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Biomedical subjects

Michael M Abecassis

Publications and source records attributed to Michael M Abecassis.

13 recordsLinked to original sources

Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation.

PURPOSE: To present the clinical data of 35 patients with T3 unresectable hepatocellular carcinoma (HCC) that were treated with (90)Y with the specific intent of downstaging to resection, radiofrequency ablation (RFA) candidate, United Network for Organ Sharing (UNOS) stage T2 or liver transplantation. MATERIALS AND METHODS: One hundred fifty patients with unresectable HCC were treated with (90)Y microspheres. Of these, 35 patients were UNOS stage T3 at the time of treatment. Patients were followed for clinical toxicities, alterations in model for end-stage-liver disease (MELD) score, tumor response, downstaging to RFA, resection, transplantation, and survival. RESULTS: Nineteen of 34 patients (56%) were successfully downstaged from T3 to T2 following treatment. 11 of 34 (32%) patients treated were downstaged to target lesions measuring 3.0 cm or less. Twenty-three of 35 (66%) were downstaged to either T2 status, lesion < 3.0 cm (RFA candidate), or resection. Seventeen of 34 (50%) had an objective tumor response by WHO criteria. Eight patients (23%) were successfully downstaged and underwent OLT following treatment. 1, 2, and 3-year survival was 84%, 54%, and 27%, respectively. Median survival by Kaplan-Meier analysis for the entire cohort was 800 days. CONCLUSION: These data suggest that intra-arterial (90)Y microspheres can be used as a bridge to transplantation, surgical resection, or RFA.

Aged↗

Proposed classification of complications after live donor nephrectomy.

OBJECTIVES: A standardized classification for the potential complications of living donor nephrectomy is an essential step in establishing a construct for monitoring and reporting the outcomes of this procedure. It is also helpful in informing potential donors about the inherent risks of the donor operation as part of the informed choice process. METHODS: We reviewed 600 laparoscopic live donor nephrectomies performed at our center. A modification of the Clavien classification system describing procedure-related complications was developed and used to grade the severity of all complications. RESULTS: We observed 43 complications (7.2%) in our series of 600 patients. Grade 1 defines all events that, if left untreated, would have a spontaneous resolution or needed a simple bedside procedure (39.5%). Grade 2 complications differ from grade 1 in that they are potentially life-threatening and usually require some form of intervention, but do not result in ongoing disability. We subdivided grade 2 complications (55.8% in our study) into 2a, 2b, and 2c. The latter describes complications requiring open conversion of laparoscopic donor nephrectomy for patient treatment. Grade 3 complications are events with residual or lasting disability (4.7% in our review). Grade 4 events are those resulting in renal failure or death because of any complication (none occurred in our series). CONCLUSIONS: A graded classification scheme for reporting the complications of donor nephrectomy may be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Humans↗

Radiotherapy for rejection of renal transplant allografts refractory to medical immunosuppression.

OBJECTIVE: To evaluate the outcome and prognostic factors of patients who underwent local graft irradiation for acute renal allograft rejection refractory to modern immunosuppressive medications. METHODS: From 1996 to 2005, 33 patients received local graft irradiation (LGI), with 3 patients receiving 2 courses of radiation. Graft rejection was diagnosed when a rise in creatinine prompted a renal biopsy that demonstrated acute allograft rejection. Upon failure of medical immunosuppresion to resolve rejection, patients were then referred by the organ transplant team for LGI. The median dose was 800 cGy (range, 600-800 cGy), and was given in 200 cGy fractions generally using AP/PA fields. A retrospective review was conducted to determine dialysis-free survival, defined as the date from initiation of radiation therapy to date of hemodialysis placement, and to analyze potential factors that may predict dialysis free survival. RESULTS: Median follow-up from date of radiation therapy to date of last follow-up was 25 months (range, 0.9-99.4 months). The median time between allograft transplantation and radiation therapy was 17.8 months. For the entire group of patients, 20.6% were alive with a functioning graft. The median dialysis-free survival for the entire group was 3.8 months. The median dialysis-free survival for those patients not on dialysis at time of irradiation versus those patients on dialysis was significantly different (5.6 versus 0 months, P = 0.02). CONCLUSION: In renal allograft transplant recipients who experienced acute rejection episodes refractory to modern chemical immunosuppression, LGI was well tolerated and remains a viable salvage treatment option.

