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Michael Abecassis

Publications and source records attributed to Michael Abecassis.

14 recordsLinked to original sources
PubMed2006

ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients.

BACKGROUND: Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. METHODS: We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunosuppressant. All patients with serum creatinine (sCr) <1.0 mg/dL (n=143) before orthotopic liver transplantation (OLTX) were included in the final analysis. Patients were than categorized into two groups based upon their most recent postliver transplant sCr level: Group 1 (n=83) with sCr <1.5 mg/dL (mean 1.1+/-0.2) and group 2 (n=60) with sCr > or =1.5 mg/dL (mean 2.5+/-1.3) RESULTS: ACE D/D genotype was found in 57% of patients with sCr > or =1.5 mg/dL compared to 20% of patients with sCr <1.5 mg/dL (P<0.0001) CONCLUSIONS: Our analysis strongly suggests that liver transplant patients with ACE gene D/D genotype are at a significant higher risk of developing CI-induced chronic nephrotoxicity.

Angiotensinogen↗
PubMed2006

Laparoscopic liver surgery: Shifting the management of liver tumors.

Laparoscopic liver surgery has evolved rapidly over the past 5 years in a select number of centers. The growing experience with these procedures has resulted in a shift in the diagnostic and therapeutic approach to common liver tumors. The fact that resection of benign and malignant hepatic masses can now be accomplished laparoscopically with relatively low morbidity has influenced the decision-making process for physicians involved in the diagnosis and management of these lesions. For example, should a gastroenterologist or hepatologist seeing a 32-year-old woman with an asymptomatic 4 cm hepatic lesion that is radiologically indeterminate for adenoma or focal nodular hyperplasia (FNH): (1) continue to observe with annual computed tomography/magnetic resonance imaging (CT/MRI) scans, (2) subject the patient to a liver biopsy, or (3) refer for laparoscopic resection? For a solitary malignant liver tumor in the left lateral segment, should laparoscopic resection be considered the new standard of care, assuming the surgeon can perform the operation safely? We present current data and representative case studies on the use of laparoscopic liver resection at 2 major medical centers in the United States. We propose that surgical engagement defined by the managing physician's decision to proceed with a surgical intervention is increasingly affected by the availability of, and experience with, laparoscopic liver resection.

Adenoma↗
PubMed2006

Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results.

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.

Adult↗
PubMed2005

Living donor liver transplant for malignancy.

Adult-to-adult living donor liver transplantation (ALDLT) is being increasingly utilized to treat patients with locally advanced hepatocellular carcinoma and cholangiocarcinoma who are not prioritized under the MELD allocation system. A single institution retrospective chart review examined ALDLTs performed for malignancy to identify indications, complications, and transplant outcome. Since 1997, 18 ALDLTs have been performed for malignancy as the primary indication. Thirteen patients were transplanted for HCC. The median survival following transplant was 18.6 months and four patients developed recurrent HCC. Five patients were transplanted for cholangiocarcinoma, with a 100% recurrence free survival at a mean follow up of 18 months among patients given neo-adjuvant chemoradiation. ALDLT can be safely performed for malignancy with an acceptable peri-operative mortality rate. However, HCC patients with large tumors experience a high rate of recurrence. The use of ALDLT for cholangiocarcinoma appears promising specifically in the context of neo-adjuvant therapy.

Adult↗
PubMed2005

Renal ischemia/reperfusion injury activates the enhancer domain of the human cytomegalovirus major immediate early promoter.

Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients and is likely to occur through transcriptional activation of immediate early (ie) gene expression through mechanisms that are not well understood. TNF-mediated activation of NF-kappaB has been proposed to be one pathway leading to transcriptional activation of CMV ie gene expression. Using transgenic mice carrying a lacZ reporter gene under the control of the HCMV major ie promoter/enhancer (MIEP-lacZ mice) and MIEP-lacZ mice deficient in TNF receptor 1 and TNF receptor 2 (MIEP-lac Z TNFR DKO mice), we demonstrate that renal ischemia/reperfusion (I/R) injury activates the HCMV enhancer independently of TNF. Induction of MIEP-lacZ expression was preceded by TNFR-independent formation of reactive oxygen species (ROS), weak and transient activation of NF-kappaB and strong and sustained activation of AP-1. Our studies show that, in addition to TNF-mediated signaling, TNF-independent signaling induced by I/R injury can contribute to the activation of the HCMV enhancer. This likely occurs through ROS-mediated activation of AP-1. Targeting MAP kinase signaling pathways as well as NF-kappaB may be of therapeutic value in patients with CMV infection.

Animals↗
PubMed2005

The economic impact of MELD on liver transplant centers.

