Treatment of infected pancreatic necrosis: Outcome in a 9-year, single-center, consecutive series (2006-2014)

Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases

OBJECTIVE To study the effect of postoperative complications (POC) on overall survival (OS) and disease-free survival (DFS) after surgical resection of colorectal liver metastases (CRLM). SUMMARY BACKGROUND DATA Morbidity rates after liver resection can reach 45%. The negative impact of POC on oncologic outcomes has been reported in various types of cancer, especially colorectal. However, data on the consequences of POC after CRLM resection on long-term survival are scarce. METHODS Eligible studies examining the association between POC after CRLM resection and OS/DFS were sought using the PubMed and Web of Science databases. A random-effects model was used to calculate pooled effect estimat…

Pancreatoduodenectomy with artery-first approach.

"Artery-first approach" encompasses different aspects for the surgical treatment of pancreatic cancer. It is a surgical technique or set of techniques which share in common the dissection of the main arterial vasculature involved in pancreatic cancer, before any irreversible surgical step is performed. On the other hand it represents the need for a meticulous dissection of the arterial planes and clearing of the retropancreatic tissue between the superior mesenteric artery, the common hepatic artery and portal vein in an attempt to achieve R0 resections. The recent expansion of this approach is based mainly on three factors: venous involvement should not be considered a contraindication for…

Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1beta and tumor necrosis factor alpha (TNF-alpha) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplifica…

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery

Objective: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. Background: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. Methods: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. Results: These guidelines analyz…

Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Simple Summary Pancreatic cancer is a digestive tumor that is most difficult to treat and carries one of the worst prognoses. The anatomical location of the pancreas makes it very difficult to obtain enough tumor material to establish a molecular diagnosis, so knowing the biology of this tumor and implementing new targeted-therapies is still a pending issue. The use of liquid biopsy, a blood sample test to detect circulating-tumor DNA fragments (ctDNA), is key to overcoming this difficulty and improving the evolution of this tumor. Liquid biopsies are equally representative of the tissue from which they come and allow relevant molecular and diagnostic information to be obtained in a faster …

490P Metastatic colorectal cancer derived organoids recapitulate genomic profile and treatment response of the original tumor

What does preoperative three-dimensional image contribute to complex pancreatic surgery?

Abstract The possibility of modelling diagnostic images in three dimensions (3D) in pancreatic surgery is a novelty that provides us multiple advantages. A better visualization of the structures allows us a more accurate planning of the surgical technique and makes it easier the surgery in complex cases. We present the case study of a borderline pancreatic head adenocarcinoma patient to illustrate the advantages of 3D modelling in complex pancreatic surgery. The help of 3D technology allowed us to optimally plan the intervention and facilitate surgical resection. The use of this tool could translate into: shorter operative time, fewer intraoperative complications or an increase in R0 resect…

Neoplasias de páncreas y periampulares: morbimortalidad, resultados funcionales y supervivencia a largo plazo

Resumen Objetivos Evaluar la morbimortalidad postoperatoria, el estado funcional y la supervivencia a largo plazo de pacientes con tumores de pancreas o periampulares a los que se intervino quirurgicamente. Pacientes y metodos Cohorte de 160 pacientes a los que se intervino consecutivamente: 80 duodenopancreatectomias cefalicas (DPC), 30 resecciones corporocaudales (RCC), 7 duodenopancreatectomias totales, 4 resecciones centrales y 3 ampulectomias; en 36 pacientes no se realizo reseccion. La funcion pancreatica se evaluo mediante test de sobrecarga oral a la glucosa, grasas en heces y elastasa fecal. Resultados La tasa de resecabilidad fue del 77,5%. En los pacientes resecados (n = 124) la …

Outcome Quality Standards in Pancreatic Oncologic Surgery in Spain

Introduction: To establish quality standards in oncologic surgery is a complex but necessary challenge to improve surgical outcomes. Unlike other tumors, there are no well-defined quality standards in pancreatic cancer. The aim of this study is to identify quality indicators in pancreatic oncologic surgery in Spain as well as their acceptable limits of variability. Methods: Quality indicators were selected based on clinical practice guidelines, consensus conferences, reviews and national publications on oncologic pancreatic surgery between the years 2000 and 2016. Variability margins for each indicator have been determined by statistical process control techniques and graphically represente…

Multiple small bowel perforations during the treatment of primary intestinal extranodal natural killer/T‐cell lymphoma, nasal type

Obese rats exhibit high levels of isoprostanes in acute pancreatitis

s / Pancreatology 12 (2012) 502–597 538 interference of Sam68 and SRSF1 expression cause a partial recovery of drug sensitivity. Conclusions: Our results show that chronic exposure of PDAC cells to gemcitabine leads to selection of a drug-resistant subpopulation overexpressing Sam68 and SRSF1. Importantly, the depletion of these proteins leads to a partial recovery of the sensibility to gemcitabine, suggesting that they may represent suitable molecular-targets to overcome drug resistance in PDAC. Arumugam T, Ramachandran V, Fournier KF, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009 Jul Shapiro IM, Cheng AW, Flytzanis NC, et…

Arterial hypertension due to primary adrenal hydatid cyst.

