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Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) ≥ 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single-center series have demonstrated the feasibility and short-term efficacy of OLT after POPH is controlled with vasodilators, but long-term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty-eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to ≤35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow-up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long-term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled with oral vasodilators.

We develop a model of predators foraging within a single patch, on prey that become temporarily immune to predation (depressed) after detecting a predator. Interference through prey depression occurs because the proportion of vulnerable prey (and hence intake rate) decreases as predator density increases. Predators in our model are not forced to move randomly within the patch, as is the case in other similar models, but can avoid areas of depressed prey and so preferentially forage over vulnerable prey. We compare the extent to which different avoidance rules (e.g., move more quickly over depressed prey or turn if approaching depressed prey) influence the amount of time spent foraging over depressed and vulnerable prey, and how this influences the strength of interference. Although based on a different mechanism, our model produces two similar general predictions to interference models based on direct interactions between predators: the strength of interference increases with (1) increased competitor density and (2) decreased prey encounter rate. This suggests that there are underlying similarities in the nature of interference even when it arises through different processes. Not surprisingly, avoidance of depressed prey can substantially reduce the strength of interference compared with random foraging. However, we identify the region of the model’s parameter space in which this reduction is particularly large and show that the only system for which suitable data are available, redshank Tringa totanus feeding on Corophium volutator, falls within this region. The model shows that, by adjusting its search path to avoid areas of depressed prey, a predator can substantially reduce the amount of the interference it experiences and that this applies over a wide range of parameter space, including the region occupied by a real system. This suggests that behavior-based interference models should consider predator search pattern if they are to accurately predict the strength of the interference.

Orthotopic liver transplantation (OLT) has become a well-established modality for treatment of previously fatal liver disease. The advent of new immunosuppressive agents and refinement of surgical techniques have accounted for remarkable progress in the years since the first OLT was performed in 1963. 1,2 The past decade has also witnessed an exponential increase in the number of patients awaiting liver transplantation. Currently, it is estimated that more than 14,500 patients are listed for liver transplantation, with only 4,500 cadaveric livers available annually. With more than 4 million Americans affected with hepatitis C, 25% to 35% of whom will develop cirrhosis, the transplant community is anticipating an epidemic of patients requiring transplantation. Such an increasing discrepancy between donor supply and demand has resulted in an increasing death rate for adult and pediatric patients awaiting OLT. In addition, in the past 5 years, there has been an increase in the number of livers transplanted into critically ill patients, with a higher rate of complications and death after OLT. To maximize donor organ use in children and adults, four procedures have evolved from the fundamental principle that a portion of the liver with a suitable vascular pedicle, bile duct, and venous drainage, along with sufficient functional hepatocyte mass, can sustain hepatic function in a patient as well as a whole organ. Reduced-size liver transplantation 3–9 was the wellspring for this effort, followed by adult-to-pediatric living-related transplantation, 10,11 cadaveric split liver transplantation (SLT), 12–32 and more recently adult-to-adult living donor transplantation. 33 Pichlmayr et al 12 in 1988 reported the first clinical attempt at an ex vivo SLT. One year later, Bismuth et al 13 described two patients with fulminant hepatic failure, each receiving a split graft. Broelsch et al 15 reported the first series of 30 SLTs in 21 children and 5 adults. In this early experience, patient survival was inferior to that reported in series of cadaveric whole-liver transplants. 28 Despite skepticism as to the lasting role of SLT, several European centers, faced with increasing waiting list death rates because of donor scarcity, pursued the split liver option. The results of a collective experience of 50 donor livers, providing 100 grafts during a 5-year period, from the European Split Liver Registry, demonstrated no significant difference from the results of conventional whole-organ orthotopic liver transplantation during the same period. 16 Such results renewed interest in SLT, as evidenced by more recent series of ex vivo SLT. 14,19,24 Despite marked improvements of outcome in these series, high-risk patients appeared to have a worse outcome than nonurgent recipients. A modification of the ex vivo splitting technique is in vivo splitting, which involves an extension of the techniques for living-related donor liver procurement that is completed in the heart-beating cadaver donor. At UCLA, we first attempted in vivo SLT in 1992. Our first experience was not favorable, but after establishing a living-related liver program and accruing experience in 30 cases, we resumed the in vivo split liver program in 1996. In that same year, Rogiers et al 30 reported their initial experience with split grafts, which demonstrated superior results compared with ex vivo split liver techniques. There have been only a few published reports of in vivo SLT 29–35 because the procedure has been performed only during the past 4 years. Initial results from these few series, which involved a limited number of patients, suggested an improvement over the ex vivo experience, with higher patient and graft survival rates and a lower incidence of complications. However, larger series of in vivo SLT are required to confirm these results. Further, a better understanding of the factors that influence the outcome of SLT is critical for the successful application of SLT to expand a severely depleted cadaveric donor pool. This report examined the outcome of in vivo SLT and analyzed the factors affecting patient survival in a large number of recipients.

Summary 1. Above a threshold density of ≈ 100 birds ha-1, strong interference occurred between redshank Tringa totanus (Linnaeus) feeding by sight on the amphipod crustacean Corophium volutator (Pallas). No aggressive interactions occurred between the birds and the probable cause was prey depression. 2. Redshank fed in a square metre of mud that had recently been exploited by another redshank much less often than would be expected by chance. By avoiding areas where prey would have been recently exploited, the feeding rate of redshank was up to three times faster than it would have been had they not avoided other foraging redshank. 3. Bar-tailed godwit fed in a square metre of mud that had been recently exploited by another godwit much more often than would be expected by chance in randomly moving birds. They tended to flock while foraging and showed no tendency to avoid areas where prey would have been recently exploited. 4. There was no evidence that interference occurred between bar-tailed godwit Limosa lapponica (Linnaeus) feeding on the polychaete lugworm Arenicola marina (Linnaeus) at densities below 300 birds ha-1, even though aggressive interactions occurred between birds.

