Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.

RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

Tratamiento de reposición enzimática en la insuficiencia pancreática exocrina asociada a la fibrosis quística. Grupo de trabajo de Fibrosis Quística de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPHGAN) / Enzyme replacement treatment in exocrine pancreatic insufficiency associated with cystic fibrosis. Cystic fibrosis Working group of the Latin American Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPHGAN)

La fibrosis quística (FQ) es un trastorno hereditario, de las glándulas de secreción exocrina, considerada la causa más frecuente de insuficiencia pancreática exocrina (IPE) en la infancia. Esta revisión resume el panorama del tratamiento de reposición enzimática en la IPE asociada a la FQ, las formulaciones disponibles, su dosificación y modo de administración, así como las limitaciones y desafíos actuales y las posibles áreas del desarrollo futuro

Cystic fibrosis (CF) is an inherited disorder of the exocrine secretion glands, considered the most frequent cause of exocrine pancreatic insufficiency (EPI) in childhood. This review summarizes the landscape of enzyme replacement therapy in PEI associated with CF, the available formulations, their dosage and mode of administration, as well as the current limitations and challenges and potential areas for future development.

Descripción clínica y epidemiológica de pacientes con pancreatitis crónica en un hospital de alta complejidad en Cali, 2011 a 2017 / Clinical and epidemiological description of patients with chronic pancreatitis treated at a quaternary care hospital in Cali, 2011-2017

Resumen Introducción: la pancreatitis crónica (PC) es una inflamación progresiva del páncreas que puede llevar a su destrucción e insuficiencia irreversibles. Es una patología desafiante para el médico, debido a que establecer su diagnóstico puede tomar meses e incluso años, el seguimiento de pacientes suele ser problemático y el conocimiento sobre la clínica y epidemiología en Colombia es incompleto. Este estudio pretende hacer una descripción de pacientes con PC en un centro de referencia en gastroenterología de Cali, Colombia. Metodología: estudio de corte transversal de pacientes adultos con PC confirmada por criterios clínicos y radiológicos entre 2011 y 2017. Resultados: se incluyeron 36 pacientes con PC. La mayoría fueron hombres (72,2%) y la media de edad fue 56 (+ 15,1) años. El dolor abdominal crónico fue la presentación clínica más común (83,3%). Cerca de un cuarto de pacientes presentaba diabetes mellitus (22,2%). Se consideró etiología idiopática en 58,3%, alcohólica en el 11,0% y biliar en el 11,0%. La tomografía axial computarizada (TAC), resonancia magnética (RMN) y colangiopancreatografía por RMN fueron los métodos diagnósticos más usados (60,5%), con los que en su mayoría se visualizó atrofia (53,1%), dilatación de conductos (49,0%) y calcificaciones del páncreas (34,7%). Conclusión: los síntomas inespecíficos de la PC en fases iniciales y su largo curso clínico favorecen al subdiagnóstico de esta patología. Los resultados presentados pueden contribuir a la futura creación de escalas clínicas locales que orienten estudios radiológicos y genéticos tempranos, con el fin de lograr un diagnóstico oportuno y mejorar la calidad de vida de estos pacientes.

Abstract Introduction: Chronic pancreatitis (CP) is a progressive inflammation of the pancreas that can lead to irreversible damage and failure. This condition poses great challenges to physicians since its diagnosis can take months or even years. Patient follow-up is often problematic and knowledge about its clinical presentation and epidemiology in Colombia is scarce. This study aims to describe patients with CP treated at a gastroenterology reference center in Cali, Colombia. Methodology: Cross-sectional study in adult patients with CP confirmed based on clinical and radiological criteria between 2011 and 2017. Results: 36 patients with CP were included. The majority were men (72.2%), and the mean age was 56 (+15.1) years. Chronic abdominal pain was the most common clinical presentation (83.3%). About a quarter of patients had diabetes mellitus (22.2%). Etiology was idiopathic in 58.3%, alcoholic in 11.0%, and biliary in 11.0%. Computed tomography (CT), magnetic resonance imaging (MRI), and MRI cholangiopancreatography were the most commonly used diagnostic methods (60.5%), showing mostly atrophy (53.1%), duct dilation (49.0%), and pancreatic calcifications (34.7%). Conclusion: Nonspecific symptoms of CP in early stages and its long clinical course favor the underdiagnosis of this condition. The results presented may contribute to the future creation of local clinical scales that guide early radiological and genetic studies to achieve a timely diagnosis and improve the quality of life of these patients.