Adoption of the model for end stage liver disease (MELD) system prioritized patients awaiting liver transplant (LT) by severity of illness including progressive renal dysfunction. Unfortunately, current reimbursement for LT is not adjusted by severity of illness or need for simultaneous liver-kidney transplantation (LKT). This study examines hospital cost and reimbursement for LT and LKT to determine the effect of MELD on transplant center (TC) financial outcomes given current reimbursement practices as well as DRG outlier threshold limits. LT was performed for 86 adults prior to and 127 following the implementation of MELD. Between the eras, there was a substantial increase in the average laboratory MELD score (17.1 to 20.7 p=0.004) and percentage of LKTs performed (5.8% to 17.3% p=0.01). Increasing MELD score was associated with higher costs ($4309 per MELD point p<0.001) and decreasing TC net income ($1512 per MELD point p<0.001). In patients not achieving the Medicare outlier status, predicted net loss was $17,700 for high-MELD patients and $19,133 for those needing LKT. In conclusion, contractual reimbursement agreements that are not indexed by severity of disease may not reflect the increased costs resulting from the MELD system. Even with outlier thresholds, Medicare reimbursement is inadequate resulting in a net loss for the TC.

Aged↗
PubMed2004

Intrahepatic biliary cystadenoma: role of cyst fluid analysis and surgical management in the laparoscopic era.

BACKGROUND: Recent interest in cyst fluid analysis (CFA) for carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), and the introduction of laparoscopic surgery (LS) in the management of hepatic cysts have resulted in sporadic reports of elevated CA 19-9 and CEA levels in intrahepatic biliary cystadenoma (IBC) CFA, and the application of LS in the management of simple cysts. However, the role of CA 19-9 and CEA in the diagnosis of IBC and the role of LS in the management of IBC have not been previously defined. METHODS: We studied 34 patients with IBC at a single institution (8 years). The first 12 patients with IBC were managed with open surgical intervention. We subsequently developed a diagnostic and treatment algorithm for IBC that included, in the last 22 patients, prospective analysis of CFA for CA 19-9 and CEA, and LS for management RESULTS: All patients with IBC who underwent CFA had elevated CA 19-9 (range, 2247-1,757,510; N <33 U/mL) and mildly elevated CEA (range, 3.3-212,; N <3 ng/ml). In all 22 patients the cyst lining consisted of biliary epithelium +/- mesenchymal stroma (MS). In 1/22 patients (highest CA 19-9 level), the cyst epithelium did not contain either MS or intestinal metaplasia. In contrast, control patients (simple cysts, n=8) had normal CFA. In the previous 12 patients managed with laparotomy, 6/12 patients had biliary epithelium alone; the other 6 also contained MS with 1 patient exhibiting intestinal metaplasia and cystadenocarcinoma. CONCLUSIONS: We have proposed a management algorithm for IBC that incorporates CFA and laproscopic surgical management that allows for selective minimally invasive cyst wall sampling for patients with IBC.

Algorithms↗
PubMed2004

Living donor liver transplantation for hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing at an alarming rate in the United States, such that HCC has become an important indication for liver transplantation. The role of liver transplantation in patients with HCC has evolved over the past 2 decades, and transplantation has become one of the few curative treatment modalities for patients with HCC, especially in selected patients with favorable tumors. The advent of living donor liver transplantation for adult recipients provides another therapeutic venue, in particular for patients with HCC who are disadvantaged by current allocation algorithms for grafts from deceased donors. Living donor transplantation may limit the waiting time and, as a result, may decrease the progression of disease so that intuitively the recurrence rate should be lower than for recipients who wait for an organ from a deceased donor. There are limited data on the efficacy of living donor liver transplantation in the setting of HCC. Based on a limited cohort of patients undergoing transplantation for HCC at Northwestern University Medical Center, a higher recurrence rate, stage for stage, was found in recipients whose transplants were accelerated ("fast-tracked") by performing a living donor transplant, especially in the era in which patients with HCC were disadvantaged by the allocation algorithm. Clearly, the role of living donor liver transplantation in management of patients with HCC requires prospective direct analysis of both recurrence and dropout rates in comparable patient cohorts with HCC undergoing either deceased or living donor liver transplantation.

Algorithms↗
PubMed2003

Mortality in candidates waiting for combined liver-intestine transplants exceeds that for other candidates waiting for liver transplants.

