore the treatment of choice in patients with a life expectancy of 2 months or longer. Because stent placement was associated with better short-term outcomes, this treatment is preferable for patients expected to live less than 2 months. (Clinical trial registration number: ISRCTN 06702358.). http://repub.eur.nl/res/pub/24094/ 2009-11-26T00:00:00Z Background: Patients with inflammatory bowel disease (IBD) and concurrent primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC) than IBD patients without PSC. The aim of this study was to investigate potential clinical differences between patients with CRC in IBD and those with CRC in IBD and PSC, as this may lead to improved knowledge of underlying pathophysiological mechanisms of CRC development. Methods: The retrospective study from 1980-2006 involved 7 Dutch university medical centers. Clinical data were retrieved from cases identified using the national pathology database (PALGA). Results: In total, 27 IBD-CRC patients with PSC (70% male) and 127 IBD-CRC patients without PSC (59% male) were included. CRC-related mortality was not different between groups (30% versus 19%, P = 0.32); however, survival for cases with PSC after diagnosing CRC was lower (5-year survival: 40% versus 75% P = 0.001). Right-sided tumors were more prevalent in the PSC group (67% versus 36%, P = 0.006); adjusted for age, sex, and extent of IBD, this difference remained significant (odds ratio: 4.8, 95% confidence interval [CI] 2.0-11.8). In addition, tumors in individuals with PSC were significantly more advanced. Conclusions: The right colon is the predilection site for development of colonic malignancies in patients with PSC and IBD. When such patients are diagnosed with cancer they tend to have more advanced tumors than patients with IBD without concurrent PSC, and the overall prognosis is worse. Furthermore, the higher frequency of right-sided tumors in patients with PSC suggests a different pathogenesis between patients with PSC and IBD and those with IBD alone. Copyright http://repub.eur.nl/res/pub/24591/ 2009-11-01T00:00:00Z Background:Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse.Method:The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.Results:A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P0.047). In addition, more early tumour stages were found in the surveillance group (P0.004).Conclusions:These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage. http://repub.eur.nl/res/pub/25049/ 2009-01-01T00:00:00Z Background/Aims: Primary sclerosing cholangitis (PSC) patients are at risk for developing cholangiocarcinoma (CCA) and colorectal carcinoma (CRC). Our aim was to assess the risk of malignancies and their influence on survival. Methods: Data from PSC patients diagnosed between 1980 and 2006 in two university hospitals were retrieved. The Kaplan-Meier method and a time-dependent Cox regression model were used to calculate risks of malignancies and their influence on survival. Results: Two hundred and eleven patients were included, 143 (68%) were male and 126 (60%) had inflammatory bowel disease (IBD). Median transplantation-free survival was 14 years. The risk of CCA after 10 and 20 years was 9% and 9%, respectively. In patients with concomitant IBD the 10-year and 20-year risks for CRC were 14% and 31%, which was significantly higher than for patients without IBD (2% and 2% (P = 0.008)). CCA, cholangitis, and age at entry were independent risk factors for the combined endpoint death or liver transplantation. Risk factors for the endpoint death were CCA, CRC, age, and symptomatic presentation. Conclusions: Patients with PSC and IBD have a high long-term risk of developing CRC and this risk is about threefold higher than the risk for CCA. Both malignancies are associated with decreased survival. http://repub.eur.nl/res/pub/14698/ 2008-11-01T00:00:00Z Pancreatic cystic lesions are uncommon and consist of pseudocysts, congenital cysts and cystic neoplasms including mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms. Mucinous cystic neoplasms are large septated cysts without connection to the ductal system, characterised by the presence of thick-walled ovarian-type stroma and mucin. They occur predominantly in women and often are malignant. Therefore, surgical resection is recommended. Intraductal papillary mucinous neoplasms are neoplasms with tall, columnar, mucin-containing epithelium involving the main pancreatic ducts or major side branches. Intraductal papillary mucinous neoplasms occur in men and women in their 60s and 70s and may differentiate into malignant neoplasms. Therefore, surgical resection is mandatory. Serous cystic neoplasms appear as multiple cysts lined with cubic flat epithelium containing glycogen-rich cells with clear cytoplasm. They mainly occur in women in their 50s and are generally benign. Therefore, a conservative approach is recommended. As both mucinous cystic neoplasm and intraductal papillary mucinous neoplasms have a high malignant potential, it is important to differentiate between the various pancreatic cystic lesions. Several imaging techniques and tumour markers have been evaluated. Nonetheless, definitive guidelines to differentiate between serous cystic neoplasms, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are still poorly defined. A number of management issues regarding these neoplasms are still under debate, for example which imaging technique to use, differentiation between malignant or benign lesions and the preferred treatment modality for each pancreatic cystic neoplasm. Further research may lead to a definitive guideline for the diagnosis and treatment of mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and serous cystic neoplasms. http://repub.eur.nl/res/pub/29069/ 2008-09-01T00:00:00Z Background and aim: To detect precancerous dysplasia or asymptomatic cancer, patients suffering from inflammatory bowel disease