Predictors of outcome after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria.

The Milan criteria have been the cornerstone of selection policies for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) globally for over two decades. Many groups have proposed the transplantation of patients with larger and more numerous tumors achieving comparable results. Many of these use radiologic morphometric criteria as surrogates for explant pathology to predict outcomes. Several other indices have been developed both within and beyond Milan incorporating biological indices as well as dynamic markers of response to pre-transplant locoregional treatments and waiting time. These have allowed for successful expansion of transplant selection criteria without compromising outcomes with limited organ supplies. In this review we will discuss the predictors of outcome in patients beyond Milan criteria.

Growth of liver allografts over time in pediatric transplant recipients.

The liver's capacity to grow in response to metabolic need is well known. However, long-term growth of liver allografts in pediatric recipients has not been characterized. A retrospective review of pediatric recipients at a single institution identified patients who had cross-sectional imaging at 1, 5, and 10 years post-transplant. Using volumetric calculations, liver allograft size was calculated and percent SLV were compared across the different time points; 18 patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2 or more time points. Measured liver volumes increased by 59% after 5 years and 170% after 10 years. The measured liver volumes compared to calculated %SLV for these patients were 123 ± 37%, 97 ± 19%, and 118 ± 27% at 1, 5, and 10 years after transplant, respectively. Our data suggest that liver allografts in pediatric recipients increase along with overall growth, and reach SLVs for height and weight by 5 years post-transplantation. Additionally, as pediatric recipients grow, the livers appear to maintain appropriate SLV.

No country for old livers? Examining and optimizing the utilization of elderly liver grafts.

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.

One Size Does Not Fit All--Regional Variation in the Impact of the Share 35 Liver Allocation Policy.

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.

Elevated preoperative recipient neutrophil-lymphocyte ratio is associated with delayed graft function following kidney transplantation.

INTRODUCTION: The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status. We studied the effect of preoperative elevated NLR in the recipient in relation to the risk of developing delayed graft function (DGF) after kidney transplantation. METHODS: We retrospectively analysed the preoperative white blood cell count of renal transplant recipients between 2003 and 2005. An NLR >3.5 was considered elevated. There were 398 kidney transplant recipients of whom 249 received organs from donors after brain death (DBD), 61 from donors after circulatory death (DCD), and 88 from living donors. RESULTS: One hundred three patients (26%) developed DGF, of which 67 (65%) had NLRs >3.5. Of 295 recipients with primary graft function, only 44 (15%) had elevated NLR. Univariate analysis revealed three factors that significantly influenced graft function: NLR >3.5, cold ischemic time (CIT) >15 hours, and donor type. On multivariate analysis, both donor type (DCD: hazard ratio [HR] = 2.421, confidence interval [CI] = 1.195-4.905, P = .014; LD: HR = 0.289, CI = 0.099-0.846, P = .024) and NLR (HR = 10.673, CI = 6.151-18.518, P < .0001) remained significant. CONCLUSIONS: Elevated recipient preoperative NLR could contribute to increase the risk of developing DGF, which appears to be more pronounced in patients receiving grafts from living donors.

Totally laparoscopic full left hepatectomy for living donor liver transplantation in adolescents and adults.

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.

Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation.

It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21,673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30,321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.

Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) provides an indicator of inflammatory status. An elevated NLR has been shown to be a prognostic indicator in primary colorectal malignancy. The aim of this study was to establish whether NLR predicts outcome in patients undergoing resection for colorectal liver metastasis. DESIGN: Retrospective analysis of the white cell and differential counts for 440 patients undergoing liver resections for colorectal liver metastasis between January 1996 and January 2006. An NLR > or = 5 was considered to be elevated. RESULTS: Two hundred and eighty-nine males and 151 females were included. Seventy-eight patients (18%) had an elevated NLR, 55 of whom died, giving elevated NLR a positive predictive value (PPV) for death of 71%. Sixty of the 78 patients had recurrent disease giving raised NLR an PPV for recurrence of 78%. The 5-year survival for patients undergoing resection with high NLR was significantly worse than that for patients with normal NLR (22% vs. 43%, p<0.0001). Univariate analysis of factors affecting survival revealed raised NLR, number of metastases > 8, tumour size > 5 cm and age > 70 significantly affected outcome. All factors except tumour size remained significant predictors of term survival on multivariate analysis (NLR:HR=2.261, CI=1.654-3.129, p<0.0001, metastases > 8:HR=1.611, CI=1.006-2.579, p=0.047, age > 70:HR=1.418, CI=1.049-1.930, p=0.027). Elevated NLR was found to be the sole positive predictor of recurrence on univariate analysis (HR=4.521, CI=2.475-8.257, p<0.0001). CONCLUSION: Elevated NLR increases both risk of death and the risk of recurrence in patients who undergo surgery for CRLM. Preoperative NLR measurement may therefore provide a simple method of identifying patients with a poorer prognosis.

