[Validation of a method for measuring the antielastolytic activity of human circulating alpha1-antitrypsin]. / Validation d'une méthode de mesure de l'activité antiélastasique de l'alpha1-antitrypsine circulante humaine.

The existence of alpha-1 antitrypsin variants with apparently unremarkable phenotypes and serum concentrations, contrasting with a clinical picture suggestive of a severe deficiency, led us to investigate whether in these cases there was a reduction or even suppression of the capacity of alpha-1 antitrypsin to inhibit elastase. To this end, in two different laboratories, we adapted and validated a method for measuring the functional activity of alpha-1 antitrypsin, based on spectrophotometric kinetic analysis of the inhibition by serum alpha-1 antitrypsin of the hydrolytic activity of porcine pancreatic elastase on a chromogenic substrate. This method has proved to be robust, reproducible and transferable and made possible to define, on the basis of an analysis of a hospital population, a functionality index with a confidence interval comprised between 0.87 and 1.2, allowing to identify subjects likely to have a functional deficiency of alpha-1 antitrypsin, whether this deficiency being of a genetic origin without any quantitative or phenotypic translation, or whether being acquired under the effect of external agents (cigarette smoke or viruses).

Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat. METHODS: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat. RESULTS: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] µg/g, p < 0.01). PEI (PE < 200 µg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01). CONCLUSION: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.

Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor.

Prior to the use of cystic fibrosis (CF) modulator therapy, exocrine pancreatic insufficiency in CF was thought to be irreversible. Improvement in pancreatic function on ivacaftor has been reported in open label studies in 1-5 year olds. The mechanism by which ivacaftor might improve exocrine pancreatic function is unclear. Although the effect of ivacaftor on pancreatic function may be more significant in younger children, evidence is mounting that there may still be potential for improvement in older children on long term therapy.

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. OBJECTIVES: The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. METHODS: Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. RESULTS: One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. CONCLUSIONS: In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Zinc deficiency in patients with chronic pancreatitis.

BACKGROUND: Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis (CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency (PEI), which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results. AIM: To investigate serum zinc levels in patients with CP of various etiologies. METHODS: Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the M-ANNHEIM classification system into the following etiological subcategories: alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal (fecal elastase 1 > 200 µg/g), mildly reduced (100-200 µg/g) and severely reduced (fecal elastase 1 < 100 µg/g). RESULTS: A total of 150 patients were included in the analysis. Zinc deficiency (< 11 µmol/L) was present in 39 (26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency (FE-1 < 200 µg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI (1.08-13.4); P = 0.04]; [OR 6.26, 95%CI (1.94-20.2), P > 0.002]. Smoking and number of pack-years were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked. Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin (HbA1c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels. CONCLUSION: Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI.

Transient Exocrine Pancreatic Insufficiency in Children: An Existing Entity?

OBJECTIVES: Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman-Diamond syndrome, or chronic pancreatitis. Fecal elastase-1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea. METHODS: We followed 43 children (age range 1 month-18 years) with low fecal elastase-1 in our institution between the years 2009 and 2017. We followed growth and laboratory results (particularly, complete blood count, albumin, transaminases, celiac serology, sweat test, and fat-soluble vitamins). Elastase levels <200 mg/g were considered as pancreatic insufficiency. RESULTS: Twenty-six were excluded due to missing data, a comorbidity or being syndromatic. Enrolled children (17) were all otherwise healthy.The median age at diagnosis was 3 years (range 0.2-15 years), 11 girls and 6 boys. Their main presenting symptoms were failure to thrive and/or diarrhea. Median fecal elastase-1 levels were 71 mg/g (range 18-160). Median time for normalization was 6 months (range 1-48 months). Abdominal sonography, celiac serology, and sweat test were normal for all patients. Most patients were treated with pancreatic enzymes until resolution. CONCLUSIONS: Transient EPI without clear etiology should be in the differential diagnosis of EPI after ruling out known etiologies. The resolving course pattern may be attributed to an unidentified infectious agent. Further studies to assess the etiology are mandated.

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated. METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.

Transient Exocrine Pancreatic Insufficiency: First Report of an Unrecognized Complication of Cytoreductive Surgery and HIPEC.

