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Biomedical subjects

K Huibregtse

Publications and source records attributed to K Huibregtse.

At least 37 records · Page 2Linked to original sources

Systemic inflammatory response in acute cholangitis and after subsequent treatment.

OBJECTIVE: To measure the concentrations of endotoxin and inflammatory mediators during an attack of acute cholangitis and see what effect endoscopic treatment had on these mediators. DESIGN: Prospective study. SETTING: University teaching hospital The Netherlands. SUBJECTS: Ten patients with acute cholangitis. INTERVENTIONS: Measurements were made during the attack and 1 week after endoscopic treatment. MAIN OUTCOME MEASURE: Changes in clinical variables, and severity of biliary obstruction. Concentrations of endotoxin, cytokines, and endotoxin binding proteins, in plasma. RESULTS: The causes of cholangitis were obstructed endoprosthesis (n = 4) and stones (n = 6). The median bilirubin concentration during the attack was 70.0 micromol/L (range 14-156) and 14.5 micromol/L (range 9-80) after treatment (p < 0.05). Median (range) plasma endotoxin concentrations were 3.6 pg/ml (3.2-107) and 3.6 (2.4-5), respectively. Concentrations of cytokines were high during the acute attack and significantly lower after treatment: median tumour necrosis factor (TNF) fell from 44.6 pg/ml (range 1.2-403) to 7.3 (0-53); soluble TNF receptor p55 from 4.9 ng/ml (2.7-13.8) to 3.6 (1.4-8.2) and TNF receptor p75 from 11.6 ng/ml (7.1-40.6) to 8.1 (2.9-31.3); interleukin 6 (IL-6) fell from 690 pg/ml (34.1-4594) to 8.2 (0-39.3), IL-8 from 226.2 pg/ml (31.6-712.7) to 21.4 (4.2-63.5) and IL-10 from 33.4 pg/ml (2.7-5605) to 4.7 (0-16.7) (p < 0.03). Values for lipopolysaccharide binding protein and soluble CD14 also fell significantly (p < 0.01) from 86.5 (43.4-200) to 21.5 (11.3-37.5) and from 200 (59-200) to 47.8 (0.47-200), respectively. The concentration of bactericidal permeability increasing protein did not change significantly, being 7.1 (2-18.9) during the acute attack and 4.6 (0.8-17.7) a week later. CONCLUSION: There is a considerable systemic inflammatory response during cholangitis, which is dramatically reduced one week after endoscopic treatment.

Acute Disease↗

Analysis of a positional candidate gene for inflammatory bowel disease: NRAMP2.

Genome scans have identified a region spanning 40 cM on the long arm of chromosome 12 as a susceptibility locus for inflammatory bowel disease (IBD). This locus contains several candidate genes for IBD, one of which is the gene for the natural resistance associated macrophage protein 2 (NRAMP2). This protein is a divalent cation transporter and is expressed in many cells and tissues. The putative role of this protein in innate immunity prompted us to investigate a possible relationship between NRAMP2 and IBD. We assessed the frequency of four restriction fragment length polymorphisms (IVS2+11A/G, IVS4+44C/A, 1254T/C, and IVS15Ex16-16C/G) in a group of 155 Crohn's disease (CD) patients, 114 ulcerative colitis (UC) patients, and 189 healthy controls. Linkage analysis was performed in a group of 70 families with multiple members suffering from IBD. We searched for additional intragenic markers and mutations by sequence analysis of the natural resistance-associated macrophage 2 gene of 33 CD patients, with a positive family history for IBD. We identified one novel restriction fragment length polymorphism in intron 15 of the gene. The frequency of the rare allele is: 0.08 in our control population. An increased frequency of this allele was found in CD patients but this difference did not reach statistical significance. A weak association between CD and homozygosity for the G allele of the IVS2+11A/G was found (OR [odds ratio] = 2.2, CI [confidence interval] = 1.3-3.9, chi2 = 8.4, p = 1.013). Nonparametric linkage analysis and transmissions disequilibrium tests did not provide evidence for linkage of NRAMP2 to IBD, UC, or CD. Sequence analysis of the exons and the iron-responsive element in a panel of 33 CD patients did not reveal any mutations in NRAMP2. Our association, linkage, and sequence analysis in IBD shows that the putative genetic risk factor on chromosome 12 likely is not NRAMP2. The weak association between the G/G genotype of IVS2+11A/G and CD may be due to linkage disequilibrium with a nearby disease-causing gene.

