Low Fecal Elastase-1: A Non-negligible Factor in Functional Dyspepsia Patients.

Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes

Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study

Cohen, et al. J Pediatr Gastroenterol Nutr 2005;40:438-44 To the Editor: In the April issue of the journal, Cohen et al. (1) aimed to assess fecal elastase-1 (FE) levels in young children with cystic fibrosis (CF) and pancreatic insufficiency (PI) and to explore the relationship between FE values and growth, nutrition, pulmonary status, and fat absorption over a 24 month period. The authors concluded that a substantial number of children with CF have a misclassified pancreatic status. Children with detectable FE concentrations had greater fat absorption, improved growth, and nutritional status over 24 months when compared with those with undetectable FE levels. The reported observation that residual pancreatic exocrine secretion as documented by detectable FE activity has a beneficial effect for CF patients and has important clinical significance. With respect to fat absorption, growth, nutritional, and skeletal maturity status, Cohen et al. (1), as expected, documented that the clinical course is more favorable in children with higher FE levels. The authors attributed better clinical status to lower fecal fat losses not to the difference in energy intake that was no-significantly higher in patients with residual FE concentrations. Fecal fat losses as assessed by coefficient of fat absorption were higher in patients with undetectable FE. Surprisingly, this finding was not confirmed by bomb calorimetry, which indicates there is no real difference between the two groups. The authors underlined that enzyme replacement therapy, although undoubtedly essential for those with severe steatorrhea, may have potential clinical and psychosocial adverse effects. These include the assumption that poor growth and nutritional status is a result of inadequate treatment of PI with the resultant possibility that other causes of nutritional failure may then be missed. On the basis of these results, a very important question has been raised regarding whether the patients with residual pancreatic secretion should be treated with pancreatic enzymes. This question will only be reliably answered by further studies. These will need to focus on those patients with residual pancreatic function but with mild steatorrhea or reduced levels of FE (<200 μg/g stool). Patients with mild steatorrhea are currently treated on the basis of clinical experience, whereas those with FE greater than 200 μg/g stool are unlikely to benefit from pancreatic enzyme therapy. Cohen et al. (1) also documented that 12% of preadolescent children who were diagnosed with PI and prescribed pancreatic enzymes were possibly misdiagnosed. A similar observation was also recently documented in a larger American multicenter study (2). The authors proved that a considerable percentage of both PI and pancreatic sufficient (PS) CF patients was misclassified. As in most of the centers participating in the Borowitz multicenter U.S. study, pancreatic function tests are seldom routinely performed in CF patients. The reliable determination of pancreatic status should be obligatory in all CF patients, and the FE test is a very useful predictor of pancreatic exocrine function (3,4). The measurement of FE concentration could serve as a screening test for maldigestion in CF (5), and, in addition, the test could be used for the longitudinal assessment of declining exocrine pancreatic function in PS patients (6). Beharry et al. (5) documented a high predictive value (99%) for ruling out PI in CF patients using a cutoff level of 100 μg/g of stool for FE measurement. In all but one Polish PI CF patient ever tested, FE concentrations lower than 200 μg/g have been found (7,8). The use by Cohen et al. (1) of stool trypsin concentrations lower than 80 μg/g of feces (in place of 72 hour fecal fat balance studies) to classify some patients as PI may have partly contributed to the high percentage of patients with detectable FE concentrations found in this group. On the other hand, as documented by Cohen et al., some of those patients with FE concentrations greater than 15 μg/g of feces, even when receiving pancreatic enzyme supplementation during the study, fulfill the criteria for PI. Jaroslaw Walkowiak Aleksandra Lisowska I Chair of Pediatrics Department of Gastroenterology and Metabolism Poznan University of Medical Sciences Poznan, Poland

BackgroundStructural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus.MethodsA total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years) were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31); 70-79 years old (n = 38) and over 80 years old (n = 37). 53 young subjects (20-28 years old) were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1.ResultsFecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P < 0.001) and were significantly lower among subjects over 70 years old compared to controls (controls vs. 70-79 years old and controls vs. over 80 years old, both P < 0.001). Among the over 60 years old subjects, the fecal elastase-1 concentrations were below the cut off level of 200 μg/g in 23 of 106 (21.7%) individuals [mean 112 (86-138) μg/g] indicating pancreatic exocrine insufficiency. Of those, 9 subjects had fecal elastase-1 level below 100 μg/g as a marker of severe pancreatic insufficiency.ConclusionIn our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.

