Pancreatic metastases from renal cell carcinoma: postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Metastases; Pancreatectomy; Renal cell carcinomaMetástasis; Pancreatectomía; Carcinoma de células renalesMetàstasis; Pancreatectomia; Carcinoma de cèl·lules renalsBackground: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods

Benchmarking; PancreatectomyBenchmarking; PancreatectomiaBenchmarking; PancreatectomíaBackground Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. Methods Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006–2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. Results Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. Conclusion Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study

Distal pancreatectomy; Pancreatic cancerPancreatectomia distal; Càncer de pàncreesPancreatectomía distal; Cáncer de páncreasBackground Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. Methods An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010–2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. Results In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. Conclusions In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

Quimioteràpia; Càncer de pàncrees localment avançat; Ablació per radiofreqüènciaQuimioterapia; Cáncer de páncreas localmente avanzado; Ablación por radiofrecuenciaChemotherapy; Locally advanced pancreatic cancer; Radiofrequency ablationBackground Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment.Olympus Netherlands BV supported the investigator-initiated PELICAN trial with material support by providing the RFA generators and electrodes for the study. They did not have and will not have any influence on the trial design, data collection, interpretation of the data, manuscript development, or decision to publish. Furthermore, the study protocol has undergone full external peer review and received a data management and monitoring grant from the Dutch Cancer Society (grant number 2014-7244)

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis

Acute pancreatitis; Artificial intelligence; Severity predictionPancreatitis aguda; Inteligencia artificial; Predicción de gravedadPancreatitis aguda; Intel·ligència artificial; Predicció de la gravetatBackground Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. Methods The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). Results The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). Conclusions The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.University of Pécs Medical School Research Fund. Grant Number: 300909. National Research, Development and Innovation Office Research Fund. Grant Numbers: K131996, FK131864, K128222, FK12463

Impact of comorbidities on hospital mortality in patients with acute pancreatitis: a population-based study of 110,021 patients

Acute pancreatitis; Comorbidity; Hospital mortalityPancreatitis aguda; Comorbilidad; Mortalidad hospitalariaPancreatitis aguda; Comorbilitat; Mortalitat hospitalàriaBackground The impact of pre-existing comorbidities on acute pancreatitis (AP) mortality is not clearly defined. Our study aims to determine the trend in AP hospital mortality and the role of comorbidities as a predictor of hospital mortality. Methods We analyzed patients aged ≥ 18 years hospitalized with AP diagnosis between 2016 and 2019. The data have been extracted from the Spanish National Hospital Discharge Database of the Spanish Ministry of Health. We performed a univariate and multivariable analysis of the association of age, sex, and comorbidities with hospital mortality in patients with AP. The role of the Charlson and Elixhauser comorbidity indices as predictors of mortality was evaluated. Results A total of 110,021 patients diagnosed with AP were hospitalized during the analyzed period. Hospital mortality was 3.8%, with a progressive decrease observed in the years evaluated. In multivariable analysis, age ≥ 65 years (OR: 4.11, p  1.5 (OR: 2.03, p  1.5 (OR: 2.71, p < 0.001) comorbidity indices were also independently associated with mortality, and ROC curve analysis showed that they are useful for predicting hospital mortality. Conclusions Advanced age, heart disease, renal disease, moderate-severe liver disease, peripheral vascular disease, and cerebrovascular disease before admission were independently associated with hospital mortality. The Charlson and Elixhauser comorbidity indices are useful for predicting hospital mortality in AP patients. Peer Review reports Background Acute pancreatitis (AP) is a prevalent acute inflammatory disease that affects the pancreas, with an increased incidence in recent years [1, 2]. Most cases are mild with a self-limited course [3]. However, patients with severe acute pancreatitis have a high mortality rate (20–50%) [4,5,6]. For this reason, many efforts have been made to find predictors of severity and mortality in patients with AP [7,8,9,10,11] to identify patients who need admission to an intensive care unit or specific treatment. In clinical practice, systems such as the Ranson score, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, the Computed Tomography Severity Index (CTSI), the Bedside Index for Severity in Acute Pancreatitis (BISAP), and various biochemical markers are used to predict severe AP and mortality [3, 12,13,14,15,16]. However, hospital mortality in AP could also be related to intrinsic patient characteristics, such as individual comorbidities. Most classic scores do not consider comorbidities before admission, except for APACHE II, but are restricted to severe chronic diseases. According to some previous studies, patients with certain comorbidities, such as obesity [17], hypertriglyceridemia [18], chronic renal failure [19], diabetes [20, 21], and systemic lupus erythematosus [22], are associated with a higher risk of AP severity and mortality. However, few studies currently evaluate the impact of comorbidities on AP severity and mortality. Our study aimed to determine the relevance of comorbidities and their indexes (Charlson and Elixhauser) as predictors of hospital mortality in patients with AP

