Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Current management of breakthrough cancer pain according to physicians from pain units in Spain.

PURPOSE: Current evidence suggests the need to improve the management of breakthrough cancer pain (BTcP). For this reason, we aimed to assess the opinion of a panel of experts composed exclusively of physicians from pain units, who play a major role in BTcP diagnosis and treatment, regarding the key aspects of BTcP management. METHODS: An ad hoc questionnaire was developed to collect real-world data on the management of BTcP. The questionnaire had 5 parts: (a) organizational aspects of pain units (n = 12), (b) definition and diagnosis (n = 3), (c) screening (n = 3), (d) treatment (n = 8), and (e) follow-up (n = 7). RESULTS: A total of 89 pain-unit physicians from 13 different Spanish regions were polled. Most of them agreed on the traditional definition of BTcP (78.9%) and the key features of BTcP (92.1%). However, only 30.3% of participants used the Davies' algorithm for BTcP diagnosis. Respondents preferred to prescribe rapid-onset opioids [mean 77.0% (SD 26.7%)], and most recommended transmucosal fentanyl formulations as the first option for BTcP. There was also considerable agreement (77.5%) on the need for early follow-up (48-72 h) after treatment initiation. Finally, 65.2% of participants believed that more than 10% of their patients underused rapid-onset opioids. CONCLUSIONS: There was broad agreement among pain experts on many important areas of BTcP management, except for the diagnostic method. Pain-unit physicians suggest that rapid-onset opioids may be underused by BTcP patients in Spain, an important issue that need to be evaluated in future studies.

Management of postoperative pain in Spain: a nationwide survey of practice.

BACKGROUND: Although the need for structured assessment and management of acute postoperative pain has been recognized, practices and responsibilities vary between and within hospitals and countries. We sought to determine current pain management practices in Spanish hospitals with and without acute pain services (APSs) or acute pain management programmes (APMPs) and compare them to practices reported for 1997-1998. METHODS: Members of the Spanish Pain Society and APS/APMP heads were asked to respond to a survey. Responses were stratified by hospital size (< 200 or ≥ 200 beds) and APS/APMP presence or not. Categorical variables were described by percentages and the 95% confidence interval and continuous ones by the median and interquartile range. RESULTS: Responses were received from 42.4% of hospitals with ≥ 200 beds (vs. 9.6% of the smaller ones). We fully analysed only data for the larger hospitals, 57.7% of which had an APS or APMP. Full-time pain physicians were on staff in 28.6% of large hospitals; 25% had full-time nurses. Patients received written information about postoperative pain in 34.8% of APS/APMP hospitals, and 72% of them recorded pain assessments routinely. Protocols reflected interdepartmental consensus in 80.8%; training in postoperative pain was organised in 54%. Respondents thought pain was well or very well managed in 46.4%. In APS/APMP hospitals the following results had improved: provision of written information for patients (58.5% vs. 0%), the recording of pain assessments (93% vs. 43.8%), consensus on a pain scale (92.5% vs. 41.9%), use of protocols (99.7% vs. 55.2%), analysis of quality indicators (52.8% vs. 15.4%), training (73% vs. 26.9%), and respondents' satisfaction with pain management in their hospital (68.6% vs. 9.5%). CONCLUSIONS: The presence of an APS or APMP is associated with better results on indicators of quality of acute postoperative pain management.

Optimal management of breakthrough cancer pain (BCP).

Breakthrough cancer pain (BCP) is common in patients with cancer, causing a negative impairment in quality of life. Recent diagnostic criteria allow for differentiation of background chronic pain and BCP, for which proportion of unpredictable episodes is very high. Five characteristics define BCP: rapid onset, high intensity, maximum intensity (minutes), mean duration 30 min, and unpredictable onset. Fentanyl is a synthetic opioid characterized by rapid absorption and start of the analgesic effects. In addition to comparing some of the marked differences between the four pharmaceutical forms of fentanyl marketed in Spain, this paper discusses the data collected in a comprehensive clinical trial program with fentanyl pectin nasal spray (FPNS), a formulation that takes advantage of the intranasal route and the PecSys™ technology. The FPNS formulation achieves analgesic action 5 min after application and significant pain relief at 10 min. FPNS, therefore, has key features to be an optimal treatment for BCP.

