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C Margarit

Publications and source records attributed to C Margarit.

At least 37 records · Page 2Linked to original sources

Outcome and hepatic hemodynamics in liver transplant patients with portal vein arterialization.

UNLABELLED: Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.

Adult↗

Analysis of risk factors following pediatric liver transplantation.

Several recipient, donor and operation factors as well as postoperative complications related to patient survival after liver transplantation (LT) in children were studied by univariate and multivariate analyses. In a 13-year period, 103 patients under 15 years of age underwent 120 LT; the mean age was 63 months and 36% were under 2 years of age. Indications for LT were cholestatic disease in 68 (56%), metabolic diseases in 18 (14%), fulminant hepatic failure in 8 (7.5%), cirrhosis in 7 (5.8%), and retransplants in 17 (14%). Whole liver was transplanted in 79% of cases and partial liver in 21%. Actuarial survival at 1, 5, and 10 years was 70%, 61%, and 57%, respectively. United Network of Organ Sharing (UNOS) I recipients (RR = 2.7), primary non-function (PNF) (RR = 13.9), and hepatic artery thrombosis (HAT) (RR = 3.8) were independent factors for lower patient survival in multivariate analysis. Thus, in our experience, postoperative mortality as a consequence of the patient's condition before transplantation, or complications such as PNF or HAT, are the major causes of decreased survival in pediatric LT.

Adolescent↗

Auxiliary heterotopic liver transplantation with portal vein arterialization for fulminant hepatic failure.

Auxiliary liver transplantation for patients with fulminant hepatic failure supports the patient's failing liver for a period of time until the native liver (NL) has recovered and immunosuppression can be withdrawn. Auxiliary heterotopic liver transplantation (AHLT) with portal vein arterialization (PVA) has several advantages over auxiliary orthotopic liver transplantation: NL resection is not required, and the hepatic hilum is left untouched; thus, the chances of liver regeneration are optimal. The successful application of emergency AHLT with PVA in a young patient who developed toxic fulminant hepatic failure caused by tuberculostatic drugs is described. Two and one-half months after the procedure, the NL had completely regenerated; the graft was removed, and immunosuppression was suspended.

Adult↗

Comparative study of sequential combinations of paclitaxel and methotrexate on a human bladder cancer cell line.

We investigated the cytotoxic effect of different sequential combinations of paclitaxel (Taxol, TX), an antimicrotuble agent, and methotrexate (MTX), a potent inhibitor of dihydrofolate reductase, on a human bladder cancer cell line (T24). The results obtained with a colony-forming assay 5 days after 24 hr of exposure to TX alone showed a strong decline in colony growth up to a concentration of 6 nM. There was a plateau phase at TX concentrations ranging from 6 to 10 nM. The IC50 values found with the different dosing sequences and 24-hr exposure to the drugs were 0.24 microM for MTX alone, 3.49 nM for TX alone, 3.84 nM for TX followed by MTX, 3.75 nM for TX and MTX simultaneously, and 2.10 nM for MTX followed by TX. The cytotoxic effect due to drug interactions in the different sequential combinations was evaluated by an algebraic method. All the combination sequences were found to be synergistic (combination index [CI] < 1) at low TX concentrations. An antagonistic effect (CI > 1) was obtained at higher TX concentrations. Our data demonstrate that the T24 cell line is sensitive to TX and that the cytotoxic effect is enhanced to different degrees depending on the treatment sequence when TX is combined with MTX. These findings could have implications in the design of appropriate administration schedules of these two drugs for the treatment of bladder cancer.

Antimetabolites, Antineoplastic↗

Outcome of hepatitis C virus-associated membranoproliferative glomerulonephritis after liver transplantation.