BACKGROUND: As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine pancreatic insufficiency (EPI) following CRS and HIPEC. PATIENTS AND METHODS: Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in all patients in the immediate postoperative period. Patients with diarrhea who had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and their symptomatic progression was followed. RESULTS: A total of 26 patients were included. Eleven patients (42.31%) developed postoperative refractory diarrhea, nine of whom had a low FE1 level. These patients were treated with PERT either directly or after completion of antibiotics course if C. difficile toxin was positive. Eight patients demonstrated symptomatic resolution of their diarrhea, and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea had lower FE1 levels, and were more likely to have had a terminal ileum resection and had a longer hospital stay. Regression analysis identified the rapid rise of a patient's core temperature by >1°C within 15 minutes as the sole predictor of EPI occurrence. CONCLUSION: EPI is a potential adverse event following CRS and HIPEC and might be largely responsible for refractory diarrhea. In our patients with refractory diarrhea and low FE1, PERT provided immediate symptomatic relief. The biological basis of this phenomenon remains unclear and warrants further investigation.

Elastase as a potential biomarker for radiation-induced gut wall injury of the distal bowel in an experimental mouse model.

BACKGROUND AND PURPOSE: Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel. MATERIAL AND METHODS: Adult male mice were exposed to two, three, or four fractions of 6 Gy or 8 Gy irradiation to the sigmoid and rectum of the large bowel, using a linear accelerator. Fecal samples were collected from mice at 1, 3, and 6 weeks post-irradiation. The fecal levels of elastase and calprotectin were analyzed using ELISA. RESULTS: Three and 6 weeks after irradiation, we found a dose-effect relationship between dose of ionizing radiation and the fecal level of elastase; that is significantly higher levels of elastase were observed in mice that had received a high irradiation dose. We also found that irradiated mice hosted in the same cage had a comparable level (either high or low) of elastase. No significant differences were observed from the calprotectin data. CONCLUSIONS: We found a clear association between the dose of ionizing radiation to the distal colon and the level of elastase in the fecal samples.

Isolated immune-related pancreatic exocrine insufficiency associated with pembrolizumab therapy.

We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.

Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment.

The Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo- and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons.

Pancreatic Exocrine Insufficiency after Bariatric Surgery.

Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/or malabsorption. Appropriate pancreatic enzyme replacement therapy should be part of the treatment algorithm in patients with confirmed PEI or symptoms suggestive of this complication.

Efficient near infrared fluorescence detection of elastase enzyme using peptide-bound unsymmetrical squaraine dye.

Extended wavelength analyte-responsive fluorescent probes are highly desired for the imaging applications owing to their deep tissue penetration, and minimum interference from autofluorescence by biomolecules. Near infra-red (NIR) sensitive and self-quenching fluorescent probe based on the dye-peptide conjugate (SQ 1 PC) was designed and synthesized by facile and efficient one-pot synthetic route for the detection of Elastase activity. In the phosphate buffer solution, there was an efficient quenching of fluorescence of SQ 1 PC (86%) assisted by pronounced dye-dye interaction due to H-aggregate formation. Efficient and fast recovery of this quenched fluorescence of SQ 1 PC (> 50% in 30s) was observed on hydrolysis of this peptide-dye conjugate by elastase enzyme. Presently designed NIR sensitive self-quenching substrate offers the potential application for the detection of diseases related to proteases by efficient and fast detection of their activities.

Histologic scoring indices for evaluation of disease activity in ulcerative colitis.

BACKGROUND: Disease activity can be determined using clinical, endoscopic or histologic criteria in patients with ulcerative colitis (UC). Persistent disease activity is associated with poor outcomes. Histologic disease activity has been shown to be associated with relapse, colectomy and colorectal cancer. The ability to objectively evaluate microscopic disease activity using histology is important for both clinical practice and clinical trials. However, the operating properties of the currently available histologic indices remain unclear. OBJECTIVES: A systematic review was undertaken to identify and evaluate the development and operating characteristics of histologic disease activity indices used to assess disease activity in people with ulcerative colitis. SEARCH METHODS: We searched MEDLINE, EMBASE, PubMed, CENTRAL and the Cochrane IBD Review Group Specialized Trials Register from inception to 2 December 2016 for applicable studies. There were no language or document type restrictions. SELECTION CRITERIA: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated a histologic index in patients with UC were considered for inclusion. Eligible patients were adults (> 18 years), diagnosed with UC using conventional clinical, radiographic, endoscopic and histologic criteria. DATA COLLECTION AND ANALYSIS: Two authors (MHM and CEP) independently reviewed the titles and abstracts of the studies identified from the literature search. A standardized form was used to assess eligibility of trials for inclusion and for data extraction.Two authors (MHM and CEP) independently extracted and recorded data, which included the number of patients enrolled, number of patients per treatment arm, patient characteristics including age and gender distribution, and the name of the histologic index. Outcomes (i.e. intra-rater reliability, inter-rater reliability, internal consistency, content validity, criterion validity, construct validity, responsiveness, and feasibility) were recorded for each trial. MAIN RESULTS: In total, 126 reports describing 30 scoring indices were identified through the screening process. Eleven of the 30 scoring indices have undergone some form of index validation. Intra-rater reliability was assessed for eight scoring indices. Inter-rater reliability was evaluated for all 11 of the scoring indices. Three of the indices underwent content validation. Two of the included scoring indices assessed criterion validity. Six of the included scoring indices explored content validity. Two of the included scoring indices were tested for responsiveness. AUTHORS' CONCLUSIONS: The Nancy Index and the Robarts Histopathology Index have undergone the most validation in that four operating properties including reliability, content validity, construct validity (hypothesis testing) and criterion validity have been tested. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the optimal endpoint for histologic healing in UC, more research is required. The optimal index would need to be fully validated.

