Exocrine pancreatic insufficiency in adults:A shared position statement of the Italian association for the study of the pancreas

This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases associated with exocrine pancreatic insufficiency(EPI)which are of common interest to internists/gastroenterologists,oncologists and surgeons,fully aware that EPI may also occur together with many other diseases,but less frequently.A preliminary manuscript based on an extended literature search(Medline/PubMed,Cochrane Library and Google Scholar)of published reports was prepared,and key recommendations were proposed.The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012.Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached.The final draft of the manuscript was then sent to the AISP Council for approval and/or modification.All concerned parties approved the final version of the manuscript in June 2013.

Diagnosis and treatment of pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis.Normal digestion requires adequate stimulation of pancreatic secretion,sufficient production of digestive enzymes by pancreatic acinar cells,a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food.Failure in any of these steps may result in pancreatic exocrine insufficiency,which leads to steatorrhea,weight loss and malnutrition-related complications,such as osteoporosis.Methods evaluating digestion,such as fecal fat quantification and the13C-mixed triglycerides test,are the most accurate tests for pancreatic exocrine insufficiency,but the probability of the diagnosis can also be estimated based on symptoms,signs of malnutrition in blood tests,fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging.Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption,dietary consultation,enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment.Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicro-spheres during meals.The dose should be in proportion to the fat content of the meal,usually 40-50000 lipase units per main meal,and half the dose is required for a snack.In cases that do not respond to initial treatment,the doses can be doubled,and proton inhibitors can be added to the treatment.This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency.

Quantification of pancreatic exocrine function of chronic pancreatitis with secretin-enhanced MRCP

AIM:To obtain reference values for pancreatic flow output rate(PFR)and peak time(PT)in healthy volunteers and chronic pancreatitis(CP);to correlate quantification of secretin enhanced magnetic resonance cholangiopancreatography(SMRCP)of pancreatic fluid output following secretin with fecal elastase-1(FE-1)tests.METHODS:The present study includes 53 subjects comprised of 17 healthy individuals and 36 patients with CP from April 2011 to January 2013.The 36 patients with CP were divided into three groups of mild CP(n=14),moderate CP(n=19)and advanced CP(n=3)by M-ANNHEIM classification for CP..Fifty-three cases underwent FE-1 test and magnetic resonance imaging using 3.0 T-device(Signa EXCITE,GE Healthcare).Coronal T2-weighted single-shot turbo spin-echo,spiratory triggered,covering the papillae,duodenum and small bowel.MRCP was performed with a heavily T2-weighted fat-suppressed long TE HASTE sequence (thick slab 2D MRCP sequence),repeated every 2 min up to 11 min after 0.1 mL/kg secretin injection(Secrelux,Sanochemia,Germany).FE-1 test used sandwich enzyme-linked immunosorbent assay(ELISA)test(ScheBo.Tech,Germany).RESULTS:A good linear correlation showed between the calculated volume and the actual volume by Phantom experiments.Fifty-three paired Quantification of secretin enhanced magnetic resonance cholangiopancreatography(MRCPQ)and FE-1 data sets were analyzed.The mean FE-1 of 53 cases was 525.41±94.44μg/g for 17 healthy volunteers,464.95±136.13μg/g for mild CP,301.55±181.55μg/g for moderate CP,229.30±146.60μg/g for advanced CP.Also,there was statistically significant difference in FE-1(P=0.0001)between health and CP.The mean values of PFR and PT were 8.18±1.11 mL/min,5.76±1.71 min for normal;7.27±2.04 mL/min,7.71±2.55 min for mild CP;4.98±2.57 mL/min,9.10±3.00 min for moderate CP;4.13±1.83 mL/min,12.33±1.55 min for advanced CP.Further,statistically significant difference in PFR(P=0.0001)and PT(P=0.0001)was observed between health and CP.Besides,there was correlation(r=0.79)and consistency(K=0.6)between MRCPQ and ELISA Test.It was related between M-ANNHEIM classification and PFR(r=0.55),FE-1(r=0.57).CONCLUSION:SMRCP can provide a safe,non-invasive and efficient method to evaluate the exocrine function of the pancreas.

Which factors determine exocrine pancreatic dysfunction in diabetes mellitus?

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes- EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings.

