RESUMEN
BACKGROUND: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. PATIENTS AND METHODS: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. RESULTS: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). CONCLUSION: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
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Insuficiencia Pancreática Exocrina , Hiperglucemia , Pancreatitis , Esteatorrea , Humanos , Pancrelipasa/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Esteatorrea/inducido químicamente , Esteatorrea/complicaciones , Esteatorrea/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedad Aguda , Pancreatitis/inducido químicamente , Pancreatitis/complicaciones , Pancreatitis/tratamiento farmacológico , Insuficiencia Pancreática Exocrina/inducido químicamente , Insuficiencia Pancreática Exocrina/epidemiología , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Hiperglucemia/inducido químicamente , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Pérdida de PesoRESUMEN
BACKGROUND: For the purpose of a better understanding of enteric hyperoxaluria in Crohn's disease (CD) in children and adolescents, we investigated the occurrence and risk factors for development of hyperoxaluria in those patients. METHODS: Forty-five children with CD and another 45 controls were involved in this cross-sectional study. Urine samples were collected for measurement of spot urine calcium/creatinine (Ur Ca/Cr), oxalate/creatinine (Ur Ox/Cr), and citrate/creatinine (Ur Citr/Cr) ratios. Fecal samples were also collected to detect the oxalyl-CoA decarboxylase of Oxalobacter formigenes by PCR. Patients were classified into 2 groups: group A (with hyperoxaluria) and group B (with normal urine oxalate excretion). The disease extent was assessed, and the activity index was calculated. RESULTS: According to the activity index, 30 patients (66.7%) had mild disease and 13 patients (28.9%) had moderate disease. There was no significant difference in Ur Ox/Cr ratio regarding the disease activity index. O. formigenes was not detected in 91% of patients in group A while it was detected in all patients in group B (p < 0.001). By using logistic regression analysis, the overall model was statistically significant when compared to the null model, (χ2 (7) = 52.19, p < 0.001), steatorrhea (p = 0.004), frequent stools (p = 0.009), and O. formigenes (p < 0.001). CONCLUSION: Lack of intestinal colonization with O. formigenes, steatorrhea, and frequent stools are the main risk factors for development of enteric hyperoxaluria in CD patients. Identifying risk factors facilitates proper disease management in future studies. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Enfermedad de Crohn , Hiperoxaluria , Esteatorrea , Adolescente , Humanos , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Esteatorrea/complicaciones , Estudios Transversales , Creatinina , Hiperoxaluria/complicaciones , Hiperoxaluria/epidemiología , Factores de Riesgo , Oxalatos/orinaRESUMEN
Objective: To investigate the clinical phenotypes and genotypic spectrum of exocrine pancreatic insufficiency in children with cystic fibrosis. Methods: This was a retrospective analysis of 12 children with cystic fibrosis who presented to Children's Hospital of Fudan University from December 2017 to December 2021. Clinical features, fecal elastase-1 level, genotype, diagnosis and treatment were systematically reviewed. Results: A total of 12 children, 7 males and 5 females, diagnosis aged 5.4 (2.0, 10.6) years, were recruited. Common clinical features included chronic cough in 12 cases, malnutrition in 7 cases, steatorrhea in 7 cases, bronchiectasis in 5 cases and electrolyte disturbance in 4 cases. Exocrine pancreatic insufficiency were diagnosed in 8 cases,the main clinical manifestations were steatorrhea in 7 cases, of which 5 cases started in infancy; 6 cases were complicated with malnutrition, including mild in 1 case, moderate in 2 cases and severe in 3 cases; 3 cases had abdominal distension; 2 cases had intermittent abdominal pain; 4 cases showed fatty infiltration or atrophy of pancreas and 3 cases showed no obvious abnormality by pancreatic magnetic resonance imaging or B-ultrasound. All 8 children were given pancreatic enzyme replacement therapy, follow-up visit of 2.3 (1.2,3.2) years. Diarrhea significantly improved in 6 cases, and 1 case was added omeprazole due to poor efficacy. A total of 20 variations of CFTR were detected in this study, of which 7 were novel (c.1373G>A,c.1810A>C,c.270delA,c.2475_2478dupCGAA,c.2489_c.2490insA, c.884delT and exon 1 deletion). Conclusions: There is a high proportion of exocrine pancreatic insufficiency in Chinese patients with cystic fibrosis. The main clinical manifestations are steatorrhea and malnutrition. Steatorrhea has often started from infancy. Pancreatic enzyme replacement therapy can significantly improve the symptoms of diarrhea and malnutrition.
