Nora Fullington

Deceased-Donor Split-Liver Transplantation in Adult Recipients: Is the Learning Curve Over?

BACKGROUND Infants have the highest wait-list mortality of all liver transplantation candidates. Deceased-donor split-liver transplantation, a technique that provides both an adult and pediatric graft, might be the best way to decrease this disproportionate mortality. Yet concern for an increased risk to adult split recipients has discouraged its widespread adoption. We aimed to determine the current risk of graft failure in adult recipients after split-liver transplantation. STUDY DESIGN United Network for Organ Sharing data from 62,190 first-time adult recipients of deceased-donor liver transplants (1995-2010) were analyzed (889 split grafts). Bivariate risk factors (p < 0.2) were included in Cox proportional hazards models of the effect of transplant type on graft failure. RESULTS Split-liver recipients had an overall hazard ratio of graft failure of 1.26 (p < 0.001) compared with whole-liver recipients. The split-liver hazard ratio was 1.45 (p < 0.001) in the pre-Model for End-Stage Liver Disease era (1995-2002) and 1.10 (p = 0.28) in the Model for End-Stage Liver Disease era (2002-2010). Interaction analyses suggested an increased risk of split-graft failure in status 1 recipients and those given an exception for hepatocellular carcinoma. Excluding higher-risk recipients, split and whole grafts had similar outcomes (hazard ratio = 0.94; p = 0.59). CONCLUSIONS The risk of graft failure is now similar between split and whole-liver recipients in the vast majority of cases, which demonstrates that the expansion of split-liver allocation might be possible without increasing the overall risk of long-term graft failure in adult recipients. Additional prospective analysis should examine if selection bias might account for the possible increase in risk for recipients with hepatocellular carcinoma or designated status 1.

Deceased Donor Liver Transplantation in Infants and Small Children: Are Partial Grafts Riskier Than Whole Organs?

Infants have the highest wait‐list mortality of all liver transplant candidates. Although previous studies have demonstrated that young children may be at increased risk when they receive partial grafts from adult and adolescent deceased donors (DDs), with few size‐matched organs available, these grafts have increasingly been used to expand the pediatric donor pool. We aimed to determine the current adjusted risks of graft failure and mortality in young pediatric recipients of partial DD livers and to determine whether these risks have changed over time. We analyzed 2683 first‐time recipients of DD livers alone under the age of 24 months in the United Network for Organ Sharing database (1995‐2010), which included 1118 partial DD livers and 1565 whole DD organs. Transplant factors associated with graft loss in bivariate analyses (P < 0.1) were included in multivariate proportional hazards models of graft and patient survival. Interaction analysis was used to examine risks over time (1995‐2000, 2001‐2005, and 2006‐2010). Although there were significant differences in crude graft survival by the graft type in 1995‐2000 (P < 0.001), graft survival rates with partial and whole grafts were comparable in 2001‐2005 (P = 0.43) and 2006‐2010 (P = 0.36). Furthermore, although the adjusted hazards for partial graft failure and mortality were 1.40 [95% confidence interval (CI) = 1.05‐1.89] and 1.41 (95% CI = 0.95‐2.09), respectively, in 1995‐2000, the adjusted risks of graft failure and mortality were comparable for partial and whole organs in 2006‐2010 [hazard ratio (HR) for graft failure = 0.81, 95% CI = 0.56‐1.18; HR for mortality = 1.02, 95% CI = 0.66‐1.71]. In conclusion, partial DD liver transplantation has become less risky over time and now has outcomes comparable to those of whole liver transplantation for infants and young children. This study supports the use of partial DD liver grafts in young children in an attempt to significantly increase the pediatric organ pool. Liver Transpl 19:721–729, 2013..

Pulmonary support on Day 30 as a predictor of morbidity and mortality in congenital diaphragmatic hernia

