Enrique de-Madaria

Cytokine genotypes in acute pancreatitis: association with etiology, severity, and cytokine levels in blood.

The circumstances that determine how acute pancreatitis (AP) becomes severe are unknown. Differences in cytokine genetic encoding may determine the severity or influence the etiology of AP. This article investigates the relationship between different polymorphisms of tumor necrosis factor &agr; (TNF-&agr;), interleukin 1 (IL-1), IL-1 receptor antagonist, IL-6, and IL-10 with the severity and etiology of AP and the serum levels of the cytokine encoded. Methods: Patients with AP were included prospectively. Severity of the disease was determined according to Atlanta classification. Serum levels of these cytokines were determined within the first 72 hours after the onset of symptoms. The following polymorphisms were determined by polymerase chain reaction: IL-1a −889, IL-1b +3954, IL-1b −511, variable number tandem repeats, IL-6 −174, IL-6 −597, IL-10 −592, TNF-&agr; 308, TNF-&agr; 238, and TNF-B250. Results: Eighty-four patients were included. The GA genotype of the TNF-&agr; 238 polymorphism was associated with more frequent respiratory failure and shock than the GG genotype. Gallstone pancreatitis was associated with the CC genotype of the IL-6 −174 CC polymorphism. Conclusions: AG genotype of the TNF-&agr; 238 polymorphism is associated with organic failure in patients with AP. The CC genotype of the IL-6 174 polymorphism is associated with biliary etiology of acute pancreatitis.

Early factors associated with fluid sequestration and outcomes of patients with acute pancreatitis.

BACKGROUND & AIMSnPredicting level of fluid sequestration could help identify patients with acute pancreatitis (AP) who need more or less aggressive fluid resuscitation. We investigated factors associated with level of fluid sequestration in the first 48 hours after hospital admission in patients with AP and effects on outcome.nnnMETHODSnWe analyzed data from consecutive adult patients with AP admitted to the Brigham and Womens Hospital in Boston, Massachusetts, from June 2005 to December 2007 (nxa0= 266) orxa0the Alicante University General Hospital in Spain from September 2010 to December 2012 (nxa0= 137). Level of fluid sequestration in the first 48 hours after hospital admission was calculated by subtracting the total amount of fluid administered and lost in the first 48 hours of hospitalization. Demographic and clinical variables obtained in the emergency department were analyzed to identify factors associated with level of fluid sequestration in the first 48 hours after hospital admission. Outcome assessed included length of hospital stay, acute fluid collection(s), pancreatic necrosis, persistent organ failure, and mortality.nnnRESULTSnThe median level of fluid sequestration in the first 48 hours after hospital admission was 3.2 L (1.4-5 L). The simple and multiple linear regression models showed that younger age, alcohol etiology, hematocrit, glucose, and systemic inflammatory response syndrome were significantly associated with increased levels of fluid sequestration in the first 48 hours after hospital admission. Increased level of fluid sequestration in the first 48 hours was significantly associated with longer hospital stays and higher rates of acute fluid collection, pancreatic necrosis, and persistent organ failure. There was a nonsignificant trend toward a higher level of fluid sequestration in the first 48 hours among patients who died.nnnCONCLUSIONnAge, alcoholic etiology of AP, hematocrit, glucose, and presence of systemic inflammatory response syndrome in the emergency department were independent predictors of increased levels of fluid sequestration in the first 48 hours after hospital admission. These patients have higher risks of local and systemic complications and longer hospital stays.

Acute and chronic hemodynamic changes after propranolol in patients with cirrhosis under primary and secondary prophylaxis of variceal bleeding: a pilot study.

Background and aim Prophylactic treatment of variceal bleeding in cirrhotic patients with &bgr;-blockers is effective in only some patients. Our aim was to determine whether the response of the hepatic venous pressure gradient (HVPG) to the intravenous administration of propranolol predicts the response after chronic oral propranolol treatment. Patients and methods We included prospectively cirrhotic patients with esophageal varices under primary prophylaxis (PP) and secondary prophylaxis (SP). The HVPG was measured at baseline and after a propranolol bolus (0.15u2009mg/kg intravenous). A patient was considered a good-responder if HVPG decreased to 12u2009mmHg or 20% from baseline. Patients then received oral propranolol (heart rate titrated). Poor-responders under SP were also included in a variceal band ligation program. After at least 3 months, a second hemodynamic study was conducted. Results Fifty-six patients were included (36 SP and 20 PP). Response rate was similar (32.1 and 41.9%, P=0.7) and the Pearsons correlation coefficient was 0.61 (P=0.001). In 81.4% patients, the first study predicted the response status of the second. Six patients rebled on follow-up between the studies, all of them were poor responders to intravenous propranolol. Conclusion A single hemodynamic study using intravenous propranolol seems to predict chronic response to propranolol.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Fluidoterapia en la pancreatitis aguda