Implicaciones pronósticas del estudio estandarizado de los márgenes de resección en el cáncer de páncreas

Resumen Introduccion La afectacion microscopica de los margenes de reseccion es un factor pronostico fundamental en la cirugia del cancer de pancreas. Sin embargo, su definicion anatomopatologica no esta estandarizada. Este estudio pretende identificar el porcentaje real de pacientes con resecciones R1 al analizar las piezas quirurgicas con un protocolo estandarizado y evaluar sus implicaciones sobre la supervivencia. Pacientes y metodos Serie de 100 pacientes consecutivos intervenidos por adenocarcinoma ductal de pancreas y resecciones macroscopicamente completas, divididos en 2 grupos: pre- y posprotocolo, segun se intervinieran antes o despues de la aplicacion de un protocolo estandariza…

Naked DNA delivery to whole pig cardiac tissue by coronary sinus retrograde injection employing non-invasive catheterization.

Background Hydrodynamic injection has demonstrated to be very efficient in the liver of small animals, although this procedure must be translated to the clinical practice in a milder but no less efficient way. The present study evaluates the capacity of non-invasive interventional catheterization as a procedure for naked DNA delivery to the heart in large animals. Methods Two catheters were placed in the coronary sinus: one of them to block blood circulation and the other to retrogradely inject 50 ml of a saline solution of DNA (20 µg/ml) containing the enhanced green fluorescent protein (EGFP) gene, at a flow rate of 5 ml/s. Results The results obtained show that EGFP protein, identified b…

¿Qué aporta la imagen tridimensional preoperatoria en la cirugía pancreática compleja?

Resumen La posibilidad de modelizacion de imagenes diagnosticas en tres dimensiones (3 D) en cirugia pancreatica es una novedad que nos aporta multiples ventajas. Una mejor visualizacion de las estructuras nos permite una planificacion de la tecnica quirurgica mas precisa y nos facilita la realizacion de la cirugia en casos complejos. Presentamos el caso de un paciente diagnosticado de un adenocarcinoma de cabeza de pancreas borderline para ilustrar las ventajas de la modelizacion 3 D en cirugia pancreatica compleja. La ayuda de la tecnologia 3 D nos permitio planificar de manera optima la intervencion facilitando la reseccion quirurgica. El uso de esta herramienta podria traducirse en: men…

Non-arbitrary minimum threshold of yearly performed pancreatoduodenectomies: National multicentric study

Abstract Background Annual hospital volume of pancreatoduodenectomies could influence postoperative outcomes. The aim of this study is to establish with a non-arbitrary method the minimum threshold of yearly performed pancreatoduodenectomies in order to improve several postoperative quality outcomes. Method Prospective follow-up of patients submitted to pancreatoduodenectomy in participating hospitals during 1 year. The influence of hospital volume on quality outcomes was analyzed by univariable and multivariable models. The minimum threshold of yearly performed pancreatoduodenectomies to improve outcomes was established by Akaike’s information criteria. Results Data from 877 patients opera…

Obese Rats Exhibit High Levels of Fat Necrosis and Isoprostanes in Taurocholate-Induced Acute Pancreatitis

BACKGROUND: Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. METHODOLOGY: Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was m…

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival

// Ana-Barbara Garcia-Garcia 1, 2, * , M. Carmen Gomez-Mateo 3, 7, * , Rebeca Hilario 2 , Pilar Rentero-Garrido 2 , Alvaro Martinez-Domenech 4 , Veronica Gonzalez-Albert 2 , Andres Cervantes 5 , Pablo Marin-Garcia 6 , Felipe Javier Chaves 1, 2 , Antonio Ferrandez-Izquierdo 3 and Luis Sabater 4 1 CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Madrid, Spain 2 Unidad de Genomica y Diagnostico Genetico. Fundacion Investigacion Clinico de Valencia, Instituto de Investigacion Sanitaria Clinico de Valencia (INCLIVA), Valencia, Spain 3 Department of Pathology, Faculty of Medicine and Odontology, University of Valencia and Clinical Hospital of Valencia, and Instituto de Investigacio…

Fisiología de la secreción pancreática

Borderline resectable pancreatic cancer. Challenges and controversies.

