Avances en pancreatitis aguda: Clasificaciones e influencia de la dieta y las características basales de los pacientes en su evolución clínica

La pancreatitis aguda (PA) constituye la tercera causa de patología gastrointestinal que requiere un mayor número de hospitalizaciones. La PA es una enfermedad heterogénea en la que dos tercios de los pacientes tendrán un curso leve de la enfermedad, pero un tercio de ellos desarrollarán complicaciones locales y/o fallo orgánico (FO) con una morbilidad y mortalidad significativas. Por este motivo es necesaria una sólida clasificación de gravedad. La antigua clasificación de Atlanta tenía limitaciones y las nuevas clasificaciones, la revisión de la clasificación de Atlanta y la clasificación basada en determinantes, necesitan ser validadas. Además, es necesario conocer los principales determinantes de gravedad en PA. Por otra parte, pronosticar la gravedad de la evolución de la PA es importante para un mejor manejo de los pacientes. Dentro de los factores pronósticos, las características basales de los pacientes como la edad, la presencia de comorbilidad y la obesidad se postulan como posibles factores pronósticos. Por último, es conocido que los ácidos grasos insaturados son componentes del páncreas y tienen un efecto tóxico a nivel local y sistémico en la PA. Como las diferencias en la dieta pueden modificar la composición de la grasa pancreática, se podría hipotetizar que diferentes consumos de grasa en la dieta podrían condicionar diferente evolución de la PA.Objetivos1. Validar las nuevas clasificaciones de gravedad de PA.2. Investigar los determinantes de gravedad en PA.3. Estudiar la importancia de la edad, la comorbilidad y la obesidad en el pronóstico de la PA.4. Evaluar si las diferencias regionales de consumo de ácidos grasos se asocian a una diferente evolución clínica de la PA.MetodologíaSe realizó un estudio prospectivo y multicéntrico en el que participaron 23 hospitales españoles. Se incluyeron pacientes mayores de 18 años con diagnóstico de PA. Se excluyeron los pacientes con pancreatitis crónica. Las complicaciones locales se evaluaron con un TAC abdominal. A los pacientes con curso leve no se les realizó TAC y se asumió ausencia de complicaciones locales. En cuanto al análisis estadístico, para comparar las clasificaciones se empleó el área bajo la curva y para valorar la asociación de los determinantes de gravedad y las características basales de los pacientes con la evolución clínica de la PA se realizó un análisis univariante y posteriormente un análisis multivariante. Para el estudio del efecto de la dieta en el curso de la PA se llevó a cabo un análisis retrospectivo de la base prospectiva de PA combinado con los datos provenientes del estudio nutricional ANIBES.Resultados y discusiónLa base prospectiva incluyó 1655 pacientes con PA. Las nuevas clasificaciones son superiores a la antigua clasificación de Atlanta estratificando a los pacientes en grupos homogéneos. No hubo diferencias significativas entre las dos nuevas clasificaciones. El FO persistente es el determinante clave de morbilidad y mortalidad en PA. Todas las complicaciones locales se asociaron a una peor evolución de la PA. La infección de la necrosis pancreática se asoció con mayor morbilidad y mortalidad, pero si en el análisis multivariante se incluye el FO persistente pierde su asociación con mortalidad por lo que puede ser innecesaria la categoría crítica de la clasificación basada en determinantes. El fallo multiorgánico se asoció con mayor morbilidad y mortalidad que el FO único por lo que debería tenerse en cuenta en las clasificaciones. En cuanto a las características basales de los pacientes, la presencia de comorbilidad y la obesidad se asociaron a mayor mortalidad a los 30 días y mayor desarrollo de FO persistente por lo que deberían incluirse en los sistemas de puntuación pronóstica de PA. Por último, los pacientes con PA provenientes de regiones con mayor consumo de ácidos grasos insaturados y monoinsaturados presentaron peor evolución clínica de la PA, aunque estos resultados deberán ser confirmados en futuros estudios con datos nutricionales directos de los pacientes con PA recogidos de manera prospectiva.<br /

Statin use is not associated with an increased risk of acute pancreatitis-A meta-analysis of observational studies

Background: Statins are perceived as potential etiological factors for acute pancreatitis (AP), but recent evidence suggests the opposite. Our aim was to evaluate the association between statin use and risk of AP in observational studies. Methods: Medline, Scopus, and Web of Science were searched for cohort (C) and case-control (CC) studies evaluating statins as intervention and AP as outcome. Pooled adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Results: Thirteen studies (seven CC, six C) with 34,899 AP patients and 5,377,894 controls were included. Prevalence of statin use was 9.8% among AP patients and 25% among controls. Pooled adjusted OR was 1.00 (95% CI = 0.63 to 1.59) with considerable heterogeneity (I-2 = 98%). CC studies were associated with increased AP risk (OR = 1.33; 95% CI = 1.20 to 1.47), unlike C studies (OR = 0.69; 95% CI = 0.37 to 1.31). No association with increased risk was found for studies from Western countries (OR = 0.90; 95% CI = 0.52 to 1.56), unlike for studies conducted in Asia (OR = 1.39; 95% CI = 1.10 to 1.75). Conclusion: Statin use is not associated with increased risk of AP. Increased risk was limited to CC studies, which are more prone to bias, while C studies showed no global effect. Further research is needed to clarify whether statin type, dosage, treatment duration or AP etiology might account for this difference.Peer reviewe

Clinical usefulness of scoring systems to predict severe acute pancreatitis : A systematic review and meta-analysis with pre and post-test probability assessment

Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking.To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP.Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned.43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity.The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making

Adherence to Pro-Vegetarian Food Patterns and Risk of Oesophagus, Stomach, and Pancreas Cancers: A Multi Case–Control Study (The PANESOES Study)