Consenso chileno de manejo de fármacos antiepilépticos en algunos síndromes electro-clínicos y otras epilepsias en niños y adolescentes / Chilean consensus on the use of antiepileptic drugs in electro-clinical syndromes

Por iniciativa de tres instituciones: Liga Chilena contra la Epilepsia (LICHE), Sociedad de Epileptología de Chile (SOCEPCHI) y Sociedad de Psiquiatría y Neurología de la Infancia y Adolescencia (SOPNIA) de Chile, se constituye un comité de trabajo que convoca a un consenso de uso de fármacos antiepilépticos (FAEs) en un grupo de 16 Síndromes electro-clínicos y otras Epilepsias en niños y adolescentes. Cuarenta y dos médicos neuropediatras especialistas en Epilepsias de todas las regiones de Chile, participaron en la discusión y realizaron una propuesta de tratamiento farmacológico para cada cuadro. El comité de trabajo realizó un análisis exhaustivo y discusión de los documentos, para finalmente concluir en una recomendación de tratamiento para cada cuadro. Este consenso es una guía práctica de orientación para ayudar a las decisiones de tratamiento en situaciones clínicas concretas. Su objetivo final es ofrecer una mejor calidad de atención a los niños y adolescentes con epilepsias, a través de decisiones fundadas que contribuyan a disminuir la variabilidad de las decisiones terapéuticas.

Committed by three institutions: Liga Chilena contra la Epilepsia (LICHE), Sociedad de Epileptología de Chile (SOCEPCHI) y Sociedad de Psiquiatría y Neurología de la Infancia y Adolescencia (SOPNIA) de Chile, a 6-member working committee called for a meeting of 42 Chilean pediatric epileptologists from all over the country, with the aim of reaching a consensus on the use of antiepileptic drugs in 16 selected children and adolescents electro-clinical syndromes and epilepsies. These treatment proposals were analyzed and fully discussed by the working committee, ending in an antiepileptic drug treatment recommendation guideline for each condition. This consensus is a practical guideline to be used in specific clinical situations, which aims to support treatment decision making. Its main purpose is to offer the best evidence based treatments to our children and adolescents patients with epilepsy, thus contributing to diminish variability in therapeutic decisions.

Pharmacological treatment of chronic pain - the need for CHANGE.

BACKGROUND: Although chronic pain affects around 20% of adults in Europe and the USA, there is substantial evidence that it is inadequately treated. In June 2009, an international group of pain specialists met in Brussels to identify the reasons for this and to achieve consensus on strategies for improving pain management. SCOPE: Literature on chronic pain management was reviewed, and information presented to and discussed by a panel of experts. FINDINGS: It was agreed that guidelines are not universally accepted by those involved in pain management, and pain treatment seems to be driven mainly by tradition and personal experience. Other factors include poor communication between patients and physicians, the side effects of analgesic drugs, and limited individualisation of therapy. Difficulty in maintaining the balance between adequate pain relief and acceptable tolerability, particularly with strong opioids, can lead to the establishment of a 'vicious circle' that alternates between lack of efficacy and unpleasant side effects, prompting discontinuation of treatment. The medical community's understanding of the physiological differences between nociceptive pain and neuropathic pain, which is often more severe and difficult to treat, could be improved. Increasing physicians' knowledge of the pharmacological options available to manage these different pain mechanisms offers the promise of better treatment decisions and more widespread adoption of a multi-mechanistic approach; this could involve loosely combining two substances from different drug classes, or administering an analgesic with two different mechanisms of action. In some circumstances, a single compound capable of addressing both nociceptive and neuropathic pain is desirable. CONCLUSIONS: To improve patient outcomes, a thorough understanding of pain mechanisms, sensitisation and multi-mechanistic management is required. Universal, user-friendly educational tools are therefore required to familiarise physicians with these topics, and also to improve communication between physicians and their pain patients, so that realistic expectations of treatment can be established.

Indications and management of everolimus after liver transplantation.