Severe acute pancreatitis (AP) is associated with an increased need for fluids due to fluid sequestration and, in the most severe cases, with decreased peripheral vascular tone. For several decades, clinical practice guidelines have recommended aggressive fluid therapy to improve the prognosis of AP. This recommendation is based on theoretical models, animal studies, and retrospective studies in humans. Recent studies suggest that aggressive fluid administration in all patients with AP could have a neutral or harmful effect. Fluid therapy based on Ringers lactate could improve the course of the disease, although further studies are needed to confirm this possibility. Most patients with AP do not require invasive monitoring of hemodynamic parameters to guide fluid therapy administration. Moreover, the ability of these parameters to improve prognosis has not been demonstrated.

Páncreas y vía biliar. Pancreatitis aguda

The present article reviews the conclusions of the most interesting studies on acute pancreatitis presented at Digestive Disease Week 2011. Specific prognostic systems for acute pancreatitis show moderate accuracy in predicting outcome, which may be improved by step-up combination rules. The presence of systemic inflammatory response syndrome seems to be a better marker of severity than the bedside index for severity in acute pancreatitis (BISAP) score. Admission hematocrit, 24 h creatinine and 24 h BUN seem to predict the development of pancreatic necrosis. Cardiovascular disease may be associated with an increased risk of severe post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis. Prognostic abdominal computed tomography scan should be avoided until the second day of admission. Endoscopic necrosectomy may be associated with shorter length of hospital stay, similar radiologic success and probably a lower incidence of complications than open necrosectomy. Combination therapy involving endoscopic plus percutaneous drainage is associated with good long-term outcomes. Outcome is better in patients who receive more than one third of their 72 h total fluid therapy within the first 24 h. The best predictor of a high need for fluid therapy in the first 48 h is leukocyte count.Resumen Las conclusiones de los estudios mas interesantes de la Digestive Disease Week 2011 respecto a la pancreatitis aguda (PA) se enumeran a continuacion. Los sistemas pronosticos especificos de PA tienen una precision moderada, que puede mejorarse mediante su combinacion escalonada. La presencia de criterios del sindrome de respuesta inflamatoria sistemica parece tener mayor valor pronostico que el sistema BISAP. El hematocrito inicial, la creatinina a las 24xa0h y el nitrogeno ureico en sangre a las 24xa0h predicen el desarrollo de necrosis pancreatica. El antecedente de enfermedad cardiovascular podria predisponer a PA grave post-colangiopancreatografia retrograda endoscopica. Se debe evitar la realizacion de una tomografia computarizada abdominal con intencion pronostica antes del segundo dia de ingreso. La necrosectomia endoscopica podria asociarse a una menor estancia hospitalaria, similar frecuencia de exito radiologico y probablemente una menor incidencia de complicaciones que la necrosectomia endoscopica. El tratamiento combinado de la necrosis pancreatica organizada mediante drenaje endoscopico y percutaneo se asocia a buenos resultados a largo plazo. Los pacientes que reciben mas de un tercio de la fluidoterapia de los primeros 3 dias durante el primer dia de evolucion tienen mejor pronostico. El parametro determinado en urgencias que mejor predice unas necesidades aumentadas de fluidos es el recuento leucocitario.

Vías biliares y páncreasPancreatitis aguda

The present review discusses eight studies, selected for their clinical importance in the field of acute pancreatitis (AP). A multicenter clinical trial demonstrated that treatment of infected pancreatic necrosis through drainage, followed by video-assisted retroperitoneal debridement in patients with poor clinical course, was superior to classical open surgery in terms of costs and complications. A retrospective study analyzed the radiation from computed tomography received by patients with necrotizing AP and warned of the high dose administered, which could have significant carcinogenic effects. A multicenter retrospective study confirmed the utility of measuring blood urea nitrogen at admission and at 24 hours in predicting mortality due to AP. A prospective study of fluid therapy reported that inadequate or excess fluid administration in the first 24 hours of admission were related to poor outcome. Two studies analyzed the bedside index for severity in AP (BISAP) score at admission; this scoring system was useful in AP in general but not in the subgroup of patients requiring admission to the intensive care unit. Lastly, two studies showed the highly promising prognostic value of determining serum concentrations of angiogenic factors in AP.