often undergo colonoscopic surveillance based on American or British guidelines. It is recommended that surveillance is initiated after 8-10 years of extensive colitis, or after 15-20 years for left-sided disease. These starting points, however, are not based on solid scientific evidence. Our aim was to assess the time interval between onset of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and subsequently evaluate how many patients developed cancer before their surveillance was recommended to commence. Methods: A nationwide automated pathology database (PALGA) was consulted to identify patients with IBD-associated colorectal carcinoma in seven university medical centres in The Netherlands between January 1990 and June 2006. Data were collected retrospectively from patient charts. Time intervals between onset of disease and cancer diagnosis were calculated in months. Results: 149 patients were identified with confirmed diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn's disease n = 59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22% of patients developed cancer before the 8 or 15 year starting points of surveillance, and 28% if surveillance was commenced 10 or 20 years after diagnosis for extensive or left-sided disease, respectively. Using onset of symptoms to calculate the time interval, 17-22% of patients would present with cancer prior to the surveillance starting points. Conclusions: These results show that the diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17-28%) when conducting surveillance strictly according to formal guidelines. http://repub.eur.nl/res/pub/13341/ 2004-05-01T00:00:00Z PURPOSE: To retrospectively assess the outcome of transjugular intrahepatic portosystemic shunt (TIPS) placement in a nonselected group of consecutive patients. MATERIALS AND METHODS: TIPS placement was attempted in 82 patients. Patients were followed up for at least 3 years according to a standard protocol that included repeated shunt evaluations. Fifty-four patients underwent TIPS placement for variceal bleeding, 24 for refractory ascites, and four for other indications. Recurrent bleeding, effect on ascites, long-term patency, development of encephalopathy, and survival and complication rates were evaluated with Kaplan-Meier survival analysis and Cox multivariate analysis. RESULTS: TIPS placement was successful in 75 patients (91%). Mean follow-up lasted 29.4 months. Primary patency was 22% and 12%, primary-assisted patency was 67% and 46%, and secondary patency was 91% and 91% at 1- and 5-year follow-up, respectively. Nonalcoholic liver disease (P =.007) and increasing platelet counts (P =.006) independently predicted development of shunt insufficiency. The 1- and 5-year rates of recurrent variceal bleeding were 21% and 27%, respectively. In the majority of patients with refractory ascites, a beneficial effect of TIPS placement was observed. The risk for encephalopathy was 25% at 1-month follow-up and 52% at 3-year follow-up. The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up and 20% at 3-year follow-up. Serum creatinine levels (P =.001) and age (P =.02) were independent risk factors. Overall survival rate was 61%, 49%, and 42% at 1-, 3-, and 5-year follow-up, respectively. Age (P =.03), serum albumin level (P =.02), and serum creatinine level (P <.001) were independently related to mortality. CONCLUSION: The risk for definitive loss of shunt function was 17% at 5-year follow-up, indicating that surveillance with shunt revision-when indicated-results in excellent long-term TIPS patency. TIPS placement effectively protects against recurrent bleeding. http://repub.eur.nl/res/pub/8293/ 2001-01-01T00:00:00Z BACKGROUND: Malignancy, hypercoagulability, and conditions leading to decreased portal flow have been reported to contribute to the aetiology of extrahepatic portal vein thrombosis (EPVT). Mortality of patients with EPVT may be associated with these concurrent medical conditions or with manifestations of portal hypertension, such as variceal haemorrhage. PATIENTS AND METHODS: To determine which variables have prognostic significance with respect to survival, we performed a retrospective study of 172 adult EPVT patients who were followed over the period 1984-1997 in eight university hospitals. RESULTS: Mean follow up was 3.9 years (range 0.1-13.1). Overall survival was 70% (95% confidence interval (CI) 62-76%) at one year, 61% (95% CI, 52-67%) at five years, and 54% (95% CI, 45-62%) at 10 years. The one, five, and 10 year survival rates in the absence of cancer, cirrhosis, and mesenteric vein thrombosis were 95% (95% CI 87-98%), 89% (95% CI 78-94%), and 81% (95% CI 67-89%), respectively (n=83). Variables at diagnosis associated with reduced survival according to multivariate analysis were advanced age, malignancy, cirrhosis, mesenteric vein thrombosis, absence of abdominal inflammation, and serum levels of aminotransferase and albumin. The presence of variceal haemorrhage and myeloproliferative disorders did not influence survival. Only four patients died due to variceal haemorrhage and one due to complications of a portosystemic shunt procedure. CONCLUSION: We conclude that mortality among patients with EPVT is related primarily to concurrent disorders leading to EPVT and not to complications of portal hypertension. http://repub.eur.nl/res/pub/9685/ 2001-01-01T00:00:00Z The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course are reported. Patients suffered severe pruritus and weight loss with progressive icteric cholestasis which did not respond to such treatments as ursodeoxycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. Further diagnostic studies and repeat biopsies confirmed the absence of liver cirrhosis as well as other potential causes of hyperbilirubinaemia. Comparison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 non-cirrhotic PBC patients indicated that in the former