The role of high serum triglyceride levels on pancreatic necrosis development and related complications

Acute pancreatitis; Pancreatic necrosis; TriglyceridePancreatitis aguda; Necrosi pancreàtica; TriglicèridsPancreatitis aguda; Necrosis pancreática; TriglicéridosBackground The relevance of elevated serum triglyceride (TG) levels in the early stages of acute pancreatitis (AP) not induced by hypertriglyceridemia (HTG) remains unclear. Our study aims to determine the role of elevated serum TG levels at admission in developing pancreatic necrosis. Methods We analyzed the clinical data collected prospectively from patients with AP. According to TG levels measured in the first 24 h after admission, we stratified patients into four groups: Normal TG (< 150 mg/dL), Borderline-high TG (150–199 mg/dL), High TG (200–499 mg/dL) and Very high TG (≥ 500 mg/dL). We analyzed the association of TG levels and other risk factors with the development of pancreatic necrosis. Results A total of 211 patients were included. In the Normal TG group: 122, in Borderline-high TG group: 38, in High TG group: 44, and in Very high TG group: 7. Pancreatic necrosis developed in 29.5% of the patients in the Normal TG group, 26.3% in the Borderline-high TG group, 52.3% in the High TG group, and 85.7% in the Very high TG group. The trend analysis observed a significant association between higher TG levels and pancreatic necrosis (p = 0.001). A multivariable analysis using logistic regression showed that elevated TG levels ≥ 200 mg/dL (High TG and Very high TG groups) were independently associated with pancreatic necrosis (OR: 3.27, 95% CI − 6.27, p < 0.001). Conclusions An elevated TG level at admission ≥ 200 mg/dl is independently associated with the development of pancreatic necrosis. The incidence of pancreatic necrosis increases proportionally with the severity of HTG

Elevated Serum Triglyceride Levels in Acute Pancreatitis: A Parameter to be Measured and Considered Early

Triglicéridos séricos; Pancreatitis agudaTriglicèrids sèrics; Pancreatitis agudaAcute pancreatitis; Serum triglycerideBackground The value of serum triglycerides (TGs) related to complications and the severity of acute pancreatitis (AP) has not been clearly defined. Our study aimed to analyze the association of elevated levels of TG with complications and the severity of AP. Methods The demographic and clinical data of patients with AP were prospectively analyzed. TG levels were measured in the first 24 h of admission. Patients were divided into two groups: one with TG values of<200 mg/dL and another with TG≥200 mg/dL. Data on the outcomes of AP were collected. Results From January 2016 to December 2019, 247 cases were included: 200 with TG<200 mg/dL and 47 with TG≥200 mg/dL. Triglyceride levels≥200 mg/dL were associated with respiratory failure (21.3 vs. 10%, p=0.033), renal failure (23.4 vs. 12%, p=0.044), cardiovascular failure (19.1 vs. 7.5%, p=0.025), organ failure (34 vs. 18.5%, p=0.02), persistent organ failure (27.7 vs. 9.5%, p=0.001), multiple organ failure (19.1 vs. 8%, p=0.031), moderately severe and severe AP (68.1 vs. 40.5%, p=0.001), pancreatic necrosis (63.8 vs. 34%, p<0.001), and admission to the intensive care unit (27.7 vs. 9.5%, p=0.003). In the multivariable analysis, a TG level of≥200 mg/dL was independently associated with respiratory, renal, and cardiovascular failure, organ failure, persistent organ failure, multiple organ failure, pancreatic necrosis, severe pancreatitis, and admission to the intensive care unit (p<0.05). Conclusions In our cohort, TG≥200 mg/dL was related to local and systemic complications. Early determinations of TG levels in AP could help identify patients at risk of complications.Open Access Funding provided by Universitat Autonoma de Barcelona