Four open core throatless batch fed rice husk gasifier reactors having internal diameters of 15.2, 20.3, 24.4 and 34.3 cm were designed and fabricated. Each reactor connected with gas cleaning unit was tested for its performance characteristics. On each reactor ten trial runs were conducted varying the air flow rate or specific gasification rate. Gas quality, gas production rate, gasification efficiency specific gasification rate, and equivalence ratio were determined for every run on each of the four reactors. It was found that for each reactor the gasifier performance was the best at a specific gasification rate of around 192.5 kg/h-m 2 . Under the best operating conditions, the equivalence ratio was 0.40 and the gasification efficiency was around 65%. These parameters may be used for designing rice husk operated throatless gasifiers in the capacity range of 3–15 kW.

Some oystercatchers are less efficient predators than others because of their age or their feeding habits. This lower feeding efficiency may reduce their survival or their chance of migrating to nesting grounds. Do these birds carry more parasites? To address this question, we studied the intestinal parasite load of oystercatchers hibernating in the Exe estuary (Great Britain) in relation to their feeding site, type of prey, and parasite load of mussels, their main prey in the estuary. We show that some birds with lower feeding efficiency carry more parasites, particularly the potentially pathogenic nematode Capillaria sp. The degree of infestation by trematodes through the mussel Ptilostomum brevicolle is not related to the degree of infestation of the mussels themselves. We suggest that some birds are resistant to infestation. [Journal translation]

Congenital anatomic anomalies often present technical obstacles during liver transplants. Biliary atresia is the most common indication for liver transplants in children, and approximately 7-10% of these patients have congenital anomalies comprising the "polysplenia syndrome." The polysplenia syndrome, which often includes abdominal situs inversus, is of particular concern in liver transplants because these anatomic anomalies result in a more complex hepatectomy, alterations in the placement of the donor grafts, and the need for additional vascular reconstruction. Earlier reports have shown mixed results for these patients who have undergone orthotopic liver transplants, reporting a high rate of postoperative complications and poor survival. The use of living-related donor grafts has produced excellent results in the general pediatric population. This is the first report of the successful use of a living-related donor graft for an orthotopic liver transplant to treat end-stage liver disease secondary to biliary atresia in a child with polysplenia syndrome.

Interference is an important component of food competition but is often difficult to detect and measure in natural animal populations. Although interference has been shown to occur between oystercatchers Haematopus ostralegus L. feeding on mussels Mytilus edulis L., four previous studies have not detected interference between oystercatchers feeding on cockles Cerastoderma edule L. In contrast, this study detected interference between cockle-feeding oystercatchers in the Baie de Somme, France. Prey stealing (kleptoparasitism), one of the main causes of interference between mussel-feeders, also occurred between oystercatchers in the Baie de Somme. The kleptoparasitism rate was related to the natural variation in the food supply, tending to be higher when cockles were rare. Feeding rate was negatively related to competitor density, so providing evidence for interference, but, as in mussel-feeders, only above a threshold density of about 50–100 birds ha−1. The strength of interference at a fixed competitor density was related to the cockle food supply, usually being greater when cockles were rare. Previous studies probably failed to detect interference between cockle-feeders because competitor densities were too low, or cockles were too abundant, or because they were not conducted during late winter when interference is most intense. The study shows that natural variation in the food supply can influence the strength of interference within an animal population and provides support for those behaviour-based interference models which predict that the strength of interference will be greatest when competitor densities are high and prey scarce.

BACKGROUND Poor linear growth after pediatric orthotopic liver transplantation (OLT) is a well-described phenomenon. We have undertaken a bivariate and multivariate analysis of multiple factors that might effect postOLT growth in all children who underwent transplantation at a single center, with survival > 1 year and adequate follow-up. METHODS Standardized height score (Z score) and height deficit (centimeters below the 50th percentile) were computed for each patient over time. The variables assessed were (i) age at OLT, (ii) gender, (iii) pretransplantation diagnosis, (iv) Z score and height deficit at OLT, (v) tacrolimus versus cyclosporine as primary immunosuppressive therapy, (vi) retransplantation, (vii) graft disease, (viii) chronic illness, (ix) posttransplant lymphoproliferative disease, (x) intractable rejection, and (xi) prednisone withdrawal. RESULTS A total of 236 children met the inclusion criteria, with a mean follow-up of 3.8+/-1.9 years. For the population as a whole, the baseline Z score was -1.72 (fourth percentile) with a significant improvement to - 1.37 (ninth percentile) at 2 years, but with no additional gain at 5 years (Z score -1.4). The baseline height deficit was -6.4 cm, with no improvement at 2 years (-6.52 cm), and was significantly worse at 5 years (-7.87 cm). In the bivariate analysis, the most important variables affecting growth were age at OLT, Z score at OLT, and diagnosis. In general, children

To formulate a model predicting survival after liver retransplantation, we analyzed in detail the last 150 cases of hepatic retransplantation at UCLA. Cox proportional hazards regression analysis identified five variables that demonstrated independent simultaneous prognostic value in estimating patient survival after retransplantation: (1) age group (pediatric or adult), (2) recipient requiring preoperative mechanical ventilation, (3) donor organ cold ischemia > or =12 hr, (4) preoperative serum creatinine, and (5) preoperative serum total bilirubin. The Cox regression equation that predicts survival based on these covariates was simplified by assigning individual patients a risk classification based on a 5-point scoring system. We demonstrate that this system can be employed to identify a subgroup of patients in which the expected outcome is too poor to justify retransplantation. These findings may assist in the rational selection of patients suitable for retransplantation.

Patellid limpets are very important grazers on NE Atlantic rocky shores, and can occur in clumps or as solitary individuals. When oystercatchers are foraging for limpets on rocky shores, they are often presented with a choice between solitary and clumped limpets. We attempted to establish whether oystercatchers express a preference for limpet prey items from these different distributions. Oystercatchers spent far more time foraging in areas of less clumped limpets than in areas of clumped limpets, despite lower prey density. We found a strong preference for solitary prey items, and increased chances of successful predation of solitary limpets. Possible explanations for this choice are discussed. This preference for attacking solitary limpets may have important implications for rocky shore dynamics by shaping the spatial patterns of limpets. This may then influence the probability of Fucus germlings escaping limpet grazing.