BACKGROUND: Hepatitis C virus was the most frequent cause of liver failure requiring liver transplantation in our series. Hepatitis C virus infection has been associated with glomerulonephritis and, more frequently, type I membranoproliferative glomerulonephritis. Renal disease in patients with liver failure is often clinically silent and difficult to diagnose; thus, biopsy is required to establish the diagnosis. Our aim was to study the evolution of six patients diagnosed with membranoproliferative glomerulonephritis some months before liver transplantation. METHODS: Liver transplantation alone was performed in four patients and combined liver-kidney transplantation in the remaining two, who were on hemodialysis for kidney failure. These patients were followed for a mean of 38.3+/-7.8 months. Evolution of proteinuria, renal function, hepatic function, and hepatitis C virus activity was studied. RESULTS: In the four patients who underwent liver transplantation alone, proteinuria became negative initially and renal function remained stable. Proteinuria reappeared and renal function was altered in two of these patients at 17 and 36 months of follow-up, respectively, coinciding with a recurrence of active chronic hepatitis. In the two patients who received a combined liver-kidney transplant, proteinuria became negative, and their renal grafts currently maintain normal renal function. CONCLUSIONS: Membranoproliferative glomerulonephritis does not constitute an absolute contraindication for liver transplantation alone; combined liver-kidney transplantations are reserved for patients with end-stage kidney failure. Proteinuria is reversed after liver transplantation, and recurrence seems to be associated with severe hepatitis C virus hepatic allograft disease relapse.

Adult↗

Analysis of the complications of the piggy-back technique in 1,112 liver transplants.

BACKGROUND: The "piggy-back" technique has gained acceptance in adult orthotopic liver transplantation during the last few years, especially in European countries. At the moment, however, there is controversy over advantages or specific complications (suprahepatic thrombosis or narrowing, etc.) related to this surgical technique. The aim of this study is to know of the immediate per-and postoperative morbidity and mortality rates in 1112 orthotopic liver transplantations performed with a vena cava preservation technique. METHODS: All liver transplant units in Spain were sent a questionnaire on retrohepatic vena cava preservation during orthotopic liver transplantation. The number of orthotopic liver transplantations that had been performed in the seven centers that answered the questionnaire, because the beginning of the program, was 1674, with the vena cava preservation technique used in 1112. RESULTS: Twenty-eight patients (2.5%) had intraoperative complications related to the vena cava preservation technique, which were treated during the operation. Eleven patients (1%) had early postoperative complications (first week), the most frequent (nine cases) being an acute Budd-Chiari syndrome in the first 48 hr. Three patients developed symptoms of massive ascites between 2 and 3 months (late postoperative complications), with patency of the retrohepatic cava verified by cavography. A hemodynamic study revealed a hyperpressure at the suprahepatic veins. This chronic Budd-Chiari syndrome was controlled in all patients with diuretics. Only six patients (0.5%) died as a result of complications related to the "piggy-back" technique. These complications were more frequent when venous reconstruction was done using two suprahepatic veins than when the three veins were used (P<0.001). CONCLUSIONS: The vena cava preservation technique can be used routinely in orthotopic liver transplantation because it is safe and efficient and involves few surgical complications especially if for venous reconstruction we use the patch obtained by joining the three suprahepatic veins.

Adult↗

Liver transplantation in patients with splenorenal shunts: intraoperative flow measurements to indicate shunt occlusion.

Two patients with previous distal splenorenal shunts (DSRSs) performed 6 years earlier underwent liver transplantation (LT). A preoperative selective mesenteric artery angiogram showed collateral veins draining mesenteric venous flow into the shunt. Intraoperative flow measurements were performed to assess the steal of portal venous flow by the shunt and determine the need for shunt occlusion. Portal vein, hepatic artery, and shunt flows were measured by ultrasound transit-time flow probes in the native liver and after graft implantation with and without temporary shunt occlusion. Hemodynamic studies showed that long-standing DSRSs are high-flow shunts that steal portal flow. After graft implantation, DSRS flows remained high. Occlusion of the shunts produced an increase in portal vein flow at an amount similar to those of splenorenal shunt. Thus, the flow measurements showed persistent steal by the shunts after graft implantation and, therefore, the DSRSs were occluded but splenectomy was not performed. We conclude that the decision to occlude a DSRS should be based on the demonstration of steal of portal flow by the shunt and reversibility once the shunt is occluded. Splenectomy is not required when the DSRS is occluded.

Adult↗

Serum cholesterol changes in long-term survivors of liver transplantation: a comparison between cyclosporine and tacrolimus therapy.

