Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose.

BACKGROUND: Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. METHODS: In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. RESULTS: In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). CONCLUSIONS: Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. IMPACT: Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.

Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis. METHODS: Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests. RESULTS: Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests. CONCLUSIONS: The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.

Delivery of pancreatic digestive enzymes into the gastrointestinal tract by pancreatic exocrine tissue transplant.

Exocrine pancreatic insufficiency, caused by disease-induced loss of pancreatic exocrine cells, may be treated through regenerative stem cell technologies that facilitate the production of pancreatic exocrine cells from induced pluripotent stem cells (iPSCs). However, delivering the digestive enzymes produced in the transplanted cells to the gastrointestinal tract remains a challenge. To generate an allogenic transplantation rat model, minced pancreas was transplanted into the gastric submucosal space with ablation of muscularis mucosa. In the allogenic transplantation, transplanted pancreatic cells were engrafted. Elevated amylase was detected in gastric juice, while transplanted cells disappeared through auto-digestion when the muscularis mucosa was not eliminated. Human iPSCs were differentiated into pancreatic exocrine cells by stage-specific treatment with growth factors and chemical compounds, and the differentiated pancreatic cells were implanted into the gastric submucosal space of nude rats. The transplanted cells were engrafted, and amylase was detected in the gastric juice in some cases. These findings suggest that transplantation of pancreatic exocrine cells into the gastric submucosal space with muscularis mucosa elimination will contribute to a regenerative approach for pancreatic exocrine insufficiency.

Pancreatic Steatosis Is Associated With Impaired Exocrine Pancreatic Function.

OBJECTIVES: The aim of this study was to investigate if pancreatic steatosis measured by proton density fat fraction (PDFF) is associated with exocrine pancreatic function defined by fecal elastase concentrations. MATERIALS AND METHODS: A total of 1458 volunteers (777 women; age range, 21-88 years) underwent magnetic resonance imaging of the pancreas, and organ fat content was quantified by using confounder corrected PDFF. Exocrine pancreatic function was categorized by fecal elastase levels using defined cutoffs: greater than 200 µg/g normal function (n = 1319) and 200 µg/g or less impaired function (n = 139). Statistical analysis to correlate pancreatic fat content with fecal elastase included linear regression, and analyses were adjusted for known confounders for pancreatic steatosis, such as age, sex, and body mass index. RESULTS: Overall mean (±standard deviation) of pancreatic fat content was 7.50% ± 3.78%. Pancreatic fat content was significantly higher in subjects with impaired pancreatic exocrine function (9.36% ± 4.95%) compared with subjects with normal function (7.30% ± 3.59%; P < 0.01). Linear regression analyses showed an inverse correlation between pancreatic fat and fecal elastase levels over the whole study population (beta, -7.19 [standard error, 1.39]; P < 0.01) as well as in the subgroup of subjects with normal function (-4.26 [1.32]; P < 0.01). Among subjects with impaired pancreatic exocrine function, a trend toward an inverse relation was detected (-1.28 [0.84]; P < 0.13). CONCLUSIONS: An inverse correlation between PDFF of the pancreas and fecal elastase suggests an association between pancreatic steatosis and impaired pancreatic exocrine function.

Symptoms that are associated with decreased pancreatic enzyme flow: MRCP assessment.

BACKGROUND: Pancreatic exocrine insufficiency is one of the causes of malabsorption syndrome. In many cases of malabsorption syndrome, pancreatic exocrine insufficiency can be treated with pancreatic enzyme replacement therapy. Therefore, it is important to detect pancreatic endocrine insufficiency as early and accurately as possible. Recent studies have shown that cine-dynamic MR cholangiopancreatography (MRCP) may be useful to evaluate pancreatic exocrine function PURPOSE: To identify abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion for which cine-dynamic MRCP should be performed to diagnose pancreatic exocrine insufficiency. STUDY TYPE: Prospective. POPULATION: In all, 111 patients with various types of abdominal symptoms. FIELD STRENGTH/SEQUENCE: 5 T or 3 T, MRCP with spatially selective inversion recovery pulse (cine-dynamic MRCP). ASSESSMENT: Cine-dynamic MRCP was performed and an 18-question clinical questionnaire on abdominal symptoms was administered. The secretion grade derived from cine-dynamic MRCP was compared between those answering "yes" and "no" for all 18 items STATISTICAL TESTS: Univariate analysis and further analyzed using multiple regression analysis. The associations between the secretion grade and the items in the clinical questionnaire were analyzed by univariate analysis and further analyzed using multiple regression analysis. RESULTS: The following three items showed significantly negative correlations with secretion grade: Q9, Does your rectal gas smell foul? (ß = -0.44, P = 0.001); Q13, Is stool quantity large? (ß = -0.41, P = 0.001); and Q18, Are your stools soft? (ß = -0.53, P < 0.001). No significant correlations with exocrine pancreatic function measured by cine-dynamic MRCP were seen for the remaining 15 abdominal symptom items. DATA CONCLUSION: Abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion were foul rectal gas, large stool, and soft stool. Pancreatic exocrine insufficiency due to decreased pancreatic enzyme flow may be suspected in patients with these abdominal symptoms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:417-423.

