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Background: Whether liver resection or liver transplantation is optimal therapy for patients with hepatocellular carcinoma (HCC) remains undefined. A meta-analysis was conducted to answer this question.Study Design: This study performed a systematic review of the published literature between January 2000 and April 2012.Results: Nine retrospective studies, totaling 2,279 patients (989 resected and 1,290 transplanted), met the selection criteria. Older patients with larger tumors and less severe cirrhosis were identified in the resection group. At 1 year, resection demonstrated significantly higher overall [odds ratio (OR) = 1.54; 95 % confidence interval (CI), 1.19-1.98; p = 0.001], but equivalent disease-free survival (OR = 0.93; 95 % CI, 0.53-1.63; p = 0.80). At 5 years, there was no difference in overall survival (OR = 0.86; 95 % CI, 0.61-1.21; p = 0.38), but a higher disease-free survival in transplanted patients was observed (OR = 0.39; 95 % CI, 0.24-0.63; p < 0.001). When limiting our analysis to studies conducted in an intent-to-treat fashion, there was no difference in 5 year overall survival (OR = 1.18; 95 % CI, 0.92-1.51; p = 0.19), but a significantly higher disease-free survival (OR = 0.76; 95 % CI, 0.57-1.00; p = 0.05) in transplanted patients. At 10 years, transplantation had higher overall and disease-free survival rates.Conclusion: Liver transplantation in patients with HCC results in increased late disease-free and overall survival when compared with liver resection. Nonetheless, the benefit of liver transplantation is offset by higher short-term mortality, donor organ availability, and long transplant wait times associated with more patient deaths. Understanding these differences in survival is helpful in guiding treatment. However, a properly controlled prospective trial is needed to define how best to treat HCC patients who are candidates for either therapy. [ABSTRACT FROM AUTHOR]

Background: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients., Methods: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed., Results: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6)., Conclusion: Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes., Methods: Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival., Results: Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%-100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%-100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios-VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors., Conclusions: Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients., Methods: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor., Findings: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation., Interpretation: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains., Funding: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases., Competing Interests: Declaration of interests LFW received research funding from Accelerate Diagnostics, bioMérieux, Hardy Diagnostics, Roche Molecular Systems, and Selux Diagnostics and honoraria from Roche Molecular Systems, Shionogi, and Talis Biomedical, all unrelated to this work. KSG received research support from ThermoFisher and has a royalty-generating collaborative agreement with ZeptoMetrix, both unrelated to this work. MRW received research grant funding from Roche/Genentech and Novartis and speaking honoraria from Genentech, Novartis, Takeda, and WebMD, all unrelated to this work. CYC received research grant funding from the Bay Area Lyme Disease Foundation and the Chan-Zuckerberg Biohub, unrelated to this work, and is on the scientific advisory board for Mammoth Biosciences, Poppy Health, and BiomeSense. MRW and CYC are consultants and co-founders of Delve Bio. CYC is a co-inventor on US patent 11380421, Pathogen Detection Using Next Generation Sequencing, under which algorithms for taxonomic classification, filtering, and pathogen detection are used by SURPI+ software., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%-29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score-matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long-term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high-risk macrosteatotic allografts to negatively affect outcomes., (Copyright © 2021 American Association for the Study of Liver Diseases.)

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background/objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM., Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM., Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001)., Conclusion: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

