Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Pancreatitis crónica para el clínico. Parte 2: Tratamiento y seguimiento. Documento de posicionamiento interdisciplinar de la Societat Catalana de Digestologia y la Societat Catalana de Pàncrees / Chronic pancreatitis for the clinician. Part 2: Treatment and follow-up. Interdisciplinary Position Paper of the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees

La pancreatitis crónica se asocia a calidad de vida deteriorada, elevada incidencia de comorbilidades, complicaciones graves y mortalidad. Los costes sanitarios son enormes. Algunas sociedades médicas han elaborado guías clínicas basadas en evidencia científica, pero el nivel de evidencia para cada aspecto de la enfermedad suele ser bajo y, consecuentemente, las recomendaciones tienden a ser vagas o débiles. En los presentes documentos de posicionamiento de la Societat Catalana de Digestologia y la Societat Catalana de Pàncrees hemos buscado redactar declaraciones bien definidas orientadas al clínico, basadas en revisiones actualizadas de la literatura y acuerdos de expertos. El objetivo es proponer el uso de terminología común y circuitos diagnóstico/terapéuticos racionales basados en el conocimiento actual. Para este fin se revisaron 51 secciones relacionadas con pancreatitis crónica por 21 expertos de 6 especialidades diferentes para generar finalmente 88 declaraciones que buscan armonizar conceptos y formular recomendaciones precisas. La parte 2 de esta serie de documentos discute temas sobre tratamiento y seguimiento. La aproximación terapéutica debe incluir la evaluación de factores etiológicos, manifestaciones clínicas y complicaciones. La complejidad de estos pacientes requiere un estudio detallado individualizado en comités multidisciplinares donde todas las opciones (conservadoras, endoscópicas, de radiología intervencionista y quirúrgicas) sean sopesadas. Deberían constituirse unidades especializadas de pancreatología. Las indicaciones quirúrgicas son dolor refractario, complicaciones locales y sospecha de neoplasia. El tratamiento enzimático está indicado si existe evidencia de insuficiencia exocrina o tras cirugía pancreática. La respuesta debe evaluarse mediante parámetros nutricionales y síntomas. Se debe planificar un programa de seguimiento para cada paciente.(AU)

Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis.(AU)

International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club

Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers. Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.

Prevención de pancreatitis recurrentes por deficiencia de lipoprotein lipasa mediante tratamiento antioxidante / Prevention of recurrent pancreatitis in lipoprotein lipase deficiency with antioxidant therapy

La hipertrigliceridemia por deficiencia de lipoprotein lipasa (LPL) es una enfermedad rara que se asocia a pancreatitis recurrente. La evidencia sugiere que la inflamación del páncreas podría estar relacionada con el daño por radicales libres. Existe bibliografía que avala el uso de antioxidantes en su prevención, en concreto la combinación de selenio, L-metionina, ácido ascórbico y tocoferol. A continuación se presenta el caso de un paciente con hipertrigliceridemia asociada a baja actividad de LPL con pancreatitis recurrentes. A partir de los 23 años comienza a sufrir episodios de pancreatitis aguda de repetición (más de 14 ingresos). Destaca un periodo de 4 años y medio en los que no presenta ningún episodio coincidiendo con el cese del hábito tabáquico. A los 46 años inicia tratamiento antioxidante; para ello se elaboran como fórmula magistral cápsulas de L-metionina y ácido ascórbico 480/120 mg y por otra parte cápsulas de selenometionina 600 mg. A lo largo del tratamiento los valores de triglicéridos se mantienen estables. Desde entonces no ha vuelto a presentar ningún diagnóstico de pancreatitis aguda. La asociación entre hipertrigliceridemia y pancreatitis es bien conocida, siendo además ésta última potencialmente mortal. En nuestro caso, la combinación de antioxidantes se muestra como una opción segura y efectiva. A tenor de los resultados y estudios parece también fundamental evitar el hábito tabáquico. Además, es esencial destacar la importancia de la formulación magistral. Sin embargo, serían recomendables estudios de eficacia y seguridad con mayor número de pacientes y durante un periodo de tiempo más prolongado

