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M Rela

Publications and source records attributed to M Rela.

At least 19 recordsLinked to original sources

Artificial neural network is superior to MELD in predicting mortality of patients with end-stage liver disease.

BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. AIMS: To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044). CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.

Area Under Curve↗

Selection of patients with hepatocellular carcinoma for liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) plays a pivotal role in the management of selected patients with initial hepatocellular carcinoma (HCC). After disappointing early results and a shortage of cadaveric grafts, patients are currently selected for OLT on the basis of tumour size and number. Limitations of these criteria and the advent of living donation have prompted their re-evaluation. The principal aims of this review were to define the limitations of current transplant criteria for HCC, and to identify potential areas for improvement. METHODS: A Medline search using the terms 'liver transplantation' and 'hepatocellular carcinoma' was conducted. Additional references were sourced from key articles. RESULTS AND CONCLUSION: In patients with HCC, biological properties of the tumour are more accurate than radiological criteria in determining outcome after transplantation. Despite the risks of tumour biopsy, which may have been previously overstated, histological evaluation before transplantation may have a role and warrants further study. By expanding the donor pool and eliminating waiting times, live donor liver transplantation is a valuable resource that has yet to fulfil its potential because of unresolved ethical issues concerning the safety of the donor. The availability of long-term outcome data may help to clarify this in the near future.

Carcinoma, Hepatocellular↗

Segmental liver transplantation from non-heart beating donors--an early experience with implications for the future.

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Adolescent↗

Ex vivo liver surgery for extraadrenal pheochromocytoma.

A case of a 15-year-old girl with a malignant extraadrenal pheochromocytoma situated between the inferior vena cava and the portal triad is described. Using ex vivo technique, the tumour was successfully resected on the bench, as a previous attempt to remove the tumour in situ had been abandoned. The surgical aspects and implications of ex vivo surgery are discussed, highlighting the increased operative risk, perioperative mortality, and poor long-term results in patients with malignant tumours.

Adolescent↗

A case of post-reperfusion syndrome following surgery for liver trauma.

We report the case of a young trauma patient who needed tight perihepatic surgical packing to control bleeding from a ruptured liver. He developed severe cardiovascular and respiratory decompensation on removal of the surgical packs as a result of the post-reperfusion syndrome. He underwent a total hepatectomy and, 35 h later, orthotopic liver transplantation. The pathophysiology of post-reperfusion syndrome is discussed, and its importance to anaesthetists in the non-transplant setting is emphasized.

Accidents, Traffic↗

Insulin-producing cells derived from human pancreatic non-endocrine cell cultures reverse streptozotocin-induced hyperglycaemia in mice.

AIMS/HYPOTHESIS: The aim of the study was to investigate the potential of human pancreatic non-endocrine cells to transdifferentiate into endocrine cells that would be capable of secreting insulin in response to glucose and ameliorating insulin-deficient diabetes after transplantation. MATERIALS AND METHODS: Cell fractions enriched with exocrine cells after human islet isolation were treated with streptozotocin to remove residual beta cells, grown in monolayer culture to allow de-differentiation, transferred to cluster culture for redifferentiation in the presence of activin A, betacellulin, nicotinamide and glucose, supplemented with 10% FCS, and administered to streptozotocin-induced diabetic SCID mice. A subset of cells was transfected with the IPF1 gene (also known as PDX1) before transdifferentiation. RESULTS: No insulin was detectable in cell preparations after 5 days of treatment with streptozotocin. In monolayer culture, 90% of the streptozotocin-treated pancreatic cells co-expressed cytokeratin-19 and vimentin at 2 weeks and 60% expressed nestin at 4 weeks. Cell cultures with a high proportion of nestin-expressing cells had greater plasticity for transdifferentiation into cells with phenotypic and functional markers of beta cells, this property being significantly enhanced by transfection with IPF1 gene and leading to 15+/-6.7% insulin-positive cells after transplantation vs. 0.01% of cells transplanted after streptozotocin treatment alone. These cells improved glucose control in all of 42 diabetic mice after transplantation, restoring normoglycaemia in 40%. CONCLUSIONS/INTERPRETATION: Human pancreatic cells are a potential source of new glucose-responsive insulin-producing cells that may be developed further for clinical use.

Adolescent↗

Long-term outcome of immunosuppression withdrawal after liver transplantation.

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.

Adolescent↗

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure.

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.

Adolescent↗

Anti-interleukin 2 receptor antibodies and mycophenolate mofetil for treatment of steroid-resistant rejection in adult liver transplantation.