Background. We have previously reported a 10% incidence of posttransplant lymphoproliferative disease (PTLD) in pediatric patients receiving first liver grafts and primarily immunosuppressed with tacrolimus. To decrease the incidence of PTLD, we developed a protocol utilizing preemptive intravenous ganciclovir in high-risk recipients (i.e., donor (D) + , recipient (R) - ), combined with serial monitoring of peripheral blood for Epstein Barr virus (EBV) by polymerase chain reaction (PCR). Methods. Consecutive pediatric recipients of a first liver graft were immunosuppressed with oral tacrolimus (both induction and maintenance), and low-dose prednisone. EBV serologies were obtained at the time of orthotopic liver transplant in recipients and donors. Recipients were divided into groups: group 1, high-risk (D + R - ), and group 2, low-risk (D + R + ; D - R - ; D - R + ). In group 1 (high-risk), all patients received a minimum of 100 days of intravenous ganciclovir (6-10 mg/kg/day), while, in group 2 (low-risk), patients received intravenous ganciclovir during their initial hospitalization and then were converted to oral acyclovir (40 mg/kg/day) at discharge. Semiquantitative EBV-PCR determinations were made at 1-2-month intervals. In both groups, patients with an increasing viral copy number by EBV-PCR had tacrolimus levels decreased to 2-5 ng/ml, Tacrolimus was stopped, and intravenous ganciclovir reinstituted for PTLD. A positive EBV-PCR with symptoms, but negative histology, was defined as EBV disease; PTLD was defined as histologic evidence of polyclonal or monoclonal B cell proliferation. Results. Forty children who had survived greater than 2 months were enrolled. There were 18 children in group 1 (high-risk; mean age of 14±15 months and mean follow-up time of 243±149 days) and 22 children in group 2 (low-risk; mean age of 64±65 months and follow-up time of 275±130 days). In group 1 (high-risk), there was no PTLD and one case of EBV disease (mononucleosis-like syndrome), which resolved. In group 2 (low-risk), there were two cases of PTLD ; both resolved when tacrolimus was stopped. Both children were 8 months old at time of transplant. Neither received OKT3, and they had one and two episodes of steroid-sensitive rejection, respectively. One child had EBV disease (mild hepatitis), which resolved. Conclusions. Since instituting this protocol, the overall incidence of PTLD has fallen from 10% to 5% for children receiving primary tacrolimus therapy after OLT. No high-risk pediatric liver recipient treated preemptively with intravenous ganciclovir developed PTLD. Both children with PTLD were less than 1 year at OLT and considered low-risk. However, their positive EBV antibody titers may have been maternal in origin and not have offered long-term protection. Serial monitoring of EBV-PCR after pediatric OLT is recommended to decrease the risk of PTLD by allowing early detection of EBV infection, which is then managed by decreasing immunosuppression and continuing intravenous ganciclovir.

OBJECTIVE: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

OBJECTIVE: The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ. METHODS: To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events. RESULTS: In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.

Mycophenolate mofetil (MMF) is the morpholinoethylester prodrug of mycophenolic acid, an agent which inhibits the proliferation of B and T lymphocytes through the noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase, itself a key enzyme in the de novo synthetic pathway of guanosine nucleotides. Currently, MMF is approved for the prevention of acute renal allograft rejection when used in combination with cyclosporin and corticosteroids. Several studies have also demonstrated that this drug is useful in the treatment of refractory rejection in renal, heart and liver transplant recipients.

Background. We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome. Methods. The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax 2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates. Results. Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P Conclusions. We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.

Background. Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejecfion. Methods. The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1 u ) donors and Lewis (RT 1 ) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9x10 9 plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting. Results. Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P

Hepatic hemangioendothelioma (HHE) is a rare vascular tumor in neonates and may cause high-output cardiac failure and coagulopathy, and rarely has been associated with hypothyroidism. Hepatic hemangioendothelioma treatment options consist of corticosteroids, alpha-interferon, surgical resection, and liver transplantation. Herein, we report the case of a 6-week-old female neonate that presented with an HHE that involved all segments of the liver, resulting in respiratory failure and severe hypothyroidism that was recalcitrant to exogenous L-thyroxine therapy. After failure of medical and supportive therapy for the HHE, the patient underwent a cadaveric orthotopic liver transplantation that resulted in successful treatment of the severe hypothyroidism, respiratory failure, and cardiac symptoms. The patient is currently 1-year posttransplantation and disease free with normal thyroid function.

Background The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation. Methods This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors. Results The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis Conclusions In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.

Background Hepatic artery thrombosis (HAT) after liver transplantation for biliary atresia (BA) is a serious complication that most often leads to retransplantation (re-OLT). The purpose of the present study was: (1) to identify risk factors associated with HAT and (2) to analyze the impact of recently introduced microsurgical hepatic arterial reconstruction (MHR) on the incidence of HAT, subsequent need for re-OLT, and patient survival. Methods A retrospective review of 194 patients transplanted for BA was performed. One hundred and sixty-six patients (group 1) underwent conventional arterial reconstruction and 28 (group 2) had MHR. Results Actuarial survival for patients with HAT was significantly worse than for patients without HAT at 1, 2, and 5 years (71%, 61%, and 57% versus 85%, 85%, and 85%, P = 0.0007). Stepwise logistic regression analysis revealed that the risk of HAT correlated best with the type of arterial reconstruction (P = 0.007) followed by pretransplant bilirubin concentration (P = 0.04) and the number of acute rejection episodes (P = 0.03). In group 1, 32 patients developed HAT (19%), and of these, 18 underwent re-OLT for HAT. No patient in group 2 developed HAT (P = 0.006 versus group 1). One-year actuarial patient survival was 81% in group 1 and 100% in group 2 (P = 0.02). Conclusions In OLT for BA, (1) the predominant risk factor for HAT is the technique of arterial reconstruction, and (2) MHR markedly reduces the incidence of HAT and the need for re-OLT while improving patient survival.

