Faculty Bibliography

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.

Hepatocellular carcinoma (HCC) is the most common liver malignancy and the third most common cause of cancer-related deaths. Liver resection (LR) and liver transplantation (LT) are the only curative modalities for HCC. Despite recent advances and the adoption of the Milan and University of California, San Francisco, criteria, HCC recurrence after LR and LT remains a challenge. Several markers and prognostic scores have been proposed to predict tumor aggressiveness and supplement radiological data; among them, neutrophil-lymphocyte ratio (NLR) has recently gained significant interest. An elevated NLR is thought to predispose to HCC recurrence by creating a protumorigenic microenvironment through both relative neutrophilia and lymphocytopenia. In the present review, we attempted to summarize the published work on the role of pretreatment NLR as a prognostic marker for HCC following LR and LT. A total of 13 LT and 18 LR studies were included from 2008 to 2015. Pretransplant NLR was most often predictive of HCC recurrence, recurrence-free survival, and overall survival. NLR was, however, more variably and less clearly associated with worse outcomes following LR.

Small bowel bleeding should be considered in patients who continue to bleed despite a negative upper endoscopy and colonoscopy. The differential diagnosis of small bowel bleeding can include infection, inflammatory conditions, vascular malformations, and, rarely, malignancy. This report demonstrates a rare, primary, small bowel, reticular cell sarcoma presenting as an overt gastrointestinal bleed. These tumors are difficult to diagnose because they are rarely seen on traditional cross-sectional imaging and can present with multiple synchronous lesions throughout the intestinal tract.

An index to predict hospital length of stay after liver transplantation could address unmet clinical needs. Length of stay is an important surrogate for hospital costs and efforts to limit stays can preserve our healthcare resources. Here, we devised a scoring system that predicts hospital length of stay following liver transplantation. We used univariate and multivariate analyses on 73 635 adult liver transplant recipient data and identified independent recipient and donor risk factors for prolonged hospital stay (>30 days). Multiple imputation was used to account for missing variables. We identified 22 factors as significant predictors of prolonged hospital stay, including the most significant risk factors: intensive care unit (ICU) admission (OR 1.75, CI 1.58-1.95) and previous transplant (OR 1.60, CI 1.47-1.75). The length of stay (LOS) index assigns weighted risk points to each significant factor in a scoring system to predict prolonged hospital stay after liver transplantation with a c-statistic of 0.75. The LOS index demonstrated good discrimination across the entire population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI 2.06-2.46) and 7.90 (7.29-8.56) for prolonged hospital stay (>30 days). The LOS index utilizes 22 significant donor and recipient factors to accurately predict hospital length of stay following liver transplantation. The index further demonstrates the basis for a clear clinical recommendation to mitigate risk of long hospitalization by minimizing cold ischemia time.

OBJECTIVE:To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA:Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS:Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS:Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS:Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

OBJECTIVE:Marginal livers (ML) have been used to expand the donor pool. National utilization of MLs is variable, and in some centers, they are never used. We examined the outcomes of MLs in the largest single center series of MLs used to date and compared outcomes to standard (SL) and living donor (LD) livers. METHODS:Analysis of a prospectively maintained database of all liver transplants performed at our institution from 1998 to 2016. ML grafts were defined as livers from donors >70, livers discarded regionally and shared nationally, livers with cold ischemic time >12 hours, livers from hepatitis C virus positive donors, livers from donation after cardiac death donors, livers with >30% steatosis, and livers split between 2 recipients. RESULTS:A total of 2050 liver transplant recipients were studied, of these 960 (46.8%) received ML grafts. ML recipients were more likely to have lower MELDs and have hepatocellular carcinoma. Most MLs used were from organs turned down regionally and shared nationally (69%) or donors >70 (22%). Survival of patients receiving MLs did not significantly differ from patients receiving SL grafts (P = 0.08). ML and SL recipients had worse survival than LDs (P < 0.01). Despite nearly half of our recipients receiving MLs, overall survival was significantly better than national survival over the same time period (P = 0.04). Waitlist mortality was significantly lower in our series compared with national results (19% vs 24.0%, P < 0.0001). CONCLUSIONS:Outcomes of recipients of ML grafts are comparable to SL transplants. Despite liberal use of these grafts, we have been able to successfully reduce waitlist mortality while exceeding national post-transplant survival metrics.