Abstract Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic…

Response to the Comment on "Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy? A Multicenter, Randomized, Controlled Trial".

Haemoglobin in ascitic fluid increases lipid peroxidation in acute pancreatitis

Modified appleby procedure for resection of advanced pancreatic body-tail tumors with hepatic artery or celiac axis involvement

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list o…

Pancreatic function after severe acute biliary pancreatitis: the role of necrosectomy.

OBJECTIVES To investigate the recovery of pancreatic function after severe acute biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine and exocrine functions. METHODS Prospective cohort study including 39 patients with severe ABP. According to need or no need for surgical necrosectomy, patients were further subdivided into 2 groups. Functional pancreatic evaluation was carried out 12 months after the ABP episode. Endocrine function was evaluated by an oral glucose tolerance test and exocrine function by fecal fat excretion, fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS Most of the patients with necrosectomy had an abnormal exocrine pancreati…

Pancreatic ascites haemoglobin up-regulates the HIF/VEGF pathway in the lung in severe acute pancreatitis

Extracellular haemoglobin (EHb) is considered a toxic molecule due to its cytotoxicity and peroxidase activity. EHb may release free hemin that increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain cell-free hemoglobin. Our aim was to determine the role of EHb in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end, taurocholate-induced necrotizing pancreatitis in rats was used. EHb levels were quantified in ascites and plasma and the hemolytic action of ascitic fluid was tested. Furthermore, we assessed if peritoneal lavage prevented the increas…

Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

INTRODUCTION: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. METHODS: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive da…

Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol

Item does not contain fulltext Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-alpha production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-alpha is responsible for glutathione depletion in acute pancreatitis; and (…

Estándares de calidad en la cirugía oncológica pancreática en España

Resumen Introduccion Identificar los estandares de calidad en la cirugia oncologica es un reto complejo necesario para poder mejorar los resultados quirurgicos. A diferencia de lo que ocurre en otros tumores, no existen unos estandares de calidad bien definidos en el cancer de pancreas. El objetivo es identificar los indicadores de calidad en la cirugia pancreatica oncologica en Espana, asi como sus limites de variabilidad. Metodos Los indicadores de calidad se han seleccionado a partir de las guias de practica clinica, conferencias de consenso, revisiones y publicaciones de ambito nacional sobre cirugia pancreatica oncologica entre los anos 2000-2016. Los margenes de variabilidad para cada…

Preoperative hepatic artery embolization before distal pancreatectomy plus celiac axis resection does not improve surgical results: A Spanish multicentre study

Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical procedure with high morbidity and mortality performed in patients with locally advanced pancreatic cancer. Preoperative embolization of hepatic artery (PHAE) has been postulated as a technical option to increase resection rate.comparison of morbidity and mortality at 90 days, operative time, hospital stay and survival between patients that performed DP-CAR with and without PHAE.Observational retrospective multicentre study.patient operated in Spanish centers with DP-CAR for pancreatic cancer from April 2004 until 23 June 2018. Preoperative (PHAE, neodjuvant treatment), intraoperative (operative time and blood loss) and …

Circulating TNF-alpha and its soluble receptors during experimental acute pancreatitis.

Clinical and experimental studies have shown increased concentrations of TNF-α and its soluble receptors in serum of patients with acute pancreatitis. In this work, we have investigated the time-course of TNF-α and its soluble receptors during taurocholate-induced acute pancreatitis. In addition, since TNF-α itself could mediate the shedding of its receptors, we have assessed the effect of inhibiting TNF-α production on the release of soluble TNF-α receptors in experimental acute pancreatitis. Our results indicate that soluble receptors are released in the early stages of the disease and this increase is concomitant with the release of TNF-α, which is mainly bound to specific proteins. The …

The role of endoscopic retrograde cholangiopancreatography in the management of iatrogenic bile duct injury after cholecystectomy

espanolIntroduccion: la lesion yatrogenica de la via biliar (LYVB) es una complicacion con elevada morbilidad tras la colecistectomia. En los ultimos anos la endoscopia ha adquirido un papel fundamental en el manejo de esta patologia. Metodos: estudio retrospectivo de LYVB tras colecistectomia abierta (CA) o colecistectomia laparoscopica (CL) tratadas en nuestro centro entre 1993 y 2017. Se analizaron los datos referentes a las caracteristicas clinicas, tipo de lesion segun la clasificacion de Strasberg-Bismuth, diagnostico, tecnica de reparacion y seguimiento. Resultados: se estudian 46 pacientes. La incidencia LYVB fue de 0,48%, 0,61% para las CL y 0,24% para las CA. El diagnostico se rea…

