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.

Manejo farmacológico del dolor agudo postoperatorio en España. Datos de la encuesta nacional de la Sociedad Española del Dolor (SED) / Pharmacological management of acute postoperative pain in Spain. Data from the national survey from the Spanish Pain Society (SED) (iasp chapter)

Introducción: La Sociedad Española del Dolor (SED), y concretamente el Grupo de Trabajo de Dolor Agudo de la misma (GTDASED), llevó a cabo una encuesta a nivel nacional para conocer la situación del manejo del dolor postoperatorio en España así como las distintas pautas analgésicas empleadas. En este artículo se analizan estas pautas y se comparan atendiendo a la presencia o no de Unidad de Dolor Agudo (UDA) o Programas de Gestión del Dolor Postoperatorio (PGDPO) entre aquellos hospitales de más de 200 camas que participaron en la misma. Pacientes y métodos: Los miembros de la Sociedad Española del Dolor y todos los responsables del tratamiento del dolor postoperatorio de los hospitales españoles fueron invitados a contestar un cuestionario estructurado. Para el análisis los hospitales se dividieron en 2 grupos: < 200 camas y ≥ 200 camas. Las variables categóricas fueron descritas como porcentajes con el 95 % de intervalo de confianza y las continuas con la mediana y el rango intercuartil. Se analizaron las pautas farmacológicas empleadas, sus asociaciones así como las vías de administración. Resultados: En total las respuestas implicaron a 112 (78 con > 200 camas y 34 con < 200 camas) hospitales del Sistema Nacional de Salud Español. Se obtuvieron respuestas del 42,4 % de hospitales con ≥ 200 camas, y del 9,6 % de los de < 200 camas, por lo que solo se analizó el primer grupo en lo que respecta a pautas de administración de analgesia, mientras que en el caso aislado de los fármacos empleados se analizaron los 112 hospitales que respondieron la encuesta. Las pautas orales se emplean en el 60,3 % de los hospitales (sin diferencias entre aquellos con y sin UDA), las intramusculares (i.m.) en un 15,8 %, subcutáneas (s.c.) 48,3 %, intravenosas (i.v) en bolos 75,9 %, intravenosas continuas 77,6 %, intravenosas PCA 60,3 %, catéteres en plexo nervioso a bolos 51,7 %, catéteres en plexo nervioso e infusión continua 56,9 %, epidurales en bolos 40,4 %, epidurales continuas 75,9 %, epidurales en PCA 43,1 %, (63,8 % anestésico local y opioide y 15,8 % anestésico local con otros fármacos [adrenalina/clonidina/ opioide]). Solo hubo diferencia estadísticamente significativa en función de la presencia o no de UDA en el centro, en las pautas: intravenosas en PCA, catéteres en plexo nervioso con infusión continua y epidural en PCA (más empleadas en los hospitales con UDA) e intramusculares (menos empleadas en los hospitales con UDA). De los centros con > 200 camas un 81,3 % utilizaron AINE en sus prescripciones orales (ibuprofeno 38,1 % y dexketoprofeno 28,6 %); un 68,8 % utilizó paracetamol (asociado a AINE en un 22 %) y un 28,1 % empleó opioides orales (tramadol en el 21,9 %). Las pautas intramusculares fueron utilizadas por un 15,8 % de los encuestados. En 55 centros (de los 112 encuestados independientemente del número de camas hospitalarias) aún se utilizan pautas subcutáneas para tratar el dolor agudo postoperatorio y de ellos el 58,3% emplea cloruro mórfico. La protocolización de co-adyuvantes es del 2,3 %. El AINE más empleado es el dexketoprofeno por vía intravenosa y el ibuprofeno por vía oral. El opioide débil más empleado es el tramadol tanto por vía oral como intravenosa. La morfina es el opioide potente más empleado, especialmente en PCA intravenosa (i.v.). El paracetamol se emplea en el 54,7 % (112 hospitales) de las pautas i.v. a bolos. El concepto de analgesia multimodal, aunque es conocido, no se práctica de modo mayoritario entre los encuestados (solo un 30 % de los centros que respondieron la encuesta lo hacen). Conclusión: El paracetamol y los AINE se emplean tanto por vía oral (67,4 y 86,1 %, respectivamente) como intravenosa (54,7 y 56,6 %, respectivamente). Cuando los hospitales de > 200 camas disponen de UDA o PGDPO utilizan significativamente más las pautas: intravenosas en PCA, catéteres en plexo nervioso e infusión continua y epidural en PCA y menos las pautas i.m. La aplicación de analgesia multimodal es baja (AU)