Adolescent↗

Liver graft volume estimation in 100 living donors: measure twice, cut once.

Estimation of graft volume (GV) is critical in living donor liver transplantation. This study examines the accuracy of formula-derived GV estimates and compares them to both radiogically-derived estimates and actual measurements. We first compared formula-derived estimates of GV and compared them to actual volumes to provide estimates for both right lobe (RL) and left lateral segment (LLS) GV. We then applied these formulae to a validation cohort. Finally, we evaluated both formula-derived and radiologically-derived estimates by comparing them to actual GV measurements. There is a marginal concordance between formula-derived calculation and GV for RL donors, but the error ratio was lower than for radiologic estimates. In contrast, MRI measurements for LLS grafts demonstrated a lower error ratio than formula-derived estimation. Formula-derived estimates of GV should be routinely used in the initial screening of potential living donors as long as their limitations are appreciated.

Biometry↗

Liver transplantation with simultaneous removal of an intracardiac transjugular intrahepatic portosystemic shunt and a vena cava filter without the utilization of cardiopulmonary bypass.

Transjugular intrahepatic shunts (TIPSs) are widely used in the management of portal hypertension complications including variceal bleeding, refractory ascites, and hepatic hydrothorax. Vena cava filters (VCFs) are an important therapeutic modality in the prevention of pulmonary emboli in patients suffering deep venous thrombosis and clinical contraindications for anticoagulation. Stent and filter misplacement or migration may occur, complicating liver transplantation (LT) surgery. We describe the intraoperative management of a patient with cirrhosis, who had a TIPS extending into the right atrium (RA) and a retrohepatic VCF. Stent and filter removals were deferred until the time of LT. Both procedures were performed successfully by complete cava and portal reconstruction. In conclusion, careful assessment and surgical management of patients with stent and filters permits successful LT.

Adult↗

Use of yttrium-90 microspheres (TheraSphere) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: a case report.

Prior to therapy, model for end stage liver disease (MELD) scoring, diagnostic imaging and tumor staging were performed in a patient with T3 HCC. The patient received an orthotopic liver transplant (OLT) 42 days after treatment. The explant specimen showed complete necrosis of the target tumor. Follow-up of this patient has demonstrated no evidence of recurrence. There was no life threatening or fatal adverse experiences related to treatment. This case report documents the natural course, history and outcome of a patient treated with yttrium-90 for unresectable HCC. The patient was downstaged from T3 to T2 and was subsequently transplanted.

Adult↗

Outcomes of 385 adult-to-adult living donor liver transplant recipients: a report from the A2ALL Consortium.

OBJECTIVE: The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). SUMMARY BACKGROUND DATA: Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. METHODS: Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. RESULTS: Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. CONCLUSIONS: This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.

Adult↗

Comparative analysis of live liver donation risk using a comprehensive grading system for severity.

We investigated whether right lobe (RL) liver donation is associated with a higher incidence or severity of donor complications than left lobe (LL) liver and left lateral segment (LLS) liver donations. We studied 80 living donors: 35 RL liver donors and 45 LL/LLS liver donors. A modification of the Clavien classification was used to grade the severity of complications. RL and LL/LLS liver donations had equivalent blood loss, readmission and reoperation rates, use of blood products, and lengths of stay in the intensive care unit and hospital. RL liver donors underwent longer surgeries and experienced more postoperative pain than LL/LLS liver donors. The overall rate of complications was 33%. There was a higher rate of complications in RL liver donors (51%) than LL/LLS liver donors (20%). When graded by severity, there were more grade 2 complications in RL liver donors than in LL/LLS liver donors. Our report confirms that RL liver donation is associated with higher morbidity than LL/LLS liver donation. When the complications are systematically graded by severity, there is a significant difference in Clavien grade 2 complications in RL liver donors.