Analysis of lipase activity in duodenal juice. Comparison of an automated spectrophotometric assay to a fluorometric microplate assay, and factors affecting sample stability.

BACKGROUND: Direct pancreas function testing (DPFT) has been regarded as gold standard for assessment of exocrine pancreas function. One of the outcomes from DPFT is pancreatic lipase activity in duodenal juice, but no standard assay for measuring pancreas lipase activity in duodenal juice exists. AIMS: To optimize and evaluate an autoanalyzer assay for measuring lipase activity in duodenal juice. METHODS: We used samples of duodenal juice from our biobank, collected through a short endoscopic secretin test in patients with suspected exocrine pancreas insufficiency. Samples were analyzed on a Cobas autoanalyzer (Roche Diagnostics), using a colorimetric, kinetic enzyme activity assay. We compared stability of samples diluted in saline to samples diluted in 3-(N-morpholino) propane sulfonic acid (MOPS) buffer added bovine serum albumin (BSA). Results from the Cobas assay were compared to Confluolip method, a fluorometric, kinetic enzyme assay, modified to fit into a microplate setting. RESULTS: We tested the stability of 54 samples from 21 patients. Diluting samples with MOPS buffer added BSA gave stable results, and was superior to diluting samples in saline. We compared the two assays in 50 samples from 20 patients and found a good correlation between the two assays (r = 0.91, p < .001). There was a significant proportional bias between the two assays, but no significant systematic bias. CONCLUSION: Pancreatic lipase activity in duodenal juice samples diluted in MOPS buffer added BSA is stable for one hour at room temperature. Quantification of lipase activity in duodenal juice using a standard automated activity assay has comparable accuracy to a manual fluorometric method.

Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study.

BACKGROUND: Patients with advanced well-differentiated neuroendocrine tumours (Wd-NETs) are commonly treated with somatostatin analogues (SSAs). Some patients may develop SSA-related side effects such as pancreatic exocrine insufficiency (PEI). METHODS: In this prospective, observational study, the frequency of SSA-induced PEI in 50 sequential patients with advanced Wd-NETs treated with SSAs was investigated. Toxicity was assessed monthly and faecal elastase-1 (FE1) and quality of life (QoL) were assessed 3-monthly. RESULTS: The median age was 65.8 years, 58% were male and the majority (92%) of patients had metastatic disease; patients received 4-weekly long acting octreotide (60%) or lanreotide (40%). Twelve patients (24%) developed SSA-related PEI after a median of 2.9 months from SSA initiation; FE1 was a reliable screening tool for PEI, especially in symptomatic (abdominal bloating, flatulence and/or diarrhea) patients (risk ratio 8.25 (95% confidence interval 1.15-59.01)). Most of these patients (11/12; 92%) required PERT. Other SSA-related adverse events (any grade) included flatulence (50%), abdominal pain (32%), diarrhoea (30%) and fatigue (20%). Development of PEI did not significantly worsen overall QoL, however gastrointestinal symptoms and diarrhoea were increased. CONCLUSION: This study demonstrated that PEI occurs at a higher rate than previously reported; clinicians need to diagnose and treat this SSA-related adverse-event which occurs in 1 in 4 patients with Wd-NETs treated with SSAs. Screening with FE1 in symtomatic patients is recommend.

Exocrine pancreatic insufficiency is common in people living with HIV on effective antiretroviral therapy.