Role of Redox Signaling, Protein Phosphatases and Histone Acetylation in the Inflammatory Cascade in Acute Pancreatitis: Therapeutic Implications

Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation trigg…

Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy? A Multicenter, Randomized, Controlled Trial

[Objective]: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD). [Background]: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. “Artery-first approach” is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies. [Methods]: A multicenter, randomized, controlled trial was conducte…

Prognostic Implications of the Standardized Study of Resection Margins in Pancreatic Cancers

Abstract Introduction Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications. Patients and methods One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided into 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized p…

Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis

Glutathione depletion is a key factor in the development of acute pancreatitis. Our aim was to study the regulation of glutamate cysteine ligase, the rate-limiting enzyme in glutathione synthesis, in edematous or necrotizing pancreatitis in rats. Glutathione levels were kept low in necrotizing pancreatitis for several hours, with no increase in protein or mRNA levels of glutamate cysteine ligase subunits, despite binding of RNA polymerase II to their promoters and coding regions. The survival signal pathway mediated by ERK and c-MYC was activated, and c-MYC was recruited to the promoters. The failure in gene up-regulation seems to be due to a marked increase in cytosolic ribonuclease activi…

Effect of simultaneous inhibition of TNF-α production and xanthine oxidase in experimental acute pancreatitis: The role of mitogen activated protein kinases

Javier Pereda et al.

Utilidad de la ultrasonografía endoscópica para el diagnóstico de localización de tumores neuroendocrinos pancreáticos: presentación de 2 insulinomas benignos

Los insulinomas son tumores neuroendocrinos que se manifiestan por episodios de hipoglucemia de ayuno. El diagnostico se basa en la sospecha clinica, que debe ir seguida de la demostracion de hiperinsulinismo y la localizacion tumoral. Sin embargo, la localizacion no siempre es posible con las tecnicas de imagen habituales, por lo que se debe recurrir a otras mas complejas. Presentamos 2 casos de insulinomas cuya localizacion tumoral no fue posible con tecnicas de imagen convencionales, pero si con ultrasonografia endoscopica.

Next-generation three-dimensional modelling software for personalized surgery decision-making in perihilar cholangiocarcinoma: multicentre study

Next-generation three-dimensional modelling software for personalized surgery allows spatially accurate depiction of the hepatic and vasculature anatomy based on the complexity and individual variation in each patient, and could facilitate decision-making about preoperative strategy in perihilar cholangiocarcinoma.

Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis

Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of pro-inflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatin modifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive eleme…

The actual management of colorectal liver metastases

Colorectal cancer is one of the most frequent cancers in the world and between 50% and 60% of patients will develop colorectal liver metastases (CRLM) during the disease. There have been great improvements in the management of CRLM during the last decades. The combination of modern chemotherapeutic and biological systemic treatments with aggressive surgical resection strategies is currently the base for the treatment of patients considered unresectable until few years ago. Furthermore, several new treatments for the local control of CRLM have been developed and are now part of the arsenal of multidisciplinary teams for the treatment of these complex patients. The aim of this review was to s…

Rotura hepática espontánea en el síndrome HELLP: tratamiento mediante packing

Resumen La rotura hepatica espontanea asociada a sindrome de HELLP (hemolisis, elevacion de enzimas hepaticas y plaquetopenia) es extremadamente rara y se acompana de una elevada tasa de complicaciones y mortalidad maternofetal. Es necesario un tratamiento urgente basado en la finalizacion del embarazo, reposicion de hemoderivados y hemostasia hepatica. Presentamos el caso de una paciente con sindrome HELLP y rotura hepatica espontanea tratada mediante cesarea urgente y packing hepatico.

Pancreatic and periampullary tumours: morbidity, mortality, functional results, and long-term survival

Abstract Aims To evaluate postoperative morbidity and mortality, pancreatic function and long-term survival in patients with surgically treated pancreatic or periampullar tumours. Patients and methods Cohort study including 160 patients consecutively operated on: 80 pancreaticoduodenectomies (PD), 30 distal pancreatectomies (DP), 7 total pancreatectomies, 4 central pancreatic resections, and 3 ampullectomies. The tumour was not resected in 36 patients. Pancreatic function was evaluated by oral glucose tolerance test, faecal fat excretion, and elastase. Results Resectability rate was 77.5%. In resected patients (n = 124), 38.7% had complications with a pancreatic fistula rate of 6.4% and a m…

Multiple intrahepatic pseudocysts in acute pancreatitis

Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.