Background: Pancreatic body and tail ductal adenocarcinomas are often diagnosed with local vascular invasion of the celiac axis (CA) and its various branches. With such involvement, these tumors have traditionally been considered unresectable. The modified Appleby procedure allows for margin negative resection of some such locally advanced tumors. This procedure involves distal pancreatectomy with en bloc splenectomy and CA resection and relies on the presence of collateral arterial circulation via an intact pancreaticoduodenal arcade and the gastroduodenal artery to maintain prograde hepatic arterial perfusion. When the resultant collateral circulation is inadequate to provide sufficient hepatic and gastric arterial inflow, arterial reconstruction (AR) is necessary to "supercharge" the inflow. Herein, we review all reported cases of AR with modified Appleby procedures that we have identified in the literature, and we report our experience of three recent cases with arterial reconstruction including two cases with arterial bypasses not requiring interposition grafting., Methods: Perioperative and oncologic outcomes from our Institutional Review Board-approved database of pancreatic resections at the Thomas Jefferson University were reviewed. Additionally, PubMed search for cases of distal or total pancreatectomy with celiac axis resection and concurrent AR was performed., Results: From the literature, 12 reports involving 28 patients were identified of distal and total pancreatectomy with AR after CA resection. The most common AR in the literature, performed in 12 patients, was a bypass from the aorta to the common hepatic artery (CHA) using a variety of interposition conduits. In our institutional experience, patient #1 had a primary side-to-end aorto-CHA bypass, patient #2 had a primary end-to-end bypass of the transected distal CHA to the left gastric artery in the setting a replaced left hepatic artery, and patient #3 required an aortic to proper hepatic artery bypass with saphenous vein graft and portal venous reconstruction. All patients recovered from their operations without ischemic complications, and they are currently 16, 15, and 13 months post-op, respectively., Conclusions: The criteria for resectability in patients with locally advanced pancreatic body and tail neoplasms are expanding due to increasing experience with AR in the setting of the modified Appleby procedure. When performing AR, primary arterial re-anastomosis may be considered preferable to interposition grafting as it decreases the potential for the infectious and thrombotic complications associated with conduits and it reduces the number of vascular anastomoses from two to one. Consideration must also be given to normal variant anatomy of the hepatic circulation during operative planning as the origin of the left gastric artery is resected with the CA. The modified Appleby procedure with AR, when used in appropriately selected patients, offers the potential for safe, margin negative resection of locally advanced pancreatic body and tail tumors.

Introduction: Ex situ liver resection is an uncommon procedure but offers an opportunity for R0 surgical resection of liver tumors that are otherwise unresectable. Liver insufficiency following extensive resections is a risk in this patient population; consequently, all measures should be taken to prevent this highly morbid complication., Method: We report a case of a patient with an extensive cholangiocarcinoma involving all three hepatic veins that required ex vivo resection and liver autotransplantation to achieve an R0 resection. Postoperatively, the patient demonstrated signs of worsening liver function that, in addition to standard medical therapy, underwent a brief treatment with molecular adsorbent recirculating system (MARS) therapy., Results: Although the role of MARS remains unclear, the patient tolerated it well and her liver graft dysfunction and hepatic encephalopathy slowly resolved. The patient was discharged to a rehabilitation facility. She is currently alive and well with no evidence of recurrence 3 years later., Conclusion: We present a review of the literature on ex situ resection and liver autotransplantation. In addition to numerous case reports, there are a few moderate series of ex situ resection and autotransplantation. We suggest that the use of artificial liver devices, if indicated, in the postoperative ex situ resection liver autotransplant patient may assist in the support of the patient while the transplanted liver remnant recovers.