PURPOSE Congenital diaphragmatic hernia (CDH) is associated with significant in-hospital mortality, morbidity and length-of-stay (LOS). We hypothesized that the degree of pulmonary support on hospital day-30 may predict in-hospital mortality, LOS, and discharge oxygen needs and could be useful for risk prediction and counseling. METHODS 862 patients in the CDH Study Group registry with a LOS ≥ 30 days were analyzed (2007-2010). Pulmonary support was defined as (1) room-air (n=320) (2) noninvasive supplementation (n=244) (3) mechanical ventilation (n=279) and (4) extracorporeal membrane oxygenation (ECMO, n=19). Cox Proportional hazards and logistic regression models were used to determine the case-mix adjusted association of oxygen requirements on day-30 with mortality and oxygen requirements at discharge. RESULTS On multivariate analysis, use of ventilator (HR 5.1, p=.003) or ECMO (HR 19.6, p<.001) was a significant predictor of in-patient mortality. Need for non-invasive supplementation or ventilator on day-30 was associated with a respective 22-fold (p<.001) and 43-fold (p<.001) increased odds of oxygen use at discharge compared to those on room-air. CONCLUSIONS Pulmonary support on Day-30 is a strong predictor of length of stay, oxygen requirements at discharge and in-patient mortality and may be used as a simple prognostic indicator for family counseling, discharge planning, and identification of high-risk infants.

Immediate extubation after pediatric liver transplantation: A single‐center experience

The care of pediatric liver transplant recipients has traditionally included postoperative mechanical ventilation. In 2005, we started extubating children undergoing liver transplantation in the operating room according to standard criteria for extubation used for general surgery cases. We reviewed our single‐center experience to determine our rates of immediate extubation and practice since that time. The records of 84 children who underwent liver transplantation from 2005 to 2011 were retrospectively reviewed. The immediate extubation rate increased from 33% during 2005‐2008 to 67% during 2009‐2011. Immediate extubation did not result in an increased reintubation rate in comparison with delayed extubation in the intensive care unit (ICU). Patients undergoing immediate extubation had a trend toward a shorter mean ICU stay as well as a significantly decreased overall hospital length of stay. Our findings suggest that there is a learning curve for instituting immediate extubation in the operating room after liver transplantation and that the majority of pediatric liver recipients can safely undergo immediate extubation. Liver Transpl 21:57‐62, 2015.

Aorto‐Mesenteric and Renal Allograft Transplant: A Novel Treatment for Midaortic Syndrome

Midaortic syndrome (MAS) is a rare condition characterized by stenosis of the aorta and often involving renal and visceral arteries. Current therapies include medical management of associated hypertension, and interventional procedures such as angioplasty or surgical bypass. We report a 2‐year‐old female with severe MAS who was initially treated with angioplasty and stents in both her aorta and superior mesenteric artery (SMA). Due to the presence of long segment stenoses, her renal arteries were not amenable to surgical reconstruction and she rapidly progressed to Stage V chronic kidney disease. The patient underwent bilateral nephrectomy and renal transplantation using a donor thoracoabdominal aorta allograft to provide inflow for the kidney as well as to bypass the nearly occluded aorta. The donor SMA was used to bypass the native SMA stenosis. Postoperatively, the patient had normalization of four limb blood pressures. She weaned from five anti‐hypertensive agents to monotherapy with excellent renal function. This is the first reported case of thoracoabdominal aortic bypass using allograft aorta to address MAS. This approach allowed for successful kidney transplantation with revascularization of the mesenteric, and distal aortic circulation using allograft conduit that will grow with the child, obviating the need for repeated interventional or surgical procedures.

Pulmonary support on day of life 30 is a strong predictor of increased 1 and 5-year morbidity in survivors of congenital diaphragmatic hernia.

PURPOSE Pulmonary support (PS) on day-of-life-30 (DOL-30) has been shown to be the strongest predictor of subsequent morbidity and in-patient mortality in congenital diaphragmatic hernia (CDH). We hypothesized that PS on DOL-30 can also predict long-term outcomes in CDH survivors. METHODS We analyzed records of 201 CDH survivors followed by a single multidisciplinary clinic (1995-2010). Follow-up was 83 and 70% at 1 and 5years respectively. PS was defined as: (1) invasive support (n=44), (2) noninvasive support (n=54), or (3) room air (n=103). Logistic regression was used to estimate the adjusted association of PS on DOL-30 with outcomes at 1 and 5-years. RESULTS Use of PS on DOL-30 was significantly associated with pulmonary and developmental morbidities at 1 and 5-years. Even after adjusting for defect-size and presence of ventilation/perfusion mismatch, greater PS on DOL-30 was associated with a significantly increased odds of requiring supplemental oxygen and developmental referral at 1-year, and asthma and developmental referral at 5-years. CONCLUSION CDH survivors continue to have significant long-term pulmonary and developmental morbidities. PS on DOL-30 is a strong independent predictor of morbidity at 1 and 5-years and may be used as a simple prognostic tool to identify high-risk infants.

Reno-portal anastomosis as an approach to pediatric kidney transplantation in the setting of inferior vena cava thrombosis.