OBJECTIVE: The purpose of this study was to analyze a single center's 12-year experience with 127 orthotopic liver transplantations (OLT) for primary sclerosing cholangitis (PSC). SUMMARY BACKGROUND DATA: Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown origin that occurs most commonly in young men and is associated frequently (70-80%) with inflammatory bowel disease (IBD). Patients with PSC also are at risk for the development of cholangiocarcinoma (CCA) and those with IBD for colon carcinoma. Although the course of PSC is variable, it frequently is progressive, leading to cirrhosis and requirement for OLT. METHODS: The medical records of 127 consecutive patients undergoing OLT for PSC from July 1, 1984, to May 30, 1996, were reviewed. Actuarial patient and graft survival was determined at 1,2, and 5 years. The incidence and outcome of patients with CCA, recurrent sclerosing cholangitis, and post-transplant colon carcinoma was determined. Results were analyzed by way of stepwise Cox regression to determine the statistical strength of independent associations between pretransplant covariates and patient survival. The median follow-up period was 3.01 years. Incidental cholangiocarcinoma (ICCA) was defined as a tumor < 1 cm in size that was discovered at the time of pathologic sectioning of the explanted liver. RESULTS: Ninety-two patients (72%) had associated IBD. Seventy-nine (62%) had undergone previous biliary tract surgery. One hundred seven patients (84%) received a single graft, whereas 20 patients (16%) required 22 retransplants. Patients received either cyclosporine- (n = 76) or tacrolimus- (n = 51) based immunosuppression. The 1-, 2-, and 5-year actuarial patient survivals were 90%, 86%, and 85%, respectively, whereas graft survival was 82%, 77%, and 72%, respectively. The presence of previous biliary surgery had no effect on patient survival. Ten patients (8%) had ICCA and their survival was not significantly different from patients without ICCA (100%, 83%, and 83% at 1, 2, and 5 years, respectively). Four patients were known to have CCA at the time of OLT, all recurred within 6 months, and had a significantly worse outcome (p < 0.0001). Recurrent sclerosing cholangitis developed in 11 patients (8.6%). The patient and graft survival in this group was not different from those in whom recurrence did not develop (patient; 100%, 90%, and 90%; graft: 80%, 70%, and 52%). Thirty patients (23%) underwent colectomy after liver transplantation for dysplasia-carcinoma or symptomatic colitis. Of the nine covariates entered into the Cox multivariate regression analysis, only common bile duct frozen section biopsy specimen showing CCA was predictive of a survival disadvantage. CONCLUSIONS: Liver transplantation provides excellent patient and graft survival rates for patients affected with PSC independent of pretransplant biliary tract surgery. Incidental cholangiocarcinoma does not affect patient survival significantly. However, known CCA or common duct frozen section biopsy specimen or both showing CCA are associated with poor recipient survival, and OLT should be proscribed in these cases. Recurrent PSC occurs in approximately 9% of cases but does not affect patient survival. Post-transplant colectomy does not affect patient survival adversely.

We report here on a newborn infant who initially presented with a history of gastroschisis, abdominal distension, and jaundice. Further studies revealed that the child had findings consistent with extrahepatic biliary atresia (EHBA). The child later developed hepatic failure and subsequently expired. The purpose of this case report is to discuss the pathogenesis of each disease process and to identify any commonality between the pathogenesis of gastroschisis and EHBA.

A few groups have endured the challenges of time, anecdotal success stories, logistic and funding impediments, to bring the field of clinical islet transplantation where it stands today. The recent improvement in clinical results has paralleled a renewed interest in islet transplantation and an increasing number of centers have entered the field. Selected institutions have now clearly demonstrated that insulin independence can be a reproducible and achievable goal. Other centers struggle with mixed results, while occasional early failures of islet transplants are still observed. This center effect underlines not just a learning curve, but also the complexity of the approach, which requires multidisciplinary expertise and attention to critical variables that need to be closely monitored to assure adequate clinical outcomes. The future success and large scale applicability of islet transplantation will rely on the synergistic research progress in critical areas that contribute to the sequential and integrated approach required for success in clinical islet transplantation.

A memory sense-amplifier timing circuit emulates the behavior of weak memory tail-bits to improve Tail-Bit Tracking (TBT) across Process, Voltage and Temperature. The TBT circuit is used to generate timing for a search operation in a 32nm Ternary Content Addressable Memory (TCAM) compiler resulting in 200mV Vmin improvement at a constant performance, and 50% improved search-time performance at a constant Vmin. This TBT circuit was implemented in 32nm High-K Metal Gate SOI process to achieve 0.60V operation and support up to 1G search/sec throughput on a 2048×640bit TCAM instance.

Improvements in surgical techniques, postoperative care, and donor and recipient selection have all contributed to the increased success of OLT and to higher survival rates in patients with advanced liver disease. This progress in liver transplantation has occurred in only 45 years, since the preliminary work of Dr. Starzl, and provides a basis for future advances.

OBJECTIVE: The authors analyze a single center's 11-year experience with 190 orthotopic liver transplants for congenital biliary atresia. SUMMARY BACKGROUND DATA: Hepatic portoenterostomy generally is the initial treatment for children with congenital biliary atresia. Despite multiple modifications of the hepatic portoenterostomy, two thirds of treated patients still develop recurrent cholestasis, portal hypertension, cholangitis, and cirrhosis. Therefore, the only hope of long-term survival in the majority of children with congenital biliary atresia is definitive correction with orthotopic liver transplantation. METHODS: The medical records of 190 consecutive patients undergoing orthotopic liver transplantation for congenital biliary atresia from July 1, 1984 to February 29, 1996 were reviewed. Results were analyzed via Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival was determined at 1, 2, and 5 years. The type and incidence of post-transplant complications were determined, as was the quality of long-term graft function. The median follow-up period was 3.21 years. RESULTS: The liver grafts were comprised on 155 whole-organ, 24 reduced-size, and 11 living donor organs. Median pretransplant values for recipient age, weight, and total bilirubin were 1.4 years, 12.3 kg, and 13.8 mg/dL, respectively. One hundred sixty-four patients (86%) had undergone prior hepatic portoenterostomy. Eighty-seven patients (46%) were United Network for Organ Sharing (UNOS) status 1 or 2 at the time of liver transplantation. The majority (15/24, 62%) of reduced-size graft recipients were UNOS status I at the time of transplantation. One hundred fifty-nine patients (84%) received a single graft, whereas 31 patients required 37 retransplants. The 1, 2, and 5 year actuarial patient survival rates were 83%, 80% and 78% respectively, whereas graft survival rates were 81%, 77%, and 76%, respectively. Cox multivariate regression analysis demonstrated that pretransplant total bilirubin, UNOS status, and graft type significantly predicted patient survival, whereas recipient age, weight, and previous hepatic portoenterostomy did not. Current median follow-up values for total bilirubin and aspartate aminotransferase levels in the 154 surviving patients were 0.5 mg/dL and 34 international units/L, respectively. CONCLUSION: Long-term patient survival after orthotopic liver transplantation for congenital biliary atresia is excellent and is independent of recipient age, weight, or previous hepatic portoenterostomy. Optimal results are obtained in this patient population when liver transplantation is performed before marked hyperbilirubinemia, and when possible, using a living-donor graft.

