The only available therapy for patients with end-stage liver disease is organ transplantation. In the United States, patients with end-stage liver disease are placed on a waiting list and offered livers based on location and waiting time, as well as current and past health. Although there is a shortage of cadaveric livers, 45% of all cadaveric liver offers are declined by the first transplant surgeon and/or patient to whom they are offered. We consider the decision problem faced by these patients: Should an offered organ of a given quality be accepted or declined? We formulate a Markov decision process model in which the state of the process is described by patient state and organ quality. We use a detailed model of patient health to estimate the parameters of our decision model and implicitly consider the effects of the waiting list through our patient-state-dependent definition of the organ arrival probabilities. We derive structural properties of the model, including a set of intuitive conditions that ensure the existence of control-limit optimal policies. We use clinical data in our computational experiments, which confirm that the optimal policy is typically of control-limit type.

Determining the Acceptance of Cadaveric Livers Using an Implicit Model of the Waiting List

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus) have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.

Cancer review: Cholangiocarcinoma.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/lt.20904

Trends and experiences in liver retransplantation over 15 years.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jlts.2003.50206

Poor survival after liver retransplantation: Is hepatitis C to blame?

Liver transplantation for hepatic malignancies has emerged as a well-documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long-term effects of immunosuppression; however, long-term and disease-free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo- and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re-evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long-term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well-designed trials.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2008.00735.x

Liver transplantation for primary and metastatic liver cancers

Aim Our goal was to retrospectively analyze graft loss and mortality risk factors using multi-centre data on liver retransplantation. Material and methods Between 1991–1995, 640 patients underwent 718 liver transplants in Barcelona. Mean age of the 74 patients receiving a second transplant was 47.6 years (range 19–65). Causes of retransplantation were immunologic in 26 patients (35.1%), technical in 23 (31.1%), primary dysfunction in 12 (16.2%), recurrent original disease in 7 (9.5%), and other causes in 6 (8.1%). Mean time between first and second transplant was less than 7 days in 20 patients (27%), between 8 and 30 days in 4 (5.4%) and more than 30 days in 50 patients (67.6%). Recipient, donor, and operative variables were analyzed using univariate (Kaplan-Meier curves) and multivariate techniques (Cox regression) to identify risk factors. Results Retransplant patient survival at 1 and 5 years was 60.8% and 49.5%, respectively, compared to 75.6% and 64.8% in a series of 640 first transplant patients. Mortality risk factors identified by multivariate analysis were bilirubin >12 mg/dL (RR 2.3; P = .010), recipient age (RR increase 0.04 for each additional year; P = .02), cause for retransplant (immunologic RR 4.01, technical RR 2.7 and other causes RR 6.9; compared to primary dysfunction RR 1; P = .020). Urea >54 mg/dL (0.02) and multiple transfusions >15 units red blood cells (0.001) were only significant in the univariate analysis. Conclusions In our experience, retransplantation for primary dysfunction is the setting that has the best prognosis. Of the other causes, retransplantation should be performed before the total bilirubin reaches >12 mg/dL or before the appearance of variables indicative of severe renal insufficiency.

Risk factors for death following liver retransplantation.

Introduction. Palliative treatment for nondisseminated irresectable hilar cholangiocarcinoma (HCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than that for other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for HCC and identify prognostic factors for survival. Methods. We retrospectively reviewed 36 patients undergoing OLT for HCC over 13 years. Results. The actuarial survival rate at 1, 3, and 5 years was 82%, 53%, and 30%, respectively. The main cause of death was tumor recurrence (53%). In the univariate analysis, the factors for a poor prognosis were vascular invasion (P .001) namely 0% survival at 3 years when present versus 63% and 35% at 3 and 5 years, respectively, when it was not; and stages III to IVA (P .05), namely 15% survival at 5 years versus 47% for stages I to II. Lymph node and perineural invasion also reduce survival. In the multivariate analysis, the factors for poor prognosis included vascular invasion (P .01) and stages III to IVA (P .01). Conclusions. OLT for nondisseminated irresectable HCC has higher survival rates at 3 and 5 years than palliative treatments, especially with initial stage tumors, which means that more information is needed to better select cholangiocarcinoma patients for transplantation.

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

Introduction Palliative treatment for nondisseminated unresectable peripheral cholangiocarcinoma (PCC) carries a 0% 5-year survival rate. The role of orthotopic liver transplantation (OLT) in these patients is controversial because the survival rate is lower than with other indications for transplantation and the lack of available donor organs. The aim of this paper was to review the Spanish experience in OLT for PCC to identify prognostic factors for survival. Methods We retrospectively reviewed 23 patients undergoing OLT in Spain for PCC over a period of 13 years. Results The actuarial survival rates were 77%, 65%, and 42% at 1, 3, and 5 years, respectively. The main cause of death was tumor recurrence (35%). Prognotic factors for an adverse outcome were pTNM classification (P Conclusions OLT for nondisseminated irresectable PCC displays higher survival rates at 3 and 5 years than palliative treatments, especially for tumors in the initial stages, which means that more information is needed to help better select PCC patients for transplantation.

http://www.biblioteca.uma.es/bbldoc/articulos/1664198x.pdf

C Margarit

Papers

Risk factors for death following liver retransplantation.

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

Liver transplantation for peripheral cholangiocarcinoma: Spanish experience

Late orthotopic liver retransplant: indications and survival. Liver Transplant Spanish Group.