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Fibrosis Quística , Insuficiencia Pancreática Exocrina , Desnutrición , Enfermedades Pancreáticas , Esteatorrea , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Diarrea/complicaciones , Insuficiencia Pancreática Exocrina/complicaciones , Insuficiencia Pancreática Exocrina/genética , Femenino , Genotipo , Humanos , Masculino , Desnutrición/complicaciones , Enfermedades Pancreáticas/complicaciones , Enfermedades Pancreáticas/genética , Fenotipo , Estudios Retrospectivos , Esteatorrea/complicaciones , Esteatorrea/genéticaRESUMEN
OBJECTIVES: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). METHODS: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. RESULTS: There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. CONCLUSIONS: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.
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Insuficiencia Pancreática Exocrina , Pancreatitis Crónica , Esteatorrea , Insuficiencia Pancreática Exocrina/etiología , Análisis Factorial , Femenino , Humanos , Masculino , Nomogramas , Pancreatitis Crónica/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Esteatorrea/complicacionesRESUMEN
BACKGROUND: Chronic diarrhea in patients with neuroendocrine tumors (NET) may be caused by bioactive products of NET, bile acid malabsorption (BAM), ileal resection (IR) or steatorrhea. AIM: To quantitate BA and fat malabsorption in NET with diarrhea. METHODS: Part of evaluation in medical oncology clinical practice, 67 patients [42F, 25 M; median age 64.0 y (17.0 IQR)] with well-differentiated NET and diarrhea underwent clinically indicated measurements of 48-h fecal BA [(FBA), fecal weight (normal < 400 g/48 h), fecal fat (normal < 7 g/day) in n = 52] and fasting serum 7αC4 (marker of hepatic BA synthesis, n = 30) between 01/2018 and 11/2020. IR had been performed in 45 patients. BAM diagnosis was based on FBA criteria: elevated total FBA (> 2337 µmol/48 h) or > 10% primary FBA or combination > 4% primary FBA plus > 1000 µmol total FBA/48 h. We also measured fecal elastase (for pancreatic insufficiency) in 13 patients. RESULTS: BAM was present in 48/52 (92%) patients with NET. There were significant correlations between total FBA and 48-h fecal weight (Rs = 0.645, P < 0.001). Mean length of IR was 47 cm; in patients with IR < 25 cm, total FBA was elevated in 85% and primary FBA > 10% in 69%. In 22 patients with no IR, 13/15 tested (87%) had BAM. Among 6 patients with pancreatic NET and no IR, 80% had BAM. Fecal fat was ≥ 15 g/day in 18/42 (43%). In 4/17 (24%) with IR < 25 cm and 8/19 (42%) patients with IR > 25 cm fecal fat was 44.0 (40.5) and 38.0 (38.0)g/day, respectively. CONCLUSION: A majority of patients with NET and diarrhea had BAM, even with < 25 cm or no IR.
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Síndromes de Malabsorción , Tumores Neuroendocrinos , Esteatorrea , Ácidos y Sales Biliares , Diarrea/etiología , Diarrea/patología , Heces , Humanos , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/etiología , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/cirugía , Esteatorrea/complicaciones , Esteatorrea/patologíaRESUMEN
PURPOSE OF REVIEW: Chronic diarrhoea remains a diagnostic challenge, with numerous causes and few effective symptomatic treatments. This review focuses on new methods for diagnosis of common disorders and alerts readers to rarer causes through a systematic approach to the underlying mechanisms. RECENT FINDINGS: New strategies are emerging to stratify the need for endoscopic investigation. Faecal immunochemical testing, combined with standard blood tests, shows promise in excluding colorectal cancers, adenoma and inflammatory bowel disease, challenging the current use of faecal calprotectin. Serum analysis for markers of bile acid synthesis has been refined, potentially streamlining diagnostic pathways of bile acid malabsorption for those who are unable to access nuclear medicine scans, but the positive predictive value of faecal elastase in low prevalence populations has been questioned. Novel markers such as volatile organic compounds and stool DNA analyses continue to develop. SUMMARY: A systematic approach to investigation of chronic diarrhoea will ensure all relevant causes are considered and minimize the chance of a missed diagnosis. Combination of clinical features with noninvasive testing supports a judicious approach to endoscopic investigations but further innovation will be needed to resolve the diagnostic challenge that diarrhoea poses.
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Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Neoplasias Colorrectales/diagnóstico , Diarrea/diagnóstico , Enfermedades Inflamatorias del Intestino/diagnóstico , Síndrome del Colon Irritable/diagnóstico , Síndromes de Malabsorción/diagnóstico , Adenocarcinoma/complicaciones , Adenoma/complicaciones , Antidiarreicos/uso terapéutico , Ácidos y Sales Biliares/metabolismo , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Crónica , Neoplasias Colorrectales/complicaciones , Diarrea/complicaciones , Diarrea/tratamiento farmacológico , Diarrea/etiología , Insuficiencia Pancreática Exocrina/complicaciones , Insuficiencia Pancreática Exocrina/diagnóstico , Heces/química , Fármacos Gastrointestinales/uso terapéutico , Humanos , Enfermedad Iatrogénica , Imidazoles/uso terapéutico , Inmunoquímica , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/metabolismo , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/tratamiento farmacológico , Complejo de Antígeno L1 de Leucocito/metabolismo , Loperamida/uso terapéutico , Síndromes de Malabsorción/complicaciones , Fenilalanina/análogos & derivados , Fenilalanina/uso terapéutico , Esteatorrea/complicaciones , Esteatorrea/diagnósticoRESUMEN
PURPOSE: Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn's disease (CD) patients with ileal resection. BAM is usually diagnosed by selenium-labelled homotaurocholic acid test (75SeHCAT) but its availability is limited. Consequently, a large proportion of patients either remain undiagnosed or subject to empirical therapy. There is a paucity of studies examining the correlation between length of ileal resection and severity of BAM, which will be of use to clinicians with no recourse to diagnostic testing for BAM. METHODS: We tested the correlation between length of resected ileum and percentage retention on 75SeHCAT of all CD patients with a prior surgical resection who underwent 75SeHCAT testing. Response to treatment with bile salt sequestrant and 75SeHCAT retention values was tested using Fisher's exact test. RESULTS: A total of 91 patients were identified with a median age of 47 (IQR 21-80). The median length of resected ileum was 24 cm (range 15-165 cm) with a median of 1 resection (range 1-4). Overall, 88 patients (97%) had 75SeHCAT retention values of < 10% and 85 (93%) had retention of < 5%. There was a modest correlation between 75SeHCAT retention and length of ileal resection (Spearman's rho - 0.392, P = 0.0001). Data on response to treatment was available for 57 (63%) patients, of who 38 (67%) responded to bile salt sequestrant. There was no difference in 75SeHCAT retention values between responders and non-responders. CONCLUSIONS: There was a modest correlation between length of ileal resection and severity of BAM as defined by 75SeHCAT retention values. Response to bile salt sequestrant therapy was not dependent on 75SeHCAT retention values.
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Ácidos y Sales Biliares/metabolismo , Enfermedad de Crohn/complicaciones , Diarrea/complicaciones , Diarrea/patología , Íleon/cirugía , Índice de Severidad de la Enfermedad , Esteatorrea/complicaciones , Esteatorrea/patología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenAsunto(s)
Heces/enzimología , Elastasa Pancreática/metabolismo , Neoplasias Pancreáticas/complicaciones , Esteatorrea/diagnóstico , Anciano , Terapia de Reemplazo Enzimático/métodos , Insuficiencia Pancreática Exocrina/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Esteatorrea/complicacionesRESUMEN
Dietary fat ingestion triggers bile secretion into the gastrointestinal tract. Bile acid malabsorption affects >1% of the population, causing loose stool and other gastrointestinal symptoms. The diagnosis is frequently missed. Treatments are often considered ineffective. We evaluated low-fat diets for managing gastrointestinal symptoms in these patients. All patients reporting type 6 or 7 stool were offered a selenium-75 homocholic acid taurine (SeHCAT) scan. Prospective data in patients with 7-day scan retention <20% were analysed. -Patients requiring a bile acid sequestrant were given this before receiving dietary advice. Patients completed a 7-day food diary before dietetic consultations. Personalised dietary interventions, providing 20% of daily energy from fat, were prescribed. Symptoms were assessed using a modified gastrointestinal symptom rating scale questionnaire before and 4-12 weeks after dietary intervention. A total of 114 patients (49 male, median age 64 years, median body mass index 27 kg/m2) were evaluated. 44% of these patients were taking colesevelam. After dietary intervention, there was statistically significant improvement in abdominal pain and nocturnal defecation (0.2% alpha, p=0.001). Improvement in bowel frequency, urgency, flatulence, belching, borborygmi and stool consistency were seen, but did not reach statistical significance (p≤0.004-0.031). Dietary intervention is an effective treatment option for patients with symptomatic bile acid malabsorption and should be routinely considered.
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Ácidos y Sales Biliares/metabolismo , Diarrea/dietoterapia , Dieta con Restricción de Grasas , Esteatorrea/dietoterapia , Dolor Abdominal , Adulto , Anciano , Anciano de 80 o más Años , Diarrea/complicaciones , Diarrea/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/terapia , Estudios Prospectivos , Esteatorrea/complicaciones , Esteatorrea/diagnóstico por imagen , Ácido Taurocólico/análogos & derivados , Ácido Taurocólico/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To compare two tests for exocrine pancreatic function (EPF) for use in M-ANNHEIM staging for pancreatitis. METHODS: One hundred and ninety four consecutive patients with acute pancreatitis (AP; n = 13), recurrent acute pancreatitis (RAP; n = 65) and chronic pancreatitis (CP; n = 116) were enrolled. EPF was assessed by faecal elastase-1 (FE-1) estimation and stool fat excretion by the acid steatocrit method. Patients were classified as per M-ANNHEIM stages separately based on the results of the two tests for comparison. Independent Student's t-test, χ2 test, Kruskal-Wallis test, Mann-Whitney U test and McNemar's test were used as appropriate. RESULTS: Sixty-one (52.5%) patients with CP had steatorrhoea when assessed by the acid steatocrit method; 79 (68.1%) with CP had exocrine insufficiency by the FE-1 test (χ2 test, P < 0.001). The results of acid steatocrit and FE-1 showed a significant negative correlation (Spearman's rho = -0.376, P < 0.001). A statistically significant difference was seen between the M-ANNHEIM stages as classified separately by acid steatocrit and the FE-1. Thirteen (6.7%), 87 (44.8%), 89 (45.8%) and 5 (2.5%) patients were placed in M-ANNHEIM stages 0, I, II, and III respectively, with the use of acid steatocrit as against 13 (6.7%), 85 (43.8%), 75 (38.6%), and 21 (10.8%) respectively by FE-1 in stages 0, I, II, and III thereby altering the stage in 28 (14.4%) patients (P < 0.001, McNemar's test). CONCLUSION: FE-1 estimation performed better than the acid steatocrit test for use in the staging of pancreatitis by the M-ANNHEIM classification since it diagnosed a higher proportion of patients with exocrine insufficiency.
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Elastasa Pancreática/análisis , Pancreatitis/diagnóstico , Enfermedad Aguda , Adulto , Anciano , Enfermedad Crónica , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Pancreática/métodos , Pancreatitis Alcohólica/diagnóstico , Pancreatitis Crónica/diagnóstico , Índice de Severidad de la Enfermedad , Esteatorrea/complicacionesRESUMEN
Chronic diarrhoea is a common entity in daily clinical practice and it leads to a loss in these patients quality of life. It may be the main symptom of multiple ethiologies including bile acid malabsorption (BAM) which has a comparable prevalence to celiac disease. The BAM results from imbalances in the homeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease or ileal dysfunction (BAM type i), it can be considered idiopathic or primary (BAM type ii) or associated with other gastrointestinal entities (BAM type iii). Among the different diagnostic methods available, 75SeHCAT study is the primary current method due to its sensitivity, specificity, safety and low cost. The main disadvantage is that it's not available in all countries, so other diagnostic methods have appeared, such as serum measurement of FGF19 and C4, however they are significantly more complex and costly. The first-line treatment of bile acid diarrhoea is bile acid sequestrant, such as cholestyramine, which can be difficult to administer due to its poor tolerability and gastrointestinal side effects. These are less prominent with newer agents such as colesevelam. In summary, the BAM is a common entity underdiagnosed and undertreated, so it is essential to establish a diagnosis algorithm of chronic diarrhoea in which the 75SeHCAT study would be first or second line in the differential diagnosis of these patients.
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Ácidos y Sales Biliares/metabolismo , Diarrea/diagnóstico por imagen , Íleon/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radioisótopos de Selenio/farmacocinética , Esteatorrea/diagnóstico por imagen , Ácido Taurocólico/farmacocinética , Algoritmos , Ácidos y Sales Biliares/clasificación , Biomarcadores , Resina de Colestiramina/uso terapéutico , Enfermedad Crónica , Clorhidrato de Colesevelam/uso terapéutico , Colestipol/uso terapéutico , Diarrea/clasificación , Diarrea/complicaciones , Diarrea/tratamiento farmacológico , Diarrea/etiología , Circulación Enterohepática , Ayuno , Heces/química , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Íleon/metabolismo , Absorción Intestinal , Sensibilidad y Especificidad , Esteatorrea/clasificación , Esteatorrea/complicaciones , Esteatorrea/tratamiento farmacológico , Imagen de Cuerpo EnteroRESUMEN
This study evaluates the efficacy of low-fat dietary interventions in the management of gastrointestinal (GI) symptoms due to bile acid malabsorption. In total, 40 patients with GI symptoms and a 7-day (75)selenium homocholic acid taurine (SeHCAT) scan result of <20%, were prospectively recruited and then advised regarding a low-fat dietary intervention. Before and after dietary intervention, patients rated their GI symptoms using a 10-point numerical scale, and recorded their intake in 7-day dietary diaries. After dietary intervention, the median scores for all GI symptoms decreased, with a significant reduction for urgency, bloating, lack of control, bowel frequency (p ≥: 0.01). Mean dietary fat intake reduced to 42 g fat after intervention (p ≥: 0.01). Low-fat dietary interventions in patients with a SeHCAT scan result of <20% leads to clinically important improvement in GI symptoms and should be widely used.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Diarrea/dietoterapia , Dieta con Restricción de Grasas , Síndrome del Colon Irritable/dietoterapia , Esteatorrea/dietoterapia , Adulto , Anciano , Anciano de 80 o más Años , Diarrea/complicaciones , Femenino , Humanos , Síndrome del Colon Irritable/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esteatorrea/complicaciones , Ácido Taurocólico/análogos & derivados , Adulto JovenRESUMEN
Bile acid malabsorption (BAM) is a common but an underestimated and often neglected sign of inflammatory bowel diseases (IBDs), especially those affecting the distal ileum. Clinically relevant BAM is most often present in patients with Crohn's ileitis and particularly in ileal-resected Crohn's disease patients. However, deterioration of bile acid (BA) metabolism occurs also in patients with IBD without ileal disease or in those in clinical remission, and the role of BAM in these patients is not well appreciated by clinicians. In a majority of cases, BAM in IBD is caused by impaired conjugated BA reabsorption, mediated by apical sodium/BA cotransporting polypeptide, localized at the luminal surface of the ileal enterocytes. As a consequence, numerous pathological sequelae may occur, including the malfunction of lipid digestion with clinical steatorrhea, impaired intestinal motility, and/or significant changes in the intestinal microflora environment. In this review, a detailed description of the pathophysiological mechanisms of BAM-related diarrhea is presented. Although BAM is present in a significant number of patients with Crohn's disease, its laboratory assessment is not routinely included in diagnostic workups, partially because of costs, logistical reasons, or the unavailability of the more sophisticated laboratory equipment needed. Simultaneously, novel findings related to the effects of the BA signaling pathways on immune functions (mediated through TGR5, cell membrane G protein-coupled BA receptor 1, nuclear farnesoid X receptor, nuclear pregnane X receptor, or nuclear vitamin D receptor) are discussed along with intestinal metabolism in its relationship to the pathogenesis of IBD.
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Ácidos y Sales Biliares/metabolismo , Diarrea/complicaciones , Enfermedades Inflamatorias del Intestino/etiología , Esteatorrea/complicaciones , Diarrea/patología , Humanos , Enfermedades Inflamatorias del Intestino/patología , Pronóstico , Esteatorrea/patologíaRESUMEN
La linfangiectasia intestinal primaria es una malformación congénita de los vasos linfáticos subserosos asociada a una enteropatía pierde-proteínas. La obstrucción del drenaje linfático del intestino origina una rotura de los vasos linfáticos intestinales con salida de linfa hacia la luz intestinal, lo que causa edemas por hipoproteinemia, inmunodeficiencia por hipogammaglobulinemia, linfopenia y esteatorrea. Presentamos el caso clínico de un lactante de 6 meses con infecciones graves, hipoalbuminemia, edemas y esteatorrea, en el que se confirmó el diagnóstico de linfangiectasia intestinal por biopsia intestinal y se descartó una causa desencadenante mediante otras pruebas complementarias (AU)
Primary intestinal lymphangiectasia is a congenital malformation of the subserosal lymph vessels associated to a protein-losing enteropathy. The obstruction of the lymphatic drainage of the intestine leads to a rupture of the intestinal lymph vessels in which the lymph spreads to the intestinal lumen, which causes hypoproteinemia-related edemas, hypogammaglobulinemia-related immunodeficiency, lymphocytopenia and steatorrhea. We present a clinical case of a lactating 6-months old infant with severe infections, hypoalbuminemia, edemas and steatorrhea in which an intestinal biopsy confirmed the diagnosis of intestinal lymphangiectasia and a triggering cause was ruled out with other complementary tests (AU)
Asunto(s)
Humanos , Masculino , Lactante , Linfangiectasia Intestinal/complicaciones , Linfangiectasia Intestinal/diagnóstico , Hipoalbuminemia/complicaciones , Enteropatías Perdedoras de Proteínas/complicaciones , Enteropatías Perdedoras de Proteínas/diagnóstico , Dietoterapia , Grasas de la Dieta/uso terapéutico , Inmunoglobulinas Intravenosas/metabolismo , Inmunoglobulinas Intravenosas/uso terapéutico , Vasos Linfáticos/anomalías , Esteatorrea/complicaciones , Linfangiectasia Intestinal/etiología , Hipoalbuminemia/etiología , Esteatorrea/diagnóstico , Linfopenia/complicaciones , Biopsia , Enteropatías Perdedoras de Proteínas/fisiopatología , Streptococcus agalactiae/aislamiento & purificación , Infecciones por Escherichia coli/diagnósticoRESUMEN
BACKGROUND: Many physicians do not consider the diagnosis of bile acid malabsorption in patients with chronic diarrhea, or do not have access to testing. We examined yield of 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning in chronic diarrhea patients, and attempted to identify predictors of a positive test. METHODS: Consecutive patients with chronic diarrhea undergoing SeHCAT scan over a 7-year period were identified retrospectively. Bile acid malabsorption was defined as present at a retention of <15%. Medical records were reviewed to obtain information regarding proposed risk factors. Gastrointestinal symptoms were recorded, and patients were classified as having diarrhea-predominant irritable bowel syndrome (IBS-D) if they reported abdominal pain or discomfort. Independent risk factors were assessed using multivariate logistic regression, and odds ratios (ORs) with 99% confidence intervals (CIs) were calculated. KEY RESULTS: Of 373 patients, 190 (50.9%) had bile acid malabsorption. Previous cholecystectomy (OR 2.51; 99% CI 1.10-5.77), terminal ileal resection or right hemicolectomy for Crohn's disease (OR 12.4; 99% CI 2.42-63.8), and terminal ileal resection or right hemicolectomy for other reasons (OR 7.94; 99% CI 1.02-61.6) were associated with its presence. Seventy-seven patients had IBS-D, and 21 (27.3%) tested positive. There were 168 patients with no risk factors for a positive SeHCAT scan, other than chronic diarrhea, and 63 (37.5%) had bile acid malabsorption. CONCLUSIONS & INFERENCES: Bile acid malabsorption was present in 50% of patients undergoing SeHCAT scanning. Almost 40% of those without risk factors had evidence of bile acid malabsorption, and in those meeting criteria for IBS-D prevalence was almost 30%.
Asunto(s)
Diarrea/etiología , Esteatorrea/complicaciones , Esteatorrea/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ácidos y Sales Biliares/metabolismo , Diarrea/complicaciones , Diarrea/epidemiología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
GOALS: To compare the clinical profile of calcific and noncalcific chronic pancreatitis (CP) in north India. BACKGROUND: The profile of calcific CP has not been adequately studied. STUDY: Detailed demographic data were recorded; hematologic, biochemical, and radiologic investigations were carried out on 225 patients with CP. The patients were divided into calcific and noncalcific groups based on the presence of pancreatic calcification, which was detected on computed tomography. RESULTS: Calcific CP was reported in 46.7% of the patients and noncalcific CP in 53.3%. The mean age, duration of symptoms before presentation, sex ratio, body mass index, and frequency of various symptoms and complications including abdominal pain, ascites, pleural effusion, and segmental portal hypertension was not statistically different between the 2 groups. However, pseudocysts occurred more frequently in noncalcific CP, whereas jaundice because of bile duct stricture, diabetes mellitus, and steatorrhea occurred more frequently in patients with calcific CP (P<0.05). On comparing calcific and noncalcific alcoholic pancreatitis, only steatorrhea was reported more frequently in patients with calcific alcoholic CP. However, pseudocysts and segmental portal hypertension occurred more frequently in noncalcific idiopathic CP, whereas diabetes mellitus occurred more frequently in patients with calcific idiopathic CP (P<0.05). On comparing calcific alcoholic CP with calcific idiopathic CP, we found significantly lower mean age in patients with idiopathic CP and a higher frequency of male patients and pseudocysts in alcoholic CP (P<0.05). CONCLUSION: Calcific CP has a higher frequency of bile duct stricture, diabetes mellitus, and steatorrhea, whereas noncalcific CP has higher frequency of pseudocysts and segmental portal hypertension.
Asunto(s)
Calcinosis/complicaciones , Pancreatitis Alcohólica/complicaciones , Pancreatitis Alcohólica/fisiopatología , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/fisiopatología , Dolor Abdominal/complicaciones , Adolescente , Adulto , Calcinosis/diagnóstico por imagen , Niño , Complicaciones de la Diabetes , Femenino , Humanos , Hipertensión Portal/complicaciones , India , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/diagnóstico por imagen , Pancreatitis Crónica/diagnóstico por imagen , Esteatorrea/complicaciones , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
CONTEXT: Malnutrition secondary to pancreatic exocrine insufficiency plays a prognostic role in chronic pancreatitis. Enzyme substitution therapy is generally prescribed to avoid diarrhea and weight loss, although it is unknown whether this is associated with normal absorption of nutrients and a normal nutritional status. OBJECTIVE: We aimed to evaluate whether an adequate clinical response to enzyme therapy can be used to predict a normal nutritional status in patients with chronic pancreatitis. PATIENTS: Thirty-one consecutive patients (25 males, 6 females; mean age 52 years,) with severe chronic pancreatitis and steatorrhea were enrolled in the study. INTERVENTION: Enzyme substitution therapy was indicated in cases with severe steatorrhea (more than 15 g/day), diarrhea and/or weight loss. Therapy was optimized in individual patients to obtain complete symptom relief. MAIN OUTCOME MEASURE: A nutritional evaluation including body mass index and serum levels of retinol-binding protein, prealbumin and transferrin was carried out. RESULTS: Ten out of ten patients with asymptomatic steatorrhea, who did not fulfill the criteria for enzyme substitution therapy, and 11 out of 21 patients (52.4%) with symptomatic or more severe steatorrhea, who were under enzyme substitution therapy, showed a deficient nutritional status. CONCLUSIONS: An appropriate clinical response to enzyme substitution therapy does not allow the prediction of a normal nutritional status in patients with chronic pancreatitis.
Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Pancreatitis Crónica/tratamiento farmacológico , Pancrelipasa/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores Farmacológicos/análisis , Femenino , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Páncreas/enzimología , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/metabolismo , Pronóstico , Esteatorrea/complicaciones , Esteatorrea/diagnóstico , Esteatorrea/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval. OBJECTIVE: This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events. RESULTS: Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P < 0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P < 0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA <50% than in those with a placebo CFA >50% (both parameters, P < 0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P < 0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events. CONCLUSIONS: In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.
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Fibrosis Quística/complicaciones , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Absorción Intestinal/efectos de los fármacos , Pancrelipasa/administración & dosificación , Cápsulas , Niño , Estudios Cruzados , Preparaciones de Acción Retardada , Método Doble Ciego , Terapia de Reemplazo Enzimático , Insuficiencia Pancreática Exocrina/etiología , Grasas/metabolismo , Heces , Femenino , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/farmacología , Humanos , Masculino , Nitrógeno/metabolismo , Pancrelipasa/efectos adversos , Pancrelipasa/farmacología , Placebos , Esteatorrea/complicaciones , Esteatorrea/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Most methods used for the assessment of severe steatorrhea in cystic fibrosis (CF) are sensitive. In fact, the tests show their usefulness in a borderline zone of the results. Yet, the existing data related to acid steatocrit (AS) are still contradictory. Therefore, in the present study we have aimed to assess CF patients without or with mild steatorhea (<10 g/day) and evaluate the applicability of AS in such a subset of patients. PATIENTS AND METHODS: In fifty-five CF patients, AS, fecal fat concentration (FFC) and fecal fat excretion (FFE) in 1-day stool collection were assessed from one to three times (149 samples). In 50 subjects, FFC, FFE, and AS were available for 3 subsequent days. It allowed for the calculations based upon 3-day fecal fat balance study. RESULTS: The correlations between FFE/FFC and AS based upon 1-day stool collection, although statistically significant, were rather weak (r = 0.208, P < 0.011; r = 0.362, P < 0.000006, respectively). The correlations between FFE/FFC and AS based upon the 3-day stool collection, although stronger, did not show values a linear relationship (r = 0.394, P < 0.005; r = 0.454, P < 0.001, respectively). With no regard to the cut-off level for AS (10% and 20%), sensitivity, specificity, negative, and positive predictive values in the determination of abnormal FFC and FFE were not satisfactory. The flow charts describing the accuracy of AS to determine FFE and FC revealed a high level of uncertainty. CONCLUSIONS: AS does not reflect in a reliable way FFE in CF patients without or mild steatorrhea. Its applicability in the assessment of FFC in such patients has therefore limited practical value.
Asunto(s)
Fibrosis Quística/complicaciones , Insuficiencia Pancreática Exocrina/complicaciones , Heces/química , Lípidos/análisis , Esteatorrea/complicaciones , Esteatorrea/diagnóstico , Adolescente , Niño , Femenino , Humanos , Masculino , Valor Predictivo de las PruebasRESUMEN
BACKGROUND/AIMS: The endoscopic ultrasound (EUS) diagnosis of chronic pancreatitis (CP) relies on the presence of up to nine distinct pancreatic parenchymal and ductal abnormalities, without considering other factors such as age, duration of disease or clinical symptoms. Our goal was to examine the impact of patient symptoms on EUS findings in patients with CP. METHODS: All patients with previously suspected CP who had symptomatic disease referred to our medical center for pancreatic EUS were identified. Patients were stratified into two groups based on their clinical symptoms--pain only and steatorrhea +/- pain. Groups were compared using two-tailed comparative testing. RESULTS: 53 patients (group 1) with pain only and 27 patients with steatorrhea +/- pain (group 2) were identified. Patients in group 1 were younger and more likely female. Compared to group 1 (pain only), group 2 (steatorrhea +/- pain) had more total (5.37 vs. 3.28, p < 0.01) and ductal abnormalities (2.56 vs. 0.83, p < 0.01), although the number of parenchymal abnormalities between groups 1 and 2 (2.45 vs. 2.88, p = 0.07) was not different. CONCLUSION: The presence of steatorrhea +/- pain in patients with CP undergoing pancreatic EUS examination is associated with more total and ductal abnormalities. Stratification based on underlying patient symptoms may be valuable as an adjunct to endosonographic findings in making or excluding the diagnosis of CP.