In pediatric renal transplantation in the setting of IVC thrombosis, the retrohepatic IVC or gonadal veins are often used for outflow. However, if use of systemic venous outflow is unsuccessful, options become limited. We report the use of the portal vein for venous outflow in kidney retransplantation in the setting of IVC thrombosis. The patient is a 19‐month‐old male who developed end‐stage renal failure at seven months of age secondary to hypotension after spontaneous rupture of an accessory renal vein. The IVC was occluded during emergent laparotomy, and the patient developed extensive IVC thrombosis. The first two transplant attempts used the retrohepatic IVC for venous outflow. Despite good initial flow, in both instances the renal vein thrombosed on post‐operative day 1. In an unsuccessful salvage attempt of the second transplant, a reno‐portal anastomosis was performed. With few options for vascular access, a third transplant was attempted. The reno‐portal stump from the second transplant was used for outflow. The patient recovered well from his third transplant (creatinine 0.6 mg/dL 35 months post‐surgery), demonstrating that the portal vein can be used for outflow in cases of extensive IVC thrombosis.

Strain induced esophageal growth in a novel rodent model

PURPOSE Longitudinal esophageal strain has been shown to increase esophageal length but the contribution of tissue hyperplasia to this growth is unknown. We used a novel model of esophageal stretch to determine the cellular response to the strain stimulus. METHODS Male Sprague-Dawley rats underwent transection of the distal esophagus. The distal stump was ligated and stretched over a silicone tube. The proximal esophageal stump was anastomosed to the stomach to restore continuity. After two, four, or seven days, the silicone tube was removed and the esophageal segment was measured and compared to its initial length. Sham animals had only a thin piece of silicone tubing placed. Standardized histologic sections were evaluated for wall thickness. Immunofluorescence with DAPI, Ki-67, and Myogenin antibodies was used to assess nuclear density, proliferation indices, and myoblast differentiation indices. RESULTS Experimental animals demonstrated a significant increase in esophageal length compared to sham controls at four and seven days with no difference at two days. There was significant lengthening between four and seven days among the experimental animals. There was no change in wall thickness between experimental and sham animals at any time point. Nuclear density was increased at all time points, although this only reached significance at day four. Proliferation indices were significantly increased relative to sham controls at all time points. Esophageal strain induced significantly increased myoblast differentiation. CONCLUSION In this novel rat model of esophageal strain, lengthening is associated with stable esophageal wall thickness, increased nuclear density, increased cellular proliferation, and increased myogenin expression. These data suggest that true tissue hyperplasia may contribute to the increased length seen after esophageal strain.

Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model

BACKGROUND We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). METHODS A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. RESULTS The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. CONCLUSIONS Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress.

The Effect of Graft Type on Mortality in Liver Transplantation for Hepatocellular Carcinoma

BACKGROUND Liver transplantation (LT) with living-donor (LD-P) and deceased-donor (DD-P) partial grafts for hepatocellular carcinoma (HCC) may be associated with worse outcomes. Using the United Network for Organ Sharing (UNOS), we aimed to: (1) examine the risk of mortality in LT for HCC, (2) to establish if this risk is affected by partial graft use, and (3) to determine if this effect is mitigated by improved tumor-associated risk stratification. MATERIAL AND METHODS All first-time adult LT recipients were analyzed (3/2002-12/2012), including 2,353 LD-P, 727 DD-P, and 47,833 DD whole (DD-W) grafts. Cox proportional hazards models were used to examine the risk of mortality given HCC. Interaction/subset analyses were used to examine the effect of tumor-risk and graft-type on outcome. Presence of an HCC exception and low alpha-fetoprotein (AFP) level (<66 ng/mL) were considered favorable. RESULTS Overall, HCC was associated with an increased mortality risk compared to the absence of HCC (HR 1.21 [1.15-1.27]), and the use of partial grafts was noted to further intensify this risk. However, HCC with a favorable risk profile had more comparable outcomes to patients without HCC and this finding was similar across all graft-types (Given LD-P: HR 1.14 [0.76-1.73]; Given DD-P: HR1.05 [0.71-1.56]; Given DD-W: HR1.08 [1.02-1.14]). On subset analysis, all graft types had similar outcomes given either favorable-risk HCC or the absence of HCC. CONCLUSIONS There is no significant difference in outcomes between whole and partial grafts given (1) patients with HCC with a favorable risk-profile or (2) patients without HCC.