BACKGROUND:Low case volume has been associated with worse survival outcomes in solid organ transplantation. Our aim was to analyze wait-list outcomes in conjunction with posttransplant outcomes. METHODS:We studied a cohort of 11,488 candidates waitlisted in the Organ Procurement and Transplantation Network (OPTN) for pediatric kidney transplant between 2002 and 2014, including both deceased- and living-donor transplants; 8757 (76 %) candidates received a transplant. Candidates were divided into four groups according to the average volume of yearly transplants performed in the listing center over a 12-year period: more than ten, six to nine, three to five, and fewer than three. We used multivariate Cox regression analysis to identify independent risk factors for wait list and posttransplant mortality. RESULTS:Twenty-seven percent of candidates were listed at low-volume centers in which fewer than three transplants were performed annually. These candidates had a limited transplant rate; only 49 % received a transplant versus 88 % in high-volume centers (more than ten transplants annually) (p < 0.001). Being listed at a low-volume center showed a fourfold increased risk for death while on the wait list [hazard ratio (HR) 4.0 in multivariate Cox regression and 6.1 in multivariate competing risk regression]. It was not a significant risk factor for posttransplant death in multivariate Cox regression. CONCLUSIONS:Pediatric transplant candidates are listed at low-volume transplant centers are transplanted less frequently and have a much greater risk of dying while on the wait list. Further studies are needed to elucidate the reasons behind the significant outcome differences.

OBJECTIVE:We sought to develop a "Model Of Recurrence After Liver transplant" (MORAL) for hepatocellular carcinoma (HCC). BACKGROUND:The Milan criteria are used to allocate livers to patients with HCC requiring liver transplantation (LT) but do not include objective measures of tumor biology. Biological markers including the neutrophil-lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) have been associated with recurrence risk. METHODS:Prospective cohort study of adults undergoing LT for HCC between January 2001 and December 2012. RESULTS:A total of 339 patients were included. On multivariable Cox regression analysis, 3 preoperatively available factors were independent predictors of worse recurrence-free survival (RFS), namely, an NLR ≥ 5 (P < 0.0001, hazard ratio, HR: 6.2), AFP > 200 (P < 0.0001, HR: 3.8), and Size >3 cm (P < 0.001, HR: 3.2). The Pre-MORAL score was constructed from the hazard ratios and assigning patients points in an additive fashion, with a minimum of 0 points (no factors) and a maximum of 13 points (all 3 factors). The highest risk patients in the Pre-MORAL had a 5-year RFS of 17.9% compared with 98.6% for the low risk group (P < 0.0001). The post-MORAL was constructed similarly using the 4 postoperatively available independent predictors of worse RFS, grade 4 HCC's (P < 0.0001, HR: 5.6), vascular invasion (P = 0.019, HR: 2.0), size >3 cm (P < 0.0001, HR: 3.2) and number >3 (P = 0.048, HR: 1.8). The pre- and post-MORAL were superior to Milan at predicting recurrence with c-statistics of 0.82 and 0.87, compared with 0.63, respectively. We then combined the scores to produce a combo-MORAL, with a c-statistic of 0.91 for predicting recurrence. CONCLUSIONS:The MORAL score provides a simple, highly accurate tool for predicting recurrence and risk-stratification pre- and postoperatively.

Since the advent of the Milan criteria in 1996 and its widespread adoption for selection of patients with hepatocellular carcinoma (HCC) who would benefit from transplant, there has been an extensive hunt for the ideal clinical biomarker to predict HCC recurrence. This is because Milan lack does not include tumor biology indices and recurrence rates remain in the 15-20% range worldwide. While a 'silver-bullet' biomarker has not been found, several useful inflammatory markers have been identified and used in scoring systems that supersede Milan in their ability to predict HCC recurrence post liver transplantation (LT). In this review, we aim to summarize the role of inflammatory markers paly in the selection of HCC patients awaiting LT.