Background: In this study, we present our experience with ureteral complications requiring revision surgery after renal transplantation and compare our results to a matched control population., Methods: We performed a retrospective analysis of our database between 1997 and 2012. We divided the cases into early (<60 d) and late repairs. Kaplan-Meier and Cox proportional hazards models were used to compare graft survival between the intervention cohort and controls generated from the Scientific Registry of Transplant Recipients data set., Results: Of 2671 kidney transplantations, 51 patients were identified as to having undergone 53 ureteral revision procedures; 43.4% of cases were performed within 60 d of the transplant and were all associated with urinary leaks, and 49% demonstrated ureteral stenosis. Reflux allograft pyelonephritis and ureterolithiasis were each the indication for intervention in 3.8%; 15.1% of the lesions were located at the anastomotic site, 37.7% in the distal segment, 7.5% in the middle segment, 5.7% proximal ureter, and 15.1% had a long segmental stenosis. In 18.9%, the location was not specified. Techniques used included ureterocystostomy (30.2%), ureteroureterostomy (34%), ureteropyelostomy (30.1%), pyeloileostomy (1.9%), and ureteroileostomy (3.8%). No difference in overall graft survival (HR 1.24 95% CI 0.33-4.64, p = 0.7) was detected when compared to the matched control group., Conclusion: Using a variety of techniques designed to re-establish effective urinary flow, we have been able to salvage a high percentage of these allografts. When performed by an experienced team, a ureteric complication does not significantly impact graft survival or function as compared to a matched control group., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Late allograft failure (LAF) is a common cause of end stage renal disease. These patients face interrelated challenges regarding immunosuppression management, risk of graft intolerance syndrome (GIS), and sensitization. This retrospective study analyzes sensitization, pathology, imaging, and transfusion requirements in 33 LAFs presenting either with GIS (22) or grafts remaining quiescent (11). All patients underwent immunosuppression weaning to discontinuation at LAF. Profound increases in sensitization were noted for all groups and occurred in the GIS group prior to transplant nephrectomy (TxN). Patients with GIS experienced a major upswing in sensitization at, or before the time of their symptomatic presentation. For both GIS and quiescent grafts, sensitization appeared to be closely linked to immunosuppression withdrawal. Most transfusion naïve patients became highly sensitized. Fourteen patients in the GIS group underwent TxN which revealed grade II acute cellular rejection or worse, with grade 3 chronic active T-cell-mediated rejection. Blinded comparisons of computed tomography scan of GIS group revealed swollen allografts with fluid collections compared with the quiescent allografts (QAs), which were shrunken and atrophic. The renal volume on imaging and weight of explants nearly matched. Future studies should focus on interventions to avoid sensitization and GIS., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO)., Methods: A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards., Results: Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr., Conclusions: Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease.

Introduction: Sarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of systemic non-caseating granulomas; however, a variation of this disease known as "sarcoid-like reaction" has been described in patients with underlying cancer., Report: Sarcoid-like reactions in patients with hepatopancreatobiliary (HPB) tumors are rare findings, with only 15 cases having been reported in the English language literature. These reactions can be found in local lymph nodes or in distant organs, and when present in patients with cancer, they can mimic metastatic disease on imaging, potentially resulting in incorrect cancer staging and management., Discussion: We describe two cases of patients with HPB tumors who had distant organ disease on cross-sectional imaging suspicious for metastases, which on further workup were found to be sarcoid-like reactions. We also discuss malignancy-induced sarcoid-like reactions and provide a review of the literature of sarcoid-like reactions in the setting of HPB tumors.

The preimplantation kidney biopsy affects utilization by diagnosing glomerulosclerosis, interstitial fibrosis (IF), arteriosclerosis, and arteriolar hyalinosis. Organ procurement organizations (OPOs) determine whether a donor warrants this biopsy and the donor hospital pathologists (DHPs) report on an OPO-specific pathology interpretation form. Biopsy slides from 40 deceased donor kidneys transplanted at our institution were used to compare interpretations between our transplant pathologist and the DHPs. Thirty-three of these kidneys also had post-perfusion biopsies (PPB). All 58 OPOs were queried for criteria used to request a preimplantation biopsy, and their pathology interpretation forms were also analyzed. The transplant and DHPs had substantial agreement for percent glomerulosclerosis with 75% of biopsies being interpreted within five percentage points. Concordance for IF was poor. The DHP rarely reported arterial pathology. Seventy percent of preimplantation and PPB were read similarly for glomerulosclerosis; concordance for other lesions was weaker. There were no cues for arterial disease on our OPO's pathology interpretation form. Criteria for obtaining a preimplantation biopsy lacked uniformity for the 21 OPOs with a self-generated policy. The pathology interpretation forms varied widely among the OPOs. Current OPO practices with regard to the preimplantation biopsy should be improved., (© 2012 John Wiley & Sons A/S.)