Factors associated with malnutrition in adolescent and adult patients with cystic fibrosis / Fatores associados à desnutrição em pacientes adolescentes e adultos com fibrose cística

ABSTRACT Objective: To determine the prevalence of malnutrition in patients attending an adult cystic fibrosis (CF) program and to investigate the associations of malnutrition with the clinical characteristics of those patients. Methods: This was a cross-sectional study involving patients with clinically stable CF patients (16 years of age or older). The patients underwent clinical assessment, nutritional assessments, pulmonary function tests, and pancreatic function assessment. They also completed a questionnaire regarding diet compliance. On the basis of their nutritional status, the patients were classified divided into three groups: adequate nutrition; at nutritional risk; and malnutrition. Results: The study has included 73 patients (mean age, 25.6 ± 7.3 years), 40 of whom (54.8%) were female. The mean body mass index was 21.0 ± 3.0 kg/m2 and the mean FEV1 was 59.7 ± 30.6% of predicted. In this sample of patients, 32 (43.8%), 23 (31.5%), and 18 (24.7%) of the patients were allocated to the adequate nutrition, nutritional risk, and malnutrition groups, respectively. The logistic regression analysis identified three independent factors associated with the risk of malnutrition: Shwachman-Kulczycki score, percent predicted FEV1; and age. Conclusions: Malnutrition remains a common complication in adolescents and adults with CF, despite dietary advice. Malnutrition is associated with age, clinical severity, and lung function impairment.

RESUMO Objetivo: Determinar a prevalência de desnutrição em pacientes de um programa para adultos com fibrose cística (FC) e investigar a relação da desnutrição com as características clínicas desses pacientes. Métodos: Trata-se de um estudo transversal com pacientes com FC clinicamente estáveis (com 16 anos de idade ou mais). Os pacientes foram submetidos a avaliação clínica, avaliação nutricional, testes de função pulmonar e avaliação da função pancreática. Eles também preencheram um questionário sobre sua adesão à dieta proposta. Os pacientes foram divididos em três grupos, de acordo com seu estado nutricional: nutrição adequada, risco nutricional e desnutrição. Resultados: O estudo incluiu 73 pacientes (média de idade: 25,6 ± 7,3 anos), dos quais 40 (54,8%) eram do sexo feminino. A média do índice de massa corporal foi de 21,0 ± 3,0 kg/m2, e a média do VEF1 foi de 59,7 ± 30,6% do previsto. Nessa amostra de pacientes, 32 (43,8%) ficaram no grupo com nutrição adequada, 23 (31,5%) ficaram no grupo com risco nutricional e 18 (24,7%) ficaram no grupo com desnutrição. A análise de regressão logística identificou três fatores independentes relacionados com o risco de desnutrição: escore de Shwachman-Kulczycki, VEF1 em % do previsto e idade. Conclusões: A desnutrição ainda é uma complicação comum em adolescentes e adultos com FC, não obstante o aconselhamento dietético. A desnutrição está relacionada com a idade, a gravidade clínica e o comprometimento da função pulmonar.

Diarrea crónica en el diabético: Una revisión de la literatura / Chronic diarrhea in the diabetic: A review of the literature

Desde hace más de 70 años se conoce la asociación de diarrea con diabetes mellitus. En pacientes diabéticos su prevalencia es de alrededor del 20%. Sus manifestaciones clínicas son diversas, y representa un reto diagnóstico y terapéutico. Existen ciertos diagnósticos de mayor prevalencia en pacientes diabéticos que en la población general. Las distintas etiologías relacionadas pueden ser diagnosticadas adecuadamente a través de la historia clínica y pruebas diagnósticas complementarias. Los medicamentos utilizados por el paciente diabético para el manejo de su enfermedad, frecuentemente causan diarrea crónica, por lo que se debe profundizar en los antecedentes farmacológicos al momento de estudiar la diarrea. Los pacientes diabéticos pueden presentar otras condiciones patológicas asociadas, como enfermedad celíaca o colitis microscópica, cuya molestia única es la diarrea. La función del páncreas exocrino puede estar disminuida en el paciente diabético, frecuentemente llevando a insuficiencia pancreática exocrina. Factores dietarios, como los edulcorantes libres de azúcar y otros agentes, pueden causar diarrea en el paciente diabético. La presencia de condiciones como la neuropatía autonómica y neuropatía periférica secundarias a la diabetes mellitus, pueden explicar desordenes como la disfunción anorrectal y la incontinencia fecal. Finalmente, la enteropatía diabética per se o con sobrecrecimiento bacteriano asociado, puede causar diarrea. Lograr un control glicémico adecuado constituye el pilar del tratamiento de la diarrea en el diabético, después de esto existen medidas adicionales que se aplican según el contexto especifico del paciente. En el presente artículo se revisan las causas de mayor incidencia diarrea en el paciente diabético y los mecanismos fisiopatológicos implicados

