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Amadeo Marcos

Publications and source records attributed to Amadeo Marcos.

At least 37 records · Page 2Linked to original sources
PubMed2005

Immunosuppression for liver transplantation in HCV-infected patients: mechanism-based principles.

We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 +/- 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology.

Analysis of Variance↗
PubMed2005

Ex situ resection techniques and liver autotransplantation: last resource for otherwise unresectable malignancy.

Ex vivo liver resection and hepatic autotransplantation allow treatment of otherwise unresectable hepatobiliary malignancy and expand the role of liver surgery. Few series are reported in the English literature, and they are mainly case reports focused on the technical aspects of the procedure more than on the long-term results. Postoperative mortality rate is still high, as well as early tumor recurrence; recently, improvement in outcomes in selected cases is being reported. The aim of this study is to describe our experience with two cases where we applied the combination of ex situ resection with hepatic autotransplantation for intended cure of two otherwise untreatable malignancies. These two cases are the paradigm of the possibility of performing extreme salvage procedures after the failure of more conventional treatments, allowing improvement in survival and quality of life in a controversial clinical scenario. This should be performed only AT referral centers for liver resection surgery and liver transplantation in light of the technical refinements reached in the era of living-related liver transplantation.

Adult↗
PubMed2005

Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath.

BACKGROUND: Multiple drug immunosuppression has allowed the near elimination of rejection, but without commensurate improvements in longterm graft survival and at the cost of quality of life. We have suggested that transplantation outcomes can be improved by modifying the timing and dosage of immunosuppression to facilitate natural mechanisms of alloengraftment and acquired tolerance. STUDY DESIGN: Two therapeutic principles were applied for kidney transplantation: pretransplant recipient conditioning with antilymphoid antibody preparations (Thymoglobulin [Sangstat] or Campath [ILEX Pharmaceuticals]), and minimal posttransplant immunosuppression with tacrolimus monotherapy including "spaced weaning" of maintenance doses when possible. The results in Thymoglobulin- (n = 101) and Campath-pretreated renal transplantation recipients (n = 90) were compared with those in 152 conventionally immunosuppressed recipients in the immediately preceding era. RESULTS: Spaced weaning was attempted in more than 90% of the kidney transplant recipients after pretreatment with both lymphoid-depleting agents, and is currently in effect in two-thirds of the survivors. Although there was a much higher rate of acute rejection in the Thymoglobulin-pretreated recipients than in either the Campath-pretreated or historic control recipients, patient and graft survival in both lymphoid depletion groups is at least equivalent to that of historic control patients. In the Thymoglobulin-conditioned patients for whom followups are now 24 to 40 months, chronic allograft nephropathy (CAN) progressed at the same rate as in historic control patients. Selected patients on weaning developed donor-specific nonreactivity. CONCLUSIONS: After lymphoid depletion, kidney transplantation can be readily accomplished under minimal immunosuppression with less dependence on late maintenance immunosuppression and a better quality of life. Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement.

Analysis of Variance↗
PubMed2005

Budd-Chiari syndrome: in evolution.

Budd-Chiari syndrome (BCS) is a rare but potentially life-threatening disorder caused by hepatic venous obstruction, distinct from cardiac causes of hepatic congestion or sinusoidal obstruction syndrome (formerly known as veno-occlusive disease). BCS may be classified as primary or secondary, depending on the underlying process. Most cases of primary BCS are due to an underlying hypercoagulable disorder. A high index of suspicion is required to make the diagnosis. In most case series, chronic, indolent cases of BCS are more common than acute presentations. Doppler ultrasound, magnetic resonance imaging (MRI), and direct venography are useful in confirming the diagnosis. Systemic anticoagulation should be started expeditiously, as long as there are no contraindications. The use of systemic thrombolysis remains controversial. However, thrombolysis may prove effective when it is administered locally following hepatic venoplasty with or without stenting. Guidelines for the management of more complex cases and of patients who fail medical management are currently in evolution. Budd-Chiari syndrome (BCS) is potentially life-threatening, depending on the extent and rapidity of hepatic venous obstruction. A high index of suspicion is required to clinch the diagnosis, since BCS may be quite indolent or even asymptomatic. Doppler ultrasound or magnetic resonance imaging (MRI) is usually definitive. Systemic anticoagulation should be offered to all patients, unless contraindicated. The role of thrombolysis in BCS remains controversial, and thus it should be reserved for cases undergoing hepatic decompression via percutaneous angioplasty. Guidelines for the management of cases who fail standard medical management are currently in evolution.