OBJECTIVES: The primary aim of this prospective study was to determine the prevalence of exocrine pancreatic insufficiency (EPI) in people living with HIV (PLHIV) on suppressive antiretroviral therapy (ART). METHODS: PLHIV ≥18 years of age and on ART for >6 months and with HIV RNA <50 copies/mL plasma were included. Faecal elastase-1 measurement was performed on a single stool sample, serum markers of malnutrition were collected, and participants answered a short questionnaire about gastrointestinal symptoms. Participants with EPI and symptoms were offered pancreatic enzyme replacement therapy (PERT), and the result of this therapy was also evaluated. RESULTS: Of 100 participants, 32% had EPI (faecal elastase-1 < 200 µg/g) and 20% severe EPI (faecal elastase-1 < 100 µg/g). We did not find any correlation between self-reported symptoms and degree of EPI. Twelve out of the 32 participants with EPI accepted to start PERT. Nine out of 12 (75%) reported improvement or became asymptomatic within 14 days. CONCLUSION: EPI is common in PLHIV on effective ART. We could, however, not find a correlation between gastrointestinal symptoms and the presence of EPI. Assessment of pancreatic exocrine function could be considered in PLHIV particularly in those with gastrointestinal discomfort, since there is a possible gain in treating them with relief of symptoms and improved quality of life. The effects of PERT in PLHIV on effective ART need further study.

The effect of primary hyperparathyroidism on pancreatic exocrine function.

BACKGROUND: Elastase-1 is a proteolytic enzyme secreted by pancreatic acinar cells, and measurements of the concentration this enzyme are used to evaluate pancreatic exocrine function. We aimed to determine whether pancreatic exocrine function declines due to chronic hypercalcemia by measuring fecal elastase levels. METHODS: 75 patients with primary hyperparathyroidism (18 men and 47 women) and 30 healthy subjects (11 men and 19 women) participated in this study. Renal function tests, lipid parameters, bone mineral density, and serum calcium, phosphorus, vitamin D, parathormone, glucose, and thyroid stimulating hormone levels as well as fecal elastase concentrations, were determined in these patients and controls. RESULTS: The mean fecal elastase level was 335.3 ± 181.4 µg/g in the PHPT group and 317.4 ± 157.3 µg/g in the control group. There was no significant difference in fecal elastase levels between the two groups (p = 0.5). CONCLUSIONS: Chronic hypercalcemia in primary hyperparathyroidism did not decrease the fecal elastase level, which is an indirect indicator of chronic pancreatitis; therefore, chronic hypercalcemia in PHPT may not cause chronic pancreatitis.

Insuficiência pancreática exócrina em cão - Relato de caso / Exocrine pancreatic insufficiency in a dog ­ Case report / Insuficiencia pancreática exócrina en perro- Relato de caso

A insuficiência pancreática exócrina é uma incapacidade na secreção de enzimas digestivas decorrentes da diminuição do tecido acinar do pâncreas acarretando uma má digestão e absorção. O presente trabalho relata o caso de uma cadela SRD de um ano e meio com histórico de emagrecimento, esteatorréia, burburinhos e polifagia que foi diagnostica com insuficiência pancreática exócrina após teste de imunorreatividade da tripsina. O tratamento instituído com suplementação de enzimas pancreáticas foi eficiente no controle e evolução da doença.(AU)

Exocrine pancreatic insufficiency is the inability to secrete digestive enzymes due to the decrease in the acinar tissue of the pancreas leading to poor digestion and absorption. This work is a case report of a 1.5-years' old mongrel bitch with a history of weight loss, steatorrhea, rumbling sounds and polyphagia that was diagnosed with exocrine pancreatic insufficiency after a trypsin immunoreactivity test. The pancreatic enzyme supplementation was efficient in controlling the evolution of the disease.(AU)

La insuficiencia pancreática exocrina es una incapacidad en la secreción de enzimas digestivas derivadas de la disminución del tejido acinar del páncreas, acarreando mala digestión y absorción. El presente trabajo relata el caso de una perra SRD de un año y medio con historial de adelgazamiento, esteatorrea, burbujas y polifagia que fue diagnosticada con insuficiencia pancreática exocrina después de la prueba de inmune reactividad de la tripsina. El tratamiento instituido con suplementación de enzimas pancreáticas fue eficiente en el control y evolución de la enfermedad.(AU)

Less common etiologies of exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Pancreas exocrine replacement therapy is associated with increased survival following pancreatoduodenectomy for periampullary malignancy.