The association of diarrhea with diabetes mellitus has been known for more than 70 years. In diabetic patients its prevalence is around 20%.Its clinical manifestations are diverse, and represents a diagnostic and therapeutic challenge.There are certain diagnoses of higher prevalence in diabetic patients than in the general population.The different related etiologies can be adequately diagnosed through the clinical history and complementary diagnostic tests.The medications used by the diabetic patient to manage their disease often cause chronic diarrhea, so the pharmacological background should be studied at the time of the study of diarrhea.Diabetic patients can present other associated pathological conditions, such as celiac disease or microscopic colitis, which only discomfort is diarrhea.Exocrine pancreatic function may be decreased in the diabetic patient, frequently leading to exocrine pancreatic insufficiency. Dietary factors, such as sugar-free sweeteners and other agents, can cause diarrhea in the diabetic patient.The presence of conditions such as autonomic neuropathy and peripheral neuropathy secondary to diabetes mellitus may explain disorders such as anorectal dysfunction and faecal incontinence. Finally, diabetic enteropathy alone or with associated bacterial overgrowth can cause diarrhea.Achieving adequate glycemic control is the pillar of the treatment of diarrhea in the diabetic, after which there are additional measures that are applied according to the specific context of the patient.This article reviews the causes of higher diarrhea incidence in the diabetic patient and the pathophysiological mechanisms involved

Type 1 autoimmune pancreatitis: case scenario and review of the disease

Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic challenge unless it is considered as a cause of acute pancreatitis, pancreatic exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and successful medical therapy is available. In this paper, we will describe a case of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a disease previously believed to affect typically older men. We will review the definition, types, clinical manifestations, radiological features, serology, histopathological findings, treatment strategies and diagnostic criteria of autoimmune pancreatitis

La pancreatitis autoinmune (PAI) es una enfermedad rara que se presenta como un reto diagnóstico a menos que sea considerada como causa de pancreatitis aguda, insuficiencia pancreática exocrina y masa pancreática. Es una enfermedad sub diagnosticada y existe una terapia médica satisfactoria. En este trabajo, describiremos un caso de una mujer hispana de 59 años diagnosticada de pancreatitis autoinmune, una enfermedad que se creía previamente que afectaba típicamente a hombres de avanzada edad. Revisaremos la definición, los tipos, las manifestaciones clínicas, hallazgos radiológicos, serología, hallazgos histopatológicos, estrategias de tratamiento y criterios diagnósticos de la pancreatitis autoinmune

Comparison of fccal elastase 1 for exocrine panreatic insufficiency evaluationn between ex-alcoholics and chronic pancreatitis patietts / Comparação da elastase fecal 1 para avaliação de insuficiência pancreática exócrina entre ex-alcoólatras e pacientes com pancreatite crônica

Context Fecal elastase is a noninvasive test for pancreatic insufficiency diagnosis. Objectives Evaluate the usefulness of fecal elastase 1 for the indication of exocrine pancreatic insufficiency among former alcohol addicts and patients with chronic pancreatitis. Methods Forty-three patients with chronic pancreatitis and thirty-three asymptomatic former alcohol addicts entered the study. The levels of fecal elastase 1 were measured using a commercial kit. Pancreatic imaging findings were used to categorize the groups. Results The levels of fecal elastase 1 were significantly lower in the patients than in the former alcohol addicts and in the group with tissue calcifications, duct alterations, or atrophy. With a cutoff level of 100 μg/g, the sensitivity of fecal elastase 1 in chronic pancreatitis was 46.51% and its specificity was 87.88% with a positive predictive value of 83.33% and a negative predictive value of 55.77%. When patients were stratified according to the severity of their pancreatitis, the sensitivity was 6.25% for mild pancreatitis and 70.37% for marked pancreatitis. Conclusion Low level of fecal elastase 1 was associated with marked rather than mild chronic pancreatitis; however, it may be useful to indicate pancreatic exocrine insufficiency in asymptomatic former alcohol addicts. .