Nuevos factores predictivos de la gravedad en la Pancreatitis Aguda en el Hospital Universitario Vall d'Hebrón

1. Antecedents: La Pancreatitis aguda (PA) representa una patologia amb incidència en augment als països desenvolupats, i que cursa amb una elevada morbiditat i mortalitat en els casos greus, entre 20% -40% segons les sèries reportades. Fins al moment no existeix el 'score' predictiu ideal de gravetat de la PA, de manera que en el millor dels casos es té un valor predictiu positiu de l' 75% a l'admissió de l'pacient, sent necessari la recerca de nous factors predictius de la gravetat de la PA en fases precoces. 2. Hipòtesi i Objectius: El objectiu de aquesta tesi doctoral és determinar nous factors pronòstic i de risc de complicacions i mortalitat en la pancreatitis aguda. S'investigarà el paper dels canvis en els valors de BUN ( Blood urea nitrogen , de les seves sigles en anglès) des de l'ingrés de l'pacient, comparant-lo amb el score BISAP, APACHE-II, així com altres scores reconeguts de predicció de mal pronòstic en la PA com ara: la hemoconcentració, la proteïna C-reactiva, entre d'altres. A més, plantegem una anàlisi de el rol de les infeccions extra pancreàtiques (IEP) per predir severitat de la PA i de la infecció de la necrosi, així com quins són els factors implicats en l'ocurrència d'aquestes IEP. 3 Metodología: Per a això es realitzarà un estudi observacional de tipus prospectiu dels pacients que ingressen al nostre centre amb diagnòstic de PA, es recullen més de les variables a estudiar, les variables demogràfiques, radiològiques i de maneig clínic relatives a la PA. Posteriorment es realitzarà l'anàlisi de les dades aplicant proves paramètriques o no paramètriques en el cas de no complir amb una distribució normal dels casos, així com el càlcul de la sensibilitat i especificitat i anàlisi multivariada i l'àrea sota la corba ROC (AUC). 4 Resultats: L'increment en el BUN a les 24 h va ser l'únic score relacionat amb la mortalitat de l'anàlisi multivariada (OR: 12.7; CI 95%: 4.2-16-63). En l'anàlisi comparatiu de l'AUC, l'increment en el BUN a les 24h, va ser un test precís per a la predicció de la mortalitat (AUC: 0842) i el fracàs multi-orgànic persistent (AUC: 0.828), similar a l'score BISAP (AUC: 0836 y 0850) i APACHE-II (AUC: 0756 y0741). Es van registrar 44 (25%) casos d'IEP a la nostra cohort de pacients amb PA. L'ús de nutrició parenteral (NPT) (OR: 9.2 CI95%: 3.3-25.7), el score APACHE-II> 8 (OR: 6.2 CI95%: 2.48-15.54) i el SIRS persistent durant la primera setmana (OR: 2.9 CI95%: 1.1-7.8), van ser factors de risc relacionats en el desenvolupament de IEP. La bacterièmia, en relació a altres IEP, va mostrar la millor capacitat de predicció de fracàs orgànic persistent, (AUC: 0.76, IC 95%: 0,64-0,88), admissió a UCI (AUC: 0.80 IC95%: 0,65-0,94), i per la mortalitat (AUC: 0.73 CI95%: 0,54-0,91); així com per les complicacions locals, incloent la infecció de la necrosi pancreàtica (INP) (AUC: 0.72 CI95%: 0,53-0,92). En l'anàlisi multivariada, els factors de risc per a INP van ser infecció pulmonar (OR: 6.25 CI95% 1.1-35.7 p = 0.039) i NPT (OR: 22.0CI95%: 2.4-205.8, p = 0.007), i per la mortalitat van ser , el SIRS persistent en la primera setmana (OR: 22.9 CI95%: 2.6-203.7, p = 0.005) i la infecció pulmonar (OR: 9.7 CI95%: 1.7-53.8). 