Introduction: The Spanish Pain Society SED-IASP launched a national survey in order to determine how was postop pain managed throughout Spain. This article analyses the drugs and routes employed comparing them according to the presence or not of an Acute Pain Unit (APU) or Acute Pain Management program (APMP) in hospitals with > 200 beds that participated and answered the survey. Patients and 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. The drugs employed, associations of them and routes of administration were also analysed. Results: A total of 112/537 hospitals responded the survey (78 with >200 beds and 34 < 200) which represents a 20,9 % response tax). Responses were received from 42.4 % of hospitals with ≥ 200 beds (vs. 9.6 % of the smaller ones). We fully analysed data concerning routes and ways of administration only for the larger hospitals, 57.7 % of which had an APS or APMP. Solely drugs were analysed considering all 112 hospitals. Oral route is employed in 60,3 % hospitals (no differences between those with or not APU), intramuscular (IM) in 15,8 %, subcutaneous (SC) 48,3 %, intravenous (IV) bolus 75,9 %, IV continuous 77,6 %, IV PCA 60,3 %, catheters in nerve plexus using bolus 51,7 %, catheters in nerve plexus with continuous infusion 56,9 %, epidurals with bolus 40,4 %, continuous epidurals 75,9 %, epidural PCA 43,1 %, (63,8 % local anesthetic and opioid and 15,8 % local anesthetic with adrenaline/clonidine/opioid). Statistical significant differences were found in IV PCA route, continuous infusión through catheters in nervous plexus and epidural PCA (more employed in hospitals having an APU) and IM route (significantly less employed in them). A total of 81,3 % hospitals with > 200 beds used oral NSAIDs to treat postoperative pain (ibuprophen 38,1 % and dexketoprophen 28,6 %); paracetamol was employed in 68,8 % of them (associated to NSAID in 22 %) and 28,1 % employed oral opioids (tramadol 21,9 %). Coadjuvants are only employed in 2,3 % of 112 hospitals. IV dexketoprophen and oral ibuprophen were the most frequent NSAIDs employed. Tramadol is the most commonly IV and oral opioid employed. Morphine is the strong opiod more frequently used, especially in IV PCA. Paracetamol is used in 54,7 % (112 hospitals) of IV bolus way of administration. Multimodal analgesia concept although well known is not widely established among the survey responders (only 30 % apply it). Conclusion: Paracetamol and NSAIDs are used by IV (54,7 y 56,6 % respectively) and oral routes (67,4 y 86,1 % respectively). Hospitals with > 200 beds having an APU or APMP significantly employ more IV PCA, nerve plexus catheters continuous infusion and epidural PCA and less IM route to treat postoperative pain. Multimodal analgesia is not widely used in Spanish Hospitals (AU)

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.

Consenso experto sobre el uso clínico de los tratamientos por vía tópica en el manejo del dolor neuropático periférico / No disponible

Objetivo: Proponer a partir del consenso de un panel de expertos de ambito estatal que integre la experiencia clinica y la evidencia disponible mas actual, recomendaciones sobre el uso clinico de los tratamientos por via topica para el manejo del dolor neuropatico periferico (DNP). Métodos: Se proponen, a partir de una revision bibliografica sobre las distintas opciones terapeuticas topicas en DNP, una serie de criterios profesionales y recomendaciones clinicas para la mejora del uso de dichos agentes topicos. Se empleo el metodo Delphi modificado en dos rondas para contrastar las opiniones de un panel nacional de 52 reconocidos expertos, seleccionados mediante una estrategia en “bola de nieve” de entre el colectivo de anestesiologos de unidades del dolor (94 %) y otros especialistas (neurologos y traumatologos). Se evaluaron 61 recomendaciones clinicas agrupadas en 6 areas tematicas: a) DNP: tratamiento topico versus sistemico (11 items); b) dolor neuropatico postquirurgico, postraumatico y munones dolorosos (12 items); c) neuralgia posherpetica, intercostal y del trigemino (9 items); d) DNP por atrapamiento (8 items); e) sindrome de dolor regional complejo (11 items); y f) neuropatia diabetica (ND) y otras polineuropatias (por VIH, alcohol, toxicidad, etc.) (10 items). Se empleo una escala ordinal de tipo Likert de 9 puntos (desacuerdo/ acuerdo) para evaluar cada recomendacion. Tras la primera ronda de encuesta, se facilito al panel informacion del resultado (resultados estadisticos y opiniones libres de los panelistas) y se solicito la reconsideracion del voto sobre los items no consensuados. Resultados: Tras la primera ronda del panel se logró consenso en 37 de las 61 cuestiones planteadas. Al final de la segunda ronda el acuerdo ascendió hasta 46 ítems (75 %). En general, se aprecia consenso entre los expertos sobre la conveniencia de introducir los tratamientos tópicos en primera línea de tratamiento del DNP y sobre su mejor aceptación por los pacientes frente a los sistémicos. Asimismo, fue criterio compartido que la combinación de estos fármacos tópicos con los tratamientos sistémicos es una opción a considerar en el manejo de varios tipos de DNP. También se alcanzó un alto grado de acuerdo en aceptar, desde un punto de vista fisiopatológico, la indicación del tratamiento con parche de capsaicina al 8 % para varios tipos de DNP. Conclusión: Los expertos en el manejo clínico del DNP muestran un elevado nivel de acuerdo profesional con diversas recomendaciones terapéuticas analizadas en el estudio. La difusión de tales recomendaciones puede ayudar a la mejora del manejo rutinario de fármacos tópicos para el dolor neuropático en nuestro sistema sanitario (AU)