We aimed to evaluate the association between three previously defined pro-vegetarian (PVG) food patterns and the cancers of the oesophagus, stomach, and pancreas in a multi case-control study. We analyzed data from a multi-case hospital-based study carried out in two Mediterranean provinces in Spain. A total of 1233 participants were included in the analyses: 778 incident cancer cases, histologically confirmed (199 oesophagus, 414 stomach, and 165 pancreas) and 455 controls. A dietary assessment was performed using a validated food frequency questionnaire (FFQ). Three PVG food patterns (general, healthful, and unhealthful) were estimated using 12 food groups for the general PVG (gPVG), scoring positive plant-based foods and negative animal-based foods, and 18 food groups, for the healthful (hPVG) and unhealthful (uPVG) food patterns. Multinomial logistic regression was used to estimate relative risk ratios (RRR) and confidence intervals (95% CI) for quintiles of adherence to PVG patterns and as a continuous variable. The RRR (95% CI) for the highest vs. the lowest quintile of gPVG were, RRR = 0.37 (0.32, 0.42) for the oesophagus, RRR = 0.34 (0.27, 0.43) for the stomach, and RRR = 0.43 (0.35, 0.52) for pancreas cancer. For the hPVG, the RRR were RRR = 0.72 (0.58, 0.90) for the oesophagus, RRR = 0.42 (0.34, 0.52) for the stomach, and RRR = 0.74 (0.59, 0.92) for pancreas cancer. The uPVG was associated with a higher risk of stomach cancer RRR = 1.76 (1.42, 2.18). Higher adherence to gPVG and hPVG food patterns is associated with a lower risk of oesophageal, stomach, and pancreas cancers, while a higher adherence to a uPVG food pattern is associated with a higher risk of stomach cancer.Funding: This work was supported by the Spanish Ministry of Health (FIS 91/0435, RCESP C03/09), the Generalitat Valenciana (EVES 030/2005, CTGCA/2002/06, G03/136), CIBERESP

Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease

As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute pancreatitis. Exosomes isolated from patients with mild pancreatitis had no effect on macrophages, while exosomes isolated from patients with severe pancreatitis triggered NFκB activation, TNFα and IL1β expression, and free radical generation. To delve deeper into the mechanism involved, we performed a proteomic analysis of the different exosomes that allowed us to identify different groups of proteins whose concentration was also correlated with the clinical classification of pancreatitis. In particular, an increase in the amount of S100A8 and S100A9 carried by exosomes of severe pancreatitis suggests that the mechanism of action of exosomes is mediated by the effect of these proteins on NADPH oxidase. This enzyme is activated by S100A8/S100A9, thus generating free radicals and promoting an inflammatory response. Along these lines, we observed that inhibition of this enzyme abolished all the pro-inflammatory effects of exosomes from severe pancreatitis. All this suggests that the systemic effects, and therefore the final severity of acute pancreatitis, are determined by the content of circulating exosomes generated in the early hours of the process. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.This work was supported by the projects PI16/00060 from Instituto de Salud Carlos III, 2019AEP057 CVSCI, and a grant ‘Gonzalo Miño’ from the Asociación Española de Gastroenterología. The Biologial and Environmental Proteomics group is a member of Proteored-PRB3 and is supported by Grant PT17/0019/0008 of the PE I+D+I 2013–2016, funded by ISCIII and FEDER

Chronic use of statins and risk of post-ERCP acute pancreatitis (STARK) : Study protocol for an international multicenter prospective cohort study

Background: Acute pancreatitis (AP) is the most common complication after endoscopic retrograde cholangiopancreatography (ERCP). Statins have been traditionally associated to an increased risk of AP, however, recent evidence suggests that statins may have a protective role against this disease. Aims: Our primary aim is to investigate whether the use of statins has a protective effect against post-ERCP pancreatitis (PEP). Secondary outcomes are: to evaluate the effect of other drugs on the incidence of PEP; to ascertain the relationship between the use of statins and the severity of PEP; and to evaluate the effect of other risk and protective factors on the incidence of PEP. Methods: STARK is an international multicenter prospective cohort study. Centers from Spain, Italy, Croatia, Finland and Sweden joined this study. The total sample size will include about 1016 patients, which was based on assuming a 5% incidence of PEP among non-statin (NSt) users, a 1-3 ratio of statin (St) and NSt consumers respectively, a 70% decrease in PEP among St consumers, an alpha-error of 0.05 and beta-error of 0.20. All patients aged >18 years scheduled for ERCP will be offered to enter the study. Discussion: STARK study will ascertain whether statins, a safe, widely used and inexpensive drug, can modify the incidence of PEP. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Peer reviewe

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 of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP

United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)

Background:There have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with United European Gastroenterology, the working group on Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed these European guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 101 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system and the answers were assessed by the entire group in a Delphi process online. The review groups presented their recommendations during the 2015 annual meeting of United European Gastroenterology. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting (Test and Evaluation Directorate). After a final round of adjustments based on these comments, a draft version was sent out to external reviewers. Results: The 101 recommendations covered 12 topics related to the clinical management of chronic pancreatitis: aetiology (working party (WP)1), diagnosis of chronic pancreatitis with imaging (WP2 and WP3), diagnosis of pancreatic exocrine insufficiency (WP4), surgery in chronic pancreatitis (WP5), medical therapy (WP6), endoscopic therapy (WP7), treatment of pancreatic pseudocysts (WP8), pancreatic pain (WP9), nutrition and malnutrition (WP10), diabetes mellitus (WP11) and the natural course of the disease and quality of life (WP12). Using the Grading of Recommendations Assessment, Development and Evaluation system, 70 of the 101 (70%) recommendations were rated as strong' and plenary voting revealed strong agreement' for 99 (98%) recommendations. Conclusions:The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research