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.

Research progress on the relationship between pancreatic exocrine insufficiency and intestinal microbiota in aging individuals / 中华肝胆外科杂志

Pancreatic exocrine insufficiency (PEI) refers to insufficient or non-synchronous secretion of trypsin caused by various reasons, resulting in dyspepsia and other symptoms. Intestinal microbiota is a large number of microbiota on the surface of intestinal mucosa. Its main functions include intestinal immune function, forming intestinal biological barrier and participating in the regulation of nutrition and metabolism. Due to aging, some elderly people often have unexplained chronic pancreatic insufficiency, which is often characterized by unexplained weight loss and malnutrition. Several studies have shown that the composition of intestinal microbiota changes significantly with age. This article focuses on aging and its related PEI and then reviews its possible effects on intestinal microbiota, in order to provide a reference basis for individualized prevention and treatment strategies according to the changes of pancreatic exocrine function and microbiota in the elderly.

Clinical value of circadian clock related biomarkers for the diagnosis of chronic pancreatitis with pancreatic exocrine insufficiency / 中华胰腺病杂志

Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.

Diagnosis and treatment of dyspepsia associated with pancreatic tumors / 临床肝胆病杂志

Dyspepsia is the one of the most common clinical manifestations of digestive system diseases and has various and complex causes， among which pancreatic tumor is a relatively uncommon cause and is easily neglected in clinical practice. The dual factors of tumor and dyspepsia may cause a significant reduction in the quality of life of patients. At present， there is still a lack of standardized diagnosis and treatment strategies for dyspepsia associated with pancreatic tumors， and this article reviews the diagnosis and treatment of this disease.

Current status of the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatectomy / 临床肝胆病杂志

Dyspepsia due to pancreatic exocrine insufficiency is a common complication after pancreatectomy； however， due to the lack of simple， efficient， and unified diagnostic methods， standardized treatment standards， and awareness of this disease among surgeons， it is difficult to get adequate diagnosis and treatment. Therefore， this article summarizes the research advances in the definition and pathogenesis of pancreatic exocrine insufficiency， the incidence rate of pancreatic exocrine insufficiency after different surgical procedures， and current diagnostic methods and treatment strategies， in order to provide a reference for further improving the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatectomy.

Advances in the diagnosis and treatment of dyspepsia in chronic pancreatitis patients / 临床肝胆病杂志

Dyspepsia is a common group of clinical symptoms and can be classified into organic and functional dyspepsia. Patients with chronic pancreatitis （CP） often have the symptoms of dyspepsia such as fatty diarrhea， abdominal distention， and abdominal pain， and most patients have pancreatic exocrine insufficiency （PEI）， which belongs to organic dyspepsia. In clinical practice， the diagnosis of PEI and dyspepsia requires a comprehensive assessment of clinical manifestations， nutritional status， and pancreatic exocrine function， and an individualized treatment regimen should be developed based on such factors. However， some patients with normal exocrine function may have the symptoms of dyspepsia， and the diagnosis and treatment of such patients are still difficulties in clinical practice. This article reviews the advances in the diagnosis and treatment of dyspepsia in CP patients.

The diagnosis and treatment of pancreatic disease-related dyspepsia / 临床肝胆病杂志

Various pancreatic diseases can cause dyspepsia due to pancreatic exocrine insufficiency （PEI） caused by pancreatic parenchymal injury and/or pancreatic duct obstruction， which further leads to impaired digestive function and a series of severe clinical outcomes such as malnutrition， weight loss， and shortened survival time. Therefore， pancreatic disease-related dyspepsia should be taken seriously in clinical practice to improve its diagnosis and treatment rates， so as to improve the quality of life of patients with pancreatic diseases and prolong overall survival time.

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.