Adult↗

Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage.

BACKGROUND: Obstructive jaundice is associated with postoperative complications related to increased endotoxaemia and the inflammatory response. In animals obstructive jaundice is associated with endotoxaemia and cytokine induction, which are reversed by internal biliary drainage. AIMS: To study endotoxaemia and the subsequent inflammatory response in obstructive jaundiced patients and after endoscopic biliary drainage. METHODS: In 15 patients with malignant distal obstructive jaundice, inflammatory and bacteriological parameters were assessed before endoscopic stent placement and after three weeks endoscopic drainage. RESULTS: Drainage reduced bilirubin from 252.5 to 45.1 micromol/l. At baseline low level endotoxaemia was detected (4.3 pg/ml) which was not affected after drainage (4.5 pg/ml). Serum interleukin 8 (IL-8) and endotoxin binding proteins were increased in jaundice and reduced after drainage (IL-8 113.6 to 20.7 pg/ml; lipopolysaccharide binding protein 24.2 to 16.5 microg/ml; sCD14 17.4 to 7.6 microg/ml; bactericidal/permeability increasing protein 2.9 to 1.8 ng/ml). Levels of other cytokines, augmented in animals, were only slightly increased and not changed after drainage (tumour necrosis factor (TNF): 21.7 and 18.4 pg/ml; sTNFr p55/75: 2.9/7.0 and 2.7/5.6 ng/ml; IL-6: 4.2 and 6.1 pg/ml; IL-10: 4.5 and 2.7 pg/ml). Elastase and lactoferrin tended towards reduction after drainage. All bile cultures were positive after stenting. CONCLUSIONS: The effects of obstructive jaundice in humans on endotoxin and cytokines are different from those in animal models. Obstructive jaundice causes alterations in circulating endotoxin binding proteins and IL-8. Concentrations of other mediators (TNF, previously suggested as being responsible for systemic endotoxaemia effects) are low and not affected by drainage.

Bile Duct Neoplasms↗

Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction: a need for guidelines.

Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.

Antineoplastic Agents, Phytogenic↗

Diagnostic p53 immunostaining of endobiliary brush cytology: preoperative cytology compared with the surgical specimen.

BACKGROUND: Endobiliary brush cytology is important in the distinction of malignant and benign causes of extrahepatic bile duct obstruction. The additional diagnostic value of p53 immunostaining on these cytology specimens was assessed. METHODS: All patients with extrahepatic bile duct obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) with endobiliary brush cytology and subsequent surgery at the Academic Medical Center in Amsterdam during a 3-year period were studied. p53 Immunocytology was compared with the corresponding conventional light microscopic cytology and p53 immunostaining of the subsequent surgical specimen. RESULTS: Fifty-three patients with the following diagnoses were included: pancreatic carcinoma (23), bile duct carcinoma (15), ampullary carcinoma (5), lymph node metastases (2), carcinoma of unknown origin (4), chronic pancreatitis (3), and primary sclerosing cholangitis (1). Fifty-one percent of the carcinomas showed positive p53 immunostaining; all four surgical specimens without carcinoma were negative. The sensitivities of conventional light microscopic cytology, p53 immunocytology, and both tests combined were 29%, 24%, and 43%, respectively. These sensitivities were higher in cases of bile duct carcinoma (46%, 40%, and 66%) compared with cases of pancreatic carcinoma (13%, 9%, and 22%). Specificities of both tests were 100%. CONCLUSIONS: p53 Immunostaining on endobiliary brush cytology may be helpful in the diagnosis of malignant extrahepatic bile duct stenosis, especially in patients with bile duct carcinoma. Cancer (Cancer Cytopathol)

Bile Duct Neoplasms↗

[Bile duct injuries after a laparoscopic cholecystectomy].