Induction of tolerance to fully major histocompatibility complex (MHC)-mismatched rat islet allografts implanted at two different islet transplant sites (liver and kidney capsule [KC]) was examined. Streptozotocin-induced diabetic Lewis (RT11) rats remained hyperglycemic (> 200 mg/dl) after intrahepatic preimmunization by injection of 200 low-temperature cultured (24°C for 7 days) Wistar-Furth (WF, RT1u) rat islets into the portal vein with one injection (1 ml) of rat antilymphocyte serum intraperitoneally. Three weeks later, 1,200 WF islets that had been cultured to remove passenger lymphoid cells were transplanted into the liver via the portal vein or under the KC. The intrahepatic transplants survived 60.2 ± 11.9 days, and all six of the KC transplants maintained normoglycemia for > 100 days after the preimmunization regimen. In contrast, survival of fresh islet transplants was not significantly improved by this preimmunization protocol at either transplantation site. This study demonstrates that indefinite islet allograft survival can be achieved across a full MHC mismatch by intrahepatic preimmunization with a small number of cultured donor islets and a brief period of immunosuppression followed by transplantation of low-temperature cultured donor islets.

An experimental determination of the optimum specific gasification rate for static bed rice hull gas producers was conducted for reactor diameters of 16–30 cm. All experiments were performed with reactors under suction from a throttled centrifugal blower. Cold-gas efficiency was observed to increase as specific gasification rate increased from 100 to about 200 kg m −2 h −1 , and then begin to decline as gasification rate was increased further. The decline in efficiency at higher gasification rates was due to decreasing gas heating value which could not be compensated by increasing gas flow. An empirical relationship derived between specific gasification rate and cold gas efficiency was found to be independent of reactor area, although further work is needed at larger scale to assess the validity of the relationship beyond the experimental range evaluated.

Indefinite survival of concordant xenogeneic Wistar Furth (WF) rat islet survival was obtained by intrahepatic transplants of cultured WF islets and a single injection of antilymphocyte sera in C57BL/6 mice. Adoptive transfer of splenocytes from mice with established WF islet xenografts produced a marked prolongation of survival of WF islets transplanted under the kidney capsule of diabetic irradiated (600 rads), naive C57BL/6 recipients (mean survival time = 48.9 +/- 17.1 days), and three of the recipients were still normoglycemic at 100 days after transplantation. Adoptive transfer of an equal mixture (3 x 10(7) cells each) of these splenocytes with normal splenocytes also prolonged survival of the kidney capsule islet xenografts (mean survival time = 26.5 +/- 7.8 days vs. 15.2 +/- 5.3 days for controls). In vitro studies on lymphocyte proliferation demonstrated a low rate of proliferation of splenocytes from established islet xenografts in the presence of irradiated WF splenocytes (stimulation index = 1.6 vs. 16.2 for naive C57Bl/6 mice), and mixing the cells with control splenocytes also decreased the proliferation of splenocytes as compared with controls (stimulation index = 5.4 vs. 16.2 in controls). The inhibitory effect was not species specific, since splenocytes from mice with established islet xenografts also produced a 42% inhibition of proliferation in the presence of irradiated Lewis splenocytes. These findings demonstrate that concordant, islet xenograft, immune unresponsiveness can be adoptively transferred by splencotyes from mice with established islet xenografts.

Background Owing to advances in both immunosuppressive protocols and pancreatic islet isolation techniques, insulin independence has recently been achieved in type 1 insulin-dependent diabetics (IDDM) via pancreatic islet transplantation (PIT). Although the dissemination of immunosuppressive protocols is relatively easy, transferring the knowledge and expertise required to isolate a large number of quality human islets for transplantation is a far greater challenge. Therefore, in an attempt to centralize the critical islet processing needed for islet transplantation and to avoid the development of another islet processing center, we have established a collaborative islet transplant program between two geographically distant transplant centers. Patients and methods Eleven consecutive type 1 IDDM patients with a history of severe hypoglycemia and metabolic instability underwent PIT at the Methodist Hospital (TMH) in Houston, Texas, utilizing pancreatic islets isolated at the Diabetes Research Institute (DRI) at the University of Miami in Miami, Florida between January 1, 2002 and June 31, 2003. Forty-one pancreata have been procured in the Houston area and have subsequently been transported for isolation at the DRI following enzymatic ductal perfusion by the automated method (Ricordi chamber). Following purification the islets were immediately transported back to TMH in Houston and transplanted via percutaneous transhepatic portal infusion. Immunosuppression regimen consisted of sirolimus, tacrolimus, and daclizumab. Results Following harvesting, donor pancreata arrived at the DRI for initiation of the isolation process within 6.5 hours of cross-clamping (median time 5.4 hours; range 4.8 to 6.5 hours). The islets were immediately transported back to TMH for final sterility and viability tests and transplanted via percutaneous transhepatic portal vein infusion. The harvesting of 41 pancreata has yielded a number of pancreatic islets sufficient for transplantation (>5000 IEQ/kg recipient body weight) 26 times (63% of harvested pancreata). Thus far, three patients have received three PITs and eight patients have received two PITs. Six remain insulin independent. All have experienced a decrease in serum hemoglobin A1c levels, and both basal and stimulated C-peptide levels have increased. There have been no major complications related to the procedure or the immunosuppressive regimen used. Conclusions Our series demonstrates that pancreatic islets isolated at a remote isolation center can successfully and safely be used for PIT and the achievement of insulin independence.