Budd-Chiari Syndrome↗
PubMed2005

Adult living donor versus deceased donor liver transplantation: a 6-year single center experience.

No long-term (>3 years) prospective comparison of adult-to-adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported. This is a prospective, IRB approved, 6-year comparison of A2ALLTx to ADDLTx. Data include: age, gender, ethnicity, primary liver disease, waiting time, pretransplant CTP/MELD score, cold ischemia time (CIT), perioperative mortality, acute and chronic rejection, graft and patient survival, charges and post-transplant complications. In 6 years, 202 ADDLTx (74.5%) and 69 A2ALLTx (25.5%) were performed at VCUHS. Hepatitis C virus (HCV) was the most common reason for transplantation in both groups (48.1% vs. 42%). Data regarding overall patient and graft survival, monetary charges and retransplantation rates were similar. Comparison of patient/graft survivals, retransplantation rates in patients with and without HCV were not statistically different. A2ALLTx patients had less acute rejection (11.5% vs. 23.9%) and more biliary complications (26.1% vs. 11.4%). Overall, A2ALLTx is as durable a liver replacement technique as the ADDLTx. Patients with A2ALLTx were younger, had lower MELD scores, less acute rejection and similar histological HCV recurrence. Biliary complications were more common in A2ALLTx but were not associated with increased graft loss compared to ADDLTx.

Adult↗
PubMed2005

Significance of the effective remnant liver volume in major hepatectomies.

The aim of this study is to identify the minimum safe amount of effective remnant liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight consecutive major hepatectomies (resection of > or = 3 Couinaud segments) performed between July 1999 and March 2004 in which a frozen section liver biopsy was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or cholestasis. The total liver volume (TLV) was calculated using the Vauthey formula, and the postsurgical liver volume (PSLV) was derived by subtracting the estimated volume of liver resected from the TLV. The PSLV minus the percentage of macrovesicular steatosis as nonfunctional liver was defined as the effective remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30% and 60%, and >60%) were correlated with liver resection type, mortality, complications, intraoperative blood transfusions, operative time, length of hospitalization, and mean value of liver function tests in the first 5 postoperative days. Comparisons between clinical parameters were performed by Pearson chi2 test. There was significant correlation between ERLV/TLV ratios and surgical resection type (P < 0.001), early postoperative mortality (P < 0.01), and complications (P < 0.003). The ERLV/TLV ratio may be a useful predictor of surgical outcome after major hepatectomy.

Cohort Studies↗
PubMed2004

Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience.

BACKGROUND: End-stage renal disease (ESRD) is an increasing problem in patients infected with the human immunodeficiency virus (HIV). The use of highly active antiretroviral therapy (HAART) has decreased the morbidity associated with HIV and has prompted renewed interest in renal transplantation. METHODS: We performed four cases of deceased donor renal transplantation in HIV+ recipients and three cases where laparoscopic live donor nephrectomy (LLDN) was utilized to obtain the kidney for transplantation into living-related HIV+ recipients. In the four deceased donor cases, conventional tacrolimus-based immunosuppression, without antibody induction was used. In the three living-related cases, the immunosuppressive regimen was based on two principles: recipient pretreatment and minimal posttransplant immunosuppression. Alemtuzumab 30 mg (Campath 1-H) was used for preconditioning followed by low-dose tacrolimus monotherapy. RESULTS: Of the four deceased donor cases, one patient continues to have good graft function, and another is not yet on dialysis but has significant graft dysfunction. Rejection was observed in three patients (75%). Infectious complications occurred in one patient (25%), all non-acquired immunodeficiency syndrome (AIDs) defining. In the three living-related cases, all had good graft function, and none have experienced acute rejection. HIV viral loads remain undetectable. CD4 counts are slowly recovering. No infectious or surgical complications occurred. There were no deaths in either group. CONCLUSIONS: These data suggest that living-related donor renal transplantation with steroid-free tacrolimus monotherapy in a "tolerogenic" regimen can be efficacious. However, long-term follow-up is needed to confirm this observation.