The aim of this study was to compare the long-term effect of tacrolimus and cyclosporine therapies on serum cholesterol levels in liver transplant recipients. We retrospectively studied 127 consecutive adult liver transplant recipients who survived for at least 1 year after transplantation. Basal immunosuppression consisted of cyclosporine plus prednisone in 100 patients and tacrolimus plus prednisone in 27 patients. Hypercholesterolemia was defined as a fasting serum cholesterol level greater than 220 mg/dL. Mean follow-up was 39 months. No statistical significance was found between cyclosporine- and tacrolimus-treated patients regarding age, sex, diagnosis, and previous cholesterol levels; both groups were similar. Significantly more tacrolimus-treated patients were steroid free in the first and second year of follow-up (tacrolimus, 37% and 63%; cyclosporine, 13% and 32%, respectively; P <.01). In the third year of follow-up, this difference was not significant (77% v 56%). The overall incidence of hypercholesterolemia was 34.6% (44 patients). At the end of the study, hypercholesterolemia was found in 24 of 51 and 14 of 70 patients with and without steroids, respectively (P <.002). Also, mean cholesterol levels were 224 +/- 70 and 191 +/- 48 mg/dL before and after steroid withdrawal, respectively, P <.001. Hypercholesterolemia was found in 43.7% of the patients during cyclosporine plus prednisone therapy compared with 46.1% of the patients during tacrolimus plus prednisone therapy (P <.9). Greater mean cholesterol levels were found in the cyclosporine group, particularly in the second and third years of follow-up (P <.01). Hypercholesterolemia was found in 22% of the patients during cyclosporine monotherapy compared with 15% during tacrolimus monotherapy (P <.5). No differences were found in mean cholesterol levels during follow-up when both monotherapy groups were compared. In conclusion, a lower incidence of hypercholesterolemia was achieved in tacrolimus-treated patients, mainly when steroids were still part of the immunosuppressive treatment.

Cholesterol↗

Cross-clamping of the three hepatic veins in the piggyback technique is a safe and well tolerated procedure.

A common stump of the three hepatic veins has always been used to fashion the upper vena cava anastomosis in 205 liver transplantations with the piggyback (PGB) technique performed in our Unit, to avoid outflow problems. The aim was to study the repercussion of lateral inferior vena cava (IVC) clamping on IVC flow and pressure as well as on systemic hemodynamics. We have studied 42 orthotopic liver transplantations performed with the PGB technique. Intraoperative IVC blood flow measurements by transit time ultrasonic volume flowmetry, IVC pressure, and systemic hemodynamics were taken before and after lateral IVC clamping. Graft outflow complications, stenosis or kinking of the upper vena cava anastomosis have not been found in any of the 205 PGB procedures. A significant decrease of IVC flow (23%) and cardiac output (12%) occurred after IVC clamping, whereas mean arterial and central venous pressures were not altered significantly, probably due to an increase (25%) of systemic vascular resistance. Only in one case was an almost total clamping of IVC needed. Venovenous bypass was not needed in any case. Renal perfusion pressure was adequate in all cases. We conclude that the use of a common stump of the three hepatic veins for upper vena cava anastomosis in the PGB technique is safe because any outflow problem of the graft is avoided and, at the same time, is well tolerated hemodynamically because most of the IVC flow is preserved.

Constriction↗

Biliary complications secondary to late hepatic artery thrombosis in adult liver transplant patients.

Biliary complications (BC) are the usual presentation of late hepatic artery thrombosis (HAT) of the liver graft. Our aim was to study the clinical features and outcome of BC secondary to HAT compared to BC which occurred in liver transplant (LT) patients with patent vessels. We present a retrospective study of 224 LTs performed in 204 patients between 1988 and 1996. The mean recipient x s age was 51 years. A choledochocholedochostomy without T-tube was used as biliary reconstruction in most cases (67%); in 12%, a choledochojejunostomy was performed. An iliac conduit was necessary in 15% of cases and back-table arterial reconstruction was performed in 10% of cases of anatomic variants in graft arteries. Different donor, recipient and intraoperative variables, as well as treatment and outcome. were studied in the two groups of patients presenting BC with or without HAT. BC occurred in 38 cases (17%) whereas HAT was diagnosed in 11 cases (4.9%). Therefore, 23% of BC encountered after LT were secondary to HAT. Nine cases of late HAT manifested as BC, septicaemia (88%) and hepatic bilomas (8 cases). Percutaneous or surgical drainage of hepatic bilomas was performed in all cases, followed by retransplantation in six cases (66%). BC secondary to HAT appeared later than the rest of BC. Donor age was the only significant predisposing factor found in our study. Graft survival is significantly reduced as most patients needed retransplantation. In conclusion, BC secondary to HAT presented later in livers from older donors in the form of biliary sepsis and hepatic biloma. Retransplantation was ultimately required in most cases and graft survival was significantly diminished.