Symptoms of malabsorption, such as diarrhea, steatorrhea, or unintended weight loss, are often reported by patients after esophagectomy for cancer. The etiology of these symptoms is hypothesized to be multifactorial, with exocrine pancreatic insufficiency being described as one of the possible contributing causes. Symptoms of malabsorption are therefore often treated with pancreatic enzymes. This study aimed to measure the exocrine pancreatic function to determine whether there is an indication for pancreatic enzymes after esophagectomy. This prospective study included patients after esophagectomy for cancer in a stable postoperative situation (≥6 months after surgery) without signs of recurrent disease. Patients with and without pancreatic enzymes or symptoms of malabsorption were included. Exocrine pancreatic function was measured by fecal elastase-1 (FE-1) and fecal fat excretion. Three-day stool collections were performed to measure mean daily fecal fat excretion (g/d). Combined with a four-day (weighted) nutritional diary, to determine the mean daily fat intake (g/d), the percentage of fat absorption was calculated. Patients who were already treated with pancreatic enzymes stopped at least two days before stool collection. This study included 38 patients after esophagectomy for cancer. Exocrine pancreatic function was measured after a median postoperative follow-up of 20 months (range 6-45). Low FE-1 (&amp;lt;200 μg/g) levels were found in seven patients (18%). Of these patients, one patient also had fat malabsorption (fat absorption &amp;lt;85%). Prior to participation in this study, 11 patients (28%) already received treated with pancreatic enzymes because of symptoms of malabsorption. In one of these patients (9%) low FE-1 levels were found and in three patients (27%) fat malabsorption was diagnosed. These preliminary results indicate that, based on FE-1 levels, the secretion of pancreatic enzymes after esophagectomy is only impaired in a subgroup of patients. Most often this did not lead to malabsorption of fat. Based on these results routine prescription of pancreatic enzymes is not recommended in patients after esophagectomy, however a trial prescription can be considered in patients suffering from gastrointestinal complaints of malabsorption.

BackgroundAppetite loss is one complication of chronic heart failure (CHF), and its association with pancreatic exocrine insufficiency (PEI) is not well investigated in CHF.AimWe attempted to detect the association between PEI and CHF-induced appetite.MethodsPatients with CHF were enrolled, and body mass index (BMI), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) cardiac function grading, B-type natriuretic peptide (BNP), serum albumin, pro-albumin and hemoglobin were evaluated. The pancreatic exocrine function was measured by fecal elastase-1 (FE-1) levels in the enrolled patients. Appetite assessment was tested by completing the simplified nutritional appetite questionnaire (SNAQ). The improvement of appetite loss by supplemented pancreatic enzymes was also researched in this study.ResultsThe decrease of FE-1 levels was found in patients with CHF, as well as SNAQ scores. A positive correlation was observed between SNAQ scores and FE-1 levels (r = 0.694, p < 0.001). Pancreatic enzymes supplement could attenuate the decrease of SNAQ scores in CHF patients with FE-1 levels <200 μg/g stool and SNAQ < 14.ConclusionsAppetite loss is commonly seen in CHF, and is partially associated with pancreatic exocrine insufficiency. Oral pancreatic enzyme replacement therapy attenuates the chronic heart failure-induced appetite loss. These results suggest a possible pancreatic-cardiac relationship in chronic heart failure, and further experiment is needed for clarifying the possible mechanisms.

Malnutrition is commonly seen in children with exocrine pancreatic insufficiency (EPI). Pancreatic enzyme replacement therapy (PERT) is the mainstay treatment of acute malnutrition in children detected with a disease closely associated with EPI (eg, cystic fibrosis). The effectiveness of PERT in children with malnutrition without any chronic disease, however, remains unclear. The aim of this study was to investigate the effectiveness of PERT on weight gain and EPI in children classified as moderately and severely malnourished according to the World Health Organization (WHO) classification. The study included a total of 40 children aged 2-16 years who were classified as moderately and severely malnourished according to the WHO classification. The patients were randomly divided into 2 groups: PERT group (n = 20) received 2000 U lipase/kg/day (in 4 doses) in addition to hypercaloric enteral supplements and control group received hypercaloric enteral supplements only. In both groups, anthropometric measurements and the assessment of fecal elastase-1 (FE-1) levels were performed both at first admission and at the end of the 8-week treatment period. On the basis of WHO classification, 10 (25%) children were classified as severely malnourished and 30 (75%) children as moderately malnourished. EPI was detected in all the patients, among whom 24 (60%) patients had severe EPI. At the end of the treatment, body weight, height, and body mass index (BMI) increased significantly in both groups compared to their pre-treatment values, whereas no significant difference was found with regard to waist circumference (WC) and FE-1 levels. Similarly, no significant difference was found between pre- and posttreatment measurements of PERT and control groups (P > 0.05) and between pre- and posttreatment measurements of patients with moderate and severe malnutrition (P > 0.05). Malnutrition remains a serious public health problem, and thus, the development of novel treatment methods is highly essential. PERT is one of the most commonly considered alternatives, although there is little documentation of PERT in the literature. In the present study, although PERT resulted in higher weight gain, it established no significant difference between the 2 groups.