Clinical Efficacy of Pancreatin Minimicrospheres Supplementation in Patients with Exocrine Pancreatic Insufficiency (EPI) : Real-world Evidence

Background : Exocrine pancreatic insufficiency (EPI), characterized by reduced secretion or activity of pancreatic enzymes, causes improper absorption of food, excessive fat excretion in the stool, and malnourishment. Methods : In this observational, real-world evidence study, patients with one or more of the following condition were enrolled: abdominal pain, acidity, diarrhea, nausea, or dyspepsia (as per ROME III criteria). Patients had either been diagnosed with gallstones, hypertriglyceridemia, alcohol consumption or undergone abdominal surgery. Patients were prescribed capsule EnzigestTM10000 (pancreatin minimicrospheres) for one month.The severity and frequency of various gastric symptoms was measured at day 0 and day 30. Results : 540 patients were enrolled with a mean age of 51.6 years. Enzigest significantly reduced the severity of functional dyspepsia by 88.67% (p<0.001) as per Rome III Criteria. There is significant improvement in frequency of symptoms (83.80%), abdominal pain severit(81.58%), epigastric pain (83.09%), nausea (84.35%) and vomiting by 89.62% (all P<0.001). The overall improvement in symptoms was significant (p<0.001). Enzigest was well tolerated.Conclusion : Enzigest improved abdominal pain, dyspepsia, and acidity in patients with exocrine pancreatic insufficiency due to alcohol consumption, gallstones, hypertriglyceridemia, diuretic (Furosemide or Thiazide) or abdominal surgery. Enzigest containing pancreatin minimicrospheres can be an easy therapeutic option to counteract EPI.

Eurytrema coelomaticum infection: correlation between parasite burden and impairment of pancreatic exocrine enzyme secretion / Eurytrema coelomaticum: correlação entre carga parasitária e insuficiência pancreática exócrina

Eurytrema coelomaticum is a trematode reported in the pancreatic ducts of ruminants. It is conjectured that may cause disorders in the pancreas, as well as digestive and metabolic processes dependent on them. This study, determined if there is an impairment of exocrine pancreatic function, and correlated it with parasite burden. Pancreas, blood, and fecal samples were collected from 119 bovines at a abattoir. Stool samples were subjected to the gelatin and x-ray film digestion tests (to detect the presence of trypsin in feces). Using blood samples, the following biochemical tests were performed: amylase, lipase, glucose, fructosamine, cholesterol, triglycerides, total protein, albumin, and globulins. Analyses were correlated with pancreatic parasite burden. Cattle with a high parasitic load presented higher incidence of negative tests in both gelatin digestion and x-ray film digestion tests (P < 0.001) when compared to non-parasitized animals and those with a low parasitic load. Changes in those tests only occurred if the parasitemia was moderate or severe. The activity of the amylase and lipase enzymes was significantly higher in animals with low parasitemia (P < 0.05), compared to non-parasitized animals and with a high parasitic burden. In this study, in cases of high parasitemia, negative results were observed in both gelatin and x-ray film in the feces digestion tests. However, the low infection of E. coelomaticum, higher levels of serum amylase and lipase that also indicated loss of pancreatic exocrine functions were reported.

Eurytrema coelomaticum, um trematódeo de ductos pancreáticos de ruminantes. Conjectura-se que possa ocasionar transtornos nas funções pancreáticas, mais especificamente nos processos digestivos e metabólicos dependentes destas. Neste estudo, o objetivo foi determinar se há comprometimento da função pancreática exócrina, correlacionado-a a carga parasitária. Foram utilizados pâncreas e respectivas amostras de sangue e fezes de 119 bovinos. As amostras de fezes foram submetidas aos testes de digestão da gelatina em tubo e digestão de filme radiográfico, ambos para detecção de tripsina nas fezes. Foram realizados os seguintes exames bioquímicos em amostras de sangue: amilase, lipase, glicemia, frutosamina, colesterol, triglicerídeos, proteínas totais, albumina e globulinas. Após isto, as análises bioquímicas foram correlacionadas com a quantidade numérica de parasitas encontrados no pâncreas (post-mortem). Houve maior quantidade de testes negativos (digestão do filme radiográfico e prova de digestão da gelatina) nos animais com alta carga parasitária (P < 0.001), quando comparados aos animais não parasitados e com baixa carga parasitária. Portanto, os exames supracitados se alteram somente se a quantidade de parasitas for moderada ou severa. As atividades das enzimas amilase e lipase foram significativamente maiores nos animais que apresentavam baixa parasitemia (P < 0.05), em comparação com os animais com alta carga parasitária e não parasitados. Conclui-se que em quadros de alta parasitemia há alteração significativa nos testes de digestão nas fezes, e que em quadros de baixa parasitemia há alterações significativas nos valores de amilase e lipase séricas, ambos comprovando alterações pancreáticas importantes, de acordo com o quadro de parasitemia.

Clinical and gene mutation features of cystic fibrosis: an analysis of 8 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and gene mutation sites of children with cystic fibrosis (CF), in order to improve the understanding of CF to reduce misdiagnosis and missed diagnosis.@*METHODS@#A retrospective analysis was performed on the medical records of 8 children with CF who were diagnosed in Hebei Children's Hospital from 2018 to 2021.@*RESULTS@#Among the 8 children with CF, there were 5 boys and 3 girls, with an age of 3-48 months (median 8 months) at diagnosis, and the age of onset ranged from 0 to 24 months (median 2.5 months). Clinical manifestations included recurrent respiratory infection in 7 children, sinusitis in 3 children, bronchiectasis in 4 children, diarrhea in 8 children, fatty diarrhea in 3 children, suspected pancreatic insufficiency in 6 children, pancreatic cystic fibrosis in 1 child, malnutrition in 5 children, and pseudo-Bartter syndrome in 4 children. The most common respiratory pathogens were Pseudomonas aeruginosa (4 children). A total of 16 mutation sites were identified by high-throughput sequencing, multiplex ligation-dependent probe amplification, and Sanger sequencing, including 5 frameshift mutations, 4 nonsense mutations, 4 missense mutations, 2 exon deletions, and 1 splice mutation. CFTR mutations were found in all 8 children. p.G970D was the most common mutation (3 children), and F508del mutation was observed in one child. Four novel mutations were noted: deletion exon15, c.3796_3797dupGA(p.I1267Kfs*12), c.2328dupA(p.V777Sfs*2), and c.2950G>A(p.D984N).@*CONCLUSIONS@#p.G970D is the most common mutation type in children with CF. CF should be considered for children who have recurrent respiratory infection or test positive for Pseudomonas aeruginosa, with or without digestive manifestations or pseudo-Bartter syndrome.

Progress in Clinical Research on Chronic Pancreatitis During Pregnancy / 胃肠病学

Chronic pancreatitis (CP) during pregnancy is rare but complicated in clinic, and its pathophysiology, clinical manifestations, diagnosis and treatment are special, which may seriously harm the health of mother and fetus if not properly treated. During pregnancy, physiological changes such as insulin resistance, mechanical pressure caused by the enlarged uterus and increased secretion of estrogen and progesterone will affect patients with CP. CP may increase the risk of pregnancy⁃related complications and adverse perinatal outcomes. The management of pregnant patients with CP mainly includes the improvement of lifestyle, symptomatic treatment and obstetric management. This article mainly reviewed the pancreatic physiology, clinical manifestations and management of pregnant patients with CP.

Comparação de custos da terapia de reposição enzimática empírica com terapia guiada por diagnóstico laboratorial da insuficiência pancreática / Costs comparison of empirical enzymatic replacement therapy with laboratory diagnosis guided therapy of pancreatic insufficiency

Introdução: a fibrose cística, também conhecida como mucoviscidose, é uma doença genética cujas manifestações resultam da disfunção do gene cystic fibrosis transmembrane conductorance regulator. Cerca de 85% dos indivíduos com essa doença desenvolvem insuficiência pancreática exógena. Objetivo: comparar os custos da terapia de reposição enzimática empírica com a terapia de reposição enzimática empírica guiada pelo teste da elastase fecal, em indivíduos com fibrose cística, acompanhados em um centro de referência para assistência à doença. Metodologia: realizou-se um estudo descritivo e comparativo, que incluiu indivíduos de 0 a 21 anos, com fibrose cística. Coletaram-se dados referentes ao período de janeiro de 2016 a fevereiro de 2020, com registros clínicos, demográficos e laboratoriais. Inicialmente, com base em critérios clínicos, os participantes foram classificados como suficientes pancreáticos ou insuficientes pancreáticos. Após o resultado da dosagem da elastase fecal, o diagnóstico do status pancreático foi reavaliado. Realizouse a estimativa dos custos do teste da elas tase fecal por participante e da terapia por reposição enzimática empírica da insuficiência pancreática em indivíduos que, posteriormente, foram diagnostica dos como suficientes pancreáticos. Resultados: incluíram-se 50 participantes, com média de idade de 9,4 anos, sendo 52% do sexo masculino. Após o resultado da dosagem da elastase fecal, 7 participantes considerados insuficientes pancreáticos e foram reclassificados como suficientes pancreáticos. No período estudado, a economia média estimada, por participante suficiente pancreático, com a suspensão das enzimas, após resultado da elastase fecal, foi de R$ 6.770,13. Conclusão: a terapia de reposição enzimática empírica no tratamento da insuficiência pancreática pode levar a custos desnecessários. A medida de dosagem da elastase fecal contribui para decisão mais objetiva da avaliação da função pancreática.

Introduction: Cystic fibrosis, also known as mucoviscidosis, is a genetic disorder whose manifestations result from dysfunction of the cystic fibrosis transmembrane conductance regulator gene. About 85% of individuals with this disease develop exogenous pancreatic insufficiency. Objetivo: to compare the costs of empirical enzyme replacement therapy with fecal elastase test-guided empirical enzyme replacement therapy in individuals with cystic fibrosis followed up at a referral center for disease care. Methodology: a descriptive and comparative study was carried out, which included individuals aged 0 to 21 years, with cystic fibrosis. Data for the period from January 2016 to February 2020 were collected, with clinical, demographic and laboratory records. Initially, based on clinical criteria, participants were classified as pancreatic sufficient or pancreatic insufficient. After the result of the fecal elastase measurement, the diagnosis of pancreatic status was reassessed. Estimates were made of the costs of the fecal elastase test per participant and of the empiric enzyme replacement therapy for pancreatic insufficiency in individuals who were later diagnosed as pancreatic sufficient. Results: fifty participants were included, with a mean age of 9.4 years, 52% male. After the result of the fecal elastase measurement, 7 participants considered as pancreatic insufficient were reclassified as pancreatic sufficient. In the period studied, the estimated mean savings, per sufficient pancreatic participant, with the suspension of enzymes, after the result of fecal elastase, was R$ 6,770.13. Conclusion: empirical enzyme replacement therapy in the treatment of pancreatic insufficiency can lead to unnecessary costs. The measurement of fecal elastase dosage contributes to a more objective decision on the assessment of pancreatic function.

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.

Research advances in pancreatic exocrine insufficiency secondary to pancreatic cancer / 临床肝胆病杂志

At present, there is still a lack of comprehensive diagnosis and treatment criteria for pancreatic exocrine insufficiency around the world. Pancreatic surgeons often ignore or misjudge pancreatic exocrine insufficiency secondary to pancreatic cancer, and as a result, pancreatic exocrine insufficiency is not adequately treated, which greatly affects the quality of life of patients with pancreatic cancer. This article summarizes the latest research advances in the pathogenesis, typical symptoms, and diagnostic methods of pancreatic exocrine insufficiency, as well as pancreatic enzyme replacement therapy in different stages of pancreatic cancer. It is pointed out that pancreatic enzyme replacement therapy can significantly improve the quality of life of patients with different stages of pancreatic cancer.

Relação entre genótipo e insuficiência pancreática em crianças e adolescentes com fibrose cística de um centro de referência no Brasil / Relationship between genotype and pancreatic insufficiency in children and adolescents with cystic fibrosis in a referral center in Brazil

Introdução: fibrose cística (FC) é uma doença genética que culmina em alterações na proteína transmembrana CFTR, resultando na produção de muco mais espesso em diversos órgãos, destacando-se os tratos respiratório e digestório. A insuficiência pancreática (IP) acomete até 95% dos pacientes com FC. Objetivos: determinar a frequência de IP através da dosagem de elastase fecal-1 (EF-1) e compará-la com o genótipo de pacientes com FC assistidos em um centro de referência. Metodologia: foi realizado um estudo transversal, incluindo-se pacientes com FC de 0 a 20 anos. Após a inclusão dos sujeitos à pesquisa, foi realizada consulta ao prontuário para a obtenção de dados clinicos e demograficos e amostras de fezes foram obtidas para dosagem da (EF-1). Os pacientes foram submetidos à análise molecular das mutações por métodos convencionais, através da extração do DNA em sangue periférico. Quando duas mutações patológicas não foram identificadas, o sequenciamento de nova geração com utilização da plataforma Illumina HiSeq foi realizado em amostras da mucosa oral. Resultados: foram incluídos 31 pacientes, 17 (54,8%) do sexo feminino, mediana de idade de 10 anos, e apenas um paciente foi classificado como branco. Vinte e dois (70,9%) pacientes apresentaram dosagem de EF-1 inferior a 200 µg/g, compatível com o diagnóstico de IP. Destes, 21 (95,4%) apresentaram dosagem de EF-1 menor ou igual a 15µg/g, caracteristica de IP grave. Todos os pacientes com IP apresentavam duas mutações de classes I a III. Conclusão: a IP foi identificada em 70% dos pacientes, ocorrendo em todos os pacientes com duas mutações de classe I-III.

Introduction: cystic fibrosis (CF) is a genetic disease that culminates in alterations in the CFTR transmembrane protein, resulting in the production of thicker mucus in various organs, especially the respiratory and digestive tract. Pancreatic insufficiency (PI) affects up to 95% of CF patients. Objectives: To determine the frequency of PI by measuring fecal elastase-1 (FE-1) and comparing it with the genotype of CF patients assisted at a referral Center. Methodology: a cross-sectional study was conducted, including patients with CF from 0 to 20 years. After the inclusion of the subjects to the research, medical records were consulted to obtain clinical and demographic data and stool samples were obtained for the measurement of (FE-1). Patients were submitted to molecular analysis of mutations by conventional methods by DNA extraction in peripheral blood. When two pathological mutations were not identified, next-generation sequencing using the Illumina HiSeq platform was performed on oral mucosa samples. Results: thirty one patients were included, 17 (54.8%) female, median age 10 years, and only one patient was classified as white. Twenty-two (70.9%) patients had an FE-1 dosage of less than 200 µg / g, compatible with the diagnosis of pancreatic insufficiency (PI). Of these, 21 (95,4%) had an EF-1 dosage less than or equal to 15µg / g, characteristic of severe PI. All patients with two mutations class I to III were PI. Conclusion: PI was identified in 70% of patients, occurring in all patients with class I-III mutations.