Bile Duct Diseases↗

Efficacy and safety of oral low-dose tacrolimus treatment in liver transplantation.

Eighty-four adult patients were recruited from four centres in Spain to evaluate the efficacy and safety of low-dose (0.1 mg/kg per day) oral tacrolimus plus corticosteroid immunosuppression in liver transplantation. The median daily dose of tacrolimus was increased during the first 3 weeks of therapy from an initial dose of 0.1 mg/kg per day to a maximum of 0.145 mg/kg per day and was subsequently decreased gradually to a minimum of 0.076 mg/kg per day at 1 year. At 7 days posttransplantation, 87.7% of patients had trough whole blood levels of tacrolimus within the therapeutic range (5-20 ng/ml), and the median levels remained fairly constant during the rest of the year (10.1-11.8 ng/ml). None of the patients required intravenous administration of tacrolimus. At 1 year, Kaplan-Meier estimates showed that 73.8% of the patients were receiving tacrolimus monotherapy without the need for corticosteroids. One-year patient and graft survival were 75.9% and 72.3%, respectively. The incidence of acute rejection was 51.2%; 9.5% of cases resolved spontaneously without antirejection therapy and 10.7% were corticosteroid resistant. Only 1 patient (1.2%) developed chronic rejection. The most important adverse events were hypertension (45.2%), tremor (44.0%), diabetes mellitus (33.3%), diarrhoea (31%) and nephrotoxicity (29.8%). Severe neurotoxicity-like convulsions (4.8%), dysarthria (9.5%), delirium (1.2%), coma (1.2%) and the need for haemodialysis (3 patients) were uncommon. In conclusion, low-dose oral tacrolimus immunosuppression is associated with low toxicity without compromising efficacy.

Administration, Oral↗

Early use of tacrolimus as rescue therapy for refractory liver allograft rejection.

The aim of this study was to compare two different periods of tacrolimus rescue therapy for intractable rejection. From January 1992 to May 1996, 140 liver transplants (LTx) were performed in our hospital under cyclosporine A-based immunosuppression. Twenty-four (17.1%) patients were switched to tacrolimus because of chronic rejection, steroid-resistant rejection or cholestasic hepatitis C recurrence. Mean follow-up was 21 months (range 12-56 months). In the first period (January 1992-March 1994), conversion to tacrolimus was indicated later, after unsuccessful repeated rejection therapy. In the second period (April 1994-May 1996), conversion to tacrolimus was indicated early, immediately after unsuccessful rejection therapy or directly at the moment of diagnosis with no further treatment. Eleven of 54 LTx were treated with tacrolimus in period 1 (20.3%), and 13 of 86 LTx in period 2 (15.1%). Only 4 of 11 (36.6%) grafts converted were rescued during the first period, while 11 of 13 (84.6%) were rescued in the second (P < 0.03). Patients in the first period received more courses of steroids than those of the second (1.7 +/- 0.7 vs 0.9 +/- 0.7, P < 0.02). Furthermore, six patients received one or two courses of OKT3 in period 1 while only one received one course in period 2 (P < 0.03). Preconversion mean bilirubin levels of patients in the first period were higher than those in the second (15.9 +/- 7.3 mg/dl vs 9.7 +/- 5.8 mg/dl, P < 0.05). Preconversion mean bilirubin levels of 6.8 +/- 5.4 mg/dl and 21.8 +/- 18.5 mg/dl were observed in patients with successful and unsuccessful tacrolimus rescue therapy, respectively, independent of the treatment period (P < 0.05). Mortality rates were higher in the first period than in the second (82% versus 23%; P < 0.02). In conclusion, conversion to tacrolimus as rescue therapy for intractable rejection or cholestasic hepatitis C recurrence is an efficacious alternative, particularly when tacrolimus is initiated early.

Graft Rejection↗