Eight years after the introduction of laparoscopic cholecystectomy a decrease of the incidence of bile duct injuries is reported in the literature. The incidence of a bile duct injury after laparoscopic cholecystectomy is now slightly higher than after open cholecystectomy. A minority of these injuries are detected during surgery. Most patients have a delayed identification of the bile duct injury, even after discharge from the hospital. An early diagnostic work-up with ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) is mandatory in every patient with persisting symptoms (more than 48 hours) after laparoscopic cholecystectomy. Still, one-third of the patients are subjected to a 'diagnostic' exploratory laparotomy without preoperative visualization of the biliary tract by ERCP or percutaneous transhepatic cholangiography. Minor lesions are mostly treated successfully by endoscopy with a stent. After transection of the bile duct surgical reconstruction by a hepaticojejunostomy has to be performed. A delayed elective reconstruction was associated with fewer complications than acute repair under suboptimal circumstances such as local inflammatory changes and bile leakage.

Adult↗

Endoscopic techniques for retrieval of proximally migrated biliary stents: the Amsterdam experience.

BACKGROUND: Endoscopic retrieval of proximally migrated biliary plastic stents may be technically challenging and sometimes unsuccessful. Despite the widespread use of such stents, there are few reports on the technique for retrieval of migrated stents. METHODS: We reviewed the records of patients who were found to have proximally migrated biliary stents during the last 3 years at a tertiary referral center. Our study analyzed the various techniques used for endoscopic retrieval and evaluated the factors influencing the choice of a particular technique. RESULTS: Endoscopic retrieval of a proximally migrated stent was attempted in 41 patients and was successful in 37 (90%). The retrieval techniques included Dormia basket, balloon, balloon and basket, basket and ball tip catheter, forceps, and Soehendra stent retriever. The Dormia basket technique was successful in the majority of cases. CONCLUSION: Proximally migrated biliary stents can be successfully removed endoscopically in most cases. The choice of a retrieval technique is dependent on several factors including biliary ductal dilatation, depth of stent migration, distal stent impaction and biliary stricture distal to the migrated stent. The placement of an additional stent alongside an irretrievable stent is a satisfactory alternative to retrieval.

Catheterization↗

Value of brush cytology for dominant strictures in primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Around 10% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma, which is cholangiographically often indistinguishable from a benign dominant stricture. The aim of the present study was to assess the value of brush cytology in discriminating between benign and malignant dominant strictures in primary sclerosing cholangitis. PATIENTS AND METHODS: The results of all brush cytology specimens from dominant strictures from patients with established primary sclerosing cholangitis, taken at endoscopic retrograde cholangiopancreatography between 1987 and 1996, were compared with the histological diagnosis or clinical status of the patients at least 2 years later. RESULTS: A total of 47 brush cytology samples, taken between 1987 and 1996, from 43 PSC patients could be included. Between 1993 and 1996, p53 immunocytochemical examination was done in 27 brush cytology specimens and K-ras mutation analysis in 25 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of brush cytology for detection of malignancy were 60%, 89%, 59%, and 89%, respectively. These figures were not improved by adding the results of p53 and K-ras analysis. Logistic regression analysis did not reveal any additional benefit of p53 or K-ras analysis either. Prior stenting did not adversely affect specificity. CONCLUSIONS: The sensitivity and positive predictive value of brush cytology for dominant strictures in PSC are rather poor. The specificity and negative predictive value are reasonably good. There was no additional value from p53 immunocytochemistry and K-ras mutation analysis. Prior stenting did not affect the results.

Bile Duct Neoplasms↗

Four years experience with short term stenting in primary sclerosing cholangitis.

OBJECTIVE: Symptomatic dominant strictures in primary sclerosing cholangitis are often treated with endoscopic stent therapy, but the optimal treatment duration is not well established. After a promising pilot study, we now report our 4 yr experience with short term endoscopic stent therapy for relief of dominant strictures. METHODS: Between January 1994 and October 1997, 32 patients with symptomatic primary sclerosing cholangitis with a dominant stricture at endoscopic retrograde cholangiopancreatography were treated with insertion of a 7- or 10-Fr polyethylene endoprosthesis, which was extracted after a mean of 11 days (range 1-23 days). Primary end points were changes in complaints and cholestasis after 2 months, and time interval until a repeat endoscopic treatment was deemed necessary. A secondary end point was the occurrence of treatment-related complications. RESULTS: Cholestatic complaints improved after 2 months in 83% of patients. Mean scores for pruritus, fatigue, and right upper quadrant pain decreased from 0.94, 1.0, and 0.87 to 0.26, 0.39, and 0.26, respectively. All improvements were significant. Of 14 patients presenting with jaundice, 12 regained normal serum bilirubin levels 2 months after short term endoscopic stenting. The mean levels of conjugated bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase dropped significantly from 36 micromol/L, 309 U/L, and 426 U/L to 7 micromol/L, 205 U/L, and 258 U/L, respectively. The reintervention-free proportions after 1 and 3 yr were 80% and 60%. Seven transient procedure-related complications occurred in 45 therapeutic endoscopic retrograde cholangiopancreatographies. CONCLUSIONS: Short term endoscopic stenting for symptomatic dominant strictures in primary sclerosing cholangitis is effective and safe, and the beneficial effect is sustained for several years.