BACKGROUND: Although many patients undergoing pancreatoduodenectomy (PD) for cancer have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy (PERT) is not routinely used, and effects upon post-operative survival are unclear. METHODS: This review of patients undergoing PD for periampullary malignancy sought to test for an association between PERT and overall survival, with post-hoc subgroup analysis performed after stratifying patients by the year of surgery, pancreatic duct width and tumour type. RESULTS: Some 202/469 (43.1%) patients received PERT. After accounting for pathological variables and chemotherapy, PERT use was found to be independently associated with improved survival on multivariable analysis [HR 0.72 (95% CI: 0.52-0.99), p = 0.044] and on propensity matched analysis (p = 0.009). The effect of PERT upon improved survival was predominantly observed amongst patients with a dilated pancreatic duct (≥3 mm). DISCUSSION: PERT use was independently associated with improved survival following PD for cancer. The validity of this observation is supported by an effect largely confined to those patients with a dilated pancreatic duct. The nutritional status of patients undergoing PD for cancer needs further investigation and the effects of PERT require verification in further clinical studies.

Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in aShwachman-Diamond like syndrome.

BACKGROUND: For the final step of the maturation of the ribosome, the nascent 40S and 60S subunits are exported from the nucleus to the cell cytoplasm. To prevent premature association of these ribosomal subunits, eukaryotic initiation factor 6 (eIF6) binds the 60S subunit within the nucleus. Its release in the cytoplasm requires the interaction of EFL1 and SDBS proteins. In Shwachman-Diamond syndrome (SDS), a defective SDBS protein prevents eIF6 eviction, inhibiting its recycle to the nucleus and subsequent formation of the active 80S ribosome. OBJECTIVE: This study aims to identify the molecular basis of an SDS-like disease, manifested by pancytopenia, exocrine pancreatic insufficiency and skeletal abnormalities in six patients from three unrelated families. METHODS: Whole exome analysis was used for mutation identification. Fluorescence microscopy studies assessed the localisation of Tif6-GFP, the yeast eIF6 homologue, in yeast WT and mutant cells. Human and yeast EFL1 proteins, WT and mutants, were expressed in Saccharomyces cerevisiae BCY123 strain, and circular dichroism and small-angle X-ray scattering were used to assess the folding and flexibility of these proteins. Green malachite colorimetric assay was performed to determine the GTPase activity of WT and Efl1 mutants. RESULTS: Four patients were homozygous for p.R1095Q variant and two patients were homozygous for p.M882K variant in EFL1. Residue R1095 and M882 are conserved across species. Neither the GTPase activity of the mutant proteins nor its activation by the SDBD protein or the 60S ribosomal subunit were affected. Complementation of efl1Δ yeast cells with the EFL1 mutants rescued the slow growth phenotype. Nonetheless, Tif6-GFP was relocalised to the cytoplasm in mutant yeast cells in contrast to its nuclear localisation in WT cells. CONCLUSIONS: Mutations in EFL1 clinically manifest as SDS-like phenotype. Similar to the molecular pathology of SDS, mutant EFL1 proteins do not promote the release of cytoplasmic Tif6 from the 60S subunit, likely preventing the formation of mature ribosomes.

Utility of Direct Pancreatic Function Testing in Children.

OBJECTIVES: Exocrine pancreatic insufficiency (EPI) can have a significant impact on a child's growth and nutrition. Our aim was to evaluate the utility of direct endoscopic pancreatic function testing (ePFT) in pediatrics. METHODS: A single-center retrospective chart review was performed of children who underwent ePFT from December 2007 through February 2015. Endoscopic pancreatic function testings were performed by 1 of 2 methods: (1) intravenous cholecystokinin, followed by the collection of a single duodenal aspirate at 10 minutes, or (2) intravenous cholecystokinin or secretin, followed by the collection of 3 duodenal aspirates at a 5, 10, and 15 minutes. Samples were tested for pH and enzyme activities. RESULTS: A total of 508 ePFTs were performed (481 single-sample tests, 27 multiple-sample tests). Based on the multiple-sample group, enzyme levels for chymotrypsin, amylase, and lipase peaked at 5 minutes, followed by a decrease in activity over time. Exocrine pancreatic sufficiency was identified in 373 (73.4%) and EPI in 93 (18.3%). Exocrine pancreatic sufficiency analysis found all pancreatic enzyme activities significantly increase with age: trypsin, chymotrypsin, amylase, and lipase, (P < 0.05). CONCLUSIONS: Endoscopic pancreatic function testing can be used in the evaluation of EPI in children. Normative data suggest that pancreatic enzyme activities mature with age.

Pancreatic exocrine insufficiency after pancreaticoduodenectomy is more prevalent with pancreaticogastrostomy than with pancreaticojejunostomy. A retrospective multicentre observational cohort study.