BACKGROUND: Steroid-resistant rejection (SRR) results in significant morbidity and mortality from the adverse effects of rescue therapy and in graft loss from chronic rejection. In our knowledge, the efficacy and safety of anti-interleukin (IL) 2r antibodies (daclizumab and basiliximab) for the treatment of SRR in adult liver transplantation has not previously been evaluated. METHODS: Twenty-five patients received either daclizumab or basiliximab as rescue therapy for SRR. Outcome and biochemical parameters were recorded before and after treatment with an anti-IL-2r antibody. RESULTS: The median time from transplantation to SRR was 25 days. Secondary immunosuppression included mycophenolate mofetil in 18 patients. Twelve patients (48%) had complete resolution of SRR. Aspartate transaminase levels normalized at a median of 37 days (range, 1-168 days). In 13 patients (52%) progressive hepatic dysfunction developed. Four of these patients received another transplant, and 6 patients had chronic rejection. Three patients died with graft failure. Of 16 patients with acute cellular rejection, 12 (75%) had resolution, 2 had chronic rejection, 1 required a repeat transplantation, and 1 died with graft failure. In contrast, all 9 patients with established chronic rejection in their pretreatment biopsy continued to have significant graft dysfunction, with 4 having persistent chronic graft dysfunction, 3 requiring repeat transplantation, and 2 dying with graft failure. CONCLUSION: Twelve (48%) of 25 patients who received an anti-IL-2r antibody because of SRR were successfully treated. All successfully treated patients had ongoing acute cellular rejection at liver biopsy (75%), whereas patients with histologic evidence of chronic rejection responded poorly.

Adolescent↗

Peribiliary cysts can mimic Caroli's disease: a case report.

Peribiliary cysts, otherwise known as cystic dilatation of the peribiliary glands, are uncommon, and are usually discovered incidentally at autopsy, or in explants following liver transplantation. Preoperative diagnosis is often difficult owing to their asymptomatic nature and small size. Exclusion of a premalignant or malignant cystic condition is mandatory. We report a case of peribiliary cysts, initially thought to represent Caroli's disease, and briefly discuss the management of this condition.

Adult↗

Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: a preliminary experience.

BACKGROUND: The role of interleukin-2 receptor antibodies as rescue therapy in steroid-resistant rejection (SRR) has not been studied. We evaluated the safety and efficacy of an interleukin-2 receptor antibody, basiliximab (Simulect, Novartis, East Hanover, NJ), in treating SRR in pediatric liver transplant recipients. METHODS: This was a prospective study of seven pediatric liver transplant recipients with biopsy-proven SRR who would have otherwise received OKT3 or antithymocyte globulin. The primary immunosuppression consisted of cyclosporine (Neoral, Novartis), azathioprine, and prednisolone in four patients and tacrolimus and prednisolone in three patients who had undergone retransplantation for chronic rejection (n=2) and hyperacute rejection (n=1). Four patients had received two cycles of high-dose steroids, and three patients had received a single cycle; all had been converted to tacrolimus, followed by the addition of mycophenolate mofetil. RESULTS: The median time from transplant to SRR was 30 days (range, 8 days-23 months). Five children received two doses of basiliximab (10 mg, 3-7 days apart), and two children received a single dose. Aspartate aminotransferase levels normalized in three children 12, 21, and 30 days after basiliximab treatment. Aspartate aminotransferase levels decreased without normalizing in two children, but there was no further evidence of cellular rejection on repeat biopsies. All five children are rejection-free with a median follow-up of 22 months (range, 5-32 months). Biochemical abnormalities persisted in the remaining two children, and both developed chronic rejection. There were no immediate side effects associated with basiliximab. Two patients were treated empirically for possible cytomegalovirus infection 21 and 57 days after basiliximab treatment, with no evidence of cytomegalovirus disease. CONCLUSION: Five of seven pediatric liver transplant recipients with SRR experienced successful outcomes with basiliximab treatment without major side effects, indicating that it is a safe alternative to OKT3 and other antilymphocyte antibodies.

Antibodies, Monoclonal↗

Surgical anatomy of segmental liver transplantation.

BACKGROUND: The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. METHODS AND RESULTS: The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. CONCLUSION: A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

Adult↗

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Adolescent↗

Hemodynamic response to continuous infusion of dobutamine in Alagille's syndrome.

BACKGROUND: Alagille's syndrome is a rare condition that is characterized by paucity of interlobular bile ducts and peripheral pulmonary artery stenosis. Liver transplantation in the setting of peripheral pulmonary stenosis and right ventricular hypertension seems to be associated with a higher mortality, which raises the concern that these patients are unable to increase their cardiac output in the immediate posttransplantation period to meet the demands of reperfusion and early graft dysfunction and cope with further increases in pulmonary vascular resistance. METHOD: Cardiac catheterization was performed in 15 children with Alagille's syndrome and peripheral pulmonary artery stenosis to measure the cardiac output response to dobutamine infusion. The cardiac output was measured before and during each increment of infusion of dobutamine at 10 microg/kg/min and 20 microg/kg/min by using a thermodilution catheter placed in the pulmonary artery. RESULTS: There was a significant change in the baseline cardiac index (P<0.001) with an infusion of 20 microg/kg/min of dobutamine with an increase from 4.4(1.0) L/min/m2 to 6.4(1.5) L/min/m2. There was, however, a wide variation between individuals in the increase in cardiac index, ranging from 7.3-95%. There was no correlation between the baseline systolic right ventricular/aortic pressure ratios and the increase in cardiac index (r=0.1086). CONCLUSION: The increase in cardiac index, in response to dobutamine in patients with Alagille's syndrome, is independent of the more conventional measurement of the right ventricular pressure. This method of producing a hemodynamic response is closer to the response that results after liver transplantation, and thus, it may be a better way of predicting the outcome of liver transplantation in these patients.

Adolescent↗