Transient low fecal elastase levels in two CF infants with G551D following newborn screening

IntroductionBariatric surgery is the most effective treatment modality in morbidly obese patients. Compared to Roux-en Y gastric bypass (RYGB), sleeve gastrectomy (SG) has better metabolic and nutritional outcomes after surgery. Exocrine pancreatic insufficiency (EPI) can be seen after RYGB but there is not any knowledge about EPI-SG association.AimTo assess exocrine pancreatic functions before and after the SG procedure.Material and methodsThis is a single-center, prospective and case-control study. Forty morbidly obese patients were included in the study. Their pre-operative and post-operative, third month fecal samples were collected. Exocrine pancreatic insufficiency was determined by using fecal elastase-1 and diagnosed when fecal elastase-1 levels were < 200 μg/g.ResultsThe mean fecal elastase-1 level was 256.25 ±137.16 μg/g and the mean post-surgical fecal elastase-1 level was 437.7 ±212.43 μg/g (p = 0.001). In the pre-operative period, half of patients had FE levels under 200 μg/g. In the third month after surgery, only 4 patients had fecal elastase-1 levels under 200 μg/g. Comparison of fecal elastase-1 between pre-surgery and post-surgery revealed a significant difference (p = 0.001).ConclusionsThis is the first study to investigate EPI-SG association. Surgery-associated morbidity and mortality are the leading limitations of bariatric surgery procedures. Exocrine pancreatic insufficiency is one of them; prior studies demonstrate its increased frequency after RYGB. Our study revealed that SG relieves exocrine pancreatic insufficiency.

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 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. 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. 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.

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan. One hundred ninety-eight consecutive patients presenting with FD (n=88), FD-P patients (n=81) based on Rome III classification and controlled group (n=39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively. There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P=0.003 and P=0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P=0.019) disturbed compared with those in FD patients in Japan. Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

Exocrine pancreatic dysfunction may contribute to malnutrition and lack of appetite in the advanced stages of heart failure. Nutritional assessment was carried out on patients diagnosed with mild or moderate/severe heart failure. Fecal elastase levels are an indicator of pancreatic exocrine function and ghrelin is an appetite hormone which is also investigated for its contribution to malnutrition. This is an observational study. 52 patients (32 males, 20 females) aged over eighteen years and hospitalized for acute decompensated heart failure (ADHF) were included in the study. They were compared with 31 people (16 male, 15 female) of the same age as Control Group (C). Patients in New York Heart Association (NYHA) stages 1 and 2 were grouped as mild (miADHF), while those in NYHA stages 3 and 4 were grouped as moderate/severe ADHF (seADHF). Fecal and blood samples were taken at admission. In ADHF patients, exocrine pancreatic functions and their relationship with malnutrition were evaluated. Statistical analyses were performed using Tukey's test, the independent-sample t-test, the Kruskal-Wallis test, the Mann-Whitney U-test, the chi-square test and Pearson's bivariate correlation analysis. Significantly decreased fecal elastase levels were found when moderate/severe ADHF patients and the control group were compared. (C 278.9±144.8, miADHF 336.6±181.7, seADHF 168.7±153.6, p=0.002). 10 seADHF patients (50%) had severe, 4 (20%) moderate, and 6 (30%) mild pancreatic insufficiency. Ghrelin levels were higher in seADHF patients compared to C and miADHF patients (C 69.7±34.6, miCHF 82.5±48.2, SeADHF 105.0±78.1 p=0.361). Fecal elastase and ghrelin hormone levels can contribute to the determination of malnutrition in ADHF patients.

