Michael Abecassis - Academia.edu (original) (raw)

Papers by Michael Abecassis

Research paper thumbnail of Risk Aversion In Liver Transplantation The Dark Side Of Quality Improvement And Regulatory Oversight

Journal of Surgical Research, 2011

Research paper thumbnail of Urine Metabolite Profiles Predictive of Human Kidney Allograft Status

Journal of the American Society of Nephrology : JASN, Jan 5, 2015

Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may... more Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε m...

Research paper thumbnail of Cellular localization of latent murine cytomegalovirus

Journal of virology, 1998

Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for ha... more Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and e...

Research paper thumbnail of Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

Liver Transplantation, 2010

Translational studies in liver transplantation often require an endpoint of graft function or dys... more Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin !10mg/dL on day 7, international normalized ratio !1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk ¼ 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk ¼ 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function. Liver Transpl 16:943-949,

Research paper thumbnail of Laparoscopic donor nephrectomy 1997 to 2003: Lessons learned with 500 cases at a single institution

Surgery, 2004

Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open neph... more 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. 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. 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. 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.

Research paper thumbnail of Outcomes of 385 Adult-to-Adult Living Donor Liver Transplant Recipients

Transactions of the ... Meeting of the American Surgical Association, 2005

The objective of this study was to characterize the patient population with respect to patient se... more 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 peri-operative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). Summary Background Data: Previous reports have been centerspecific 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. (Ann Surg 2005;242: 314 -325)

Research paper thumbnail of Proposed classification of complications after live donor nephrectomy

Urology, 2006

A standardized classification for the potential complications of living donor nephrectomy is an e... more 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. 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. 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). 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.

Research paper thumbnail of Laparoscopic donor nephrectomy: analysis of donor and recipient outcomes

Transplantation Proceedings, 2001

L APAROSCOPIC donor nephrectomy (LDN) holds the promise of increasing living donation by providin... more L APAROSCOPIC donor nephrectomy (LDN) holds the promise of increasing living donation by providing a less invasive alternative to open donor nephrectomy (ODN). Concerns have been raised regarding the safety of LDN, as well as for the short and long-term function of LDN kidneys. A higher incidence of recipient urologic complications, secondary to intraoperative ureteral trauma, has been reported with LDN organs. 1

Research paper thumbnail of COMPARATIVE ANALYSIS OF LIVE LIVER DONATION RISK USING A COMPREHENSIVE GRADING SYSTEM FOR SEVERITY

Transplantation, 2004

We investigated whether right lobe (RL) liver donation is associated with a higher incidence or s... more 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.

Research paper thumbnail of A Prospective Study of Rapid Corticosteroid Elimination in Simultaneous Pancreas-Kidney Transplantation

Transplantation, 2002

We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney t... more We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. 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. 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. 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.

Research paper thumbnail of The Role of PCR in the Diagnosis and Management of CMV in Solid Organ Recipients

Transplantation, 1997

... 1. Abecassis, Michael M.; Koffron, Alan J.; Kaplan, Bruce; Buckingham, Marguerite; Muldoon, J... more ... 1. Abecassis, Michael M.; Koffron, Alan J.; Kaplan, Bruce; Buckingham, Marguerite; Muldoon, Joseph P.; Cribbins, Allan J.; Kaufman, Dixon B.; Fryer, Jonathan P.; Stuart, Joan; Stuart, Frank P. Article Outline. Collapse Box Author Information. ...

Research paper thumbnail of Living Donor Liver Transplant for Malignancy

Transplantation, 2005

Adult-to-adult living donor liver transplantation (ALDLT) is being increasingly utilized to treat... more 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.

Research paper thumbnail of Liver Graft Volume Estimation in 100 Living Donors: Measure Twice, Cut Once

Transplantation, 2005

Estimation of graft volume (GV) is critical in living donor liver transplantation. This study exa... more 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.

Research paper thumbnail of Technical and immunologic progress in simultaneous pancreas-kidney transplantation

Surgery, 2002

During the past few years the use of new immunosuppressants and refinements in surgical technique... more 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.