Preoperative fecal elastase-1 is a useful prognostic marker following curative resection of pancreatic cancer.

BACKGROUND: The clinical relevance of fibrosis with regard to tumor progression is supported by the correlation between fibrosis and poor outcomes. Fecal elastase-1 (FE-1) level has been used to assess exocrine dysfunction of the pancreas and to predict pancreas fibrosis. The aim of this study was to assess the impact of FE-1 on the survival of pancreatic cancer patients. METHODS: Between January 2006 and December 2014, 136 patients with pancreatic adenocarcinoma underwent R0 resection at Gangnam Severance Hospital, Korea. Preoperative FE-1 levels were available in 94 patients who were enrolled in the study. Patients were classified into two groups according to preoperative FE-1: "normal" (≥200 µg/g) or "reduced" (<200 µg/g). RESULTS: Median preoperative FE-1 level was 130.1 µg/g (IQR 32.0; 238.3). 62 patients (66.0%) had reduced pancreatic function and 32 patients (34.0%) had normal pancreatic function. The two groups had significantly different disease-free survival (P < 0.001). On multivariate analysis, normal FE-1, no lymph node metastasis and completion of adjuvant chemotherapy were found to be independent prognostic factors for better DFS (P = 0.001, P = 0.017, P = 0.038, respectively). CONCLUSION: FE-1 is a simple and non-invasive predictive clinical marker for prognosis of pancreatic cancer after attempted curative resection.

Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study.

BACKGROUND AND AIMS: Pancreatic exocrine insufficiency may be under recognised in gastroenterological practice. We aimed to identify the prevalence of pancreatic insufficiency in secondary care gastroenterology clinics and determine if co-morbidity or presenting symptoms could predict diagnosis. A secondary aim was to assess response to treatment. METHODS: A dual centre retrospective analysis was conducted in secondary care gastroenterology clinics. Patients tested for pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and 2013 were identified in two centres. Demographics, indication and co-morbidities were recorded in addition to dose and response to pancreatic enzyme replacement therapy. Binary logistic regression was used to assess if symptoms or co-morbidities could predict pancreatic insufficiency. RESULTS: 1821 patients were tested, 13.1% had low FEL-1 (<200µg/g). This prevalence was sub-analysed with 5.4% having FEL-1 100-200µg/g (mild insufficiency) and 7.6% having faecal elastase readings <100µg/g. Low FEL-1 was most significantly associated with weight loss or steatorrhoea. Co-morbidity analysis showed that low levels were significantly associated with excess alcohol intake, diabetes mellitus or human immunodeficiency virus; 80.0% treated with enzyme supplements reported symptomatic benefit with no difference in response between high and low dose supplementation (p=0.761). CONCLUSION: Targeting the use of FEL-1 in individuals with specific symptoms and associated conditions can lead to improved recognition of pancreatic exocrine insufficiency in a significant proportion of secondary care patients. Intervening with lifestyle advice such as smoking cessation and minimising alcohol intake could improve outcomes. In addition, up to 80% of patients with low faecal elastase respond to supplementation.

A simple biomarker scoring matrix for early gastric cancer detection.

Gastric cancer (GC) is a major cause of death in many parts of the world. While 90% of early GC is curable by resection, only about 5% of patients diagnosed in the late stages survive beyond five years. This provides strong impetus to push for early GC detection through the use of non-invasive biomarkers, before metastatic complications arise. It is also of strong medical interest to identify patients of the diffuse subtype at the earliest time possible, since the disease variant progresses very rapidly and is associated with much higher mortality rate. In this study, we compared quantitatively the gastric fluid proteome of 70 GC patients to 17 individuals with benign gastritis in search of potential biomarkers that aid in GC diagnosis, prognosis and subtype stratification. We report that as much as half of the gastric fluid proteome is subject to regulation in diseased states, and propose a simple biomarker panel scoring matrix for early GC detection with diagnostic sensitivity of 95.7%. We also demonstrate as proof-of-concept that a digitised record generated with SWATH-MS based on 380 protein abundance signatures from the gastric fluid could segregate patients with diffuse-type GC.