Objective: To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN., Materials & Methods: From December 2005 to January 2011, 25 patients underwent right-sided LDN or RALDN. An IRB-approved retrospective review was performed of both donor and recipient medical charts. Primary endpoints included both intraoperative and postoperative outcomes., Results: Twenty right-sided LDNs and 5 RALDNs were performed during the study period. Neither estimated blood loss (76.4 mL vs. 30 mL, P = .07) nor operative time (231 min vs. 218 min, P = .61) were significantly different between either group (LDN vs. RALDN). Warm ischemia time for LDN was 2.6 min vs. 3.8 min for RALDN (P = .44). Donor postoperative serum estimated glomerular filtration rates (eGFR) were similar (53 vs. 59.6 mL/min/1.73 m2, LDN vs. RALDN, P = .26). For the recipient patients, posttransplant eGFR were similar at 6 months (53.4 vs. 59.8 mL/min/1.73 m2, LDN vs. RALDN, P = .53)., Conclusion: In this study, robotic-assistance did not improve outcomes associated with LDN. Larger prospective studies are needed to confirm any perceived benefit of RALDN.

Introduction: The results of orthotopic liver transplantation in patients with end-stage liver disease continue to improve. Refinements in surgical techniques represent an important part of this improvement., Materials and Methods: With the advent of split-liver and living-donor liver transplantation, inferior vena cava (IVC) preservation transitioned from being a potential option to being mandatory for many cases. Preserving the IVC can be a demanding technical maneuver in many liver transplants and several different approaches have been developed. When utilizing IVC preservation, there are several options for implantation of the graft. The piggyback technique, when feasible, is considered safe and provides hemodynamic stability for the recipient., Results and Discussion: In some cases it may be difficult to perform the piggyback technique if intense inflammatory adhesions and severe significant collateral circulation exist between the IVC and the posterior segments of the liver. In these cases, the retro-hepatic dissection can be carried out with a different approach: the infrahepatic vena cava and the confluence of the three hepatic veins can be cross-clamped en-bloc without dissection., Conclusion: This technique broadens the transplant surgeons' armamentarium and can be used in the setting of a very difficult retro-hepatic dissection. It is safe, and allows a shorter anhepatic phase with caval preservation.

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling to all pre and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. The NTPR has acquired experience with 2000 pregnancy outcomes in female transplant recipients. For the NTPR's largest group, female kidney recipients, 71-76% of the pregnancies produce a livebirth. For the other organs combined, the livebirth likelihood ranges from 50-86%. The incidence of birth defects in the liveborn appears similar to the general population, except for pregnancies with MPA exposure that have a 23% incidence of birth defects. Long-term follow-up of the offspring of transplant recipients has provided reassurance after 20 years of observation. The continued recording of data in registries such as the NTPR is essential for assessing the safety of pregnancy in solid organ transplant recipients. Key benefits of the NTPR are the personal contact between registry staff and participants, the wide range of pregnancy-related variables that are analyzed, and the opportunity for health-care providers to obtain information that helps them care for transplant recipients on a case-by-case basis.

Objective: To quantify the independent association between obesity and access to liver transplantation., Background: Obesity is associated with higher complication rates, longer hospitalization, and worse survival after liver transplantation. Nevertheless, transplantation provides survival benefit to patients with end-stage liver disease, regardless of body mass index (BMI). We hypothesized that, despite survival benefit, providers were reluctant to transplant obese patients because of the inherent difficulty of these cases and their inferior outcomes. Our goal was to quantify the independent association between BMI and waiting time for orthotopic liver transplantation as a surrogate marker for this reluctance., Methods: We studied 29,136 wait-list candidates in the model for end-stage liver disease (MELD) era, categorized as severely obese (BMI 35-40), morbidly obese (BMI 40-60), and reference (BMI 18.5-35). All models were adjusted for factors relevant to the allocation system, factors possibly influencing access to healthcare, and factors biologically related to disease progression and outcomes., Results: The odds of receiving a MELD exception were 30% lower in severely obese and 38% lower in morbidly obese patients. Similarly, the likelihoods of being turned down for an organ were 10% and 16% higher, and the rates of being transplanted were 11% and 29% lower in severely obese and morbidly obese patients, respectively., Conclusions: Current practice seems to indicate a reluctance to transplant obese patients. If indeed as a community we feel that liver allografts should not be distributed to patients with excessive postoperative risk, we should consider expressing this as a formal change to our allocation policy rather than through informal practice patterns.