Research paper thumbnail of Failed primary management of iatrogenic biliary injury: Incidence and significance of concomitant hepatic arterial disruption

Surgery, 2001

Vasculobiliary injury (VBI) is a well-recognized complication of laparoscopic cholecystectomy (LC... more Vasculobiliary injury (VBI) is a well-recognized complication of laparoscopic cholecystectomy (LC). In patients with failed primary management of bile duct injury (BDI), an assessment of the hepatic arterial system may be important to determine the presence of VBI. This study was conducted to determine the incidence of VBI in patients with failed primary management of LC-related BDI and to establish a potential correlation between the level of BDI and the incidence of VBI. A retrospective review was conducted on 18 patients referred for failed primary management of LC-related BDI who underwent prospective arteriography as part of the preoperative work-up. Of the 18 patients who sustained BDI, Bismuth level 4 lesions were found in 7 patients (39%), level 3 in 8 patients (44%), and level 2 in 3 patients (17%). VBI was identified on arteriography in 11 patients (61%). VBI was present in 71% of patients with level 4 lesions, 63% of patients with level 3 lesions, and 33% of patients with level 2 lesions. The time interval from primary management to its failure was longer in VBI than in BDI alone. We have observed a high incidence of VBI in patients with failed primary management of LC-related BDI. Arterial disruption may affect the outcome of primary management of BDI.

Research paper thumbnail of Intrahepatic biliary cystadenoma: Role of cyst fluid analysis and surgical management in the laparoscopic era

Surgery, 2004

Recent interest in cyst fluid analysis (CFA) for carbohydrate antigen 19-9 (CA 19-9) and carcinoe... more 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. 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 All patients with IBC who underwent CFA had elevated CA 19-9 (range, 2247-1,757,510; N &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;33 U/mL) and mildly elevated CEA (range, 3.3-212,; N &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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. 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.

Research paper thumbnail of The impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story

Surgery, 2009

increasingly being used to address organ shortages. Despite encouraging reports, standard surviva... more increasingly being used to address organ shortages. Despite encouraging reports, standard survival metrics have overestimated the effectiveness of DCD livers. We examined the mode, kinetics and predictors of organ failure and resource utilization to more fully characterize outcomes after DCD LT.

Research paper thumbnail of Use of yttrium-90 microspheres (TheraSphere®) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: A case report

Liver Transplantation, 2005

Prior to therapy, model for end stage liver disease (MELD) scoring, diagnostic imaging and tumor ... more 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.

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

Liver Transplantation, 2005

Transjugular intrahepatic shunts (TIPSs) are widely used in the management of portal hypertension... more 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.

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

Liver Transplantation, 2003

In living liver donation, a fatty liver poses risks for both recipient and donor. Currently, live... more 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 gradientecho 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.

Research paper thumbnail of Risk Aversion In Liver Transplantation The Dark Side Of Quality Improvement And Regulatory Oversight

Journal of Surgical Research, 2011

Research paper thumbnail of Urine Metabolite Profiles Predictive of Human Kidney Allograft Status

Journal of the American Society of Nephrology : JASN, Jan 5, 2015

Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may... more Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε m...

Research paper thumbnail of Cellular localization of latent murine cytomegalovirus

Journal of virology, 1998

Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for ha... more Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and e...

Research paper thumbnail of Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

Liver Transplantation, 2010

Translational studies in liver transplantation often require an endpoint of graft function or dys... more Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin !10mg/dL on day 7, international normalized ratio !1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk ¼ 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk ¼ 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function. Liver Transpl 16:943-949,

Research paper thumbnail of Laparoscopic donor nephrectomy 1997 to 2003: Lessons learned with 500 cases at a single institution

Surgery, 2004

Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open neph... more 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. 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. 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. 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.

Research paper thumbnail of Outcomes of 385 Adult-to-Adult Living Donor Liver Transplant Recipients

Transactions of the ... Meeting of the American Surgical Association, 2005

The objective of this study was to characterize the patient population with respect to patient se... more 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 peri-operative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). Summary Background Data: Previous reports have been centerspecific 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. (Ann Surg 2005;242: 314 -325)

Research paper thumbnail of Proposed classification of complications after live donor nephrectomy

Urology, 2006

A standardized classification for the potential complications of living donor nephrectomy is an e... more 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. 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. 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). 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.

Research paper thumbnail of Laparoscopic donor nephrectomy: analysis of donor and recipient outcomes

Transplantation Proceedings, 2001

L APAROSCOPIC donor nephrectomy (LDN) holds the promise of increasing living donation by providin... more L APAROSCOPIC donor nephrectomy (LDN) holds the promise of increasing living donation by providing a less invasive alternative to open donor nephrectomy (ODN). Concerns have been raised regarding the safety of LDN, as well as for the short and long-term function of LDN kidneys. A higher incidence of recipient urologic complications, secondary to intraoperative ureteral trauma, has been reported with LDN organs. 1

Research paper thumbnail of COMPARATIVE ANALYSIS OF LIVE LIVER DONATION RISK USING A COMPREHENSIVE GRADING SYSTEM FOR SEVERITY

Transplantation, 2004

We investigated whether right lobe (RL) liver donation is associated with a higher incidence or s... more 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.