Hypertriglyceridemia due to lipoprotein lipase deficiency (LPL) is a rare disease associated with recurrent pancreatitis. Evidence suggests that inflammation of the pancreas could be related to damage by free radicals. Bibliography supports the use of antioxidants in its prevention, specifically the combination of selenium, L-methionine, ascorbic acid and tocopherol. The following is the case of a patient with hypertriglyceridemia associated with low LPL activity with recurrent pancreatitis. From the age of 23, he begins to suffer episodes of recurrent acute pancreatitis (more than 14 admissions). It highlights a period of 4 and a half years in which there is no episode coinciding with the cessation of smoking. At the age of 46, he starts antioxidants treatment. For this purpose, master formula L-methionine and ascorbic acid capsules 480/120 mg and selenomethionine capsules 600 mg were performed. Throughout the treatment the values of triglycerides remain stable. Since then he has not presented any diagnosis of acute pancreatitis. The association between hypertriglyceridemia and pancreatitis is well known, and the latter is potentially fatal. In our case, the combination of antioxidants is shown as a safe and effective option. In view of the results and studies, it also seems essential to avoid smoking. In addition, it is essential to highlight the importance of the master formula. However, efficacy and safety studies with a greater number of patients and for a longer period of time would be recommended

Extracción endoscópica de cálculos pancreáticos en pancreatitis crónica para evitar reagudizaciones / Endoscopic extraction of pancreatic stones in chronic pancreatitis with the aim to prevent acute flares

Chronic pancreatitis (CP) is defined by chronic inflammation of the pancreas with progressive replacement by fibrosis that produces characteristic morphological changes. The clinical picture is variable, being the main problem the pain and relapses of pancreatitis with possible local complications. Over time, the result is the development of exocrine and endocrine failure. In the initial phase, flare-ups of CP can not be distinguished from recurrent acute pancreatitis (RAP). If there are intraductal stones in the duct of Wirsung, endoscopic extraction of obstructive stones may be the first step to prevent new relapses and complications. We present the case of a patient with five episodes of acute pancreatitis (AP), three of them in the past five months. The patient was referred for study and management of RAP. His recent imaging study already showed dilatation of the main pancreatic duct, calcifications and pancreatic stones, compatible with CP. Although the hypertriglyceridemia participated in the etiology of AP, the last two episodes already occurred with normal values of triglycerides. Another possible etiologic factor was not found. His laboratory results did not show endocrine or exocrine insufficiency. The patient was treated with papillotomy, pancreatic stone extraction and installation of terapeutic pancreatic stent. He has been asymptomatic, free from new episodes of AP in the past six months. In conclusion, the CP is one of the possible causes of RAP. Endoscopic treatment by obstructive stone extraction is an efficient therapy to avoid new relapse.

La pancreatitis crónica (PC) se define por la inflamación crónica del páncreas con reemplazo progresivo por fibrosis que produce cambios morfológicos característicos. El cuadro clínico es variable, siendo el principal problema el dolor, reagudizaciones de pancreatitis con eventuales complicaciones locales. Con el tiempo, el resultado final es el desarrollo de insuficiencia exocrina y endocrina. En la fase inicial, no se puede distinguir las reagudizaciones de la PC de una pancreatitis aguda recurrente (PAR). Si se encuentran cálculos intraductales en el conducto de Wirsung, la extracción endoscópica de cálculos obstructivos puede ser el primer paso para prevenir nuevas recaídas y complicaciones. Se presenta el caso de un paciente con cinco episodios de pancreatitis aguda (PA), tres de ellos en los últimos cinco meses. El paciente fue derivado para estudio y manejo de PAR. Su estudio imagenológico reciente ya demostró dilatación del conducto pancreático principal, calcificaciones y cálculos pancreáticos, compatible con PC. Aunque la hipertrigliceridemia participó en la etiología de las PA, los últimos dos episodios ocurrieron con valores normales de triglicéridos. No se encontró otro factor etiológico posible. Su estudio de laboratorio no mostró insuficiencia exocrina ni endocrina. El paciente fue tratado mediante papilotomía, extracción de cálculos pancreáticos e instalación de prótesis pancreática terapéutica. Ha estado asintomático, libre de nuevos episodios de PA en los seis meses transcurridos. En conclusión, la PC es una de las posibles causas de PAR. El tratamiento endoscópico mediante extracción de cálculos obstructivos es una terapia eficiente para evitar nuevas recaídas.