Warm ischemia in transplantation: search for a consensus definition.

UNLABELLED: "Warm ischemia" is a term used to describe ischemia of cells and tissues under normothermic conditions. In the transplant setting, this term is used to describe two physiologically distinct periods of ischaemia: (1) Ischemia during implantation, from removal of the organ from ice until reperfusion, and (2) Ischemia during organ retrieval, from the time of cross clamping (or of asystole in non-heart-beating donors), until cold perfusion is commenced. These periods of warm ischemia differ in their nature and the magnitude of their pathophysiologic consequences. In much transplant literature, however, the term "warm ischaemia" is used to describe both of these periods indiscriminately. This paper attempts to produce a definition to distinguish between the two periods of warm ischemia. METHODS: We conducted a questionnaire survey of all UK transplant surgeons. The definitions proposed in the survey were: (a) warm ischemia and re-warm ischemia; (b) first warm ischemia and second warm ischemia; (c) in-situ warm ischemia and ex-vivo warm ischemia; (d) warm ischemia in donor and warm ischemia in recipient; (e) no opinion or other opinion. RESULTS: There was a 64% response rate among 134 consultants with no consensus definition being reached. The majority of consultants (31.4%) preferred the terms "warm ischemia in donor", and "warm ischemia in recipient" to distinguish the two periods. CONCLUSIONS: This paper highlights the need to adopt uniform terms to avoid confusion between different types of warm ischemia in transplantation.

Hyperhomocysteinaemia is associated with the rate of abdominal aortic aneurysm expansion.

OBJECTIVES: Previous literature has suggested an association between AAA and the presence of elevated plasma homocysteine levels (HCY). Homocysteine can stimulate elastolysis in the arterial media via activation of elastase and matrix metalloproteinases. No evidence in the literature exists correlating aneurysm expansion and HCY. The study objective is to identify whether the rate of AAA expansion is related to HCY. METHODS: 108 patients undergoing surveillance for AAA were identified at our vascular surgical unit. AAA size and growth rate were assessed by serial ultrasonographic measurements. Fasting total HCY levels were measured using fluorescence polarisation immunoassays. Demographic details and atherosclerotic risk factors were noted all AAA patients. A multivariate analysis was performed for growth rate vs. HCY, hypertension and hypercholesterolaemia. The correlation between AAA growth rate, AAA size and HCY levels were calculated. RESULTS: 60% of patients with AAA had some degree of hyperhomocysteinaemia (> 15 micromol/l). Multivariate analysis showed HCY to be the only significant factor affecting AAA growth rate. A positive correlation was demonstrated between HCY levels and AAA growth rate using a linear regression model (R=0.28, p=0.003). Median growth rate among patients with hyperHCY was double that of patients with normal HCY (0.5 mm/month vs. 0.25 mm/month, p=0.003). A growth rate of > 10 mm/year was seen in 25% of hyper HCY patients and in only 2% of patients with normal HCY. In addition patients with hyper HCY and larger AAAs (> 4 cm) had a growth rate twice as fast as patients with hyper HCY and AAAs < 4 cm. CONCLUSIONS: A correlation between HCY and growth rate exists, although this is weak due to the multifactorial aetiology of AAAs. HyperHCY patients have faster expansion rates than patients with normal HCY, with significant numbers demonstrating rapid expansion (> 10 mm/year) and therefore an increased risk of rupture.