From April, 1980 to November, 1988, 163 one or two haplotype-mismatch living related (LR) or living unrelated (LUR) potential renal transplant recipients received three 200 ml aliquots of donor specific transfusion (DST) at biweekly intervals with concomitant azathioprine (2 mg/kg/day). Following transplantation, only prednisone and azathioprine were given for immunosuppression. The results for the DST group are compared with those for HLA identical living recipients (57 patients) transplanted during this same interval (1980-1988). Comparison is also made with a group of one or two haplotype-mismatched living donor recipients (54 patients) not treated with DST but with triple drug therapy (prednisone, azathioprine, cyclosporine) and antithymocyte globulin (ATG) or OKT-3 induction. Permanent T cell crossmatch sensitization occurred in 11 of 163 patients (7%). Successful DST donor transplants were performed between 121 one HLA haplotype-mismatched, 14 two HLA haplotype-mismatched LR, and 7 two haplotype-mismatched LUR pairs. Actual one- and five-year graft survivals were 94%, 100%, 100%, and 72%, 85%, and 71%, respectively, for these three subgroups of DST treated patients. The graft survival for all DST pretreated recipients at one, five, and ten years was comparable to the HLA-identical group (94%, 79%, 64% vs. 91%, 80% and 77%). At a mean follow-up of 10 1/2 years, 54% (80 patients) of the entire group of 147 patients transplanted after DST have functioning transplants with a mean serum creatinine of 1.7 mg/dl. Fifteen percent of DST patients (21 patients) died with a functioning graft 2 to 132 months after transplantation, 26% (37 patients) rejected the DST graft after 1 to 128 months, and 6% (9 patients) were lost for nonimmunological reasons. No lymphoproliferative disease developed in the DST group and the incidence of cytomegalovirus sepsis was only 2% (3 patients). The long-term beneficial effects of DST on renal allograft survival and function and the lower incidence of the complications of nonspecific immunosuppression should encourage increased utilization of DST in renal transplantation.

Background. We have previously reported the induction of donor-specific tolerance to cardiac allografts after intrathymic injection of alloantigen with simultaneous administration of antilymphocyte serum treatment to eliminate peripheral T cells. The present study determines whether prolongation of a fully major histocompatibility complex-mismatched cardiac allograft is achieved after a single administration of anti-CD4 monoclonal antibody (MoAb) combined with intrathymic injection of alloantigen. Methods. Male Buffalo rats were given Lewis splenocytes via the intrathymic or intravenous route in combination with a single administration of anti-CD4 monoclonal antibody (OX-38) or anti-CD8 MoAb (OX-8) or both. Heterotopic cardiac transplantation was performed 21 days after intrathymic alloantigen or MoAb pretreatment or both. Fluorescence-activated cell sorter analysis determined changes in lymphocyte compartment T-cell subsets, and in vitro studies examined recipient cellular reactivity. Results. By 21 days after anti-CD4 MoAb treatment earlier nonspecific immunosuppression had resolved with 80% recovery of peripheral CD4+ T cells and restoration of recipient immunocompetence to allow normal rejection of a cardiac allograft. Combined treatment with intrathymic, but not intravenous, alloantigen plus anti-CD4 MoAb induced donor-specific tolerance to subsequent rat cardiac allografts. However, anti-CD8 MoAb combined with intrathymic alloantigen failed to induce tolerance despite a profound depletion of the CD8+ T-cell subset. Conclusions. Combined treatment of rats with intrathymic donor alloantigen and a single administration of anti-CD4, but not anti-CD8, MoAb significantly prolongs cardiac allograft survival across a fully major histocompatibility complex mismatched strain combination.

The second reported case of common variable immunodeficiency (acquired agammaglobulinemia) after renal transplantation is presented. Agammaglobulinemia presumably resulted from long-standing immunosuppression. This case and our review of the literature indicate that agammaglobulinemia is a rare event after transplantation but can be treated successfully with intravenous immunoglobulin. Additionally, hypogammaglobulinemia occurs frequently after transplantation and should be monitored and treated in appropriate clinical situations. The treatment of our patient with intravenous immunoglobulin also suggests that patients with common variable immunodeficiency can undergo renal transplantation.

The recent success of islet transplantation using the Edmonton protocol involved the use of sirolimus, tacrolimus, and daclizumab for immunosuppression. Islets were infused into the portal circulation after transhepatic access. This protocol provided a unique opportunity to measure sirolimus and tacrolimus levels from the portal vein and compare them to systemic venous levels. A total of 11 portal venous samples with a corresponding peripheral venous sample were obtained from patients undergoing a first or second islet infusion and medication levels were obtained on both types of specimens. The portal-to-systemic drug level ratio ranged from 0.95 to 2.71 for sirolimus and 1.0 to 3.12 for tacrolimus. Given the potential toxicity of these agents to islets, the findings in this study may have implications for designing the next generation of immunosuppressive protocols for islet transplantation.

Induction of tolerance to concordant rat islet xenografts (150 Wistar-Furth [WF] islets) in streptozocin-induced (STZ) diabetic mice (C57BU/6) was determined at three different sites for islet implantation (thymus, kidney capsule, and liver). Islets transplanted into the thymus or kidney capsule were either fresh or cultured at 24°C for 7 days, and the mice received a single injection of either anti-mouse lymphocyte serum (MALS) alone or anti-rat lymphocyte serum (RALS) and MALS. Islets transplanted into the liver via the portal vein were cultured at 24°C for 7 days, and the mice received a single injection of MALS and RALS. To document the induction of tolerance, recipients with islet xenografts surviving >100 days were made diabetic again by STZ (thymus and liver) or nephrectomy (kidney capsule) and received a second transplant of 150 fresh WF islets in the kidney capsule. Kidney capsule placement of fresh or cultured islets with MALS alone or MALS and RALS did not induce tolerance in a significant number of recipients. The intrathymic transplantation of fresh or cultured islets with MALS alone resulted in prolonged WF islet xenog raft survival (mean survival time of 39.7 ± 7.9 days) but did not result in tolerance, whereas the administration of MALS and RALS with the intrathymic placement of fresh or cultured islets induced tolerance in ∼50% of the mice. Intrahepatic transplantation of cultured islets with MALS and RALS resulted in tolerance to donor islets in 90% of the recipients. Donor specificity was evaluated by a third major histocompatability complex–disparate fresh Lewis islet xenograft. Approximately 50% of these xenografts were not rejected, suggesting that the tolerance may not be haplotype-specific. The mechanisms involved in inducing tolerance to islet xenografts are not clearly established; however, this study clearly demonstrates that tolerance to xenogeneic islets can be achieved by using a brief period of immunosuppression in the intrathymic or intrahepatic transplantation site, with intrahepatic implantation achieving tolerance in a higher percentage of recipients than the intrathymic site.