Contexto O teste de elastase fecal é um teste não invasivo para diagnosticar insuficiência pancreática. Objetivos Avaliar a utilidade da elastase fecal 1 como indicador de insuficiência pancreática entre ex alcoólatras e pacientes com pancreatite crônica. Métodos Quarenta e três pacientes com pancreatite crônica e 33 ex alcoólatras assintomáticos entraram no estudo. Os níveis de elastase fecal 1 foram medidos usando kit comercial. Os achados de imagem pancreática foram usados para categorizar os grupos. Resultados Os níveis de elastase fecal 1 foram significantemente menores nos pacientes que nos ex alcoólatras e no grupo com calcificações teciduais, alterações de ductos, ou atrofia. A sensibilidade da elastase fecal 1 na pancreatite crônica foi de 46,51% e a especificidade foi de 87,88%, com valor preditivo positivo de 83,33% e valor preditivo negativo de 55,77%. Quando os pacientes foram estratificados segundo a severidade da pancreatite, a sensibilidade foi de 6,25% para pancreatite crônica leve e 70,37% para pancreatite crônica severa. Conclusão Baixo nível de elastase fecal foi associado com pancreatite crônica severa mais do que com a leve; entretanto, pode ser útil para indicar insuficiência pancreática exócrina entre os ex alcoólatras. .

Utilidade da concentração da elastase-1 fecal monoclonal na avaliação da função pancreática nos pacientes com fibrose cística / Use of monoclonal faecal elastase-1 concentration for pancreatic status assessment in cystic fibrosis patients

OBJETIVO: Avaliar a concentração da elastase-1 (EL-1) fecal em pacientes pediátricos com fibrose cística, portadores da mutação ∆F508. MÉTODOS: Estudo transversal com amostras colhidas consecutivamente de 51 pacientes com idade entre 4 meses e 17 anos (média 9,11±4,74), sendo 32 (62,8 por cento) pacientes do sexo masculino. Houve coleta de dados clínico-demográficos e do tipo de mutação. A insuficiência pancreática exócrina foi definida pela atividade da EL-1 fecal < 200 µg/g. A quantificação da EL-1 foi realizada pelo método ELISA monoclonal (ScheBo Biotech AG, Germany). A suplementação pancreática foi utilizada em 46 (90,2 por cento) pacientes. RESULTADOS: Quarenta e um (80,4 por cento) pacientes apresentaram insuficiência pancreática (EL-1 fecal < 100 µg/g), sendo 17 (41,5 por cento) homozigotos, 14 heterozigotos (34,1 por cento) e 10 sem ∆F508 (24,4 por cento). Ao considerar a mutação, houve associação estatisticamente significativa entre os homozigotos e a concentração da EL-1 fecal < 100 µg/g (p = 0,010). Todos os pacientes considerados insuficientes pancreáticos (n = 41) pelo teste utilizavam suplemento pancreático. Dez (19,6 por cento) apresentaram EL-1 fecal > 200 µg/g, e 5/10 (50 por cento) utilizavam enzimas. CONCLUSÕES: A atividade de EL-1 fecal < 100 µg/g, indicativa de insuficiência pancreática, apresentou-se em 17/17 (100 por cento) dos homozigotos, conforme o esperado, sendo menos frequente nos heterozigotos para ∆F508 e nos pacientes com ausência dessa mutação. Não houve relação entre a concentração da EL-1 fecal com idade e sexo dos pacientes. O teste foi padronizado, é de fácil execução e poderá ser utilizado para avaliação da função pancreática dos pacientes com fibrose cística.

OBJECTIVE: To assess the concentration of faecal elastase-1 (EL-1) in pediatric patients with cystic fibrosis with mutation ∆F508. METHODS: Cross-sectional study with samples collected consecutively from 51 patients aged 4 months to 17 years old (mean 9.11±4.74); 32 (62.8 percent) patients were male. Clinical-demographic data were collected, as well as data on the type of mutation. Exocrine pancreatic insufficiency was established by the activity of faecal EL-1 < 200 µg/g. EL-1 was quantified through the monoclonal ELISA method (ScheBo Biotech AG, Germany). Pancreatic supplements were used in 46 (90.2 percent) patients. RESULTS: Forty-one (80.4 percent) patients presented with pancreatic insufficiency (EL-1 fecal < 100 µg/g): 17 (41.5 percent) were homozygous, 14 were heterozygous (34.1 percent) and 10 were non-∆F508 (24.4 percent). Regarding the mutation, there was a statistically significant association of homozygosity with faecal EL-1 concentration < 100 µg/g (p = 0.010). All patients considered to be pancreatic insufficient (n = 41) by the test were using pancreatic supplements. Ten (19.6 percent) presented faecal EL-1 > 200 µg/g, and 5/10 (50 percent) used enzymes. CONCLUSIONS: The activity of faecal EL-1 < 100 µg/g, indicating pancreatic insufficiency, was observed in 17/17 (100 percent) of homozygous patients, as expected, and was less frequent in patients who were heterozygous for ∆F508 and in patients without the mutation. There was no association of faecal EL-1 concentration with age and sex of patients. The test was standardized, is easy to execute, and can be used to assess the pancreatic status of patients with cystic fibrosis.