5 Conclusions: L'increment de l'BUN a les 24 h és un test ràpid i eficient en la predicció de mortalitat i fracàs multi-orgànic persistent en els pacients amb PA. En el nostre estudi les IEP, van jugar un paper important en la predicció de la gravetat i en el desenvolupament de complicacions en els pacients amb PA.1. Antecedentes: La Pancreatitis aguda (PA) representa una patología con incidencia en aumento en los países desarrollados, y que cursa con una elevada morbilidad y mortalidad en los casos graves, entre 20%-40% según las series reportadas. Hasta el momento no existe el 'score' predictivo ideal de gravedad de la PA, por lo que en el mejor de los casos se tiene un valor predictivo positivo del 75% a la admisión del paciente, siendo necesario la búsqueda de nuevos factores predictivos de la gravedad de la PA en fases precoces. 2. Hipótesis y Objetivos: Esta tesis doctoral tiene como objetivo determinar nuevos factores pronóstico y de riesgo de complicaciones y mortalidad en la pancreatitis aguda. Se investigará el rol de los cambios en los valores de BUN (Blood urea nitrogen, de sus siglas en inglés) desde el ingreso del paciente, comparándolo con el score BISAP, APACHE-II, así como otros scores reconocidos de predicción de mal pronóstico en la PA tales como: la hemoconcentración, la proteína C-reactiva, entre otros. A su vez, planteamos un análisis del rol de las infecciones extra pancreáticas (IEP) para predecir severidad de la PA y de la infección de la necrosis, así como cuales son los factores implicados en la ocurrencia de dichas IEP. 3. Metodología: Para ello se realizará un estudio observacional de tipo prospectivo de los pacientes que ingresan a nuestro centro con diagnóstico de PA, se recogen además de las variables a estudiar, las variables demográficas, radiológicas y de manejo clínico relativas a la PA. Posteriormente se realizará el análisis de los datos aplicando pruebas paramétricas o no paramétricas en el caso de no cumplir con una distribución normal de los casos, así como el cálculo de la sensibilidad y especificidad y análisis multivariado y el área bajo la curva ROC (AUC). 4. Resultados: El incremento en el BUN a las 24 h fue el único score relacionado con la mortalida den el análisis multivariado (OR: 12.7; CI 95%: 4.2-16-.63). En el análisis comparativo del AUC. el incremento en el BUN a las 24 h, fue un test preciso para la predicción de la mortalidad (AUC: 0.842) y el fracaso multi-orgánico persistente (AUC: 0.828), similar al score BISAP (AUC: 0.836 and 0.850) y APACHE-II (AUC: 0.756 and 0.741). Se registraron 44 (25%) casos de IEP en nuestra cohorte de pacientes con PA. El uso de nutrición parenteral (NPT) (OR:9.2 CI95%: 3.3-25.7), el score APACHE-II>8 (OR:6.2 CI95%:2.48-15.54) y el SIRS persistente durante la primera semana (OR:2.9 CI95%: 1.1-7.8), fueron factores de riesgo relacionados al desarrollo de IEP. La bacteriemia, en relación a otras IEP, mostró la mejor capacidad de predicción de fallo orgánico persistente, (AUC:0.76, IC95%:0.64-0.88), admisión a UCI (AUC:0.80 IC95%:0.65-0.94), y para la mortalidad (AUC:0.73 CI95%:0.54-0.91); así como para las complicaciones locales, incluyendo la infección de la necrosis pancreática (INP) (AUC:0.72 CI95%:0.53-0.92). En el análisis multivariado, los factores de riesgo para INP fueron infección pulmonar (OR:6.25 CI95%1.1-35.7 p=0.039) y NPT (OR:22.0CI95%:2.4-205.8, p=0.007), y para la mortalidad fueron, el SIRS persistente en la primera semana (OR: 22.9 CI95%: 2.6-203.7, p=0.005) y la infección pulmonar (OR: 9.7 CI95%: 1.7-53.8). 