Adult↗

Clinical value of K-ras codon 12 analysis and endobiliary brush cytology for the diagnosis of malignant extrahepatic bile duct stenosis.

Extrahepatic biliary stenosis can be caused by benign and malignant disorders. In most cases, a tissue diagnosis is needed for optimal management of patients, but the sensitivity of biliary cytology for the diagnosis of a malignancy is relatively low. The additional diagnostic value of K-ras mutational analysis of endobiliary brush cytology was assessed. Endobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreaticography were prospectively collected from 312 consecutive patients with extrahepatic biliary stenosis. The results of conventional light microscopic cytology and K-ras codon 12 mutational analysis were compared and evaluated in view of the final diagnosis made by histological examination of the stenotic lesion and/or patient follow-up. The sensitivities of cytology and mutational analysis to detect malignancy were 36 and 42%, respectively. When both tests were combined, the sensitivity increased to 62%. The specificity of cytology was 98%, and the specificity of the mutational analysis and of both tests combined was 89%. Positive predictive values for cytology, mutational analysis, and both tests combined were 98, 92, and 94%, whereas the corresponding negative predictive values were 34, 34, and 44%, respectively. The sensitivity of K-ras mutational analysis was 63% for pancreatic carcinomas compared to 27% for bile duct, gallbladder, and ampullary carcinomas. K-ras mutational analysis can be considered supplementary to conventional light microscopy of endobiliary brush cytology to diagnose patients with malignant extrahepatic biliary stenosis, particularly in the case of pancreatic cancer. The presence of a K-ras codon 12 mutation in endobiliary brush cytology per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or equivocal.

Bile Duct Neoplasms↗

The wallstent for malignant biliary obstruction.

The self-expandable metal Wallstent was introduced in late 1980 for the treatment of malignant biliary strictures. The technique of insertion in distal and hilar bile duct strictures is described in detail. The author presents the reported data and discusses the indications for the stent's use. This stent still does not fulfill all the criteria for an ideal stent; further improvements should be made.

Bile Duct Neoplasms↗

Endoscopic retrograde wire-guided cytology of malignant biliary strictures using a novel scraping brush.

BACKGROUND: Tissue sampling to differentiate benign from malignant pancreatobiliary strictures remains problematic despite the availability of several new sampling methods. A new device is described which attempts to correct some of the drawbacks. METHODS: The device consists of a 10F dilator which has an attached pad of Velcro. The Velcro has semi-rigid, mushroom-shaped bristles. A cytologic sample is obtained by the abrasive action of the brush when it is passed through the stricture. Fifteen patients with obstructive jaundice underwent brushing of the bile duct using this device. RESULTS: Cytologic samples obtained with this device were positive for malignancy in all 15 patients. Diagnostic confirmation was obtained by assessment of clinical course, radiologic findings, and during surgery. CONCLUSION: Preliminary experience indicates that this new device enhances the yield of tissue sampling from malignant bile duct strictures.

Aged↗

Improvement in the management of bile duct injuries?

