Faculty Bibliography

OBJECTIVE:Centers offering adult living donor liver transplantation (LDLT) mostly use right lobe grafts due to fears of providing recipients with insufficient hepatic volume, and the technical challenges presented by using left lobe grafts (LLGs). LLGs therefore represent approximately 5% of adult LDLTs performed in the United States. Here we present the largest North American experience with the use of LLG for adult LDLT. METHODS:Analysis of a prospectively maintained database of LDLTs performed from 1998 to 2015 at our institution. RESULTS:A total of 214 adult LDLTs were studied. Fifty-six patients (26%) received LLG. LLG recipients were more likely to be women, had significantly lower BMI, graft weight, and graft-weight-recipient-weight ratios (P < 0.05 for all). There were no significant differences in vascular or biliary complication between the groups. No significant differences existed in patient or graft survival at 1, 3, and 5 years (P = 0.747 and P = 0.398 respectively). Despite significantly increased risk of small-for-size syndrome in LLG, there was no increased risk of retransplant within 90-days or perioperative mortality in LLG recipients (P = 0.308 and P = 0.932 respectively). Graft type did not predict patient or graft outcomes on regression analysis (P = 0.857 and 0.399 respectively). CONCLUSIONS:Despite smaller graft sizes, outcomes of adult LDLT using LLG are comparable to right lobe grafts transplants. Left lobes can provide an important resource in an era of severe organ shortages, and these data should serve to allay the concerns of the transplant community in the United States.

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre-Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post-Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan-Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End-stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ-perfusion support at transplant post-Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre-Share 35 and post-Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post-Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting "sicker patients" with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.

BACKGROUND: Low case volume has been associated with poorer surgical outcomes in a multitude of surgical procedures. We studied the association among low case volume, outcomes, and the likelihood of pediatric liver transplantation. METHODS: We studied a cohort of 6628 candidates listed in the Organ Procurement and Transplantation Network for primary pediatric liver transplantation between 2002 and 2012; 4532 of the candidates went on to transplantation. Candidates were divided into groups according to the average volume of yearly transplants performed in the listing center over 10 years: >15, 10 to 15, 5 to 9, and <5. We used univariate and multivariate Cox regression analyses with bootstrapping on transplant recipient data and identified independent recipient and donor risk factors for wait-list and posttransplant mortality. RESULTS: 38.5% of the candidates were listed in low-volume centers, those in which <5 transplants were performed annually. These candidates had severely reduced likelihood of transplantation with only 41% receiving a transplant. For the remaining candidates, listed at higher volume centers, the transplant rate was 85% (P < .001). Being listed at a low-volume center was a significant risk factor in multivariate Cox regression analysis for both wait-list mortality (hazard ratio, 3.27; confidence interval, 2.53-4.23) and posttransplant mortality (hazard ratio, 2.21; confidence interval, 1.43-3.40). CONCLUSIONS: 38.5% of pediatric transplant candidates are listed in low-volume transplant centers and have lower likelihood of transplantation and poorer outcomes. If further studies substantiated these findings, we would advocate consolidating pediatric liver transplantation in higher volume centers.

Living donor liver transplantation has failed to become a major means of transplantation in the United States, where <5% of the transplants are performed with living donors. At least 30% to 50% of the complications of donor hepatectomy appear to be related to abdominal wall trauma, including hernia, bowel obstruction, and chronic abdominal discomfort. We analyzed our experience with laparoscopically procured donor hepatectomy. We compared 22 full laparoscopic donor hepatectomies to 20 open/hybrid hepatectomies over an 11-year period. Donor and recipient demographics, complications, and graft and recipient outcomes were analyzed. All 22 laparoscopically procured liver allografts were transplanted successfully. The laparoscopically procured grafts took longer to procure (7 hours 58 minutes versus 6 hours 38 minutes; P < 0.001). The laparoscopically procured cases had lower blood loss (177.3 versus 3753 cc; P < 0.001), a shorter length of stay, and significantly reduced days off work (P = .01). The 1-year graft survival was not different (90% in the laparoscopic group and 85% in the open group; P = 0.70). The 1-year patient survival was not different (95% in the laparoscopic group and 85% in the open group; P = 0.32). There was a trend toward lower wound issues in the laparoscopic group, but this did not reach significance (the hybrid/open group had a 15% hernia rate versus 5% for the laparoscopic group). In experienced living donor centers, laparoscopic liver donation appears to be feasible for all pediatric recipients and some adult recipients. Outcomes for the recipients of laparoscopically procured grafts do not appear significantly different from outcomes with hybrid/open techniques.

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD.

