Challenges, highlights, and opportunities in cellular transplantation: A white paper of the current landscape.

Although cellular transplantation remains a relatively small field compared to solid organ transplantation, the prospects for advancement in basic science and clinical care remain bountiful. In this review, notable historical events and the current landscape of the field of cellular transplantation are reviewed with an emphasis on islets (allo- and xeno-), hepatocytes (including bioartificial liver), adoptive regulatory immunotherapy, and stem cells (SCs, specifically endogenous organ-specific and mesenchymal). Also, the nascent but rapidly evolving field of three-dimensional bioprinting is highlighted, including its major processing steps and latest achievements. To reach its full potential where cellular transplants are a more viable alternative than solid organ transplants, fundamental change in how the field is regulated and advanced is needed. Greater public and private investment in the development of cellular transplantation is required. Furthermore, consistent with the call of multiple national transplant societies for allo-islet transplants, the oversight of cellular transplants should mirror that of solid organ transplants and not be classified under the unsustainable, outdated model that requires licensing as a drug with the Food and Drug Administration. Cellular transplantation has the potential to bring profound benefit through progress in bioengineering and regenerative medicine, limiting immunosuppression-related toxicity, and providing markedly reduced surgical morbidity.

Phosphorus ans an early predictive factor in patients with acute liver failure.

BACKGROUND: This study analyzes the prognostic significance of serum phosphorus in patients with acute liver failure (ALF). METHODS: We performed a retrospective analysis of 112 patients with ALF. Univariate and bivariate analyses based on Kaplan-Meier recovery curves and a multivariate Classification Tree Structure Survival Analysis were performed to identify independent predictors of outcome. The variables analyzed were age, gender, race, ABO blood group, etiology of liver disease, grade of encephalopathy, serum bilirubin, prothrombin time, creatinine, serum phosphorus, phosphorus administered, phosphorus binders, and hemodialysis. RESULTS: The median follow-up time was 5 days, the median age was 28 years, and 62% of the patients were female. The patients' outcomes were as follows: 28% recovered, 52% required orthotopic liver transplantation, and 20% died. White patients showed the best prognosis (58% recovered in the first week), and Hispanics showed the worst prognosis (0.3% recovered at 1 week) (P=0.0001). Encephalopathy and bilirubin were significant predictors of recovery (P<0.0001 and P=0.004). The analysis of the serum phosphorus showed a statistically significant better prognosis in patients with low phosphorus (P<0.001). The recovery rate at 1 week was 74% in patients with serum phosphorus less than 2.5 mg/dL, 45% if phosphorus ranged between 2.5 to 5 mg/dL, and 0% if phosphorus was more than 5 mg/dL. The bivariate analysis on the effects of phosphorus administration showed that phosphorus replacement was associated with a significant improvement in recovery in patients with low (P<0.004) or normal serum phosphorus levels (P<0.017) CONCLUSIONS: Hypophosphatemia and early phosphorus administration are associated with a good prognosis in ALF, whereas hyperphosphatemia is predictive of poor recovery.

Operative parameters that predict the outcomes of hepatic transplantation.

BACKGROUND: A growing discrepancy between the number of patients awaiting liver transplantation and the number of organs available mandates the use of even marginal organ donors in whom there is major risk of suboptimal graft function. A comprehensive analysis of operative parameters on the outcomes of liver transplantation has not been reported. STUDY DESIGN: We analyzed the impact of 24 operative variables on the survival of 942 consecutive primary liver allografts performed at a single center from June 1992 through December 1997. Univariate and Cox proportional hazards analysis was used to identify those variables with independent prognostic significance in graft survival. Resource utilization for variables with multivariate significance was also analyzed. RESULTS: Of 12 intraoperative variables found to have significance in univariate analysis, three were significant by Cox multivariate analysis: 1) lack of immediate bile production by the graft intraoperatively, 2) platelet transfusion > or = 20 U, and 3) recipient urine output < or =2.0 mL/kg/h intraoperatively. Each of the three variables was associated with marked increases in hospital and Intensive Care Unit length of stay and hospital charges accrued during the admission for transplantation. CONCLUSION: We identified three operative parameters that predict a poor outcome after liver transplantation. The presence of these indicators suggests that early retransplantation should be considered. Early identification of grafts likely to have poor function might also provide an opportunity for therapeutic intervention to salvage graft function.

Portal vein resection in management of hilar cholangiocarcinoma.

BACKGROUND: Vascular reconstruction along with major liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased risk. The purpose of this report is to assess the role of portal vein resection and reconstruction in the surgical management of hilar cholangiocarcinoma. STUDY DESIGN: Ninety-five patients with hilar cholangiocarcinoma who underwent resection between 1999 and 2010 were reviewed. Liver resections performed along with biliary resection included 84 trisegmentectomies (63 right, 21 left) and 11 lobectomies (8 left, 3 right). Thirteen patients also had simultaneous pancreaticoduodenectomy performed. Forty-two patients underwent portal vein resection and reconstruction. Five patients required reconstruction of the hepatic artery. Preoperative portal vein embolization was used in 38 patients. RESULTS: Patients undergoing resection had a 5% mortality rate, with an overall morbidity rate of 36%. Patients who underwent portal vein resection had perioperative mortality and morbidity similar to those who did not have portal vein resection. Median survival was 38 months (95% CI, 29-51 months), with a 5-year survival rate of 43%. There was no difference in long-term survival between those patients who had portal vein resection and those that did not. Negative margins were achieved in 84% of cases and were associated with improved survival (p < 0.01). Five-year survival rate in patients undergoing R0 resection was 50%. Patients with positive lymph nodes appeared to have a worse 5-year survival rate than patients with node-negative status (23% versus 49%); however, only negative margin status was associated with improved survival by multivariate analysis. CONCLUSIONS: Surgical resection of hilar cholangiocarcinoma that requires resection of the portal vein can be performed safely and should not be a contraindication to resection.

New era of liver transplantation for hepatitis B: a 17-year single-center experience.

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.