The United Network for Organ Sharing (UNOS) reports indicate that mortality on the intestine transplant waiting list is higher than on other transplant waiting lists. The goals of this study were (1) to determine whether most of the intestinal transplant candidate deaths have occurred in those who also need liver transplants, and (2) to compare the waiting list mortality in the liver-intestine candidate subset with the overall liver transplant candidate population. We found that 90% of intestine transplant waiting list deaths have occurred in candidates who also needed liver transplants. Since 1994, annual mortality has been higher in liver-intestine transplant candidates than in the overall liver transplant candidate population, and these differences have been statistically significant since 1996. These mortality differences applied to all age groups. Also, status 2B, 3, and 7 candidate mortality was significantly higher in liver-intestine candidates than in the overall liver transplant candidate population. Because there were so few liver-intestine transplant candidates listed as status 1 or 2A, a meaningful comparison was not possible in these statuses. These data indicate that liver-intestine transplant candidates are a unique subset of liver transplant candidates with a significantly higher risk of dying on the waiting list. Recent changes in UNOS liver allocation policy that gives higher priority to liver-intestine candidates may help to reduce this discrepancy. However, further research into the etiology of liver disease in patients on long-term parenteral nutrition and earlier referral of high-risk short bowel syndrome patients to centers with special expertise in their management are needed for an ultimate solution to this problem.

Adult↗
PubMed2003

Dual-echo, chemical shift gradient-echo magnetic resonance imaging to quantify hepatic steatosis: Implications for living liver donation.

In living liver donation, a fatty liver poses risks for both recipient and donor. Currently, liver biopsy is the standard for assessing the presence and extent of steatosis. The goals of this study were to correlate a steatosis index derived from magnetic resonance imaging (MRI) to the histologic grade on biopsy as well as to determine the topographic distribution of steatosis within the liver. We examined the ability of dual-echo, chemical shift gradient-echo MRI to predict the degree of steatosis on liver biopsy. A total of 22 subjects received both a liver biopsy and detailed MRI evaluation. These individuals included 15 potential living donors and 7 patients with nonalcoholic fatty liver disease. MRI steatosis index was then compared with histologic grade on liver biopsy. The topographic distribution of hepatic steatosis was determined from those subjects in whom MRI detected hepatic steatosis. The steatosis index had a positive correlation with grade of steatosis on liver biopsy (correlation coefficient, 0.84). There was no significant variation in the degree of steatosis among segments. A steatosis index of >0.2 had good positive and negative predictive value for the presence of significant steatosis (>15%) on biopsy. Our quantitative MRI protocol can predict the degree of hepatic steatosis when it is minimal to moderate, and may obviate the need for liver biopsy for the purpose of quantification of steatosis in living donors. Fat saturation added to the MRI protocol may further improve diagnostic accuracy. This technique may be applicable to the larger population with hepatic steatosis.

Adult↗
PubMed2003

Preoperative evaluation of the entire hepatic vasculature in living liver donors with use of contrast-enhanced MR angiography and true fast imaging with steady-state precession.

PURPOSE: To preoperatively assess the entire hepatic vasculature in living related liver donors with use of a combination of contrast material-enhanced magnetic resonance (MR) angiography and true fast imaging with steady-state precession (FISP). MATERIALS AND METHODS: Twenty-five living potential liver donors were examined preoperatively on a 1.5T Siemens Sonata system. Twenty-four underwent surgery and two had catheter angiography performed to delineate complex anatomy. Contiguous 5-mm-thick, sub-second true FISP images of the liver were initially obtained during breath-holding in axial and coronal planes (repetition time [TR]/echo time [TE], 3.2/1.6; flip angle, 70 degrees ). MR angiography was performed with use of a three-dimensional (3D) gradient-echo fast low-angle shot (FLASH) pulse sequence (TR/TE, 3.0/1.2; flip angle, 25 degrees ), with 40 mL of Gadolinium DTPA injected at a rate of 2 mL/sec. One precontrast and two postcontrast coronal 3D volumes were acquired, each in a 20-second breath-hold, and two subtracted 3D sets were calculated. Arterial anatomy was assessed with use of maximum-intensity projection, volume rendering, and multiplanar reformatting algorithms. Hepatic and portal venous anatomy was evaluated with use of the true FISP images and the venous phase of the MR angiogram. Visualization of hepatic arterial branches was noted. Visualization of portal vein branches was scored on a scale of 0-5. The presence of anatomic variants was noted. Vascular anatomy was confirmed at the time of surgery and at catheter angiography. RESULTS: Segmental branch vessels were visualized on MR angiography in the majority of cases. The segment four branch was identified in 96% patients. Variant arterial anatomy was seen in 50% of patients. MR angiography detected 10 of 11 arterial variants found at surgery and angiography. Visualization of portal vein branches was generally higher with true FISP compared to MR angiography. Twenty-four percent of patients had variant portal venous anatomy. Caudal hepatic veins were identified in 60% of patients, of which eight were significant (>5 mm). Hepatic and portal venous anatomy was accurately predicted by true FISP and MR angiography in all patients who went on to undergo surgery. CONCLUSION: Preoperative imaging with use of a combination of contrast-enhanced MR angiography and true FISP provides a comprehensive assessment of the entire hepatic vasculature in living liver donors.

Adult↗