New steps of elastography for the diagnosis of chronic pancreatitis

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Estudio español multicéntrico de estimacion de incidencia de la pancreatitis crónica / Spanish multicenter study to estimate the incidence of chronic pancreatitis

Objetivo: estimar la incidencia de pancreatitis crónica en España diagnosticada mediante ecoendoscopia y evaluar los factores de riesgo y las complicaciones locales detectadas. Material y métodos: estudio observacional, descriptivo, de los casos diagnosticados de pancreatitis crónica en los centros sanitarios españoles con unidad de ecoendoscopia. Mediante un cuestionario estructurado se valoró la incidencia de la enfermedad (casos detectados en 18 meses: de enero 2011 a junio 2012), los factores de riesgo, el número de criterios ecoendoscópicos y la clasificación de Rosemont, así como la frecuencia de complicaciones locales. Resultados: se seleccionaron 23 centros sanitarios con un área de referencia total de 14.752.704 habitantes. En el periodo de estudio se diagnosticaron 1.031 casos de pancreatitis crónica, con una incidencia de 4,66 casos por 105 habitantes-año (IC 95% 4,65-4,67). El consumo de tabaco y el de alcohol aparecen como factores de riesgo en el 63,8% y 66,7% de los casos, respectivamente. El 53,3% de los pacientes tenía > 5 criterios endoscópicos de pancreatitis crónica y el 69% presentó hallazgos sugestivos o consistentes para pancreatitis crónica según la clasificación de Rosemont. Las calcificaciones (34,7%), los pseudoquistes (16%) y la presencia de un tumor pancreático inflamatorio (10,4%) fueron las complicaciones más prevalentes. Conclusiones: la incidencia de pancreatitis crónica en España es similar a otros países europeos. Dada la amplia difusión de la técnica, las unidades de ecoendoscopia son esenciales en la detección de la enfermedad, y su actividad y resultados permiten la estimación de la incidencia de pancreatitis crónica sobre áreas poblacionales amplias y representativas (AU)

Objective: To estimate the incidence of chronic pancreatitis in Spain as diagnosed with endoscopic ultrasound (EUS), and to assess the risk factors and complications detected. Material and method: A descriptive, observational study of chronic pancreatitis cases diagnosed in Spanish health care centers with an EUS unit. A structured questionnaire was used to evaluate the incidence of the disease (cases identified over 18 months: from January 2011 to June 2012), risk factors, EUS criteria, Rosemont classification, and frequency of local complications. Results: Twenty-three centers were selected serving a total reference area of 14,752,704 population. During the study period 1,031 chronic pancreatitis cases were diagnosed, with an incidence of 4.66 cases per 105 inhabitants/year (95% CI: 4.65-4.67). Tobacco and alcohol use appear as risk factors in 63.8% and 66.7% of cases, respectively. Of these, 53.3% met > 5 EUS criteria for chronic pancreatitis, and 69% had findings suggestive of or consistent with chronic pancreatitis according to the Rosemont classification. Most prevalent complications included calcifications (34.7%), pseudocysts (16%), and presence of an inflammatory pancreatic tumor (10.4%). Conclusions: The incidence of chronic pancreatitis in Spain is similar to that of other European countries. Given the widespread use of the technique, EUS units are key in detecting the disease, and their activity and results allow to estimate the incidence of chronic pancreatitis over wide, representative population areas (AU)