When considering advocacy of split-liver transplantation, it is important to understand whether comparable outcomes can be achieved. The goal of this study was to identify donor and transplant characteristics predictive of comparable outcomes by risk factor analysis. Using the United Network for Organ Sharing/ Organ Procurement and Transplantation Network data base between January 1996 and May 2006, first time adult/child split cases (568 adults, 508 children) were examined. In multivariate analysis, recipient medical condition (hospitalization), status 1 assignment, ABO incompatibility, donor age (>40 years), donor body weight (< or = 40 kg), calculated whole graft volume to recipient body weight ratio (cGRWR < or = 1.5%) and no sharing between centers were significant risk factors in adult recipients. Recipient diagnosis of tumor, dialysis prior to transplant, recipient body weight (< or = 6 kg), donor age (>30 years), donor history of cardiac arrest after declaration of death and cold ischemia time (CIT > 6 h) increased the risk of graft failure in pediatric recipients. The livers from young donors showed comparable outcomes to whole deceased liver transplantation (LT) when other transplant-related risk factors were minimized in adult recipients. Reducing CIT is important to obtain comparable outcomes to living donor LT in pediatric recipients.

Background: When the United Network for Organ Sharing changed its algorithm for liver allocation to the model for end-stage liver disease (MELD) system in 2002, highest priority shifted to patients with renal insufficiency as a major component of their end-stage liver disease. An unintended consequence of the new system was a rapid increase in the number of simultaneous liver-kidney transplants (SLK) being performed yearly., Methods: Adult recipients of deceased donor liver transplants (LT, n=19,137), kidney transplants (n=33,712), and SLK transplants (n=1,032) between 1987 and 2006 were evaluated based on United Network for Organ Sharing data. Recipients were stratified by donor subgroup, MELD score, pre- versus post-MELD era, and length of time on dialysis. Matched-control analyses were performed, and graft and patient survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses., Results: MELD era outcomes demonstrate a decline in patient survival after SLK. Using matched-control analysis, we are unable to demonstrate a benefit in the SLK cohort compared with LT, despite the fact that higher quality allografts are being used for SLK. Subgroup analysis of the SLK cohort did demonstrate an increase in overall 1-year patient and liver graft survival only in those patients on long-term dialysis (> or =3 months) compared with LT (84.5% vs. 70.8%, P=0.008; hazards ratio 0.57 [95% CI 0.34, 0.95], P=0.03)., Conclusion: These findings suggest that SLK may be overused in the MELD era and that current prioritization of kidney grafts to those liver failure patients results in wasting of limited resources.

Steroid use after liver transplantation (LT) has been associated with diabetes, hypertension, hyperlipidemia, obesity, and hepatitis C (HCV) recurrence. We performed meta-analysis and meta-regression of 30 publications representing 19 randomized trials that compared steroid-free with steroid-based immunosuppression (IS). There were no differences in death, graft loss, and infection. Steroid-free recipients demonstrated a trend toward reduced hypertension [relative risk (RR) 0.84, P = 0.08], and statistically significant decreases in cholesterol (standard mean difference -0.41, P < 0.001) and cytomegalovirus (RR 0.52, P = 0.001). In studies where steroids were replaced by another IS agent, the risks of diabetes (RR 0.29, P < 0.001), rejection (RR 0.68, P = 0.03), and severe rejection (RR 0.37, P = 0.001) were markedly lower in steroid-free arms. In studies in which steroids were not replaced, rejection rates were higher in steroid-free arms (RR 1.31, P = 0.02) and reduction of diabetes was attenuated (RR 0.74, P = 0.2). HCV recurrence was lower with steroid avoidance and, although no individual trial reached statistical significance, meta-analysis demonstrated this important effect (RR 0.90, P = 0.03). However, we emphasize the heterogeneity of trials performed to date and, as such, do not recommend basing clinical guidelines on our conclusions. We believe that a large, multicenter trial will better define the role of steroid-free regimens in LT., ((c) 2008 AASLD.)

Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.

Unlabelled: Elderly liver donors (ELDs) represent a possible expansion of the donor pool, although there is great reluctance to use ELDs because of reports that increasing donor age predicts graft loss and patient death. The goal of this study was to identify a subgroup of recipients who would be least affected by increased donor age and thus best suited to receive grafts from ELDs. A national registry of deceased donor liver transplants from 2002-2005 was analyzed. ELDs aged 70-92 (n = 1043) were compared with average liver donors (ALDs) aged 18-69 (n = 15,878) and ideal liver donors (ILDs) aged 18-39 (n = 6842). Recipient factors that modified the effect of donor age on outcomes were identified via interaction term analysis. Outcomes in recipient subgroups were compared using Kaplan-Meier survival analysis. Recipients preferred for ELD transplants were determined to be first-time recipients over the age of 45 with body mass index <35, non-status 1 registration, cold ischemic time <8 hours, and either hepatocellular carcinoma or an indication for transplantation other than hepatitis C. In preferred recipients, there were no differences in outcomes when ELD livers were used (3-year graft survival: ELD 75%, ALD 75%, ILD 77%, P > 0.1; 3-year patient survival: ELD 81%, ALD 80%, ILD 81%, P > 0.1). In contrast, there were significantly worse outcomes when ELD livers were used in nonpreferred recipients (3-year graft survival: ELD 50%, ALD 71%, ILD 75%, P < 0.001; 3-year patient survival: ELD 64%, ALD 77%, ILD 80%, P < 0.001)., Conclusion: The risks of ELDs can be substantially minimized by appropriate recipient selection.

Several treatment options exist for the management of Budd-Chiari syndrome (BCS), yet the relative role and timing of liver transplantation (LT) remain poorly defined. Small case series published to date have not been able to delineate the impact of comorbidities and thromboembolic complications of BCS on survival after LT. To better understand the outcomes after LT for BCS, we analyzed 510 liver transplants performed for this disease in the United States between 1987 and 2006. Risk factors predicting graft loss or patient death included increased recipient age, hyperbilirubinemia, elevated creatinine, life support or hospitalization at the time of transplantation, prior transplantation, prior abdominal surgery, increased donor age, and prolonged cold ischemic time (CIT). Prior transjugular intrahepatic portosystemic shunt (TIPS) was not associated with worse outcomes. Transplantation in the Model for End-Stage Liver Disease (MELD) era was associated with significantly lower risk of graft loss (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.30-0.86; P = 0.012) and death (HR, 0.52; 95% CI, 0.29-0.93; P = 0.027). Similarly, MELD era was associated with significantly lower risk of early graft loss (odds ratio [OR], 0.35; 95% CI, 0.16-0.79, P = 0.012) and early death (odds ratio, 0.37; 95% CI, 0.14-0.95; P = 0.040). However, patients with BCS transplanted in the MELD era were less likely to have life support, hospitalization, prior transplants, and prolonged cold ischemia times. In conclusion, outcomes of LT for BCS are excellent, with further improvements since 2002 associated with a selection shift imposed by MELD-based organ allocation., (Copyright 2007 AASLD.)