Background. No definitive antiviral therapy exists for adenovirus (ADV) in immunosuppressed hosts. Cidofovir (CDV), a broad spectrum anti-DNA viral agent, has previously been shown to be of therapeutic benefit in life-threatening adenoviral disease in bone marrow stem-cell recipients. Methods. A 71/2-month-old girl with a history of biliary atresia developed fevers, hematochezia, tachypnea, and laboratory evidence of hepatitis and pancreatitis 12 days after liver transplantation. A stool culture, oropharyngeal culture, blood viral culture, and blood polymerase chain reaction (PCR) confirmed ADV. Cidofovir 1 mg/kg intravenously three times per week was initiated. The patient received intravenous hydration and probenecid with the infusions to reduce the nephrotoxicity of CDV. Immunosuppression was reduced to achieve tacrolimus trough levels of approximately 8 ng/mL and prednisone at 0.1 mg/kg per day. Complete blood cell count, urinalysis, and viral studies were obtained weekly. Results. Detection of ADV DNA by PCR made a transition from positive to negative during CDV therapy. Blood viral cultures became negative after two CDV doses. Alanine aminotransferase normalized by 5 weeks of therapy. CDV was discontinued after 7 weeks secondary to transient acidosis and proteinuria. The patient never developed azotemia, neutropenia, or ocular abnormalities. Conclusions. CDV was associated with improved clinical status, viral clearance, and minimal transient side effects in a pediatric liver transplant recipient with disseminated adenoviral disease. The current report documents clearance of disseminated ADV infection in a liver transplant recipient receiving CDV infusions.

Several criteria are used to differentiate between standard and extended allograft donors. These criteria include deceased after cardiac death, advanced donor age, steatosis, previous malignancy in the donor, hepatitis C virus-positive allografts, human T-cell lymphotropic virus-positive allografts, active infections in the donor, high-risk donors, split liver transplantations, and living donor liver transplantations. Review of the literature can lead each practitioner to incorporate extended criteria donors into their transplant program, thereby individualizing the use of these allografts, increasing the donor pool, and decreasing overall waitlist mortality.

Patients diagnosed with Neuroendocrine Tumors (NET) often are also diagnosed with Neuroendocrine Liver Metastases (NLM) during the course of their disease. NLM can cause significant morbidity and mortality, oftentimes much more than compared to patients with NET. Treatment options have been limited in the past, focusing on surgical resections, for which only a minority of patients are candidates. However, developments of new treatment modalities have progressed rapidly and patients with NLM now have significantly more options, including surgical-directed therapies; liver-directed therapies; and nonsurgical, non-liver-directed therapies. This review provides information about the roles of hepatic resection, orthotopic liver resection, radiofrequency ablation, hepatic artery embolization and hepatic artery chemoembolization, hepatic artery radioembolization and selective internal radiation therapy, peptide receptor radionuclide therapy, systemic chemotherapy, biotherapies including somatostatin analogs and interferon-α, vascular endothelial growth factor and mTOR targets, and microRNA-regulated pathways. Given these new options, the clinician can tailor therapy specific to the patient diagnosed with NLM, thereby giving the patient the best possible chance of prolonged survival.

Liver transplantation remains a controversial therapy for Neuroendocrine liver metastases (NLM), with coflicting suvival data reported. The aim was to assess the evolution of outcomes for patients transplanted for NLM in the US, both before and after the introduction of the MELD scoring system in 2002. The UNOS/OPTN database was reviewed to identify patients diagnosed with NLM who subsequently underwent a liver transplantation from 1988 to March 2011 ( 𝑛 = 1 8 4 ); Patient survival was determined using Kaplan-Meier methods and log-rank tests, and cox regression analysis was performed, using SPSS 15.0 (SPSS, Inc, Chicago, IL). The overall NLM patient survivals in the pre-MELD era were 79.5%, 61.4%, and 49.2% at 1, 3, and 5 years, respectively. After the introduction of the MELD score, NET/NLM patients had improved overall patient survivals at 1, 3, and 5 years of 84.7%, 65%, and 57.8%. Patients transplanted after 2002 had an improved survival outcome. Notably, the overall patient survival for NET is not significantly different when compared to the outcomes of patients transplanted for HCC, in the current era. This progress acknowleges the significant improvement in outcomes for NLM patients after liver transplantation and the potential for further gain in the survival of otherwise nonsurgical, terminal patients.

Background & Aims Cirrhotic liver diseases are associated with abnormalities in cardiac geometry and function in adults (cirrhotic cardiomyopathy) but rarely explored in cirrhotic infants or children. We proposed that features of cirrhotic cardiomyopathy are present in infants with cirrhosis due to biliary atresia (BA) as early as the time of evaluation for liver transplant and will correlate with mortality and postoperative morbidity. Methods Two-dimensional echocardiography (2DE) of infants with BA (n = 40; median age, 8 months), listed for transplantation at the Texas Children's Hospital from 2004 to 2010, were reviewed and compared with age- and sex-matched infants without cardiac or liver disease (controls). Length of stay and correlation with 2DE results were assessed. Results Compared with controls, children with BA had significant increases in multiple 2DE parameters, notably left ventricle wall thickness (23% increase), left ventricular (LV) mass indexed to body surface area (51% increase), and LV shortening fraction (8% increase). Overall, features of cirrhotic cardiomyopathy were observed in most infants (29/40; 72%); 17 had hyperdynamic contractility, and 24 had altered LV geometry. After liver transplantation (33), infants with abnormal 2DE results had longer stays in the intensive care unit (median, 6 vs 4 days) and the hospital (21 vs 11 days) compared with infants who had normal 2DE reports. On univariate analysis, the length of hospital stay correlated with LV mass index. Conclusions Cardiomyopathy is a prevalent condition in infants with end-stage cirrhotic liver disease due to BA (>70%). This underrecognized condition likely contributes to the prolongation of posttransplant hospitalization.