Research paper thumbnail of A Prospective Study of Rapid Corticosteroid Elimination in Simultaneous Pancreas-Kidney Transplantation

Transplantation, 2002

We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney t... more We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. 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. 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. 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.

Research paper thumbnail of The Role of PCR in the Diagnosis and Management of CMV in Solid Organ Recipients

Transplantation, 1997

... 1. Abecassis, Michael M.; Koffron, Alan J.; Kaplan, Bruce; Buckingham, Marguerite; Muldoon, J... more ... 1. Abecassis, Michael M.; Koffron, Alan J.; Kaplan, Bruce; Buckingham, Marguerite; Muldoon, Joseph P.; Cribbins, Allan J.; Kaufman, Dixon B.; Fryer, Jonathan P.; Stuart, Joan; Stuart, Frank P. Article Outline. Collapse Box Author Information. ...

Research paper thumbnail of Living Donor Liver Transplant for Malignancy

Transplantation, 2005

Adult-to-adult living donor liver transplantation (ALDLT) is being increasingly utilized to treat... more 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.

Research paper thumbnail of Liver Graft Volume Estimation in 100 Living Donors: Measure Twice, Cut Once

Transplantation, 2005

Estimation of graft volume (GV) is critical in living donor liver transplantation. This study exa... more 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.

Research paper thumbnail of Technical and immunologic progress in simultaneous pancreas-kidney transplantation

Surgery, 2002

During the past few years the use of new immunosuppressants and refinements in surgical technique... more 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.

Research paper thumbnail of Failed primary management of iatrogenic biliary injury: Incidence and significance of concomitant hepatic arterial disruption

Surgery, 2001

Vasculobiliary injury (VBI) is a well-recognized complication of laparoscopic cholecystectomy (LC... more Vasculobiliary injury (VBI) is a well-recognized complication of laparoscopic cholecystectomy (LC). In patients with failed primary management of bile duct injury (BDI), an assessment of the hepatic arterial system may be important to determine the presence of VBI. This study was conducted to determine the incidence of VBI in patients with failed primary management of LC-related BDI and to establish a potential correlation between the level of BDI and the incidence of VBI. A retrospective review was conducted on 18 patients referred for failed primary management of LC-related BDI who underwent prospective arteriography as part of the preoperative work-up. Of the 18 patients who sustained BDI, Bismuth level 4 lesions were found in 7 patients (39%), level 3 in 8 patients (44%), and level 2 in 3 patients (17%). VBI was identified on arteriography in 11 patients (61%). VBI was present in 71% of patients with level 4 lesions, 63% of patients with level 3 lesions, and 33% of patients with level 2 lesions. The time interval from primary management to its failure was longer in VBI than in BDI alone. We have observed a high incidence of VBI in patients with failed primary management of LC-related BDI. Arterial disruption may affect the outcome of primary management of BDI.

Research paper thumbnail of Intrahepatic biliary cystadenoma: Role of cyst fluid analysis and surgical management in the laparoscopic era

Surgery, 2004

Recent interest in cyst fluid analysis (CFA) for carbohydrate antigen 19-9 (CA 19-9) and carcinoe... more 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. 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 All patients with IBC who underwent CFA had elevated CA 19-9 (range, 2247-1,757,510; N &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;33 U/mL) and mildly elevated CEA (range, 3.3-212,; N &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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. 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.

Research paper thumbnail of The impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story

Surgery, 2009

increasingly being used to address organ shortages. Despite encouraging reports, standard surviva... more increasingly being used to address organ shortages. Despite encouraging reports, standard survival metrics have overestimated the effectiveness of DCD livers. We examined the mode, kinetics and predictors of organ failure and resource utilization to more fully characterize outcomes after DCD LT.

Research paper thumbnail of Use of yttrium-90 microspheres (TheraSphere®) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: A case report

Liver Transplantation, 2005

Prior to therapy, model for end stage liver disease (MELD) scoring, diagnostic imaging and tumor ... more 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.

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

Liver Transplantation, 2005

Transjugular intrahepatic shunts (TIPSs) are widely used in the management of portal hypertension... more 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.

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

Liver Transplantation, 2003

In living liver donation, a fatty liver poses risks for both recipient and donor. Currently, live... more 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 gradientecho 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.