OBJECTIVE: Recently, pancreaticogastrostomy (PG) has attracted renewed interest as a reconstruction technique after pancreaticoduodenectomy (PD), as it may imply a lower risk of clinical pancreatic fistula than reconstruction by pancreaticojejunostomy (PJ). We hypothesise that pancreatic exocrine insufficiency (PEI) is more common during clinical follow-up after PG than it is after PJ. RESEARCH DESIGN AND METHODS: This study compares the prevalence of PEI in patients undergoing PD for malignancy with reconstruction by PG versus reconstruction by PJ. PEI during the first year of follow-up was defined as the intake of pancreatic enzyme replacement therapy (PERT) within one year postoperatively and/or an abnormal exocrine function test. RESULTS: A total of 186 patients, having undergone surgery at two university hospitals, were included in the study. PEI during the first year postoperatively was present in 75.0% of the patients with PG, compared to 45.7% with PJ (p < 0.001). Intake of PERT within one year after surgery was found to be more prevalent in the PG group, i.e. 75.8% versus 38.5% (p < 0.001). There was a trend towards more disturbed exocrine function tests after PG (p = 0.061). CONCLUSIONS: PEI is more common with PG reconstruction than with PJ reconstruction after pancreaticoduodenectomy for malignancy.

Specificity of a Polyclonal Fecal Elastase ELISA for CELA3.

INTRODUCTION: Elastase is a proteolytic pancreatic enzyme that passes through the gastrointestinal tract undergoing only limited degradation. ELISA tests to determine stool elastase concentrations have therefore been developed for the diagnosis of exocrine pancreatic insufficiency. Five different isoforms of pancreatic elastase (CELA1, CELA2A, CELA2B, CELA3A, CELA3B) are encoded in the human genome. We have investigated three different polyclonal antisera that are used in a commercial fecal elastase ELISA to determine their specificity for different pancreatic elastase isoforms. MATERIAL AND METHODS: Different polyclonal rabbit antisera against human elastase peptides (BIOSERV Diagnostics GmbH, Germany) were tested by Western blot analysis of human pancreatic juice, in HEK-293 cells expressing Elastase constructs, and in the protein content of porcine pancreatin, used for treatment of exocrine pancreatic insufficiency. RESULTS: In human pancreatic juice the polyclonal antisera detected proteins at the corresponding size of human pancreatic elastase isoforms (~29kDa). Transiently expressed GFP fusion protein of elastase isoform CELA3A (CELA3A-GFP), but not CELA2A (CELA2A-GFP) could be precipitated from HEK-293 cell lysates with the elastase antisera. We detected no cross-reactivity with elastases in the porcine pancreatic extracts (pancreatin) used for enzyme replacement therapy. CONCLUSION: The polyclonal antisera used in a commercial fecal elastase ELISA are specific for the human pancreatic elastase isoform CELA3 and do not cross-react with elastase contained in pig pancreatin. While pancreatic elastase 1 (CELA1) is not expressed in the adult human pancreas, possible differences between the other isoforms regarding their cellular expression, pathophysiological role and relevance in exocrine pancreatic insufficiency deserve further investigation.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Pancreatic exocrine insufficiency in critically ill adult patients.

Pancreatic exocrine insufficiency is usually present in patients with pancreatic diseases. Surprisingly, recent studies indicated that patients with critical illness often suffer from pancreatic injury due to non-specific reasons other than pancreatic diseases, and pancreatic exocrine insufficiency is also commonly observed in critically ill adult patients without preexisting pancreatic diseases. It is well known that malnutrition is the main clinical consequence of pancreatic exocrine insufficiency, thus, the high incidence of pancreatic exocrine insufficiency is most likely to be an important contributor of malnutrition which is a frequent problem associated with detrimental clinical outcomes in critically ill patients admitted into intensive care unit. In order to prevent pancreatic exocrine insufficiency due to primary pancreatic diseases, pancreatic enzyme replacement therapy is indispensable to treat indigestion, malabsorption and nutritional deficiency. Similarly, pancreatic enzyme supplementation has the potential to be an adjuvant therapy in critically ill patients with enteral nutrition therapy, which may be helpful to improve the nutritional status and the prognosis of critically ill patients by reducing the occurrence of malnutrition. Here, we reviewed the diagnostic methods of pancreatic exocrine function, the epidemiology and risk factors of pancreatic exocrine insufficiency, and potential treatment strategies for pancreatic exocrine insufficiency in critically ill adult patients.