Pancreatitis autoinmune: pseudotumor inflamatorio, afectación multifocal, hipertensión portal y evolución a largo plazo

Autoimmune pancreatitis is a recently characterized disease that still constitutes a diagnostic challenge, especially regarding differential diagnosis from neoplasia. Long-term outcome is poorly known. We herein report a case of a patient with autoimmune pancreatitis and 14 years of follow-up, and show its clinical, biochemical, and morphological characteristics. A 54-year-old female presented with obstructive jaundice and abdominal tenderness, as well as a mass at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery showed an increase of the whole pancreas, malignancy was intraoperatively ruled out, and a cholecystectomy and choledochoduodenostomy were carried out.…

Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: a key role for protein phosphatases.

Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreat…

Redox signaling in acute pancreatitis

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…

Pentoxifylline Prevents Loss of PP2A Phosphatase Activity and Recruitment of Histone Acetyltransferases to Proinflammatory Genes in Acute Pancreatitis

Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activiti…

Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 2 (tratamiento).

Chronic pancreatitis (CP) is a complex disease with a wide spectrum of clinical manifestations ranging from asymptomatic disease to disabling forms or serious complications. The management of CP frequently differs among geographical areas and even among centers. These differences are due to the scarcity of high-quality studies and clinical practice guidelines that focus on the diagnosis and treatment of this disease. The aim of the Spanish Pancreatic Club was to create evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. These experts were selected on the basis of their clinical and research experience in CP…

Disulfide stress: a novel type of oxidative stress in acute pancreatitis.

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis…

Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was …

DNA delivery to 'ex vivo' human liver segments.

Hydrodynamic injection is an efficient procedure for liver gene therapy in rodents but with limited efficacy in large animals, using an 'in vivo' adapted regional hydrodynamic gene delivery system. We study the ability of this procedure to mediate gene delivery in human liver segments obtained by surgical resection. Watertight liver segments were retrogradely injected from hepatic vein with a saline solution containing a plasmid bearing the enhanced green fluorescent protein (eGFP) gene, under different conditions of flow rate (1, 10 and 20 ml s(-1)) and final perfused volume. Samples were cultured for 1 to 2 days and used for microscopy and molecular analysis of gene expression. The fluore…

Impact of type and severity of postoperative complications on long‐term outcomes after colorectal liver metastases resection

Background and objectives Postoperative complications (POCs) after hepatic resection for colorectal liver metastases (CRLM) adversely affect long-term survival. The aim of this study was to analyze the effect of POC etiology and severity on overall survival (OS) and disease-free survival (DFS). Methods A retrospective study of 254 consecutive hepatectomies for CRLM was performed. Univariate and multivariate analyses were performed to determine the effects of demographic, tumor-related and perioperative variables on OS and DFS. A 1:1 propensity score matching (PSM) was then used to compare patients with different POC etiology: infective (Inf-POC), noninfective (Non-inf POC), and no-complicat…

ACTIVIDAD DE LA SER/THR FOSFATASA PP2A Y REGULACIÓN EPIGENÉTICA DE GENES PRO-INFLAMATORIOS EN LA PANCREATITIS AGUDA

Objetivos 1) Estudiar el papel de las serin/treonin protein fosfatasas en la induccion de genes pro-inflamatorios en el pancreas en la pancreatitis aguda, 2) Investigar el papel de las serin/treonin fosfatasas en el mecanismo de accion de la pentoxifilina como agente inflamatorio en la PA. Diseno Modelo de PA necrotica en ratas inducida por taurocolato sodico al 3,5%. Determinacion en pancreas de ratas de la fosforilacion de ERK y MEK1/2 (western blotting), las actividades de las serin/treonin fosfatasas PP2A, PP2B y PP2C, la induccion de genes pro-inflamatorios (RT-PCR e immunoprecipitacion de la cromatina) y el reclutamiento de factores de transcripcion e histonas acetiltransferasas/deace…

Randomized clinical trial of pancreaticogastrostomy versus pancreaticojejunostomy on the rate and severity of pancreatic fistula after pancreaticoduodenectomy

Abstract Background Anastomotic leakage of pancreaticojejunostomy (PJ) remains the single most important source of morbidity after pancreaticoduodenectomy (PD). The primary aim of this randomized clinical trial comparing PG with PJ after PD was to test the hypothesis that invaginated PG would result in a lower rate and severity of pancreatic fistula. Methods Patients undergoing PD were randomized to receive either a duct-to-duct PJ or a double-layer invaginated PG. The primary endpoint was the rate of pancreatic fistula, using the definition of the International Study Group on Pancreatic Fistula. Secondary endpoints were the evaluation of severe abdominal complications (Clavien–Dindo grade …