CC chemokine receptor 5delta32 polymorphism-a risk factor for ischemic-type biliary lesions following orthotopic liver transplantation.
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Ischemic-type biliary lesions are a major complication following orthotopic liver transplantation. They occur in up to 26% of liver transplant recipients. Among other factors, unknown immunologic factors have always been assumed to be partly responsible for these lesions. CC-chemokines and their receptors play a key role in postoperative immunomodulation after liver transplantation. The non-function CC-chemokine receptor 5delta32 polymorphism (CCR5delta32) has been shown to lead to a lower rate of acute rejection after kidney transplantation; in liver transplantation the role of CCR5delta32 is unclear. We investigated the influence of the CCR5delta32 after liver transplantation with special regard to ischemic-type biliary lesions. The CC-chemokine receptor-5 (CCR5) of 146 recipients was analyzed by polymerase chain reaction to detect CCR5delta32 in blood samples of patients after liver transplantation. One hundred twenty patients with wild-type CCR5 and 26 patients with CCR5delta32 (1 homozygote, 25 heterozygote) were identified. Ischemic-type biliary lesions occurred in 14 of 120 patients with wild-type CCR5 and in 8 of 26 patients with CCR5delta32 polymorphism (P = = 0.01). 5 year patient survival with CCR5delta32 and CCR5 was 70% and 85%, respectively (P =.0067). Our results show that the CCR5delta32 is a significant risk factor for the development of ischemic-type biliary lesions after liver transplantation and leads to a reduction in 5-year survival. In conclusion, the CCR5 status should be screened prospectively before liver transplantation. (+info)
Resource and manpower calculations for the provision of hepatobiliary surgical services in the UK.
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BACKGROUND: The provision of specialist non-transplant hepatobiliary services in the UK is fragmented and there is little consensus on the manpower and resource requirements to meet the needs of defined populations. METHODS: We report our experience with a hepatobiliary service established 5 years ago in Sheffield to provide a tertiary referral service to the population of the North Trent health area and attempt to provide estimates of resource requirements based on patterns of current use. RESULTS: A total of 615 patients with hepatobiliary conditions requiring specialist treatment were referred to the service during 1997-2002. The majority of patients (69%) were referred for consideration of liver resection for colorectal liver metastases. In all, 251 resections were performed in 240 (39% of all referred) patients. The current operation rates for colorectal metastases are about 4 per 100,000 population per year and for other complex hepatobiliary procedures are also 4 per 100,000 population per year giving a total "need" of 8 procedures per 100,000 population per year. For the current population in England and Wales, this would mean 25 specialist hepatobiliary centres performing in total approximately 2000 hepatic resections for colorectal cancer metastases and 2000 other tertiary hepatobiliary procedures each year. CONCLUSIONS: Our experience supports the model of centralisation of non-transplant hepatobiliary surgical services and indicates the extent of hitherto unmet demand in our geographical area. We estimate that a minimum of two full-time specialist hepatobiliary surgeons with appropriate ancillary support are required for a typical population of 2 million people in the UK. (+info)
Histologic changes mimicking biliary disease in liver biopsies with venous outflow impairment.
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Impairment of venous outflow from the liver manifests as zone 3 sinusoidal dilatation and congestion (SDC) in liver biopsy. The spectrum of histologic changes in portal tracts has not been described. We studied liver biopsies from 34 patients with a confirmed diagnosis of venous outflow impairment (VOI). Liver transplant recipients and biopsies with cirrhosis and hepatic neoplasms were excluded. Clinical records were reviewed for laboratory tests and radiographic findings. In all, 19 patients had right heart disease, 13 had classic Budd-Chiari syndrome and two had veno-occlusive disease. Liver chemistry tests showed elevated liver transaminases (n=21; 61.8%), elevated alkaline phosphatase (n=31; 91.2%) and GGT (all 13 cases tested). The elevation in ALT and AST was mild (below 200 U/l in all cases), while alkaline phosphatase (ALP) was elevated above 500 U/l in nine (26.5%) patients and above 1000 U/l in three cases. On biopsy, all cases showed SDC. The portal tracts showed (a) portal expansion with bile ductular proliferation (n=16; 47.1%) accompanied by lymphoplasmacytic infiltrate (n=10), lymphocytic cholangitis (n=3) and portal or periportal fibrosis (n=11), (b) Portal and/or periportal fibrosis without ductular proliferation (n=3; 8.8%) or (c) Normal portal tracts (n=15; 44.1%). The combination of elevated ALP and bile ductular changes on biopsy suggested chronic bile duct disease. Ultrasound/CT scan evaluation of bile ducts in 26 patients showed no biliary tree abnormality. Antimitochondrial antibody testing in eight cases also yielded negative results. In conclusion, bile ductular proliferation, portal inflammation and portal-based fibrosis are commonly seen in liver biopsies of patients with VOI even in the absence of bile duct disease. These changes are often accompanied by elevated ALP and GGT and can lead to the suspicion of chronic biliary disease. In the absence of demonstrable abnormalities in the biliary tree, these changes can be attributed to venous outflow impairment. (+info)
Cdc42 and the actin-related protein/neural Wiskott-Aldrich syndrome protein network mediate cellular invasion by Cryptosporidium parvum.
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Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a remodeling of the host cell actin cytoskeleton. In addition, an actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated actin remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell actin remodeling at the attachment site. (+info)
Relationship between myalgias/arthralgias occurring in patients receiving quinupristin/dalfopristin and biliary dysfunction.
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OBJECTIVES: To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction. METHODS: We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy. RESULTS: Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05). CONCLUSIONS: Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate. (+info)
Biochemical and radiological predictors of malignant biliary strictures.