Pancreatic Elastase-1 Quick Test for rapid assessment of pancreatic status in cystic fibrosis patients.

BACKGROUND: At present, fecal elastase-1 ELISA determination is the most sensitive and specific tubeless pancreatic function test available. However, the results are not available the same day in routine clinical practice. This prospective study aims at evaluating the sensitivity and specificity of the Elastase-1 Quick™ Test by comparing the results with the ELISA test. METHODS: The study was composed of three groups: the screening-diagnosed cystic fibrosis (CF) patients (n=28), the screened, but non-CF subjects (n=36) and non-screened CF patients (n=62). Pancreatic status (normal vs abnormal) was evaluated using the Pancreas Elastase-1 Quick™ Test. Fecal elastase-1 concentration was determined with a commercially available ELISA kit, used as reference. The cut-off for abnormal results was set at <200µg/g of stool. RESULTS: The Pancreatic Elastase-1 Quick Test™ showed the following sensitivities and specificities in the studied groups: 92.8% and 96.6% in all subjects, 90.5% and 100% in screening samples, and 92.8 and 90.5% in CF patients. CONCLUSION: Pancreatic Elastase-1 Quick Test™ proves to be a rapid and reliable option to qualitatively evaluate pancreatic function for diagnostic purposes in a clinical setting of CF care.

Fecal Calprotectin, Elastase, and Alpha-1-Antitrypsin Levels After Roux-en-Y Gastric Bypass; Calprotectin Is Significantly Elevated in the Majority of Patients.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) causes several alterations in gastrointestinal function. We hypothesized that levels of three commonly used fecal tests change after RYGB. METHODS: Fecal levels of calprotectin, elastase, and alpha-1-antitrypsin were determined in 122 patients without signs of gastrointestinal disease 1 to 2 years after RYGB. Medians, distribution of values, and the percentage of patients with levels above or below reference values were determined. RESULTS: Median fecal calprotectin level was 163.5 (<30-1587) µg/g; in 87 % of patients, it was above the reference value (<50 µg/g). Median fecal elastase level was 444 (<15-647) µg/g; 13 % was below the reference value (>200 µg/g). Median fecal alpha-1-antitrypsin level was 0.51 (<0.20-2.20) mg/g, comparable to the reference values. CONCLUSIONS: Fecal calprotectin levels are significantly higher than the reference value in most patients after RYGB. Fecal elastase is significantly lower. This might indicate that the validity of fecal calprotectin testing is impaired after RYGB and the specificity for fecal elastase is decreased. Clinical awareness of altered fecal markers after RYGB is essential to prevent unnecessary diagnostic tests, such as colonoscopy. Fecal alpha-1-antitrypsin is not influenced by RYGB.

The role, yield and cost of paediatric faecal elastase-1 testing.

OBJECTIVE: Faecal elastase-1 (FE1) is a sensitive marker for exocrine pancreatic enzyme insufficiency. Pancreatic insufficiency (EPI) leads to maldigestion and subsequent poor weight gain. Thus, FE1 is performed as work-up for children with failure to thrive (FTT). However, EPI in the paediatric population outside of cystic fibrosis (CF) is rare. This study aimed to identify the indications for FE1 testing and their diagnostic yield in children. The secondary aim was to evaluate the cost per case of EPI detected for the various indications. DESIGN: All FE1 tests performed on children (0-18 years) at a tertiary paediatric hospital in Sydney, Australia between 2010 and 2013 (inclusive) were identified. A retrospective chart audit was performed to identify the indication for testing FE1. The diagnostic yield based on FE1 cut-offs <200 and < 100 µg/g were assessed. RESULTS: The most common indication for testing FE1 was "FTT only" (71/216, 32.9%), however, in this cohort of patients, FE1 was least likely to be positive with only 2 out of the 71 (2.8%) patients returning a positive result. In comparison, CF was the second most common indication for testing (60/216, 27.8%), but nearly half (48.8%) of tests returned a positive result in this cohort. The cost per case detected (FE1 <200 µg/g) reflected the test yield with an average cost per positive test of $262.50 (AUD2015) for FTT with short-gut syndrome and $420.00 (AUD2015) for CF-related indications. CONCLUSION: Our study shows that for patients with isolated failure to thrive, FE1 testing is low yield and costly.