IMPORTANCE/OBJECTIVE:The field of transplantation has made tremendous progress since the first successful kidney transplant in 1954. OBJECTIVE:To determine the survival benefit of solid-organ transplant as recorded during a 25-year study period in the United Network for Organ Sharing (UNOS) database and the Social Security Administration Death Master File. DESIGN, SETTING, AND PARTICIPANTS/METHODS:In this retrospective analysis of UNOS data for solid-organ transplant during a 25-year period (September 1, 1987, through December 31, 2012), we reviewed the records of 1,112,835 patients: 533,329 recipients who underwent a transplant and 579 506 patients who were placed on the waiting list but did not undergo a transplant. MAIN OUTCOMES AND MEASURES/METHODS:The primary outcome was patient death while on the waiting list or after transplant. Kaplan-Meier survival functions were used for time-to-event analysis. RESULTS:We found that 2,270,859 life-years (2,150,200 life-years from the matched analysis) were saved to date during the 25 years of solid-organ transplant. A mean of 4.3 life-years were saved (observed to date) per solid-organ transplant recipient. Kidney transplant saved 1,372,969 life-years; liver transplant, 465,296 life-years; heart transplant, 269,715 life-years; lung transplant, 64,575 life-years; pancreas-kidney transplant, 79,198 life-years; pancreas transplant, 14,903 life-years; and intestine transplant, 4402 life-years. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Our analysis demonstrated that more than 2 million life-years were saved to date by solid-organ transplants during a 25-year study period. Transplants should be supported and organ donation encouraged.

UNLABELLED:Priority is given to patients with hepatocellular carcinoma (HCC) to receive liver transplants, potentially causing significant regional disparities in organ access and possibly outcomes in this population. Our aim was to assess these disparities by comparing outcomes in long waiting time regions (LWTR, regions 5 and 9) and short waiting time regions (SWTR regions 3 and 10) by analyzing the United Network for Organ Sharing (UNOS) database. We analyzed 6,160 HCC patients who received exception points in regions 3, 5, 9, and 10 from 2002 to 2012. Data from regions 5 and 9 were combined and compared to data from regions 3 and 10. Survival was studied in three patient cohorts: an intent-to-treat cohort, a posttransplant cohort, and a cohort examining overall survival in transplanted patients only (survival from listing to last posttransplant follow-up). Multivariate analysis and log-rank testing were used to analyze the data. Median time on the list in the LWTR was 7.6 months compared to 1.6 months for SWTR, with a significantly higher incidence of death on the waiting list in LWTR than in SWTR (8.4% versus 1.6%, P < 0.0001). Patients in the LWTR were more likely to receive loco-regional therapy, to have T3 tumors at listing, and to receive expanded-criteria donor (ECD) or donation after cardiac death (DCD) grafts than patients in the SWTR (P < 0.0001 for all). Survival was significantly better in the LWTR compared to the SWTR in all three cohorts (P < 0.0001 for all three survival points). Being listed/transplanted in an SWTR was an independent predictor of poor patient survival on multivariate analysis (P < 0.0001, hazard ratio = 1.545, 95% confidence interval 1.375-1.736). CONCLUSION/CONCLUSIONS:This study provides evidence that expediting patients with HCC to transplant at too fast a rate may adversely affect patient outcomes.

There is conflicting literature regarding the superiority of transarterial chemoembolization (TACE) versus bland transarterial embolization (TAE), and this has not been well studied before transplantation. Twenty-five TAE patients were matched in a 1:2 ratio with TACE patients by the initial radiographic tumor size and number in a retrospective, case-controlled study. The patients were otherwise treated according to the same protocols. The method of embolization was chosen on the basis of interventionalist practices at 2 sites within the program. Kaplan-Meier survival analyses at 1 and 3 years were the primary endpoints. There were no significant demographic differences between the groups. The mean adjusted Model for End-Stage Liver Disease scores at transplantation and waiting times were not significantly different between the TAE and TACE patients (MELD scores: 26 +/- 3 versus 24 +/- 3 points, P = 0.12; waiting times: 13 +/- 8 versus 11 +/- 10 months, P = 0.43). TAE patients (16%) were less likely than TACE patients (40%) to require 2 procedures (P = 0.04). Explant tumors were completely necrotic for 36% of the TAE patients and for 26% of the TACE patients. The 3-year overall survival rates were 78% for the TAE patients and 74% for the TACE patients (P = 0.66), and the 3-year recurrence-free survival rates were 72% for the TAE patients and 68% for the TACE patients (P = 0.67). On an intention-to-treat basis, there was no significant risk of wait-list dropout associated with TAE or TACE (P = 0.83). In conclusion, there were no significant differences in wait-list dropout or in overall or recurrence-free survival between HCC patients undergoing TAE and HCC patients undergoing TACE before transplantation.

In recent years different minimal access strategies have been designed in order to perform living donor liver surgery for adult recipients with less morbidity. Techniques involve shortening the length of the incision with or without previous laparoscopic mobilization of the liver. Herein we present two cases of totally laparoscopic living donor left hepatectomy, with and without removal of the middle hepatic vein, respectively. We describe in detail the anatomical and technical aspects of the procedure focusing on relevant points to enhance safety.