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AIM: Differentiation of benign biliary strictures (BBS) from malignant biliary strictures (MBS) remains difficult despite improvement in imaging and endoscopic techniques. The aim of this study was to identify the clinical, biochemical and or radiological predictors of malignant biliary strictures. METHODS: We retrospectively reviewed all charts of patients who had biliary strictures (BS) on endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous cholangiography (PTC) in case of unsuccessful ERCP from March 1998 to August 2002. Patient characteristics, clinical features, biochemical, radiological and biopsy results were all recorded. Stricture etiology was determined based on cytology, biopsy or clinical follow-up. A receiver operator characteristic (ROC) curve was constructed to determine the optimal laboratory diagnostic criterion threshold in predicting MBS. RESULTS: One hundred twenty six patients with biliary strictures were enrolled, of which 72 were malignant. The mean age for BBS was 53 years compared to 62.4 years for MBS (P=0.0006). Distal bile duct stricture was mainly due to a malignant process 48.6% vs 9% (P=0.001). Alkaline phosphates and AST levels were more significantly elevated in MBS (P=0.0002). ROC curve showed that a bilirubin level of 84 micromol/L or more was the most predictive of MBS with a sensitivity of 98.6%, specificity of 59.3% and a positive likelihood ratio of 2.42 (95% CI=0.649-0.810). Proximal biliary dilatation was more frequently encountered in MBS compared to BBS, 73.8% vs 39.5% (P=0.0001). Majority of BBS (87%) and MBS (78%) were managed endoscopically. CONCLUSION: A serum bilirubin level of 84 micromol/L or greater is the best predictor of MBS. Older age, proximal biliary dilatation, higher levels of bilirubin, alkaline phosphatase, ALT and AST are all associated with MBS. ERCP is necessary to diagnose and treat benign and malignant biliary strictures. (+info)
Cholangio-duodenal interposition of an isolated jejunal segment after central resection.
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BACKGROUND: Bilio-intestinal drainage is routinely performed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of an isolated jejunal segment (CDJI). This method offers the benefit of potential endoscopic control and intervention during follow-up. Critics of CDJI assume a higher rate of postoperative cholangitis compared to the Roux-en-Y construction. METHODS: Seventy-six patients with malignant tumors (n=56) or benign strictures and choledochal cysts (n=20) were treated between 1989 and 2002 by cholangio-duodenal interposition of an isolated jejunal segment (measuring 15-25 cm) after central bile duct resection. In 22 patients endoscopic control was first performed postoperatively during hospitalization. In 12 patients bilio-intestinal anastomosis could be inspected endoscopically. In the remaining patients the anastomosis could not be visualized endoscopically because of kinking of the jejunal segment, but in all patients it could be evaluated by endoscopic retrograde cholangiography (ERC). RESULTS: During follow-up, 25 (33%) patients died from extrahepatic tumor recurrence. Three patients receiving CDJI after severe iatrogenic bile duct injury developed anastomotic strictures. Two of these patients were treated by endoscopic pigtail drainage, and one was treated by percutaneous drainage. Two patients who had received CDJI after choledochal cyst resection developed cholestasis postoperatively because of sludge formation (1 patient) and an intrahepatic concrement (1), which could be solved endoscopically. One patient after resection of a Klatskin tumor developed an anastomotic stricture which could not be visualized endoscopically, making percutaneous drainage necessary. The rate of postoperative cholangitis after CDJI in our patients was comparable to that after the Roux-en-Y reconstruction. CONCLUSION: Interposition of an isolated jejunal segment for reconstruction after bile duct resection should be performed in patients with a high risk of postoperative stenosis. To benefit endoscopic follow-up the jejunal segment should be shorter than 20 cm (+info)
Reoperation for benign biliary tract diseases in 149 cases: causes and prevention.
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BACKGROUND: Failure to diagnose and treat benign biliary tract disease relatively common surgical disease may cause serious consequences. Since the introduction of B-mode ultrasonography, CT, or MRI early and accurate diagnosis of the disease has been possible. In clinical practice, however, these methods have not been adequately used. Inappropriate surgical procedures can also lead to bile duct injury or stenosis after injury, residual cholecystitis, stenosis after cholangiojejunostomy, or stenosis of the Oddi's sphincter. But improvement of the diagnosis and treatment of benign biliary tract disease remains a great challenge to clinicians. METHODS: A total of 149 patients with benign biliary tract disease who had received reoperation from June 1988 to June 2001 were analyzed retrospectively. Among them 95 patients (63.76%) received operation twice and 38 (25.5%) underwent 3 operations. Sixteen patients (10.74%) needed 4 or more operations. The procedures for the first operation included cholecystectomy (71 patients, 47.65%), cholecystectomy with exploration of the common bile duct (42, 28.19%), cholangiojejunostomy (21, 14.1%), and laparoscopic cholecystectomy (15, 10.06%). RESULTS: The causes for reoperation included residual and recurrent bile duct stones in 53 patients (35.57%), bile duct injury or stenosis after injury in 41 (27.52%), residual cholecystitis with or without stones in 28 (18.8%), stenosis after cholangiojejunostomy in 17 (11.41%), stenosis of the Oddi's sphincter in 5 (5.35%), and others in 5 (5.35%). Four patients (2.68%) died after operation. CONCLUSIONS: To prevent reoperation for benign biliary tract diseases, the following measures should be taken to increase preoperative diagnostic rate, to understand conditions of the biliary tract by using imaging techniques and cholangiography, to examine comprehensively and carefully with choledochoscopy, cholangiography and B-mode ultrasonography intraoperatively, to choose appropriate operative procedures to decrease the rate of residual stones, and to decide the time for the first repair according to injury type of the bile duct. Roux-en-Y hepaticojejunostomy with cholangioplasty is the best operation for the reconstruction of the biliary tract. (+info)