Faculty Bibliography

BACKGROUND:The incidence of hepatocellular carcinoma (HCC) is rising, and the options for surgical therapy of HCC have evolved recently, but use of surgical therapy has not been characterized on a representative, nationwide basis. We quantified trends in use, mortality, and patient and hospital characteristics for 3 surgical therapies for HCC (resection, ablation, and transplantation) in the United States from 1998 to 2008. METHODS:Hospital discharge data from the Nationwide Inpatient Sample were used to quantify procedure-related data for each year. Trends over time were summarized as the average annual percent change (AAPC) and corresponding 95% confidence interval (CI). RESULTS:The number of surgical procedures for HCC increased from 1416 to 6769 (AAPC, 13.5%; 95% CI, 10.2%-16.8%). Volumes increased for all surgical procedures, most notably for ablation (AAPC, 17.3%; 95% CI, 6.6%-29.2%) and transplantation (AAPC, 20.9%; 95% CI, 14.1%-28.1%). When analyzed as a proportion of total procedures, there were declines in the relative use of major hepatectomy (35% to 16%; AAPC, -7.2%, 95% CI, -8.8% to -5.6%) and wedge resection (37% to 22%; AAPC, -4.8%; 95% CI, -6.2% to -3.4%), while the proportion accounted for by transplantation increased (16% to 35%; AAPC, 4.4%; 95% CI, 0.2%-8.9%). Inpatient mortality decreased for each procedure individually and overall from 7.3% to 4.6% (AAPC, -7.7%; 95% CI, -10.8% to -4.5%), despite increasing age and comorbidity burden. CONCLUSIONS:The use of surgical therapy for HCC has increased dramatically over the last decade, with a relative shift away from liver resection and toward liver transplantation. These therapeutic modalities must be better targeted to make the most appropriate use of limited health care resources.

BACKGROUND: ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United States have been limited to single-center studies. METHODS: Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume. RESULTS: When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43-3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99-1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume. CONCLUSIONS: These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.

Expanding the pool of available deceased donor kidneys is critical for improving the outcomes of prospective and current renal transplant candidates. A number of interventions have been proposed that may increase the pool of donors in the US. However, these interventions have variable levels of empirical evidence supporting their potential beneficial impact. Proposed interventions include the instigation of policies for presumed donor consent, the expansion of donor registration, increased quality oversight of transplant providers, financial incentives for donors, increased reimbursement for higher risk donors, alterations in organ allocation policies and distribution, and the selective use of donors with potential or known risk for disease transmission. Many of these interventions have contentious elements that may have delayed or impeded their implementation; however, these options should be considered in the context of the diminishing prognoses for prospective transplant patients, given the increasing scarcity of donor organs relative to the population need. In this Review, we outline the proposed interventions and briefly discuss salient issues that characterize the debates concerning their implementation and effectiveness. Ultimately, any intervention must be based on the best evidence available, with consideration of numerous stakeholders and in conjunction with a careful evaluation of long-term and potential unintended consequences.

INTRODUCTION: Deceased donors are considered high infectious risk donors (IRDs) based on criteria thought to be associated with risk of HIV transmission. Significant variation exists in provider willingness to utilize IRD kidneys. Little is known about how patients view these organs. Our aim was to explore patient attitudes toward IRDs and IRD kidney transplantation. METHODS: Patients were recruited from a single-center deceased donor waitlist. Focus groups stratified by age and race were conducted to ascertain patient attitudes toward IRD kidney transplantation. Transcripts were examined using standard qualitative methods. RESULTS: Patients considered IRD kidneys most appropriate for patients at high risk of death or with poor quality of life on dialysis. Patients felt unprepared to receive organ offers, especially from IRDs. They desired information about IRD behaviors, kidney quality, and probability of undetected infection. Patients weighed the opinion of their nephrologist most heavily when deciding about organ offers. A brief education session about donor screening resulted in increased willingness to consider IRD kidneys. CONCLUSIONS: Lack of preparedness contributes to patient apprehension toward IRD organs. Ongoing transplant education seems necessary. The non-transplant nephrologist seems to be the most trusted source of information.

The ability to predict outcomes following a kidney transplant is limited by the complex physiologic decline of kidney failure, a latent factor that is difficult to capture using conventional comorbidity assessment. The frailty phenotype is a recently described inflammatory state of increased vulnerability to stressors resulting from decreased physiologic reserve and dysregulation of multiple physiologic systems. We hypothesized that frailty would be associated with delayed graft function, based on putative associations between inflammatory cytokines and graft dysfunction. We prospectively measured frailty in 183 kidney transplant recipients between December 2008 and April 2010. Independent associations between frailty and delayed graft function were analyzed using modified Poisson regression. Preoperative frailty was independently associated with a 1.94-fold increased risk for delayed graft function (95% CI, 1.13-3.36; P = .02). The assessment of frailty may provide further insights into the pathophysiology of allograft dysfunction and may improve our ability to preoperatively risk-stratify kidney transplant recipients.

BACKGROUND & AIMS: We sought to estimate the risk of perioperative mortality or acute liver failure for live liver donors in the United States and avoid selection or ascertainment biases and sample size limitations. METHODS: We followed up 4111 live liver donors in the United States between April 1994 and March 2011 for a mean of 7.6 years; deaths were determined from the Social Security Death Master File. Survival data were compared with those from live kidney donors and healthy participants of the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: Seven donors had early deaths (1.7 per 1000; 95% confidence interval [CI], 0.7-3.5); risk of death did not vary with age of the liver recipient (1.7 per 1000 for adults vs 1.6 per 1000 for pediatric recipients; P = .9) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 1.5 per 1000 for right lobe; P = .8). There were 11 catastrophic events (early deaths or acute liver failures; 2.9 per 1000; 95% CI, 1.5-5.1); similarly, risk did not vary with recipient age (3.1 per 1000 adult vs 1.6 per 1000 pediatric; P = .4) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 3.3 per 1000 for right lobe; P = .9). Long-term mortality of live liver donors was comparable to that of live kidney donors and NHANES participants (1.2%, 1.2%, and 1.4% at 11 years, respectively; P = .9). CONCLUSIONS: The risk of early death among live liver donors in the United States is 1.7 per 1000 donors. Mortality of live liver donors does not differ from that of healthy, matched individuals over a mean of 7.6 years.

A causal link has been proposed between presumed consent (PC) and increased donation; we hypothesized that too much heterogeneity exists in transplantation systems to support this inference. We explored variations in PC implementation and other potential factors affecting donation rates. In-depth interviews were performed with senior transplant physicians from 13 European PC countries. Donation was always discussed with family and would not proceed against objections. Country-specific, nonconsent factors were identified that could explain differences in donation rates. Because the process of donation in PC countries does not differ dramatically from the process in non-PC countries, it seems unlikely that PC alone increases donation rates.

OBJECTIVES: To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. DESIGN: Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. SETTING: Retrospective analysis of national registry data. PARTICIPANTS: Model development: Medicare-primary older recipients (aged >/= 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). MEASUREMENTS: Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. RESULTS: The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer-Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. CONCLUSION: A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults.