Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

OBJECTIVE: This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. METHODS: The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. RESULTS: Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P < 0.01). The difference in smoking frequency was not significant between the patients with idiopathic pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. CONCLUSIONS: Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

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. .

Comparison of fecal elastase 1 for exocrine pancreatic insufficiency evaluation between ex-alcoholics and chronic pancreatitis patients.

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.

Genetic risk for alcoholic chronic pancreatitis.

In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.

Nutritional profile of asymptomatic alcoholic patients.

CONTEXT: Alcoholism may interfere with nutritional status, but reports are often troubled by uncertainties about ingested diet and organ function, as well as by ongoing abuse and associated conditions. OBJECTIVE: To identify nutritional and body compartment changes in stable alcoholics without confounding clinical and dietetic variables, a prospective observational pilot study was designed. Three well-matched populations were considered: subjects with chronic alcoholic pancreatitis, alcoholics without visceral disease, and healthy never-drinking adults (controls). METHODS: Subjects (n = 60) were asymptomatic males with adequate diet, no superimposed disease or complication, and alcohol-free for at least 6 months. After exclusions, 48 patients were compared. Variables encompassed dietary recall, bioimpedance analysis, biochemical profile and inflammatory markers. Main outcome measures were body fat, lean body mass, serum lipids, C-reactive protein, and selected minerals and vitamins. RESULTS: Both alcoholic populations suffered from reduced lean body mass (P = 0.001), with well-maintained body fat.Magnesium was depleted, and values of vitamin D and B12 correlated with alcohol abuse. LDL and total cholesterol was increased in alcoholics without pancreatitis (P = 0.04), but not in those with visceral damage. C-reactive protein and serum amyloid A correlated with duration of excessive drinking (P = 0.01). CONCLUSIONS: Undernutrition (diminished lean body mass, risk of magnesium and vitamin deficiencies) contrasted with dyslipidemia and increased cardiovascular risk. This second danger was masked during chronic pancreatitis but not in alcoholics without visceral disease. Further studies should focus special requirements of this population.

Nutritional profile of asymptomatic alcoholic patients / Perfil nutricional de pacientes alcoólatras assintomáticos

CONTEXT: Alcoholism may interfere with nutritional status, but reports are often troubled by uncertainties about ingested diet and organ function, as well as by ongoing abuse and associated conditions. OBJECTIVE: To identify nutritional and body compartment changes in stable alcoholics without confounding clinical and dietetic variables, a prospective observational pilot study was designed. Three well-matched populations were considered: subjects with chronic alcoholic pancreatitis, alcoholics without visceral disease, and healthy never-drinking adults (controls). METHODS: Subjects (n = 60) were asymptomatic males with adequate diet, no superimposed disease or complication, and alcohol-free for at least 6 months. After exclusions, 48 patients were compared. Variables encompassed dietary recall, bioimpedance analysis, biochemical profile and inflammatory markers. Main outcome measures were body fat, lean body mass, serum lipids, C-reactive protein, and selected minerals and vitamins. RESULTS: Both alcoholic populations suffered from reduced lean body mass (P = 0.001), with well-maintained body fat.Magnesium was depleted, and values of vitamin D and B12 correlated with alcohol abuse. LDL and total cholesterol was increased in alcoholics without pancreatitis (P = 0.04), but not in those with visceral damage. C-reactive protein and serum amyloid A correlated with duration of excessive drinking (P = 0.01). CONCLUSIONS: Undernutrition (diminished lean body mass, risk of magnesium and vitamin deficiencies) contrasted with dyslipidemia and increased cardiovascular risk. This second danger was masked during chronic pancreatitis but not in alcoholics without visceral disease. Further studies should focus special requirements of this population.

CONTEXTO: O alcoolismo pode interferir no estado nutricional, todavia, os relatos frequentemente sofrem com o viés das incertezas sobre dieta consumida, danos orgânicos subjacentes e persistência do abuso. OBJETIVO: Para identificar alterações nutricionais e de compartimentos corpóreos em alcoólatras estáveis sem variáveis de confusão clínica e dietética, foi desenhado o presente estudo piloto observacional prospectivo. Três populações bem pareadas foram consideradas: casos de pancreatite crônica alcoólica, alcoólatras sem enfermidade visceral e adultos que nunca consumiram etanol (controles). MÉTODOS: Os pacientes (n = 60) eram homens assintomáticos com dieta satisfatória, nenhuma evidência de enfermidade ou complicação exceto as do protocolo e afastados do etanol por no mínimo 6 meses. Após exclusões, 48 pacientes foram comparados. As variáveis abrangeram recordatório alimentar, análise de bioimpedância, perfil bioquímico e marcadores inflamatórios. Os principais resultados buscados foram gordura corporal, massa magra, lípides séricos, proteína C reativa e vitaminas e minerais selecionados. RESULTADOS: Os dois grupos que ingeriam álcool exibiram redução da massa magra (P = 0,001) com gordura corporal bem conservada. O magnésio estava diminuído e as taxas de vitamina D e B12 se correlacionaram com o abuso de álcool. O colesterol total e LDL estavam aumentados nos alcoólatras sem pancreatite (P = 0,04), porém, não naqueles com dano pancreático. A proteína C reativa e o seroamilóide A correlacionaram-se com a duração do excesso etílico (P = 0,01). CONCLUSÕES: A desnutrição (menor massa magra, possibilidade de carência de magnésio e vitaminas) contrastou com a dislipidemia e o risco cardiovascular elevado. Este segundo perigo permaneceu mascarado na vigência de pancreatite crônica, porém, não nos alcoólatras sem lesão visceral. Estudos adicionais deverão focalizar as necessidades nutricionais específicas desta população.

CFTR polymorphisms in patients with alcoholic chronic pancreatitis.

INTRODUCTION: Pancreas susceptibility to alcohol is variable and only 5-10% of chronic alcohol abusers develop chronic pancreatitis; the role of genetic factors in this process is unknown. The CFTR gene encodes a protein that acts on epithelial cells and plays a key role in normal exocrine pancreatic function. METHODS: This study investigated the frequency of polymorphisms in intron 8 of the CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients were studied: group A - 68 adult alcoholics with a diagnosis of chronic pancreatitis; group B - 68 adult alcoholics without pancreatic disease or liver cirrhosis and group C - 104 healthy nonalcoholic adults. RESULTS: T5/T7 genotype was more frequent in group A (11.8%) than in group B (2.9%) (p = 0.0481), and there was no statistical difference when groups A and C (5.8%) were compared (p = 0.1317). The haplotype combination (TG)10-T7/(TG)11-T7 was more frequent in groups B (23.5%) and C (20.2%) than in group A (7.3%) (p = 0.0080 and 0.0162). CONCLUSION: There are differences when these three groups are compared and individuals with T5/T7 genotype might have a greater risk of developing chronic pancreatitis when they become chronic alcoholics.

CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients.

CONTEXT: Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), in cationic trypsinogen (PRSS1) and in serine protease inhibitor Kazal type 1 (SPINK1) genes have been associated with chronic pancreatitis (alcohol related, idiopathic and hereditary). However, the inheritance pattern is still not clear. PATIENTS: Eighty-two unrelated Brazilian patients with chronic pancreatitis (alcohol-related disease in 64, idiopathic disease in 16, and hereditary disease in 2). Two hundred unrelated individuals with an ethnic distribution comparable to the patients were studied as controls. MAIN OUTCOME MEASURE: Detection of mutations in CFTR, PRSS1, and SPINK1 genes. RESULTS: Mutations in the CFTR gene were found in 8 patients (9.8%) with chronic pancreatitis, 5 of them with idiopathic disease. Interestingly, the only clinical symptom in a male patient in the alcoholic group, who was a compound heterozygote (DeltaF508/R170C) for two CFTR mutations, was pancreatitis without infertility or pulmonary involvement. In the PRSS1 gene, the E79K change in exon 3 was found in one patient (1.2%) with alcohol-related chronic pancreatitis. Four different alterations were identified in the SPINK1 gene. CONCLUSIONS: Mutations in the CFTR gene represent the major cause of idiopathic chronic pancreatitis in Brazilian patients. No mutation was found in the PRSS1 gene among our patients suggesting further genetic heterogeneity for hereditary and idiopathic chronic pancreatitis. Interestingly, the most frequent SPINK1 N34S mutation was not present in patients or controls. Moreover, the -253C allele for the SPINK1 gene was significantly more frequent in patients than controls (P=0.004), suggesting that it might represent a risk factor for the development of pancreatitis in our population.

Insufuciência exócrina do pâncreas / Pancreatic disorders

O pâncreas tem um papel importante no processo digestivo, levando à síndrome de má-absorção quando sofre processos patológicos (inflamatórios ou neoplasicos). São apresentadas várias etiologias possíveis para o desencadear da insuficiência exócrina pancreática. É discutida também a insuficiência exócrina do pâncreas secundária à pancreatite crônica. Os autores finalizam, analisando o tratamento atual diante do nosso arsenal terapêutico.

Complicaçöes das pancreatites crônicas em Säo Paulo / Complications of chronic pancreatitis in Sao Paulo (Brasil)

As pancreatites cronicas (PC) apresentam caracteristicas peculiares em diferentes areas geograficas. Com o intuito de avaliar as caracteristicas clinicas, em particular a frequencia e a etiopatogenia das complicacoes das PC em Sao Paulo comparativamente a outros centros, foram analisados, retrospectivamente, 545 portadores desta afeccao. Destes, 493 (90,5 por cento) eram do sexo masculino e 52 (9,5 por cento) do feminino, com idades variando entre 8 e 88 anos (38,2 + ou - 9,3 anos). Os principais fatores etiologicos foram apresentados por: alcoolismo cronico em 509 dos 545 pacientes (93,4 por cento), hereditariedade em quatro (0,7 por cento), desnutricao em tres (0,5 por cento), alteracoes metabolicas em tres (0,5 por cento), alteracoes metabolicas em tres (0,5 por cento) e obstrucao ao fluxo pancreatico em dois pacientes (0,3 por cento)...

Avaliaçäo do esvaziamento da vesicula biliar em portadores de pancreatite cronica calcificante, através do estudo cintilografico com Tc-99m disida / Gallblader emptying evaluation in calcific chronic pancreatitis using Tc-99m DISIDA scintigraphy

O propósito deste trabalho foi analisar o comprometimento motor da vesicula biliar em portadores de pancreatite crônica. O esvaziamento vesicular foi avaliado em 11 pacientes, sem e com o uso de extrato pancreatico (pancreatina) e em dez controles e os resultados analisados e comparados estatisticamente. Utilizou-se o metodo cintilografico calculando-se a fraçäo de ejeçäo (FE) da vesicula biliar (VB) aos 30, 45 e 60 minutos. A FE da VB aos 60 minutos foi significantemente maior nos controles quando comparada aos pacientes, porém, entre os resultados foram semelhantes, sem e com a administraçäo da pancreatina. Os resultados sugerem que o retardo no esvaziamento vesicular independe de eventual alteraçäo na fase intestinal do estímulo vesicular, mas provavelmente resulta de um fator mecanico, dependente do processo patologico cronico situado na cabeça do pancreas

Secretory, endoscopic and histophatologic changes and prevalence of Helicobacter pylori in the gastroduodenal mucosa in patients with chronic alcoholic pancreatitis

Com o intuito de determinar, em nosso meio, a prevalência de ulcera péptica em pancreatopatas crônicos de etiologia alcoólica, e sua eventual relaçäo com alteraçöes histopatológicas, endoscópicas e da produçäo ácida, bem como a ocorrência de colonizaçäo pelo Helibacter pylori na mucosa gastroduodenal desses pacientes, foram investigados prospectivamente 30 pancreatopatas crônicos (Grupo I) e dez controles (Grupo II). Todos os pacientes foram submetidos a avaliaçäo clinica, teste de secreçäo ácida, basal e estimulada por pentagastrina, dosagem de gastrinemia basal, esofagogastroduodenoscopia com biopsia de fundo, corpo e antro gastricos e de bulbo duodenal, para identificaçäo e gradaçäo da inflamaçäo e ocorrência do Helicobacter pylori

Changes in capillary permeability during severe experimental acute pancreatitis in rats

As alteraçöes da permeabilidade capilar foram estudadas em trinta ratos com pancreatite aguda grave induzida por injeçäo retrogada de taurocolato de sódio no canal pancreatico. Os animais foram distribuidos em tres grupos; avaliaram-se os espaços de distribuiçäo compartimental e a distribuiçäo tecidual de hemacias e albuminas marcadas com cromo radioativo e o volume da água corporea, empregando-se água triciada

Primary extranodal non-Hodgkin lymphoma of the extrahepatic bile duct mimmicking Klatskin tumor

Relatamos um caso de linfoma nao-Hodgkin primário das vias biliares extra-hepaticas, cujo sintoma inicial foi ictericia. A colangiografia demonstrou estenose do ducto biliar, de aspecto semelhante a um tumor de Klatskin tipo II. O tratamento cirurgico permitiu completa ressecçäo do tumor e a análise histopatologica mostrou tratar-se de um linfoma näo-Hodgkin folicular centrocitico-centroblastico. No seguimento pos-operatório de 48 meses, a paciente permaneceu assintomatica. O diagnóstico e as operaçöes terapeuticas säo discutidos

Neoplasia pancreática intraductal produtora de mucina / Mucine-producing intraductal pancreatic neoplasm

A neoplasia pancreática intraductal produtora de mucina (NIPM) é neoplasia rara entre as patolooias pancreáticas; entretanto, merece atençao, pois apresenta bom prognóstico e seu diagnóstico é facilmente realizado com o auxílio da colangiopancreatografia endoscópica. A pancreatografia endoscópica assume papel relevante na investigaçao de pacientes com crises recidivantes de pancreatite aguda e que apresentem dilataçao do ducto pancreático sem evidência de obstruçao mecânica a CPER. Os autores apresentam o relato de um caso e análise das características desta entidade quanto aos métodos diagnósticos, tratamento e diagnóstico diferencial.

Derrames cavitarios em portadores de pancreatite cronica / Internal pancreatic effusion in patients with chronic pancreatitis

Com o intuito de investigar eventuais causas responsaveis pelos derrames cavitarios em portadores de pancreatite cronica de etiologia alcoolica, bem como a elevada frequencia dessa complicacao em nosso meio, foram analisados e comparados varios parametros referentes a dados gerais, epidemiologicos, clinicos, laboratoriais e radiologicos em 98 portadores de pancreatite cronica, todos alcoolatras cronicos, divididos em dois grupos: Grupo I: 49 pacientes sem derrame cavitario, Grupo II: 49 pacientes com derrame cavitario. A analise comparativa dos resultados evidenciou a participacao fundamental das fistulas pancreaticas na genese dos derrames cavitarios, resultantes da ruptura de cistos e/ou dos proprios ductos pancreaticos. A elevada frequencia dos DCP observada em portadores de PC de etiologia alcoolica em nosso meio deve-se, provavelmente, as lesoes morfologicas mais intensas e frequentes comparativas a outros centros.

Management of pain in chronic pancreatitis

Durante muitos anos o controle dos quadros dolorosos na pancreatite cronica baseou-se na abstinencia ao alcool, no uso de refeicoes pequenas e frequentes, visando diminuir a magnitude da secrecao pancreatica pos-prandial e na utilizacao de analgesicos comuns, tipo acido salicilico e acetaminofen, com adicao de codeina, se necessario. A partir da decada de 70, com os trabalhos iniciais sobre reposicao de enzimas pancreaticas, os estudos com alcoolizacao do plexo celiaco na decada de 80, seguidos pela utilizacao de proteses endoscopicas, abriram-se novas perspectivas na abordagem da dor pancreatica. Com relacao as drogas, a meperidina, por sua pequena interferencia na pressao intrabiliar, tem sido a droga recomendada. Uma alternativa tambem e eficaz: e a pentazocina. No Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, infusao venosa continua de nevocaina a 10 por cento, em doses de 1 a 4 g, tem sido utilizada com bons resultados. Enzimas pancreaticas, em dose diaria de 2,5 g devem ser mantidas por um mes; nao havendo resposta, a dose pode ser dobrada e mantida por mais 30 dias. Cerca de 50 por cento dos pacientes tratados se beneficiam com esta terapeutica. Os resultados dos estudos com alcoolizacao do plexo celiaco sao controversos.

Etiologia das pancreatites crônicas em Säo Paulo: estudo de 407 casos / Etiology of chronic pancreatitis in Säo Paulo: study of 407 cases

Foram investigados os fatores etiológicos das pancreatites crônicas em 407 portadores desta afecçäo. Observou-se que 381 dos pacientes (93,6%) apresentaram história de importante ingestäo alcoólica (média =295,3 ñ 171,3 gramas de etanol puro), num período médio de 19,2 ñ 6,0 anos. O início da ingestäo alcoólica situou-se, em média, aos 19,4 ñ 8,0 anos. Nos 26 pacientes restantes, ficou caracterizada a forma hereditária em quatro (1,0%), a obstrutiva em dois (0,5%) e a carencial em dois (0,5%). Nenhum fator etiológico pôde ser detectado em 18(4,4% dos pacientes. A média de idade do início dos sintomas e do estabelecimiento do diagnóstico variou de acordo com os diferentes fatores etiológicos. O inquérito alimentar evidenciou que, de maneira geral, os portadores de pancreatites crônicas consumiam significativamente (< 0,01) mais proteínas que os controles. Säo discutidas certas particulariedades dos portadores de pancreatites crônicas em nosso meio e realçada a elevada incidência do estilismo crônico nesta afecçäo