Características clínicas y epidemiológicas de pacientes pediátricos con fibrosis quística en Panamá, de Enero 2008 a Diciembre 2017 / Clinical and epidemiological characteristics of pediatric patients with cystic fibrosis in Panama, from January 2008 to December 2017

Introducción.La presente investigación plantea como objetivo principal, describir las características clínicas y epidemiológicas de la fibrosis quística (FQ) en Panamá, que nos permiten hacer el diagnóstico temprano y dar a conocer las características bioquímicas, fenotípicas y morbilidades asociadas para así poder mejorar las necesidades de los pacientes con esta enfermedad. Materiales y métodos. Se realizó un estudio retrospectivo de los pacientes con diagnóstico de fibrosis quística entre el mes de enero 2008 a diciembre 2017, en los hospitales en Ciudad de Panamá: Hospital del Niño Dr. José Renán Esquivel, Hospital de Especialidades Pediátricas y en Chiriquí Hospital José Domingo de Obaldía previa aprobación de las autoridades correspondientes.Se analizaron las características demográficas, fenotípicas, resultados bioquímicos, complicaciones y tratamiento de pacientes con diagnóstico de Fibrosis quística. Mediante un diseño descriptivo, se analizó la información de las mismas.Resultados.El promedio de edad para el diagnóstico de fibrosis quística fue de 2.8 años. El 52% correspondía a sexo masculino y 48% a sexo femenino. El promedio de hospitalización previo al diagnóstico de Fibrosis quística fue de 3.8. En el 72 % de los pacientes los primeros síntomas aparecieron antes del primer año de vida.En la mayoría de los pacientes las manifestaciones clínicas fueron una combinación de síntomas gastrointestinales y/o nutricionales y respiratorios (96 y 92% respectivamente).En el 44% de los pacientes se realizó examen genético molecular. De acuerdo con la clasificación del defecto genético, el 20 % de los pacientes eran del grupo delta F 508. La edad promedio de sobrevida es 8.2, años. Durante el período 2008-2017 se registraron 6 defunciones de pacientes con fibrosis quística, lo que corresponde a una tasa de letalidad del 22%.Conclusiones.Los resultados de nuestro estudio mostraron condiciones tales como falla de medro, infecciones respiratorias recurrentes, esteatorrea como la forma de presentación clínica más frecuente. Encontramos correlación con la literatura con la presencia de manifestaciones respiratorias asociadas a compromiso nutricional. El genotipo no se hace a todos los pacientes, reconociendo la importancia de esta valoración por la disponibilidad y costos de las pruebas genéticas. A pesar del diagnóstico temprano, nuestros pacientes cursan con compromiso nutricional importante. En los últimos años se ha evidenciado una media de edad de diagnóstico más temprana comparada con años anteriores. Es necesaria la estandarización de pruebas diagnósticas y de seguimiento, puesto que no todos los pacientes cumplen en su totalidad con los criterios diagnósticos. En la actualidad, un alto índice de sospecha clínica es obligatorio para su detección e intervención inmediata del tratamiento hasta actualización de las instalaciones de diagnóstico.

Introduction .The main objective of the present investigation is to describe the clinical and epidemiological characteristics of cystic fibrosis (CF) in Panama, which allow us to make a nearly diagnosis and make known the biochemical, phenotypic and associated morbidities in order to improve the needs of the patients with this disease. Materials and methodsA retrospective study of patients diagnosed with cystic fibrosis was conducted between January 2008 and December 2017, in hospitals in Panama City: Hospital del Niño Dr. José Renán Esquivel, Hospital de Especialidades Pediátricas Omar Torrijos Herrera and Hospital José Domingo de Obaldía, upon approval of the corresponding authorities. We analyzed the demographic, phenotypic characteristics, biochemical results, complications and treatment of patients diagnosed with Cystic Fibrosis. Through a descriptive design, the information of them was analyzed. Results. The average age for the diagnosis of cystic fibrosis was of 2.8 years, 52% corresponded tomale and 48% female. The average number of hospitalizations prior tothe diagnosis of cystic fibrosis was 3.8. In 72% of the patients the first symptoms appeared before the first year of life. In the majority of patients, the clinical manifestations were a combination of gastrointestinal and / or nutritional and respiratory symptoms (96 and 92% respectively). Molecular genetics examination was performed in 44% of the patients. According to the classification of the genetic defect, 20% of the patients were from the delta F 508 group. The average age of survival is 8.2 years. During the period 2008-2017 there were 6 deaths of patients with cystic fibrosis, which corresponds to a case-fatality rate of 22%.Conclusions.The results of our study showed conditions such as failure to thrive, recurrent respiratory infections, steatorrhea as the most frequent form of clinical presentation. We found correlation with the literature with the presence of respiratory manifestation associated with nutritional compromise. The genotype is not made to all patients, recognizing the importance of assessing the availability and costs of genetictesting. Despite early diagnosis, our patients have an important nutritional commitment. In recenty ears there is evidence of a lower age of diagnosis earlier compared with previous years.It is necessary to standardize diagnostic tests and follow-up, since not all patients fully meet the diagnostic criteria. At present, a high index of clinical suspicion is mandatory for early detection and immediate intervention of the treatment until updating of the diagnostic facilities.

Cystic Fibrosis: Clinical Phenotypes in Children and Adolescents / 대한소아소화기영양학회지

PURPOSE: The objective of this study was to describe the clinical phenotypes of children and adolescents with cystic fibrosis (CF); and to assess the role of pancreatic insufficiency and neonatal screening in diagnosis. METHODS: A cross-sectional study was conducted, which included 77 patients attending a reference center of CF between 2014 and 2016. Epidemiological data, anthropometric measurements, and the presence of pulmonary, pancreatic, gastrointestinal and hepatobiliary manifestations were evaluated based on clinical data and complementary examinations. RESULTS: Of the 77 patients, 51.9% were male, with a median age of 147 months (7.0-297.0 months), and the majority showed adequate nutritional status. The most common phenotype was pulmonary (92.2%), followed by pancreatic (87.0%), with pancreatic insufficiency in most cases. Gastrointestinal manifestation occurred in 46.8%, with constipation being the more common factor. Hepatobiliary disease occurred in 62.3% of patients. The group with pancreatic insufficiency was diagnosed earlier (5.0 months) when compared to the group with sufficiency (84.0 months) (p=0.01). The age of diagnosis was reduced following implementation of neonatal screening protocols for CF (6.0 months before vs. 3.0 months after, p=0.02). CONCLUSION: The pulmonary phenotype was the most common, although extrapulmonary manifestations were frequent and clinically relevant, and should mandate early detection and treatment. Neonatal screening for CF led to earlier diagnosis in patients with pancreatic failure, and therefore, should be adopted universally.

Research progress of pancreatic enzyme replacement therapy after gastric resection / 国际外科学杂志

Gastric resection can cause a multifactorial clinical manifestations of dyspepsia,such as flatulence,diarrhea,weight loss,and fat diarrhea.Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat maldigestion following gastric surgery,the main causes may be related to rapid gastric emptying;asynchrony between gastric emptying and bilio-pancreatic secretion due to new tracts of various reconstructions;bacterial overgrowth after gastrectomy and so on.Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for EPI,due to lack of available evidence so far,the efficacy and safety of pancreatic enzyme substitution in patients following gastric resection remains unclear and cannot be generally recommended.This review will sum up the revelant studies addressing EPI and PERT after gastric resection in recent years,and summarizes the mechanisms,clinical diagnostic methods and PERT treatment perscription of EPI after gastrectomy to improve the cognition of clinicans.

Research progress of exocrine pancreatic insufficiency after pancreatic operation / 中华消化外科杂志

Exocrine pancreatic insufficiency is a commom complication after pancreatic operation with high morbidity.At present,surgeons have insufficient understanding of it,and there is no internationally normalized standard for the diagnosis and treatment of exocrine pancreatic insufficiency.Through systematic reviewing of the relevant literature,this review summarizes the research progress of exocrine pancreatic insufficiency after pancreatic operation,including the definition of exocrine pancreatic insufficiency,aetiological agent,diagnosis,treatment,prevention,and morbidity of pancreatic exocrine insufficiency in different surgical procedures,in order to provide a reference for the improvement of diagnosis and treatment of exocrine pancreatic insufficiency in the future.