S1366 Prognostic Scores for Acute Pancreatitis Within 24 Hours of Admission: BISAP Versus APACHE-II

Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation, is Associated With Persistent Organ Failure in Patients With Acute Pancreatitis From the United States and Germany David C. Whitcomb, Venkata Muddana, Christopher J. Langmead, Frank D. Houghton, Annett Guenther, Patricia K. Eagon, Julia Mayerle, Ali Aghdassi, Frank U. Weiss, Janette Lamb, Gilles Clermont, Markus M. Lerch, Georgios I. Papachristou

Últimos avances en pancreatitis aguda

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission.Resumen En el presente articulo se analizan las principales comunicaciones presentadas en la Digestive Disease Week 2013 sobre pancreatitis aguda (PA). La tomografia computarizada de perfusion permite el diagnostico temprano de la necrosis pancreatica. La lipocalina asociada con la gelatinasa de los neutrofilos predice el desarrollo de mortalidad, insuficiencia renal aguda y PA grave. La etiologia alcoholica, un hematocrito elevado y la presencia de criterios de sindrome de respuesta inflamatoria sistemica se asocian a mayor secuestro de fluidos en PA; el secuestro de fluidos se asocia a peor evolucion de la enfermedad. Los verdaderos seudoquistes (colecciones liquidas sin necrosis de duracion mayor a 4 semanas) son una complicacion muy infrecuente en la PA. Los pacientes con colecciones necroticas tienen peor pronostico, sobre todo si se asocian a infeccion. Un metaanalisis sobre fluidoterapia sugiere que la administracion agresiva de fluidos precoz se asocia a mayor mortalidad y complicaciones respiratorias. Segun un metaanalisis, la nutricion enteral iniciada en las primeras 24xa0h de ingreso mejora la evolucion de la PA respecto a la nutricion enteral iniciada posteriormente. La pentoxifilina podria ser un farmaco prometedor en la PA, mostrando en un estudio aleatorizado doble ciego disminuir la estancia hospitalaria y en la unidad de cuidados intensivos asi como la necesidad de esta. La asociacion de octreotido y celecoxib parece disminuir la frecuencia de fallo organico frente a octreotido solo. Las PA leves pueden manejarse ambulatoriamente mediante unidades de hospitalizacion domiciliarias tras un corto ingreso de 24xa0h.

NEOPLASIA MUCINOSA PAPILAR INTRADUCTAL PANCREÁTICA EN EL HOSPITAL GENERAL UNIVERSITARIO DE ALICANTE

Introduccion La neoplasia mucinosa papilar intraductal (NMPI) es un tumor pancreatico productor de mucina que crece en el sistema ductal. Objetivos Describir las caracteristicas clinicas de los casos de NMPI diagnosticados en nuestro centro. Pacientes y metodos Estudio retrospectivo de pacientes diagnosticados de NMPI en el Hospital General Universitario de Alicante entre 2005 y 2008. Resultados Se diagnosticaron 9 pacientes, 6 (66,7%) varones. La edad al diagnostico fue 70±10 anos (rango 55-81). En 8 (88,9%) pacientes se sospecho la neoplasia por imagen tipica en TAC, en 1 (11,1%) paciente se sospecho por ecoendoscopia (moco en papila). En 5 (55,6%) de los casos la NMPI era de rama periferica y en 4 (44,4%) de ducto principal. La clinica de presentacion mas frecuente fue pancreatitis aguda: 5 (55,6%) pacientes, seguida de dolor abdominal en 2 (22,2%), diagnostico casual en prueba de imagen en 1 (11,1%) y sindrome constitucional en 1 (11,1%) paciente. En 2 (22,2%) casos la NMPI se asociaba a calcificaciones pancreaticas por pancreatitis cronica obstructiva. El diagnostico definitivo en 8 (88,9%) pacientes se realizo por ecoendoscopia (citologia positiva en 5, en el resto con citologia negativa: presencia de moco en 2 pacientes y CEA elevado con lesion tipica en 1). En 1 (11,1%) paciente se diagnostico por moco en PAAF percutanea. En total se objetivo moco en la puncion o en papila en 5 (55,6%) pacientes. La histologia fue adenoma en 5 (55,6%) casos, borderline en 3 (33,3%, todos ellos de ducto principal) y desconocida en 1 (11,1%). El tratamiento fue quirurgico en 4 (44,4%) pacientes (duodenopancreatectomia cefalica en todos ellos). En 3 (33,3%) de ellos la indicacion fue NMPI sintomatica (pancreatitis aguda o dolor abdominal) y en 1 (11,1%) por NMPI de ducto principal. En 2 casos con NMPI borderline no se realizo cirugia por rechazo del paciente asociado a edad elevada. No hubo casos de neoplasia invasiva ni mortalidad. Conclusiones La presentacion mas frecuente de la NMPI es la pancreatitis aguda. El TAC es la prueba que suele sugerir el diagnostico y la ecoendoscopia la tecnica que lo confirma. El analisis del liquido es eficaz en el diagnostico. La histologia mas frecuente es adenoma. La NMPI de ducto principal es mas agresiva histologicamente.