OBJECTIVE: Our aim was to assess our experience with the use and management of everolimus after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Among the 759 patients who underwent transplantation from 1988 to 2008, 25 (3.2%) received immunosuppression with everolimus. Their mean age was 55.6 years. We analyzed indications for use, time between transplantation and introduction of everolimus, as well as its efficacy, side effects, and patient survival. RESULTS: The indications for everolimus treatment were: extended hepatocellular carcinoma (HCC) in the explanted liver (n = 6; 24%); HCC recurrence during follow-up (n = 4; 16%); de novo tumor (n = 6; 24%); refractory rejection (n = 3; 12%); side effects of calcineurin inhibitors (CNI; n = 3; 12%); and other causes (n = 3; 12%). Mean time between OLT and everolimus treatment was 40 +/- 33 months (range, 10 days-178 months). Mean follow-up after conversion was 10 +/- 9 months (range, 1.5-25 months). More than half of the patients resolved the event for which the drug was indicated: 75% of patients with refractory rejection; 60% of those with renal insufficiency; and 100% of those converted for neurotoxicity or hepatotoxicity. Two patients with recurrent HCC and 1 with extended HCC died at a mean time of 10.5 months. The 6 cases of de novo tumors were operated and are healthy. Side effects were dyslipidemia in 8 and infection in 2. Five patients (20%) discontinued the drug. CONCLUSIONS: In the early posttransplantation period, everolimus is indicated for refractory rejection or as prophylaxis for recurrence of extended tumors. In any time but especially in the late period, everolimus is indicated for patients with serious side effects due to a CNI or to a de novo tumor.

Intraoperative flow measurement of native liver and allograft during orthotopic liver transplantation in children.

Hepatic hemodynamic changes during liver transplantation (OLT) in children have not yet been studied. We measured intraoperative portal vein flow (PVF) and hepatic arterial flow (HAF) (mL/min) in 53 children and 58 grafts during OLT. Flows were measured in the native organ and in the allograft. In the native liver, PVF and HAF are similar; after transplantation they return to the physiological situation. No flow differences were seen between whole and partial grafts. Among the 8 (14%) portal vein thromboses, PVF was lower in both the native liver and the graft than in the no thrombosis group (P < .05). PVF <5 mL/min/kg was a risk factor to develop PV thrombosis. No graft loss occurred in 3 cases without PVF at the time of OLTs despite the observation that repermeabilization was not possible. In 4 patients with PVF <5 mL/min/kg, after tying a spontaneous spleno-renal shunt (n = 3) or performing a porto-renal vein anastomosis (n = 1), PVF reached >20 mL/min/kg, avoiding thrombosis. In conclusion, PVF and HAF measurements during pediatric OLT may predict patients at high risk for development of PV thrombosis.

Liver transplantation in childhood with more than 10 years of follow-up: analysis of a single-center experience.

UNLABELLED: We pioneered pediatric liver transplantation (OLT) in Spain (June 1985). The aim of this study was to evaluate the current status of our OLT recipients with more than 10 years follow-up. MATERIALS AND METHODS: The 50 patients with >10 years follow-up had a mean age at OLT of 5.6 years with 60% showing a main indication of biliary atresia. All but one (tacrolimus) received cyclosporine. RESULTS: No patient loss occurred among these patients. Eighteen patients had follow-up >15 years and 12 >20 years. The incidence of acute rejection was 56%; chronic rejection, 16%; and lymphoproliferative disorders, 12%. Seven (14%) required retransplantation at a mean of 4.2 years after the first OLT due in four instances to chronic rejection. After 10 years of follow-up, one patient developed portal vein thrombosis and three biliary strictures. All patients remain on immunosuppression. In 64% cyclosporine was switched to tacrolimus or another agent. One patient developed acute rejection at 19.2 years. In 14% of patients the liver function test is abnormal with serum creatinine is >1.5 mg/dL in 10%; one requires insulin and three, antihypertensive drugs. Noncompliance with medications was detected in 10%. Three recipients had offspring. CONCLUSIONS: OLT was an effective treatment with a good quality of life also on long-term follow-up.

Multiparameter immune profiling of operational tolerance in liver transplantation.

Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for gammadelta T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+ CD25+ T-cells and Vdelta1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.

[Peripheral cholangiocarcinoma: results of surgical treatment]. / Colangiocarcinoma periférico: resultados del tratamiento quirúrgico.