Adult↗

Laparoscopic donor nephrectomy 1997 to 2003: lessons learned with 500 cases at a single institution.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open nephrectomy that has several potential advantages. However, there have been few large series reports describing the complications of LDN and the details of their management. METHODS: We performed a retrospective review of 500 LDNs performed at our center between October 1997 and September 2003. We evaluated preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. A modification of the Clavien classification was developed and used to grade the severity of all complications. RESULTS: The overall rate of intraoperative complications was 2.8%. There were 9 open conversions (1.8%), of which 6 were in the first 100 cases. Six of the 9 open conversions were for management of complications; 3 were elective. Seven renovascular incidents (1.4%) all required open conversion except one. The overall rate of postoperative complications was 3.4%. Thirty of 500 patients in our LDN series experienced an intraoperative or procedure-related complication (6.0%). When graded by severity, 18 of 31 (58.1%) of all complications were grade 1, 11 of 31 (35.4%) grade 2, and 2 of 31 (6.5%) grade 3. Only 1 recipient experienced delayed graft function, and only 1 recipient had a urologic complication. CONCLUSIONS: Our series supports the safety and efficacy of LDN with very low intraoperative complication and conversion rates. Most of the intraoperative complications can be managed laparoscopically. Readmissions are extremely rare (1.5%). Aberrant vascular anatomy and obesity are not contraindications to LDN, but they require experience. With careful surgical technique, delayed graft function and urologic complications in recipients can be avoided. A graded classification scheme for reporting complications of donor nephrectomy might be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Adolescent↗

A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.

BACKGROUND: We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. METHODS: Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids. RESULTS: Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups. CONCLUSIONS: We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.

Adolescent↗

A model for reactivation of CMV from latency.

BACKGROUND: Reactivation of CMV from latency results in serious morbidity and mortality in immunocompromised transplant recipients. The mechanism by which CMV reactivates from latency has not been well understood. OBJECTIVE: In this review we discuss three models for reactivation from latency and present evidence in favor of the model that reactivation is a multi-step process which is initiated by the allogeneic response to the transplanted organ. Study design (J. Virol. 75 (2001) 4814). Mice latently infected with murine cytomegalovirus (MCMV) were used as donors for allogeneic or syngeneic kidney transplants into immunocompetent recipients. The contralateral donor kidneys were used as controls. Transplanted kidneys were removed at various times after transplant and analyzed for expression of viral genes associated with productive infection and for expression of inflammatory cytokines. Electrophoretic mobility shift assay was performed on nuclear extracts of control and transplanted kidneys to examine activation of AP-1 and NFkappaB. Latently infected mice were also injected with tumor necrosis factor (TNF) to examine the effect of TNF alone on induction of MCMV immediate-early (IE) gene expression. Transgenic major immediate early promoter-lacZ mice carrying a beta-galactosidase reporter gene under the control of the human cytomegalovirus (HCMV) IE promoter/enhancer were used as donors for allogeneic kidney transplants to study the effect of allogeneic transplantation on induction of HCMV IE gene expression. RESULTS: Allogeneic, but not syngeneic transplantation induces MCMV IE-1 expression and expression of inflammatory cytokines, including TNF. Allogeneic transplantation activates transcription factors, including NFkappaB and AP-1. TNF alone can induce MCMV IE-1 gene expression and activation of NFkappaB and AP-1 in some tissues. CONCLUSIONS: We propose that induction of IE-1 gene expression is the first step in reactivation of the virus in an immunocompromised transplant recipient, and that it occurs as a result of the allogeneic response, which induces expression of TNF and subsequent activation of NFkappaB, and ischemia/reperfusion injury, which induces activation of AP-1. We speculate that the natural stimulus for reactivation in an immunocompetent host is an inflammatory immune response to infection and that allogeneic transplantation mimics this process.

Animals↗

Technical and immunologic progress in simultaneous pancreas-kidney transplantation.

BACKGROUND: During the past few years the use of new immunosuppressants and refinements in surgical technique of simultaneous pancreas-kidney (SPK) transplantation have resulted in markedly improved outcomes. This is a retrospective study of 208 SPK transplants performed at Northwestern University, demonstrating the advances made at a single center that are reflective of the field at large. METHODS: An 8.5-year time span was split into 4 distinct eras marking sequential changes in immunosuppression and surgical technique that ensued. SPK transplant outcomes of patient and graft survival and rejection rates were compared. Also examined were end points related to the changing risk profile of the recipients, as well as quality of allograft function and rates of rehospitalizations. RESULTS: Recipients receiving tacrolimus/mycophenolate mofetil-based immunosuppression had patient, kidney, and pancreas survival rates significantly higher than those of earlier cohorts. The elimination of corticosteroids did not reduce survival rates or increase rejection risk. The use of pancreatic exocrine enteric drainage technique over bladder drainage reduced rehospitalizations. CONCLUSIONS: Advances in immunosuppression management combined with technical refinements have made SPK transplantation a safer and more effective treatment option for the diabetic, uremic patient.

Adolescent↗