Mary Ann Simpson

Incidence of death and potentially life‐threatening near‐miss events in living donor hepatic lobectomy: A world‐wide survey

The incidence of morbidity and mortality after living donor liver transplantation (LDLT) is not well understood because reporting is not standardized and relies on single‐center reports. Aborted hepatectomies (AHs) and potentially life‐threatening near‐miss events (during which a donors life may be in danger but after which there are no long‐term sequelae) are rarely reported. We conducted a worldwide survey of programs performing LDLT to determine the incidence of these events. A survey instrument was sent to 148 programs performing LDLT. The programs were asked to provide donor demographics, case volumes, and information about graft types, operative morbidity and mortality, near‐miss events, and AHs. Seventy‐one programs (48%), which performed donor hepatectomy 11,553 times and represented 21 countries, completed the survey. The average donor morbidity rate was 24%, with 5 donors (0.04%) requiring transplantation. The donor mortality rate was 0.2% (23/11,553), with the majority of deaths occurring within 60 days, and all but 4 deaths were related to the donation surgery. The incidences of near‐miss events and AH were 1.1% and 1.2%, respectively. Program experience did not affect the incidence of donor morbidity or mortality, but near‐miss events and AH were more likely in low‐volume programs (≤50 LDLT procedures). In conclusion, it appears that independently of program experience, there is a consistent donor mortality rate of 0.2% associated with LDLT donor procedures, yet increased experience is associated with lower rates of AH and near‐miss events. Potentially life‐threatening near‐miss events and AH are underappreciated complications that must be discussed as part of the informed consent process with any potential living liver donor. Liver Transpl 19:499–506, 2013.

Living donor adult liver transplantation: a longitudinal study of the donor's quality of life.

We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF‐36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty‐nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between

Epoxyeicosanoids promote organ and tissue regeneration

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Improved Survival After Live Donor Adult Liver Transplantation (LDALT) Using Right Lobe Grafts: Program Experience and Lessons Learned

25 000 in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.

Defining Benchmarks for Major Liver Surgery: A multicenter Analysis of 5202 Living Liver Donors.

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

Defining Benchmarks for Major Liver Surgery

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6‐year period. After an ‘early’ 2‐year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1‐year survival in recipients during our ‘later’ experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post‐transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

Ambivalence in living liver donors

Objective: To measure and define the best achievable outcome after major hepatectomy. Background: No reference values are available on outcomes after major hepatectomies. Analysis in living liver donors, with safety as the highest priority, offers the opportunity to define outcome benchmarks as the best possible results. Methods: Outcome analyses of 5202 hemi-hepatectomies from living donors (LDs) from 12 high-volume centers worldwide were performed for a 10-year period. Endpoints, calculated at discharge, 3 and 6 months postoperatively, included postoperative morbidity measured by the Clavien-Dindo classification, the Comprehensive Complication Index (CCI), and liver failure according to different definitions. Benchmark values were defined as the 75th percentile of median morbidity values to represent the best achievable results at 3 month postoperatively. Results: Patients were young (34 ± [9] years), predominantly male (65%) and healthy. Surgery lasted 7 ± [2] hours; 2% needed blood transfusions. Mean hospital stay was 11.7± [5] days. 12% of patients developed at least 1 complication, of which 3.8% were major events (≥grade III, including 1 death), mostly related to biliary/bleeding events, and were twice higher after right hepatectomy. The incidence of postoperative liver failure was low. Within 3-month follow-up, benchmark values for overall complication were ⩽31 %, for minor/major complications ⩽23% and ⩽9%, respectively, and a CCI ⩽33 in LDs with complications. Centers having performed ≥100 hepatectomies had significantly lower rates for overall (10.2% vs 35.9%, P < 0.001) and major (3% vs 12.1%, P < 0.001) complications and overall CCI (2.1 vs 8.5, P < 0.001). Conclusions: The thorough outcome analysis of healthy LDs may serve as a reference for evaluating surgical performance in patients undergoing major liver resection across centers and different patient populations. Further benchmark studies are needed to develop risk-adjusted comparisons of surgical outcomes.

Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study

Fabian Rössler, MD, Gonzalo Sapisochin, MD,y GiWon Song, MD,z Yu-Hung Lin, MD,§ Mary Ann Simpson, MD, PhD, Kiyoshi Hasegawa, MD, PhD,jj Andrea Laurenzi, MD, Santiago Sánchez Cabús, MD, PhD,yy Milton Inostroza Nunez, MD,zz Andrea Gatti, MD,§§ Magali Chahdi Beltrame, MD, Ksenija Slankamenac, MD, PhD, Paul D. Greig, MD,y Sung-Gyu Lee, MD, PhD,z Chao-Long Chen, MD, PhD,§ David R. Grant, MD,y Elizabeth A. Pomfret, MD, PhD, Norihiro Kokudo, MD, PhD,jj Daniel Cherqui, MD, Kim M. Olthoff, MD,jjjj Abraham Shaked, MD,jjjj Juan Carlos Garcı́a-Valdecasas, MD, PhD,yy Jan Lerut, MD, PhD,zz Roberto I. Troisi, MD, PhD,§§ Martin De Santibanes, MD, Henrik Petrowsky, MD, Milo A. Puhan, MD, PhD, and Pierre-Alain Clavien, MD, PhD

Successful Algorithm for Selective Liver Biopsy in the Right Hepatic Lobe Live Donor (RHLD)

All right hepatic lobe (RHL) donors in our program are asked to participate in a longitudinal quality‐of‐life study that begins at their evaluation and continues throughout the first postdonation year. Here we report the characteristics of donor candidates who completed the donation process despite ambivalence. In all, 183 RHL candidates consented, and 133 became donors. Ambivalent donors (ADs; n = 45) identified themselves through verbal statements or written comments, or they were identified by staff during the evaluation. ADs were predominantly male (73.3%), were older than unambivalent donors (UADs; >35 years: 76% of ADs versus 53% of UADs, P = 0.008), and were well educated (college graduate: 60% of ADs versus 17% of UADs, P = 0.01). Brother‐to‐brother and son‐to‐father combinations were most common among ADs. Alcohol (22% versus 11%, P = 0.04) and hepatitis C virus (51% versus 27%, P = 0.008) were more common as disease etiologies for recipients with ADs versus recipients with UADs. More ADs than UADs considered themselves to be religious (68.9% versus 43.2%, P = 0.007). Ambivalence about RHL donation was present in 33.8% of the candidates who completed the donation process. These results suggest that ambivalence should not be the sole reason for disqualifying a potential donor who otherwise satisfies program requirements. Liver Transpl 17:1226–1233, 2011.

Checking the harness: Safety for living liver donors

Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. Trial Registration ClinicalTrials.gov NCT00548405