INTRODUCTION: Peripheral cholangiocarcinoma (PC) is an uncommon primary hepatic tumor that represents 10% of hepatic resections for primary malignant tumors in our experience. PATIENTS AND METHODS: From 1988 to 2004, 29 patients with a diagnosis of PC were treated in our unit. One patient was treated with chemoembolization and the remainder underwent surgery. In 7 patients, hepatectomy was not performed due to the presence of an extrahepatic tumor or massive hepatic invasion. The resectability index was 75%. Twenty-one patients underwent radical excision of PC and comprised the study group. RESULTS: The mean age was 60 years with a slight predominance of women. Sixty-two patients were symptomatic and tumoral markers were elevated in 58%. PC developed in normal liver in 15 patients, in cirrhotic liver in 2 patients and in the context of chronic hepatitis in 4 patients. The mean tumoral size was 7 cm (between 1.6 and 13 cm). Multiple tumors were found in 3 patients, invasion of the hepatic hilum lymph nodes was found in 8 patients and vascular invasion was observed in a further 8 patients. Major hepatectomy was performed in 90% of the patients; radical lymphadenectomy of the hepatic hilum was performed in 15 patients and excision of the extrahepatic biliary tract followed by Roux-en-Y hepaticojejunostomy in 4 patients. Operative mortality occurred in 3 patients (14%); one cirrhotic patient died 4 days after surgery from cardiovascular causes and 2 patients died from liver failure after extensive hepatectomies that included resection of the inferior vena cava and suprahepatic veins. Complications occurred in 33% of the patients. Ten patients (47%) died. Of these, 6 died from tumoral recurrence. Tumoral recurrence occurred in 9 patients (5 hepatic and 4 extrahepatic). Hepatic recurrences were treated with radiofrequency ablation in 2 patients and chemotherapy in 5 patients. The median survival was 11 months. Actuarial survival at 1, 3 and 5 years was 60%, 47% and 47% respectively. Disease-free survival at 1, 3 and 5 years was 50%, 31% and 31% respectively. In univariate analysis, significant risk factors for mortality were lymphatic invasion and a resection margin of less than 1 cm. In multivariate analysis, negative factors for tumoral recurrence were lymphatic invasion, satellitosis, and poor tumoral delimitation. CONCLUSION: Surgical treatment of PC through radical hepatic resection with margins of more than 1 cm in patients without nodal invasion provides good results with a 5-year survival of 79%.

Five-year follow-up of a trial comparing Tacrolimus and cyclosporine microemulsion in liver transplantation.

We evaluate 5-year results of a prospective randomized trial that compared cyclosporine microemulsion (CsA-me) and Tacrolimus (Tac) for primary immunosuppression. One hundred one adult patients undergoing liver transplantation were randomized to receive Tac (n = 50) or CsA-me (n = 51). The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism. Survival rates at 1, 3, and 5 years were 86%, 75%, and 72%, respectively; there was no significant difference between CsA-me versus Tac arms. Acute rejection occurred in 30 cases (30%), independent of the type of primary immunosuppression. Serious adverse events were reported significantly more among patients under CsA-me (48 episodes) than under Tac (32 episodes). Nineteen patients were switched to the other calcineurin inhibitor. The switch was much more frequent from CsA-me to Tac (n = 15; 29.4%), mainly because of lack of efficacy (n = 10; 19.6%). There were no cases of chronic rejections in the Tac arm. Four patients were switched from Tac to CsA-me for side effects; only 1 remains alive, after treatment was changed from CsA-me to an antimetabolite. There were no statistical differences in renal dysfunction, diabetes, hypertension, neurologic disorders, new-onset malignancies, or infections. There were no differences in survival or rejection among the intention-to-treat groups. Serious adverse events, total patients with switch of calcineurin inhibitor, as well as switches due to lack of efficacy, were statistically more frequent under CsA-me. Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation.

Analysis of discarded livers for transplantation.

The aims were to study the causes of nonacceptance of a liver for transplantation after exploration by the donor surgical team and to compare donor characteristics of transplanted and discarded livers. All donor harvesting procedures performed by our unit from 1988 to 2004 were retrospectively studied. Donors were divided in those accepted and transplanted and those discarded by the donor surgical team. The causes of rejection were classified as hepatic and nonhepatic. Donor characteristics of accepted, transplanted livers were compared with those rejected for hepatic reasons. Seven hundred fifty four donor liver procurements were performed: 628 livers were accepted and transplanted (TL), 126 (17.5%) were discarded owing to extrahepatic (n = 16) or hepatic causes (n = 110). Extrahepatic causes were: technical (5.6%), and incidental tumors infection (7.2%). Hepatic causes were: chronic disease or cirrhosis (26.4%), ischemic or septic liver (16.8%), and steatosis (44%). Univariate analysis of donor characteristics showed a significant difference in older age, diabetes, alcohol intake, arterial hypertension, abnormal liver ultrasound (US) exam, and abnormal liver function tests in the group of discarded livers. Obesity and the finding of steatosis in US exam were the only two factors that maintained statistical significance upon multivariate analysis.

Portacaval shunt and inferior vena cava preservation in orthotopic liver transplantation.