5. Conclusiones: El incremento del BUN a las 24 h es un test rápido y eficiente en la predicción de mortalidad y fracaso multi-orgánico persistente en los pacientes con PA. En nuestro estudio las IEP, jugaron un rol importante en la predicción de la gravedad y en el desarrollo de complicaciones en los pacienes con PA.1. Background: Acute pancreatitis (AP) represents a pathology with an increasing incidence in developed countries, and it is related to high morbidity and mortality in severe cases, between 20% -40% according to the reported series. So far there is no ideal predictive score for AP severity, so in the best of cases there is a positive predictive value of 75% upon admission of the patient, making it necessary to search for new predictive factors of the severity of AP in early stages. 2 Hypothesis and Objectives: This doctoral thesis aims to determine new prognostic and risk factors for complications and mortality in acute pancreatitis. The role of changes in BUN ( Blood urea nitrogen) values since the patient's admission will be investigated, comparing it with the BISAP score, APACHE-II, as well as other recognized scores for predicting poor prognosis in AP such as: hemoconcentration, C-reactive protein, among others. Additionally, we propose an analysis of the role of extrapancreatic infections (EPI) to predict the severity of AP and necrosis infection, as well as the factors involved in the occurrence of EPI. 3 Methodology: A prospective observational study of patients admitted to our centre with a diagnosis of AP will be carried out. In addition to the variables to be studied, the demographic, radiological and clinical management variables related to AP are collected. Subsequently, the data analysis will be carried out applying parametric or non-parametric tests in the case of not complying with a normal distribution of the cases, as well as the calculation of the sensitivity and specificity and multivariate analysis and the area under the ROC curve (AUC). 4. Results: The increase in BUN at 24 h was the only score related to mortality in the multivariate analysis (OR: 12.7; 95% CI: 4.2-16-.63). In the comparative analysis of the AUC, the increase in BUN at 24 h, was an accurate test for the prediction of mortality (AUC: 0.842) and persistent multi-organ failure (AUC: 0.828), similar to the BISAP score (AUC: 0.836 and 0.850) and APACHE-II (AUC: 0.756 and 0.741). Forty-four (25%) cases of EPI were registered in our cohort of patients with AP. The use of parenteral nutrition (TPN) (OR: 9.2 95% CI: 3.3-25.7), the APACHE-II score> 8 (OR: 6.2 95% CI: 2.48-15.54) and persistent SIRS during the first week (OR: 2.9 CI95%: 1.1-7.8), were risk factors related to the development of EPI. Bacteremia, in relation to other EPIs, showed the best ability to predict persistent organ failure, (AUC: 0.76, 95% CI: 0.64-0.88), admission to ICU (AUC: 0.80 95% CI: 0.65-0.94), and for mortality (AUC: 0.73 95% CI: 0.54-0.91); as well as for local complications, including infection of pancreatic necrosis (IPN) (AUC: 0.72 CI95%: 0.53-0.92). In the multivariate analysis, the risk factors for IPN were pulmonary infection (OR: 6.25 CI95% 1.1-35.7 p = 0.039) and TPN (OR: 22.0CI95%: 2.4-205.8, p = 0.007), and for mortality: persistent SIRS in the first week (OR: 22.9 CI95%: 2.6-203.7, p = 0.005) and lung infection (OR: 9.7 CI95%: 1.7-53.8). 5. Conclusions: The increase in BUN at 24 h is a rapid and efficient test in the prediction of mortality and persistent multi-organ failure in patients with AP. In our study, EPIs played an important role in predicting severity and in the development of complications in patients with AP