Objective: To propose consensus from a panel of state level that integrates clinical experience and the most current evidence, recommendations on the clinical use of topical treatments for the management of peripheral neuropathic pain (PNP). Methods: We propose, based on a literature review on topical therapeutic options in PNP, a series of professional standards and clinical recommendations for improving the use of these topical agents. We used the modified Delphi method in two rounds to contrast the views of a national panel of 52 renowned experts, selected by a “snowball” strategy among the group of anesthesiologists pain units (94 %) and other specialists (neurologist and trauma). We evaluated 61 clinical recommendations grouped into 6 areas: a) PNP systemic versus topical treatment (11 items); b) postsurgical neuropathic pain, post-traumatic and painful stumps (12 items); c) post-herpetic neuralgia, intercostal and trigeminal (9 items); d) PNP entrapment (8 items); e) CRPS (11 items); and f) diabetic neuropathy (DN) and other polyneuropathy (HIV, alcohol, toxicity, etc.) (10 items). We used a Likert- type ordinal scale of 9 points (disagree/agree) to evaluate each recommendation. After the first round of the survey, information was provided requested to reconsider the vote on itemsnot agree. Results: After the first round the panel consensus was achieved in 37 of the 61 issues raised. At the end of the second round of the agreement amounted to 46 (75 %). In general, there was consensus among experts on whether to introduce topical treatment in first line treatment of PNP and its greater acceptance by patients compared with systemic. He was also a shared view consider in the management of various types of PNP. Also reached a high level of agreement to accept, from a physiological point of view, the indication for treatment with capsaicin patch 8 % for various types of PNP. Conclusions: Experts in the clinical management of PNP show a high level of professional agreement with various therapeutic recommendations for study. The dissemination of such recommendations can help improving the routine management of topical drugs for neuropathic pain in our health system (AU)

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 (AU)

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.

Colecistectomía laparoscópica durante la gestación / Laparoscopic cholecystectomy during pregnancy

No disponible

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%.

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

Introducción: El colangiocarcinoma periférico (CP) es un tumor hepático primario poco frecuente, que supone el 10% de las resecciones hepáticas por tumor maligno primario en nuestra experiencia. Pacientes y métodos: Desde 1988 a 2004 tratamos en nuestra unidad a 29 pacientes diagnosticados de CP. Uno se trató con quimioembolización y el resto fueron intervenidos, aunque en 7 casos no se realizó hepatectomía por presencia de tumor extrahepático o invasión hepática masiva. El índice de resecabilidad fue del 75%. A 21 pacientes se les practicó una exéresis radical del CP y son los que forman el grupo de estudio. Resultados: La edad media de los 21 pacientes era de 60 años, entre ellos había un ligero predominio femenino, 62 eran sintomáticos y los marcadores tumorales estaban elevados en el 58%. El CP apareció en un hígado normal en 15 casos, 2 eran cirróticos y 4 presentaban hepatitis crónica. El tamaño tumoral medio fue de 7 cm (rango: 1,6-13), 3 eran múltiples, se halló invasión de los ganglios del hilio hepático en 8 casos e invasión vascular en otros 8. Se realizó hepatectomía mayor en el 90% de los casos, linfadenectomía radical del hilio hepático en 15 casos y exéresis de la vía biliar extrahepática seguida de hepaticoyeyunostomía en Y de Roux en 4 ocasiones. La mortalidad operatoria fue del 14%. El 33% de los pacientes presentó complicaciones. Fallecieron 10 pacientes (47%), 6 de ellos por recidiva tumoral. Nueve pacientes presentaron recidiva tumoral (5 hepática y 4 extrahepática). Las recidivas hepáticas se trataron con ablación por radiofrecuencia en 2 casos y 5 pacientes recibieron quimioterapia. La supervivencia mediana fue de 11 meses y la supervivencia actuarial al año, 3 y 5 años fue del 60, el 47 y el 47%, respectivamente. La supervivencia libre de enfermedad al año, 3 y 5 años fue del 50, el 31 y el 31%, respectivamente. La invasión linfática y el margen de resección inferior a 1 cm fueron factores de riesgo de mortalidad significativos en el estudio univariado, mientras que la invasión linfática, la satelitosis y la mala delimitación tumoral fueron factores negativos de recidiva tumoral en el estudio univariado. Conclusión: El tratamiento quirúrgico del CP mediante resección hepática radical con márgenes superiores a 1 cm en los pacientes que no presentan invasión ganglionar obtiene unos buenos resultados, con una supervivencia del 79% a los 5 años

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.