Since the advent of the human genome, the era of personalized genomic medicine is indisputably in progress.In an effort to contribute to the evolving knowledge of genomic medicine, we have aimed directly at building a bioresource bank for hepatocellular carcinoma. This tumor bank is based on the rigorous guidelines set forth by the National Cancer Institute, and it offers analytes to help elucidate the mechanisms of progression from cirrhosis to malignancy, risk factors for recurrence, and applicability of current treatment options to a diverse group of people.Surgeons have a privileged position between patients (and their cancer) and the benches of basic science. Thus, we offer a primer based on our own experiences, from which surgeons may take elements to build their own bioresource bank for use in collaboration with others. We highlight some practicalities and pitfalls that could be overlooked, as well as a discussion of possible solutions.

Introduction. Familial hypercholesterolemia (FH) is caused by nonfunctioning low-density lipoprotein (LDL) receptors, resulting in high serum cholesterol. Two types of FH are described: the heterozygous form is diagnosed in adults and responds well to medical therapy; the homozygous form is rare, diagnosed in children, and often requires multiple treatments to prevent complications. Cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, coronary artery disease, and aortic stenosis. Treatment options consist of lifestyle modifications, lipid-lowering medications, LDL aphaeresis, and orthotopic liver transplantation (OLT).Case Presentation. Two patients with FH presented at young ages due to characteristic cutaneous xanthomas. The patients underwent cardiac testing that revealed atherosclerotic changes. The patients received maximal medical therapy, but only experienced a small decrease in serum cholesterol and LDL levels. After several years of medical treatment without improvement of symptoms, the patients were listed for OLT. The transplantations were successful, and only one patient had a postoperative complication of acute rejection, treated successfully. Currently, both patients are doing well with regression of the cutaneous xanthomas and atherosclerotic changes.Conclusion. OLT is a safe and effective option for patients with homozygous FH refractory to maximal medical therapy and may represent the optimal treatment for these patients.

Introduction: Primary liver cancer arises from hepatocytes or biliary epithelium resulting in hepatocellular carcinoma or cholangiocarcinoma, respectively. Mixed hepatocellular carcinoma-cholangiocarcinomas are rare; therefore, medical literature addressing these tumors is limited. As treatment modalities for mixed hepatocellular carcinoma-cholangiocarcinomas are few, the role of orthotopic liver transplantation remains controversial. Aim: To determine the survival outcomes of patients with incidentally discovered mixed hepatocellular carcinomacholangiocarcinomas after orthotopic liver transplantation. Methods and Materials: We present five patients with mixed hepatocellular carcinoma-cholangiocarcinomas who received orthotopic liver transplantation at our institution between September 1998 and July 2011. Characterization of the combined lesion was based on the Allen and Lisa classification scheme: type A: separate neoplasms of liver cell or bile duct cell; type B: different masses that mingle as they grow; and type C: masses that display both features of liver and bile duct cells. Results: Preoperatively, all patients met Milan criteria based on presumed hepatocellular carcinoma prior to orthotopic liver transplantation. Multifocal disease was present in all patients on pathological diagnosis, which was not appreciated during preoperative screening, and histologic characterization of the lesions revealed both Allen and Lisa types A (60%) and C (40%). All of our patients had underlying cirrhosis. The post-operative course was uneventful in all of the cases. Vascular invasion was observed in one patient who developed bone metastases and subsequently died 600 days post-transplant despite post-transplant chemoradiation therapy. The other four patients have remained disease-free; the mean overall survival is 800 days. Our population is unique in prevalence of cirrhosis and multiple hepatic lesions as compared to other case series. Conclusions: Although orthotopic liver transplantation is not recommended for patients with known mixed hepatocellular carcinoma-cholangiocarcinomas, in the event that a patient is transplanted, this case series shows that orthotopic liver transplantation is an acceptable treatment modality with appropriate survival outcomes.

Aim: Liver transplantations (LT) have proven to be a successful treatment for many tumors of the liver. The goal of this study was to evaluate the outcomes of liver transplantations in patients with primary liver tumors with a focus on rarer malignancies. Methods: The UNOS database catalogues all adult patients who underwent LT for a primary liver tumor from 1992-2008. Of the 73, 231 liver transplantations, 5,682 patients with liver tumors were identified and categorized by indication for LT: hepatocellular carcinoma (HCC, n=5272), hepatic epithelioid hemangioendothelioma (HEH, n=85), cholangiocarcinoma (n=249), sarcomas (n= 11) and combined HCC-Cholangiocarcinomas (HCC-CC, n=12). Survivals were calculated using Kaplan-Meier and log rank tests. Results: 5,629 patients received LT for solid liver tumors. HCC patients and their allografts survived longer than those transplanted for cholangiocarcinomas (p=0.001, 0.002) or for HCC-CC (p=0.025, 0.004). Overall survival rates of HCC patients were 86.4%, 71.3%, and 61.2% at 1, 3 and 5 years, respectively. Cholangiocarcinoma patients had survival rates of 79.7%, 60.3% and 45.5% at 1-, 3- and 5-years from transplant. HCC-CC patients had the worst overall survival of 72.9%, 39.1% and 39.1% at 1, 3 and 5 years. Allograft survival in HCC-CC patients was comparatively low, averaging 65.6%, 35.2% and 0% at 1-, 3- and 5-years. HEH patients and their allografts survived the longest with overall survival of 83.9%, 77.8% and 73.5% at 1, 3 and 5 years, respectively, and allograft survival at 76.8%, 69.8% and 64.3%. Conclusion: Our data reveals overall survival was significantly better in HEH patients when compared to HCC, cholangiocarcinoma and HCC-CC patients after LT. In fact, HCC-CC patients fared the worst, both in patient and allograft survival, as compared to HCC and HEH. Results of cholangiocarcinoma patients show worse survival after LT compared to HCC and HEH, though recent evidence suggests adjuvant therapy will change outcomes for the future. Our findings suggest transplantation for HCC-CC may not be sufficient treatment. Other forms of adjuvant and neoadjuvant therapy may be indicated, warranting further research.