BACKGROUND: Previous studies have suggested that improvements in diagnostic workup and treatment of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy can be expected as experience increases with the laparoscopic procedure. Many published articles reported that early diagnosis, proper classification, and optimal timing of treatment of BDI increase the likelihood of successful treatment. This study determined whether diagnosis and management of BDI have improved over the years. STUDY DESIGN: Between June 1990 and November 1996, 106 patients were diagnosed and treated in the Amsterdam Academic Medical Center for BDI sustained during laparoscopic cholecystectomy. Detailed information was obtained about peroperative findings, time interval from laparoscopic cholecystectomy to symptoms, and interval from symptoms to diagnosis. Bile duct injuries were classified into four types. Two patient groups were compared: BDI patients diagnosed from 1990 until 1994 ("learning phase") and patients diagnosed from 1995 until 1996. RESULTS: Bile duct injuries combined with bile leakage were diagnosed significantly earlier in the second period after the learning phase. The percentages of injuries diagnosed peroperatively, "blind laparotomies," and suboptimal timed hepaticojejunostomies were not different between the groups. CONCLUSIONS: Except for earlier diagnosis of BDI in the later period than in previous years, there appeared to be no significant improvement in diagnostic workup and management during the past 2 years.

Bile Ducts↗

A prospective randomized trial of Teflon versus polyethylene stents for distal malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Clogging of biliary stents continues to be a major clinical problem. Different polymer materials may have different effects on clogging. In vitro studies have shown a direct relation between the frictional coefficient of a polymer and the amount of encrusted material. Teflon appeared to be the best polymer for biliary stents. Two different types of stents made of Teflon have been tested in clinical practice and showed favourable patency rates. However, a randomized trial has never been performed. We compared the patency of an Amsterdam-type polyethylene stent with a Teflon stent in a prospective randomized trial. PATIENTS AND METHODS: Between September 1995 and November 1996, 42 patients received a Teflon stent and 42 patients a polyethylene stent. All patients had a distal malignant biliary stricture without a previous drainage procedure. Diagnoses included carcinoma of the pancreas (n = 76), papilla (n = 1), bile duct (n = 5) and metastases (n = 2). The internal and external diameter (10 Fr), length (9 cm) and stent design (a straight stent with two side flaps and one side hole at each end) were similar for both stents. RESULTS: A reduction in bilirubin of more than 20% within one week was seen in 91% of the patients. Early complication rates were similar in both groups (10%). The median follow-up was 142 days. Stent dysfunction occurred in 28 Teflon and 29 polyethylene stents. The thirty-day mortality was 14% in both groups. Patient survival did not differ significantly between the groups (median survival: Teflon 165 days, polyethylene 140 days). The median stent patency was 83 days for Teflon and 80 days for polyethylene stents, and was not significantly different either. CONCLUSION: Teflon material did not improve patency in biliary stents with an Amsterdam-type design.

Aged↗

Biliary stenting with a prototype expandable Teflon endoprosthesis.

BACKGROUND AND STUDY AIMS: A new balloon-expandable Teflon endoprosthesis was developed for endoscopic placement in the biliary tree. After deployment to its maximum diameter the stent is hardened by exposure to UV light. We present our preliminary results with a prototype 18 Fr prosthesis. PATIENTS AND METHODS: Three patients with a distal common bile duct obstruction due to unresectable pancreatic head carcinoma were treated with this stent. Insertion of the stent was the only palliative procedure. Patients were followed up until stent dysfunction or death. RESULTS: Stent placement was successful in all patients and no procedural complications occurred. Distal migration occurred in one patient, clogging of the stent after 149 days in another. CONCLUSION: In patients with a malignant biliary stricture this newly developed expandable endoprosthesis is effective in relieving obstructive jaundice. The technique has potential advantages over placement of current expandable metal mesh stents.

Aged↗

Endoscopic dilatation of the biliary sphincter for removal of bile duct stones: an overview of current indications and limitations.

Endoscopic balloon dilatation (EBD) of the biliary sphincter may be an alternative to endoscopic sphincterotomy (EST) for removal of bile duct stones. After EBD of the biliary sphincter to a diameter of 8 mm, stones are removed according to standard guidelines. In the event that stone removal fails after EBD, an additional EST is performed. The overall success rate of stone removal after EBD (90%) is comparable to that of EST. After EBD, an additional EST and mechanical lithotripsy are required in 10% and 30% of patients, respectively. In patients with bile duct stones < 10 mm and a stone number < or = 3, EBD is nearly always successful without the need for additional EST or mechanical lithotripsy. Pancreatitis post-EBD occurs at a rate of 5-7%, which is not significantly different from that after EST. Significant bleeding post-EBD has not been observed in over 400 patients undergoing EBD. EBD is a valuable alternative to EST, especially in patients with smaller bile duct stones and in patients with haemostatic disorders.

Catheterization↗