the severity of bile duct loss relative to the amount of fibrosis was significantly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3--100%) for controls (p<0.001). Three patients received a liver transplant 6--7 years after the first manifestation of PBC because of progressive cholestasis, refractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplantation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensive "premature" or accelerated intrahepatic bile duct loss. Although the extent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and absence of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients. http://repub.eur.nl/res/pub/20418/ 2000-11-22T00:00:00Z Immullocholangitis is a collective for chronic inflammatory disorders affecting the biliary tree, presumably with an autoimmune-mediated pathogenesis. Destruction and distortion of bile ducts, leading to impaired bile flmv, are key features of immunocholangitis. In general, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are considered to be the main diseases of immunochoiangitis. PBC, a chronic cholestatic liver disease, is one of the most common vanishing bile duct disorders. Gradual loss of interlobular and septal bile ducts, histologically described as chronic non-suppurative destructive cholangitis, leads to chronic cholestasis, fibrosis and biliary cirrhosis which may ultimately cause liver failure, necessitating transplantation. Since 1988, PBC has been the third leading indication for liver transplantation in Europe (European Liver Transplant Association (ELTA) registration). Typical symptoms of patients with PBe are pmritus, fatigue, arthralgia and dryness of the eyes and mouth. A large proportion of patients, especially those with early stage PBC are however often asymptomatic. Physical examination may reveal jaundice, scratch marks, xanthelasma and xanthoma, in particular in the event of marked cholestasis. PBC is a relatively rare disorder in comparison with chronic viral hepatitis and alcoholic liver disease. It affects primarily middle-aged (40-60 years) women (male:female ratio 1:9). In the 1970's, reported prevalences ranged from only 18 to 54 cases per one million inhabitants. Since then, substantially higher prevalence rates have been reported. Recent studies in Wales and the Newcastle area revealed a prevalence of 200-250 PBC patients per one million inhabitants in 1994, suggesting a more than tenfold increase in less than 20 years! Whether these data reflect a true increase in the number of cases is uncertain. The development of more sophisticated epidemiological case fmding methods, increased awareness of PBC as a possible cause of chronic liver disease and routine assessment of serum liver tests for medical examinations (i.e. for insurance) may all have contributed to the identification of more, in particular asymptomatic, cases. Moreover, the diagnosis of asymptomatic subjects might result in higher prevalence rates because of longer survival. PSC is a cryptogenic chronic cholestatic liver disease characterised by progressive strichlring and obliteration of intrahepatic andlor extrahepatic bile ducts, leading to fibrosis and biliary cirrhosis which may cause hepatic decompensation. Since 1988, PSC has been the sixth leading indication for transplantation (ELTA registration). The signs and symptoms of PSC resemble those of PEe. PSC is regarded as an even more rare disease than PBC, but reliable epidemiological data on prevalence and incidence are lacking. Data from Sweden suggest a prevalence of 60-80 patients per one million inhabitants. There is a strong association with inflammatory bowel disease (IBD). It has been found that approximately four percent of patients with IBD have concomitant PSC. Conversely, 50-70% of patients with PSC also have IBD. PSC has a male predominance (male:female ratio 2: 1). The median age at diagnosis is 35 years. http://repub.eur.nl/res/pub/9467/ 2000-01-01T00:00:00Z In a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). We compared 43 BCS patients and 92 PVT patients with 474 population-based controls. The relative risk of BCS was 11.3 (95% CI 4.8-26.5) for individuals with factor V Leiden mutation, 2.1(95% CI 0.4-9.6) for those with prothrombin gene mutation, and 6.8 (95% CI 1.9-24.4) for those with protein C deficiency. The relative risk of PVT was 2.7 (95% CI 1.1-6.9) for individuals with factor V Leiden mutation, 1.4 (95% CI 0.4-5.2) for those with prothrombin gene mutation, and 4.6 (95% CI 1.5-14.1) for those with protein C deficiency. The relative risk of BCS or PVT was not increased in the presence of inherited protein S or antithrombin deficiency. Concurrence of either acquired or inherited thrombotic risk factors was observed in 26% of the BCS patients and 37% of the PVT patients. We conclude that factor V Leiden mutation and hereditary protein C deficiency appear to be important risk factors for BCS and PVT. Although the prevalence of the prothrombin gene mutation was increased, it was not found to be a significant risk factor for BCS and PVT. The coexistence of thrombogenic risk factors in many patients indicates that BCS and PVT can be the result of a combined effect of different pathogenetic mechanisms. http://repub.eur.nl/res/pub/8625/ 1996-01-01T00:00:00Z To determine the postantibiotic effect of aminoglycosides, two methods are currently being used to remove the test drug: repeated washing and dilution. An enzymatic inactivation method of removing gentamicin and tobramycin was developed and compared with the dilution method. This enzymatic method provides a rapid and simple alternative method of removing aminoglycosides which results in reliable postantibiotic-effect values. http://repub.eur.nl/res/pub/8627/ 1996-01-01T00:00:00Z The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro pharmacokinetic model simulating human pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable.