Long-Term Functional Outcome After Pancreatoduodenectomy for Periampullary Carcinoma With Morphological Correlation.

OBJECTIVE: The aim of the study was to evaluate the long-term functional outcome (exocrine and endocrine) and morphological changes in remnant pancreas after pancreatoduodenectomy and its clinical impact. METHODS: Periampullary carcinoma patients with minimum follow-up of 2 years and without recurrence were included (N = 102). Exocrine insufficiency includes clinical steatorrhea and fecal elastase-1 (FE-1) levels; endocrine insufficiency, glucose levels and glycated hemoglobin; and morphological changes, main pancreatic duct (MPD) diameter and thickness of remnant pancreas. RESULTS: The mean (standard deviation) follow-up period was 59 (26) months. Of the 102 patients, 81 (80%) had severely deficient FE-1 (0-100 µg/g). The preoperative MPD was significantly more and thickness of remnant pancreas was significantly less in patients with severely deficient FE-1. Overall, 15.6% (16/102) developed steatorrhea and improved on enzyme replacement therapy. The presence of MPD stricture (P = 0.008) and weight loss (P = 0.001) were significantly associated with steatorrhea. New-onset diabetes was seen in 17% (15/90) patients, of whom 3 of 5 developed it after 4 years (range, 4-7 years). The blood glucose was controlled on oral hypoglycemics in 2 (10/15) of 3 patients. CONCLUSIONS: The assessment by FE-1 indicates loss of exocrine function in more than 90%, whereas only 1 of 6 developed steatorrhea and new-onset diabetes. Morphological changes especially MPD stricture affect the functional status of remnant pancreas.

Chronic diarrhoea in adults: what not to miss.

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.

Serum Concentrations of 7α-hydroxy-4-cholesten-3-one Are Associated With Bile Acid Diarrhea in Patients With Crohn's Disease.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) often have bile acid diarrhea (BAD), due to bile acid malabsorption following ileal resection (IR). Bile acid malabsorption increases production of 7α-hydroxy-4-cholesten-3-one (C4), a bile acid precursor. We investigated relationships between serum concentrations of C4 and BAD in patients with CD. METHODS: We collected demographic data, serum samples, and information on the presence of diarrhea (>3 liquid bowel movements/day), as well as clinical, endoscopic, and histologic scores from 26 patients with CD and IR, 21 patients with CD without IR, and 37 patients with ulcerative colitis (UC). We compared serum concentrations of C4 and fibroblast growth factor 19 (FGF19) between groups. We performed area under the receiver operating characteristic curve (AUROC) analysis to identify the optimal cutoff C4 concentrations for the diagnosis of diarrhea attributable to bile acid malabsorption (BAD), defined as diarrhea and a serum concentration of FGF19 <60 pg/mL. RESULTS: Patients with UC had a median serum C4 concentration of 11.8 ng/mL, whereas patients with CD and IR with ileitis (documented endoscopically) had a median concentration of 100.0 ng/mL (P compared to UC < .0001) and patients with CD and IR without ileitis had a median concentration of 51.6 ng/mL (P compared to UC < .001). Patients with CD without IR did not have a significantly higher median concentration of C4 than patients with UC (P = .71), regardless of ileitis (P = .34). When endoscopic findings were confirmed histologically, similar results were found to analyses using endoscopic findings alone. A higher proportion of patients with active UC had diarrhea (72.0% vs 0 patients with inactive UC; P < .001), but their median concentrations of C4 did not differ significantly from that of patients with inactive UC (12.1 ng/mL vs 9.7 ng/mL; P = .3). A cutoff concentration of C4 of 48.3 ng/mL or greater identified patients with diarrhea attributable to bile acid malabsorption with 90.9% sensitivity, 84.4% specificity, and an AUROC 0.94. A significantly higher proportion of patients with concentrations of C4 above this cutoff had BAD (50.0%) than below this cutoff (1.8%) (P < .001). When we analyzed only patients with diarrhea, a C4 cutoff of 48.3 ng/mL identified those with low FGF19 concentrations (<60 pg/mL) with 91% sensitivity and 95.5% specificity (AUROC, 0.99). Above this cutoff, 83.3% of patients had a serum concentration of FGF19 <60 pg/mL compared to 4.5% below this threshold (P < .0001). C4 concentrations correlated with the number of daily bowel movements (r = 0.41; P = .004) and correlated inversely with FGF19 concentrations (r = -0.72; P<.0001). CONCLUSION: We observed significantly increased serum concentrations of C4 in patients with CD with IR, compared to patients with UC. A cutoff concentration of C4 above 48.3 ng/mL identifies patients with diarrhea likely attributable to bile acid malabsorption (BAD) with an AUROC value of 0.94. Increased serum levels of bile acid precursors identify patients with diarrhea and a low serum concentration of FGF19, and concentrations of C4 correlate with daily liquid bowel movements and correlate inversely with FGF19 concentrations. C4 may be a biomarker to identify patients with diarrhea attributable to bile acid malabsorption.

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

OBJECTIVES: Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort. METHODS: We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene-environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan-Meier model. RESULTS: We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups. CONCLUSIONS: We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.

Exocrine Pancreatic Insufficiency and Malnutrition in Chronic Pancreatitis: Identification, Treatment, and Consequences.

OBJECTIVES: The purpose of this study was to examine the impact of exocrine pancreatic insufficiency (EPI) on chronic pancreatitis (CP) patients and to identify challenges with its diagnosis and treatment. METHODS: Ninety-one patients with CP diagnosed with endoscopic ultrasound were identified and assessed for symptoms of EPI, fat-soluble vitamin levels, dual-energy x-ray absorptiometry scan T-scores, and treatment with pancreatic enzyme replacement therapy. All patients were also screened with the Malnutrition Universal Screening Test. RESULTS: Exocrine pancreatic insufficiency was diagnosed in 84.6% (77/91) of patients based on symptoms of bloating, steatorrhea, or weight loss. Of these patients, 35.2% (19/54) had vitamin A deficiency, 62.5% (55/88) had vitamin D deficiency, and 17.7% (9/51) had vitamin E deficiency. Either osteopenia or osteoporosis was found in 68.9% (31/45). A medium or higher risk for malnutrition based on Malnutrition Universal Screening Test score of 1 or higher was found in 31.5% (28/89). Malnutrition Universal Screening Test score of 1 or higher was associated with an increased risk for osteopenia and osteoporosis on Fisher's exact test (P = 0.0037). CONCLUSIONS: There is a high prevalence of fat-soluble vitamin deficiencies, osteopathy, and malnutrition in CP patients, which is underestimated due to a lack of effective diagnosis and suboptimal therapies for EPI.

Clinical decision-making in managing changes in gastrointestinal function following cancer therapies: Is experience enough?

In patients with gastrointestinal (GI) disorders, identical symptoms may occur for many different reasons. This prospective study assessed whether experienced clinicians can predict accurately the underlying diagnosis or diagnoses contributing to specific symptoms based on the history and physical examination. Three clinicians assessed 47 patients referred for management of troublesome GI symptoms identified after treatment for cancer. Investigations were requested following our comprehensive, peer-reviewed algorithm. The clinicians then recorded their predictions as to the results of those investigations. After each patient had completed all their investigations, had received optimal management and had been discharged from the clinic, the predicted diagnoses were compared to those made. The clinicians predicted 92 diagnoses (1.9 per patient). After investigation, a total of 168 unique diagnoses were identified (3.5 per patient). Of the 92 predicted diagnoses, 41 (43%) matched the diagnosis. Of the 168 actual diagnoses identified, only 24% matched the prediction. None of the clinicians predicted the correct combination of diagnoses contributing to bowel symptoms. Clinical acumen alone is inadequate at determining cause for symptoms in patients with GI symptoms developing after cancer therapy.

Valores normales de la prueba Sudan III en niños sanos menores de un año de edad / Normal range for Sudan III test in under children under one year of age

La esteatorrea es la pérdida de grasa en las heces. Se manifiesta clínicamente con heces fétidas, grasosas y abundantes. Se puede determinar por el método Van de Kamer, el esteatocrito acidificado y la tinción sudan III en heces. El objetivo del presente trabajo es precisar el valor normal de la prueba Sudan III en heces. Se incluyeron las muestras de heces de 2000 niños sanos (recién nacidos pre-término, recién nacidos a término, lactantes de 1-4 meses y de 5-12 meses de edad), 500 muestras por grupo. Se realizó en el Hospital Universitario de los Andes, en Mérida-Venezuela, durante los años 1999-2009. En la prueba se utilizó la tinción sudan III y el reactivo de Saathoff, con lente microscópico de 40 y se tomaron en cuenta las gotas grandes y medianas de grasa por campo. Es una investigación clínica con enfoque epidemiológico, observacional de tipo aleatoria. Del total de niños 53% fueron varones y 47% niñas. El promedio de evacuaciones por día fue de 3 en los recién nacidos, de 2 a 3 en los lactantes menores de 4 meses y de 1 a 2 en los de 5 a 12 meses de edad. El valor normal de la prueba Sudan III en heces varía dependiendo de la edad. En RN pre-término un promedio de 5.4 gotas (12-0 gotas)de grasa por campo, en RN a término 7.9 gotas (16-0), en lactantes menores de 4 meses de edad 4.3 gotas (10-0) y en los lactantes de 5-12 meses 3.8 gotas (6-0) de grasa por campo. La prueba Sudan III orienta en el diagnostico de esteatorrea en niños, en pacientes con mala absorción intestinal y en la evaluación del uso de enzimas pancreáticas. Es una técnica sencilla, económica y fácil de realizar. El conocer los valores normales dependiendo de la edad pediátrica permite al médico tratante plantear la existencia de esteatorrea patológica.Palabras claves: esteatorrea, prueba Sudan III en heces

Steatorrhea is the loss of fat through the stools. It becomes clinically apparent with the presence of increased amounts of foul and fatty stools. It can be determined through the Van de Kamer method, the acid steatocrit and the Sudan III stain test of stools. The objective of this paper is to specify the normal value of the Sudan III Stain Test of stools. 2000 healthy children stools samples were included. Age groups were preterm’s, newborns, and infants between 1-4 and 5-12 months of age, 500 samples were collected for every group. The study was performed at the Hospital Universitario de los Andes, in Mérida-Venezuela, during years 1999 through 2009. The Sudan III Stain Test and the Saathoff reactive were employed, as well as a highpower objective lens. The number of large and medium fat drops by field was considered for the classification. This is a prospective, observational, randomized clinical trial. For the total number of children (53% males and 47% females) the average of evacuations per day showed a total of 3 times inthe newborns, from 2 to 3 times in the infants between 1-4 months of age and from 1 to 2 times in the infants between 5 and 12 months of age. The normal value of the Sudan III Stain Test of stools varies according to age: in preterm newborns this test shows an average of 5,4 drops (12-0) of fat per field, in full term newborns 7,9 drops (16-0), in infants from 0 to 4 months 4,3 drops (10-0) and in infants between 5 and 12 months 3,8 drops (6-0) of fat per field. Sudan III Stain Test guides in the diagnosis of steatorrhea in children, in patients with intestinal malabsorption syndrome and in the evaluation of the indication of pancreatic enzymes. This is a cheap, simple and easy technique .To know the normal values in the different pediatric age groups, allows to establish the presence of steatorrhea

Chylomicron retention disease: report of two cases from a Greek Island.

Chylomicron retention disease (CRD), or Anderson disease, is a rare, hereditary cause of fat malabsorption. It is one of the familial hypocholesterolaemia syndromes, along with homozygous hypobetalipoproteinaemia (HBL) and abetalipoproteinaemia (ABL). We report clinical, laboratory and histological data as well as molecular DNA analysis in the case of a 4-month-old boy with failure to thrive and steatorrhea who was diagnosed with CRD. His mother's first cousin, who was diagnosed as hypobetalipoproteinaemia 30 years ago, was also reviewed and his diagnosis was revised to CRD. Both patients were treated with a low fat diet and supplementation with fat-soluble vitamins resulting in significant improvement. In conclusion, CRD is a well-defined cause of fat malabsorption and can be distinguished from other forms of familial hypocholesterolaemia because of its specific lipid profile.

Acid steatocrit determination is not helpful in cystic fibrosis patients without or with mild steatorrhea.

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.

Novel CFTR mutations in a Korean infant with cystic fibrosis and pancreatic insufficiency.

Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in Asians: only a few cases have been reported in Korea. We treated a female infant with CF who had steatorrhea and failure to thrive. Her sweat chloride concentration was 102.0 mM/L. Genetic analysis identified two novel mutations including a splice site mutation (c.1766+2T >C) and a frameshift mutation (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble vitamin supplementation enabled the patient to get a catch-up growth. This is the first report of a Korean patient with CF demonstrating pancreatic insufficiency. CF should therefore be considered in the differential diagnosis of infants with steatorrhea and failure to thrive.

Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.

The diagnosis of cystic fibrosis (CF) can be confusing when only a part of the typical symptoms is present. In children, CF is usually suspected when dealing with chronic pulmonary symptoms (chronic productive cough, recurrent pneumonia or bronchiolitis). The pediatric gastroenterologist will exclude CF in all children with a meconium ileus, rectal prolaps or a poor weight gain. Atypical CF symptoms are hypochloremic alkalosis, recurrent pancreatitis and increased appetite to compensate for the pancreatic insufficiency. This case report shows how a diagnosis can be delayed when you are mislead by atypical symptoms. It shows the importance of looking in napkins and argues for the inclusion of CF in the differential diagnosis of polyuria in infants.

Spontaneous exocrine pancreas hypoplasia in specific pathogen-free C3HeB/FeJ and 101/H mouse pups causes steatorrhea and runting.

Under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our inbred 101/H and C3HeB/FeJ mouse colonies had pups with steatorrhea and runting. Clinically affected male and female pups were first identified when they were from 14 to 25 d old. Unaffected littermates were healthy and were weaned successfully. Postmortem findings in 8 clinically affected mice included a small, poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like structures but lacking recognizable acinar cells with their normal carboxypeptidase B-positive zymogen granules. Endocrine pancreas islets were unremarkable and contained insulin-positive beta cells and glucagon-positive alpha cells. There was mild inflammation of the hindgut but no evidence of intestinal pathogens or marked inflammation or necrosis of pancreas, either alone or as part of a multisystemic inflammatory condition. Sera from pups in 4 affected litters did not contain antibodies to reovirus 3, mouse coronavirus, rotavirus, or mouse adenovirus 2. Furthermore, 4 sets of parental mice and sentinel mice from the facility were negative for 13 viruses, bacteria, and parasites. C3HeB/FeJ and 101/H inbred strains may be genetically predisposed because the steatorrhea and runting was absent in 13 other mouse strains and subspecies bred in the specific pathogen-free facility. This condition resembles exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication is that runting coupled with steatorrhea are phenotypic criteria to suspect pancreatic disease that could be used in the context of a mouse N-ethyl-N-nitrosourea-mutagenesis program to identify potential mutants with defects in pancreas development.

Diagnóstico de los síndromes de malabsorción / Malabsorption syndrome diagnosis

Los síndromes de malabsorsión son una de las principales causas de diarrea crónica de tipo entérico y con compromiso del estado general. Los tres principales síndromes de malabsorción son la enfermedad celíaca; la insuficiencia pancreática exocrina y los síndromes de asa ciega con proliferación de la flora intestinal y colonización del intestino delgado. La sospecha diagnóstica inicial de malabsorción es clínica y luego se comprueba mediante la demostración de esteatorrea y con el test de absorsión de D-xylosa. El diagnóstico se confirma finalmente mediante el estudio histológico de la biopsia de intestino delgado, que revela la existencia de atrofia vellositaria y microvellositaria. Ultimamente han adquirido importancia los exámenes inmunológicos (anticuerpos antiendomisio), los que son altamente sensibles y específicos. El tratamiento es propio de cada variedad fisiopatológica de malabsorción y consiste en: - Régimen sin gluten (enfermedad celíaca)- Antibióticos (síndrome de asa ciega)- Pancreatina o extractos pancreáticos (insuficiencia pancreática exocrina).

Faecal pancreatic elastase--1 a non invasive measure of exocrine pancreatic function.

BACKGROUND: Faecal pancreatic elastase-1 is a laboratory based test used for the diagnosis or exclusion of exocrine pancreatic insufficiencies. Pancreatic elastase-1, is released into blood circulation during inflammation of the pancreas, but unlike most pancreatic enzymes it is stable during intestinal passage and not degraded. OBJECTIVES: The major objective of this work was to establish the assay of faecal pancreatic elastase-1 in spot stool samples as an exocrine pancreatic function test at Korle-Bu (a referral) hospital in Ghana, for the diagnosis of pancreatic diseases. METHOD: Twenty-five apparently healthy persons; mean age of 43.4 years and thirty-two patients with various pancreatic diseases, mean age 51.4 years were referred for the test based on clinical presentation, imaging studies and biopsy findings. The male to female ratio was 6.4:3.6 and 8.1:1.9 respectively. An ELISA technique which recognizes human pancreatic elastase-1 from spot stool samples was employed for the test and read photometrically at 405nm. RESULTS: Elastase-1 activity in spot stool samples from apparently healthy group ranged from 165 to 870mg/g with a mean of 379 (SE 41)mg/g, and a range of 20 to 285mg/g with a mean of 112.9 (SE 11.6)mg/g obtained for the pancreatic disease group. Disease severity was classified as mild to moderate with elastase-1 concentration between 100 and 200mg/g stool and the severe pancreatic insufficiency group with elastase-1 concentration of less than 100mg/g stool. The pancreatic elastase-1 was found to be stable in faeces for several weeks when stored frozen, hence the convenience for batch determinations. CONCLUSION: The test is non invasive and can assist with the diagnosis of inflammatory conditions of the pancreas where imaging results are equivocal.

Fat malabsorption screening in chronic pancreatitis.

OBJECTIVES: As the major metabolic complications of chronic pancreatitis are exocrine and endocrine dysfunction, leading to malabsorption and diabetes, the aims of this study were to screen patients with chronic pancreatitis for exocrine dysfunction, to correlate the prevalence of such dysfunction with the etiology and severity of pancreatitis, and to evaluate the effect of dysfunction on weight loss. METHODS: Sixty patients were studied. In 44 patients, pancreatitis was alcoholic, and in 16, idiopathic. Patients' age, sex, alcohol consumption and smoking habits, duration of the disease, body mass index, and the presence of steatorrhea were recorded. The severity of pancreatitis was assessed by imaging procedures, including secretin-enhanced magnetic resonance cholangiopancreatography, and patients were classified according to the Cambridge system. Exocrine function was evaluated by the triolein breath test and acid steatocrit. RESULTS: A significant positive correlation was found between breath test and steatocrit values. As a screening test for exocrine pancreatic dysfunction, the sensitivity of clinical steatorrhea was insufficient (38%). Of the 60 patients, 38 (63%) developed exocrine dysfunction within 5 yr of the onset of the pancreatitis and 56 (94%) after 10 yr. Moreover, undetected or untreated malabsorption had a harmful effect on weight, even in the absence of overt clinical steatorrhea. CONCLUSIONS: To avoid nutritional deterioration, early screening for fat malabsorption should be recommended in chronic pancreatitis, whatever its etiology, using the acid steatocrit, a reliable, easy, and inexpensive test.

Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes.

UNLABELLED: Despite treatment with supra-physiological doses of pancreatic enzyme supplements, residual steatorrhoea is a common problem in patients with cystic fibrosis (CF) and pancreatic insufficiency. Strategies to enhance the activity of pancreatic enzymes include decreasing duodenal acidity. The aim of this study was to evaluate the effect of omeprazole (Losec), a proton-pump inhibitor, on fat absorption in CF patients with residual steatorrhoea despite high dose pancreatic enzyme supplements (> or =10,000 U lipase/kg per day). A random cross-over design was chosen. Fat digestion was evaluated with and without omeprazole by means of chemical fat measurements in 3-day stool collections together with 3-day weighed food records for calculation of fat absorption. The results of 15 patients (3 girls and 12 boys) with confirmed steatorrhoea during the control evaluation were analysed. Median age was 8.7 years (range 3.5-15.9 years). Median daily lipase intake was 13,500 U/kg per day (range 10,000-22,000 U/kg per day). During treatment with omeprazole, median faecal fat loss (g fat/day) decreased from 13 g (quartiles 11.5-16.5 g/day) to 5.5 g (quartiles 4.9-8.1 g/day) (P<0.01). The same improvement was noted when fat absorption was calculated: 87% (quartiles 81-89%) without versus 94% (quartiles 90-96%) with omeprazole (P<0.001). CONCLUSION: Omeprazole improves fat digestion and absorption in cystic fibrosis patients with residual faecal fat loss despite maximal pancreatic enzyme substitution.