The aim was to study the advantages of the use of a temporary portacaval shunt (PCS) with inferior vena cava (IVC) preservation during the piggyback technique for the anhepatic phase of orthotopic liver transplantation (OLT) performed in cirrhotic patients. Two groups of cirrhotic patients who underwent OLT with piggyback technique were compared; one with a PCS (n = 57) and the other, without PCS (n = 54). Patients with fulminant hepatitis, retransplantation, portal thrombosis, and previous portosystemic shunts were excluded. In both groups graft reperfusion was achieved by simultaneous arterial and venous revascularization. Donor, recipient, and surgical characteristics were similar in both groups. The PCS group had a significantly higher portal venous flow (PVF) than the no-PCS group (773 +/- 402 mL/min vs 555 +/- 379 mL/min, P = .004). Therefore, two subgroups were studied; the high PVF subgroup A (>800 mL/min), mean 1099 +/- 261 mL/min, and the low PVF subgroup B (<800 mL/min), mean 433 +/- 423 mL/min. Subgroup A, who were treated with PCS, required fewer blood transfusions and displayed better postoperative renal function; whereas, no differences were observed among subgroup B patients with versus without PCS. In conclusion, the use of a temporary PCS with piggyback technique during OLT in cirrhotics has advantages in patients who still maintain a high portal venous flow.

Analysis of INF-gamma, TNF-alpha and dendritic cells to predict hepatitis C virus recurrence in liver transplant patients.

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease and the reason for more than 50% of liver transplantations (OLT). Recurrent HCV infection occurs in almost all transplant recipients and has an unfavorable course. Although immunosuppressive agents are necessary to avoid allograft rejection, these drugs may favor viral replication facilitating viral-mediated graft injury. METHODS: To predict the evolution of two HCV(+) patients who underwent OLT, we studied INF-gamma and TNF-alpha production and the maturation capacity of dendritic cells (DCs) at three time points: before transplantation (Pre-Tx) and at 2 (2M) and 6 (6M) months after transplantation. Cytometric bead assays were used to quantify INF-gamma and TNF-alpha production in the supernates of mixed leukocyte reactions (MLR) between spleen cells from the liver donor and CD4(+) cells from the recipients. Immature and mature DCs were generated in vitro from patient monocytes. RESULTS: The one patient who experienced recurrent HCV showed loss of CD4(+) responses to donor antigens and INF-gamma and TNF-alpha production after OLT. In contrast, the other patient maintained detectable levels of these cytokines after OLT. It was possible to generate mature DCs from monocytes with the aid of CD40L in both cases, but decreased expression of HLA-DR, CD80, and CD86 markers was observed upon posttransplantation analyses in the patient with recurrent HCV. CONCLUSION: Loss of the proliferative response as well as INF-gamma and TNF-alpha production, together with a decreased HLA-DR, CD80, and CD86 (markers of mature DCs), indicated an inadequate immune response to viral progression in the liver transplant recipient with relapsing HCV infection.

Outcome of 28 split liver grafts.

UNLABELLED: Our aim is to present our experience with split liver transplantation. From 1992-2002, 14 livers were split to obtain 28 grafts that were transplanted to 12 adults and 16 children. Ex situ splitting was performed in all cases. The left graft consisted of the left lateral segment (segments II-III) in 11 cases and the left lobe in three, depending on the size of the pediatric recipient. Pediatric recipients were of mean age 3, 4 years; mean weight 13 kg; six emergency cases for fulminant hepatic failure or urgent retransplantation and seven of 10 elective cases for biliary atresia. Postoperative mortality rate was 31% (five cases), including four of six emergency cases and one elective case (10%). The main cause was multiorgan failure. Technical complications were: one arterial thrombosis, one portal vein thrombosis, and four biliary complications. Eleven patients are alive and well. Adult recipients were of mean age 53 years. The indications were hepatocellular carcinoma in six cases, liver cirrhosis of various etiologies in five, and one recurrence of hepatitis C in a graft. Two patients died during the postoperative period from sepsis after retransplantation for primary nonfunction of the split graft and multiorgan failure with sepsis. One-year actuarial survival was 84%. CONCLUSIONS: The results of split liver transplantation in elective cases are similar to whole liver transplantation, whereas patient survival among emergency cases is low due to the critical condition of the patients.

Liver transplantation for hilar cholangiocarcinoma: Spanish experience.

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). CONCLUSION: 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 peripheral 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<.05) in the univariate analysis and perineural invasion (P<.05) and stages III or IVA (P<.05) in the multivariate analysis. 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.