Adult↗
PubMed2004

Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation: with particular reference to hepatitis C virus.

We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened ("spaced weaning") after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV recipients but not HCV recipients.

Adult↗
PubMed2004

De novo malignancies after intestinal and multivisceral transplantation.

BACKGROUND: Maintenance immunosuppression required after organ transplantation creates a permissive environment in which cancer cells can proliferate because of lack of natural immunologic surveillance. With more than a decade of clinical experience, this report is the first to address the risk of de novo cancer after intestinal transplantation. METHODS: A total of 168 consecutive intestinal transplant recipients (86 children and 82 adults) were studied, of whom 52% were male and 91% were white. Surveillance, Epidemiology, and End Results data was used to count expected rates of de novo cancers in the general population matched for age, sex, and length of follow-up. RESULTS: With a mean follow-up of 47+/-41 months, 7 (4.2%) patients developed nonlymphoid de novo cancer, with a cumulative risk of 3% at 5 years and 28% at 10 years. Of these malignancies, one was donor-driven adenocarcinoma. With 0.58 being the expected rate of malignancy for the general population, the risk among intestinal recipients was 8.7 times higher (P =0.01). Such morbidity was significantly higher (50 times) among younger patients (<25 years), with a slight male preponderance. Induction immunosuppression was associated with early onset of de novo cancer. Patient survival after diagnosis of de novo cancer was 72% at 1 year, 57% at 2 years, and 29% at 5 years. CONCLUSION: With conventional immunosuppression, intestinal recipients are at a significantly higher risk of developing de novo cancer when compared with the general population. Thus, a novel tolerogenic immunosuppressive strategy has been recently implemented to reduce the lifelong need for immunosuppression.

Adenocarcinoma↗
PubMed2004

Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience.

BACKGROUND: Chronic renal failure leads to amenorrhea, and successful pregnancy is rare. The aim of the present report is to examine the outcome of pregnancies under tacrolimus after kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHOD: All pregnancies under tacrolimus after KTx or SPKTx from 1993 to April 2002 were retrospectively examined. Renal function and the mother's survival were followed until December 2002. RESULTS: Thirteen mothers after KTx delivered 19 babies, and 2 mothers after SPKTx delivered 3 babies. All mothers survived the pregnancy and retained allograft function. One mother had a stillborn baby from an unrecognized amniotic fluid leak and a small ischemic placenta. The mean gestational period was 34.4 +/- 5.1 weeks. Mean birth weight was 2373 +/- 1001 g. Birth-weight percentile to gestational period was 40 +/- 28. None of the mothers experienced rejection during the pregnancy. Three pregnancies in mothers with KTx experienced toxemia of pregnancy, and one mother with SPKTx developed pre-eclampsia during both pregnancies. Five mothers (6 deliveries, 27.3%) required caesarian section. During the follow-up period, one mother died from a cerebrovascular accident. Another five mothers returned to dialysis 55.6 +/- 32.4 months after the last delivery and 99.4+28.5 months after the last KTx. Both SPKTx mothers have maintained normal renal and pancreatic allograft function 42 and 62 months postdelivery. CONCLUSION: All mothers survived the pregnancy. One baby was stillborn. Forty-one percent of babies were either preterm or premature, and 27% of babies were delivered by caesarean section. Toxemia of pregnancy or pre-eclampsia was observed in 23% of pregnancies postKTx and SPKTx. None of the mothers experienced rejection during their pregnancy.