Background: Liver transplantation from donation after cardiac death (DCD) donors is an increasingly common approach for expansion of the donor organ supply. However, transplantation with DCD livers results in inferior graft survival. In this study, we examined donor and recipient characteristics that are associated with poor allograft outcomes and present a set of criteria that permit allograft survival that is comparable to that of donation after brain death (DBD) grafts in both low- and high-risk recipients., Methods: The United Network for Organ Sharing/Organ Procurement and Transplantation Network Liver Transplantation Registry between January 1996 and March 2006 was investigated. Adult DCD liver transplants (n = 874) were included., Results: A DCD risk index was developed using the statistically significant factors from a multivariate Cox model: history of previous transplantation, life support status at transplantation, donor age, donor warm ischemia time (DWIT), and cold ischemia time (CIT). Favorable DCD donor criteria were donor age < or =45 years, DWIT < or =15 min, and CIT < or =10 hr. Four risk groups were developed based upon index scores that showed different graft survival. Graft survival of the favorable DCD group (84.9% at 1 year, 75.2% at 3 years, and 69.4% at 5 years) was comparable to that for DBD liver transplantation irrespective of recipient condition. Increasing donor age was more highly predictive of poor outcomes in DCD compared to DBD, especially in recipients in poor preoperative condition., Conclusions: DCD livers from young donors with short DWIT and CIT should be given greater consideration in order to expand the number of available donor organs.

This tool, which takes one or two minutes to use, provides a structured approach to promote effective interdisciplinary communication and teamwork in the operating room--or any other area, such as an intensive care unit, inpatient unit, or outpatient clinic.

Context: First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States., Objective: To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors., Design, Setting, and Patients: Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk., Intervention: Kidney paired donation and live donor renal transplantation., Main Outcome Measures: Patient survival, graft survival, serum creatinine levels, rejection episodes., Results: A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%)., Conclusions: This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.

Most successful protocols for renal transplantation across ABO incompatible (ABOi) barriers have utilized splenectomy as part of the pre-conditioning process. We recently described successful ABOi transplantation using anti-CD20 monoclonal antibody in lieu of splenectomy. In the current study, we hypothesized that plasmapheresis (PP) and low dose CMV hyper-immunoglobulin (CMVIg) alone would be sufficient to achieve successful engraftment of ABOi kidneys. We describe four blood type incompatible patients who received live donor renal transplants from A1 (two patients), A2 (one patient), and B (one patient) donors. All patients started with antihuman globulin (AHG) phase titers of 64 or higher and were pre-conditioned with PP/CMVIg but not splenectomy or anti-CD20. All 4 patients underwent successful transplantation and have a mean current serum creatinine of 1.1 (range: 0.9-1.2). There were no episodes of antibody mediated rejection. Rapid allograft accommodation may limit the need for long-term antibody suppression provided by splenectomy or anti-CD20, thereby eliminating the added infectious risk of these modalities and removing another disincentive to ABOi transplantation.

The study goal was to determine the technical feasibility and outcomes associated with pancreaticoduodenectomy for periampullary malignancies with near (>80%) or complete (100%) superior mesenteric venous (SMV) obstruction. A retrospective examination of 11 patients with high-grade or complete SMV obstruction who underwent pancreaticoduodenectomy at five academic medical centers is reviewed. Pancreaticoduodenectomy for locally advanced periampullary malignancies causing high-grade or complete SMV obstruction is technically feasible. Operative approaches and outcomes are presented. One 30-day death was observed. Median survival of the cohort is 18 months. Survivals exceeding 2 years post-resection have been observed. In a number of cases, significant palliation of pain and of biliary and duodenal obstruction were achieved. Based on this initial series, pancreaticoduodenectomy in the presence of near or total SMV obstruction is feasible, may result in an R0 resection, and may be beneficial in select patients with a periampullary malignancy. We suggest such an approach be considered particularly following completion of neoadjuvant therapy without systemic progression. Further studies and more long-term follow-up at high-volume centers are required, however, to better determine the indications and potential benefit of such an undertaking.