Background: Determination of faecal elastase 1 (FE1) is a simple, relatively inexpensive, non-invasive, highly specific and sensitive test for determining pancreatic function. Secretion of pancreatic enzymes varies during infancy, but...

Pancreatic exocrine insufficiency (PEI) is a well-defined complication of malignant diseases and pancreatic resection; however, study results of PEI are less consistent. Assessment of PEI by estimation of fecal elastase (FE)-1 in stool by enzyme-linked immunosorbent essay (ELISA) is a relatively inexpensive, noninvasive, and simple test. This study assessed exocrine function of pancreas following pancreaticoduodenectomy (PD) by estimating FE-1. This prospective hospital-based study involved 30 patients who had undergone PD for malignancy. All 30 patients had an uneventful postoperative period under the unit's enhanced recovery after surgery (ERAS) protocol with no Grade B, C postoperative pancreatic fistula/postpancreatectomy hemorrhage as per the International Study Group of Pancreatic Surgery (ISGPS) definitions. Stool samples were collected postoperatively 3 months after surgery from all patients irrespective of clinical symptoms. The analysis was based on a solid phase ELISA used for the quantitative determination of human elastase 1 in feces. Fecal elastase was considered normal if >200 μg/gm stool, moderately reduced if 100-200 μg/gm stool, and severely reduced if <100 μg/gm stool. Among 30 patients included, fecal elastase levels were moderately reduced in 10 (33.33%) and severely reduced in 20 (66.67%) patients (P <0.0001). Mean (± standard deviation) of fecal elastase was 87.12 ± 38.76 with median of 74.6 μg/gm stool. There was no significant difference in the fecal elastase levels between men and women (P = 0.057), age (P = 0.48), pancreatic duct diameter (P = 0.609), pancreatic texture (P = 0.286), and presence or absence of clinical symptoms (P = 0.181). PD was frequently associated with PEI. Unfortunately PEI is an under recognized and under treated long-term sequel of PD. Fecal elastase 1 should be performed routinely in both symptomatic and asymptomatic patients. Pancreatic enzyme replacement therapy should be considered in every patient after PD.

Background: In the pancreatic cancer can occur pancreatic exocrine insufficiency (PEI) that can be detected by measurement of fecal elastase-1 level. The aim of this study was to identify the proportion and the degree of PEI, proportion of steatorrhea in pancreatic cancer, the concentration difference of faecal elastase-1 between resectable and unresectable pancreatic cancer and mean concentration difference of faecal elastase-1 based on the stage of pancreatic cancer.Method: This was a cross-sectional study to determine the concentration difference of faecal elastase-1 between resectable and unresectable pancreatic cancer. This research was conducted at Cipto Mangunkusumo hospital, several network hospitals of Cipto Mangunkusumo hospital, and Wahidin Sudirohusodo Makasar hospital from November 2014 until May 2015. The statistical test used to assess differences in the levels of faecal elastase-1 between resectable and unresectable pancreatic cancer was Mann Whitney and Kruskal Wallis test was performed to assess the differences between the mean levels of faecal elastase 1 based on staging pancreatic cancer.Results: A total of 48 subjects with pancreatic cancer participated in this study, with resectable category was 19 (39.6%) subjects, and 29 (60.4%) subjects were unresectable. The proportion of patients with pancreatic cancer who experienced PEI was 75% (CI 95% 0.63 - 0.87) and the proportion of patients with pancreatic cancer who showed steatorrhea symptoms was 68.8% (CI 95% 0.557 - 0.819). There was no significant difference of faecal elastase-1 levels (P = 0.738) between the resectable and unresectable whereas the resectable group median value was 38.0 (15-500) μg/g and in unresectable group was 35.0 (15-500) μg /g. There was no significant difference (p = 0.767) in faecal elastase-1 levels based on the stage of pancreatic cancer with median (range) in stage IB 36 (15-100) pg/g, stage IIA 62 (15-500) pg/g, stage III 15 (15-500) μg/g, and stage IV 36 (15-500) μg/g.Conclusion: This study found a high proportion of PEI and steatorrhea in pancreatic cancer. There was no significant difference in faecal elastase-1 levels between the resectable and unresectable pancreatic cancer. There was no significant difference between mean levels of faecal elastase-1 based on the stage of pancreatic cancer.