Birth Weight↗
PubMed2004

Lessons of organ-induced tolerance learned from historical clinical experience.

Although the reductionist approach has served science well for 400 years, the accumulation of details can obscure the truth if the original premise is incorrect. One such premise has been that successful organ transplantation and bone marrow engraftment are fundamentally different outcomes involving separate and distinct mechanisms. Some historical clinical observations pointed to a different conclusion almost from the beginning and included clues about how to induce tolerance with the aid of immunosuppression.

Bone Marrow Transplantation↗
PubMed2004

Porcine partial liver transplantation: a novel model of the "small-for-size" liver graft.

Increasing shortage of cadaveric grafts demands the utilization of living donor and split liver grafts. The purpose of this study was to 1) define the "small-for-size" graft in a pig liver transplant model 2) evaluate pathological changes associated with small-for-size liver transplantation. Pigs were divided into four groups based on the volume of transplanted liver: (a) control group (n=4), 100% liver volume (LV) (b) group I (n=8), 60% LV (c) group II (n=8), 30% LV (d) group III (n=15), 20% LV. Tacrolimus and methyl prednisone were administered as immunosuppression. Animals were followed for 5 days with daily serum biochemistry, liver biopsies on day 3 and 5 for light microscopy, and tissue levels of thymidine kinase (TK) and ornithine decarboxylase (ODC). Liver grafts were weighed pretransplant and at sacrifice. All the recipients of 100%, 60%, and 30% grafts survived. Transplantation of 20% grafts (group III) resulted in a 47% mortality rate. Group III animals showed significantly prolonged prothrombin times (p<0.05), elevated bilirubin levels (p<0.05), and ascites. The rate of regeneration, as indicated by TK activity and graft weight was inversely proportional to the size of the transplanted graft. The severity of the microvascular injury was inversely proportional to graft size and appeared to be the survival-limiting injury. Frank rupture of the sinusoidal lining, parenchymal hemorrhage, and portal vein injury were prominent in group III animals 1 hour following reperfusion. This study established a reproducible large animal model of partial liver grafting; it defined the small-for-size syndrome in this model and described the associated microvascular injury.

Animals↗
PubMed2004

Diagnosis and treatment of intracardiac thrombosis during orthotopic liver transplantation.

Intracardiac thrombus formation during orthotopic liver transplantation can be a catastrophic event leading to death. Most often this devastating complication occurs after reperfusion and may be related to massive blood transfusion, marginal liver grafts, tendencies towards hypercoagulability, or the potential role of antifibrinolytics. We report a case of an intracardiac thrombus occurring during the hepatectomy stage (stage I) of orthotopic liver transplantation. Transesophageal echocardiography was used to quickly diagnose the thrombus, allowing rapid pharmacological intervention and later guide surgical evacuation of the intracardiac thrombus via the inferior vena cava.

Acute Kidney Injury↗
PubMed2004

Pancreatic transplantation at the University of Pittsburgh.

Campath-1H preconditioning with tacrolimus monotherapy is an effective immunosuppressive regimen for pancreas transplantation, with acceptable patient and graft survival rates early after transplantation. Rejection rates are low under this protocol if the tacrolimus level is kept consistently >10 ng/ml. This immunosuppressive protocol, combined with recent technical refinements, has resulted in lower rates of thrombosis and overall complications. Pancreatic transplantation en-bloc with visceral grafts has the following unique features: Diabetes is a rare indication, and HLA matching is not required. The gland is immunologically protected by the simultaneously transplanted visceral organs. Disease gravity, surgical complexity and gut alloimmunity influence the overall pancreatic allograft survival. The current UNOS listing criteria and data registry should be modified for obvious logistic and scientific reasons.

Adolescent↗