Liver transplantation is a successful therapeutic option for patients with chronic liver disease and liver failure in that 1-year survival is greater than 80%. Orthotopic transplantation is usually performed from a cadaveric or living adult donor. The necessary evaluation of recipients and donors prior to transplantation can be successfully performed with computed tomography (CT). CT is useful in determining clinically relevant information for recipients such as size of the caudate lobe, exclusion of advanced hepatocellular carcinoma and other malignancy, patency of the venous system, presence of perihepatic varices, patency of the celiac artery, exclusion of splenic artery aneurysm, and position of iatrogenic venous shunts. CT in living donors may help to determine clinically relevant information about variant hepatic arterial anatomy, source of the artery to segment IV, intraparenchymal anatomy of the hepatic veins and accessory hepatic veins, trifurcation of the portal vein or hepatic duct, liver volume, and fatty change of the parenchyma. Surgical approaches and the imaging findings that influence management are reviewed.

Background: Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease., Methods: In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed., Results: All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation., Conclusion: With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.

Background: Immunosuppression involves the nature of the immunosuppressive agents and individual differences in patient factors. We investigated whether the effect of mycophenolate mofetil (MMF) is measurable using an in vitro measure of immunocompetence and related its effects to cyclosporine (CsA) in vitro., Methods: Liver or kidney transplant recipients receiving prednisone; CsA or tacrolimus; and MMF, azathioprine (AZA), or neither, were studied. Immunocompetence was assessed by one-way mixed lymphocyte culture using patients' peripheral blood leukocytes (PBL) and three validated stimulators. The effect of immunosuppressive agents added in vitro on normal PBL stimulation by Staphylococcus enterotoxin B was determined by the carboxyfluorescein diacetate succinimidyl ester measurement of division., Results: Patients receiving MMF had an average immunocompetence level of 12+/-23, compared with 39.7+/-65 and 25.5+/-42 for those receiving AZA or neither AZA nor MMF, respectively. Thus, there was an approximately 80% suppression of the response in the MMF group. Assessment of normal cell division revealed that CsA allowed multiple cell generations but suppressed the numbers of cells in each, whereas MMF blocked proliferation into subsequent generations. Addition of clinically relevant levels of mycophenolic acid, the active agent for MMF, added to more moderate levels of CsA, was required to achieve greater than 80% suppression, consistent with the degree of immunocompetence depression measured in patients., Conclusions: These data provide the novel finding that the effect of MMF treatment on patients is measurable in their PBL as decreased immunocompetence in vitro. The effect of MMF on normal PBL approximates the 80% inhibition that we found in patients. Moreover, the effect of MMF on cell division provides a rationale for the superior effectiveness of regimens including MMF.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.

Background: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death., Methods: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature., Results: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood., Conclusion: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells may be impacted by immunosuppressive agents. We examined this for mycophenolate mofetil (MMF) compared with cyclosporine (CYA). Peripheral blood leukocytes (PBL) were stimulated by either Staph enterotoxin B (SEB) or by anti-CD3 plus anti-CD28. Cell division analysis (sequential reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations. Apoptosis was measured by annexin V staining, and FasL expression by anti-FasL antibody staining, of activated cells using flow cytometry. CSA and mycophenolic acid (MPA, the active agent of MMF) were added in titration in 3-day cultures. We found that CSA caused diminution in apoptosis but MPA increased it with SEB stimulation. The CSA effect on apoptosis was present when a more calcineurin-dependent stimulus. anti-CD3+ anti-CD28, was used but the MPA effect was less, producing a decrease only in the undivided cells. To look more directly at the differential effect on calcineurin-dependent AICD gene induction of the two agents, we measured Fas-L expression with anti-CD-3 + CD28 stimulation, and confirmed that CYA caused a major decrement in appearance of Fas-L, whereas MPA caused a converse accumulation of it. This seems to be explained by the block more distal in cell activation, resulting in a build-up of a precursor in the activation pathways. We conclude that MMF treatment may be rationale as an adjunct to calcineurin inhibitor treatment because of its converse effect on T cell regulatory apoptosis.

Background: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor., Methods: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group)., Results: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks)., Conclusions: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.