Experimental study on operative methods of pancreaticojejunostomy with reference to anastomotic patency and postoperative pancreatic exocrine function

AIM:To assess the patency of pancreaticoenterostomy and pancreatic exocrine function after three surgical methods. METHODS: A pig model of pancreatic ductal dilation was made by ligating the main pancreatic duct. After 4 wk ligation, a total of 36 piglets were divided randomly into four groups. The piglets in the control group underwent laparotomy only; the others were treated by three anastomoses: (1) end-to-end pancreaticojejunostomy invagination (EEPJ); (2) end-to-side duct-to- mucosa sutured anastomosis (ESPJ); or (3) binding pancreaticojejunostomy (BPJ). Anastomotic patency was assessed after 8 wk by body weight gain, intrapancreatic ductal pressure, pancreatic exocrine function secretin test, pancreatography, and macroscopic and histologic features of the anastomotic site. RESULTS: The EEPJ group had significantly slower weight gain than the ESPJ and BPJ groups on postoperative weeks 6 and 8 (P < 0.05). The animals in both the ESPJ and BPJ groups had a similar body weight gain.Intrapancreatic ductal pressure was similar in ESPJ and BPJ. However, pressure in EEPJ was significantly higher than that in ESPJ and BPJ (P < 0.05). All three functional parameters, the secretory volume, the flow rate of pancreatic juice, and bicarbonate concentration, were significantly higher in ESPJ and BPJ as compared to EEPJ (P < 0.05). However, the three parameters were similar in ESPJ and BPJ. Pancreatography performed after EEPJ revealed dilation and meandering of the main pancreatic duct, and the anastomotic site exhibited a variable degree of occlusion, and even blockage. Pancreatography of ESPJ and BPJ, however, showed normal ductal patency. Histopathology showed that the intestinal mucosa had fused with that of the pancreatic duct, with a gradual and continuous change from one to the other. For EEPJ, the portion of the pancreatic stump protruding into the jejunal lumen was largely replaced by cicatricial fibrous tissue. CONCLUSION: A mucosa-to-mucosa pancreatico- jejunostomy is the best choice for anastomotic patency when compared with EEPJ. BPJ can effectively maintain anastomotic patency and preserve pancreatic exocrine function as well as ESPJ.

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 3 c(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.

Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).

Relationship between the exocrine and endocrine pancreas after acute pancreatitis

AIM: To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.

Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency

The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.

Challenges in the management of pancreatic exocrine insufficiency

Pancreatic exocrine insufficiency(PEI) occurs when the insufficient secretion or function of pancreatic enzymes leads to maldigestion, most commonly as a result of chronic pancreatitis and pancreatic cancer. The condition is associated with significant morbidity and reductions in quality of life, even in milder forms. The challenges in approaching this condition include the non-specific presentation of mild to moderate PEI, and the lack of a convenient, accurate diagnostic test in this cohort. Classical symptoms appear late in the disease, and the diagnosis should be considered before steatorrhoea develops. Direct pancreatic function tests are the reference standard for diagnosis, but are invasive and not widely available. The faecal elastase-1(FE-1) stool test is widely available and has been shown to be as effective as the 13 C-mixed triglyceride breath test in more advanced disease. We recommend a pragmatic diagnostic approach that combines clinical history, assessment of nutritional status and measurement of FE-1. The critical first step is to consider the diagnosis. Once the diagnosis is confirmed, pancreatic enzyme replacement therapy should be initiated. The variety of enzyme preparations and recommended dosing regimens can present a challenge when selecting an adequate initial dose. Non-response should be actively sought and addressed in a systematic manner. This article discusses these challenges, and presents a practical approach to the diagnosis and management of PEI.

Exocrine pancreatic function during the early recovery phase of acute pancreatitis

BACKGROUND:Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis,but the data are scarce and conflicting.This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding. METHODS:Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their first episode of the disease.They were 75 patients including 60(80.0%)patients with mild acute pancreatitis and 15(20.0%)patients with severe acute pancreatitis. Etiologically 61 patients(81.3%)had biliary disease,1(1.3%) had alcoholic disease and 3(4.0%)had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients(13.3%).The mean(±SD)refeeding time after the attack of acute panereatitis was 11.2±10.2 days. RESULTS:Pathological values of FE-1 were found in 9 of the 75 patients(12.0%):7(9.3%)patients with mild pancreatitis and 2(2.7%)patients with severe pancreatitis(P=1.000). The frequency of the pathological values of fecal elastase-1 was significantly different from that of various etiologies of the disease(P=0.030).It was significantly lower in patients with biliary pancreatitis(9.8%;P=0.035)than in one patient with alcoholic pancreatitis(P=0.126),one patient with hypertriglyceridemia-induced pancreatitis(33.3%; P=0.708),and one patient with idiopathic pancreatitis (10.0%;P=0.227).Pathological fecal elastase-1 was not significantly related to sex,age or day of refeeding.CONCLUSION:Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.

Pancreatic exocrine insufficiency after pancreaticoduodenectomy: Current evidence and management

Pancreaticoduodenectomy(PD)is the commonest procedure performed for pancreatic cancer.Pancreatic exocrine insufficiency(PEI)may be caused or exacerbated by surgery and remains underdiagnosed and undertreated.The aim of this review was to ascertain the incidence of PEI,its consequences and management in the setting of PD for indications other than chronic pancreatitis.A literature search of databases(MEDLINE,EMBASE,Cochrane and Scopus)was carried out with the MeSH terms“pancreatic exocrine insufficiency”and“Pancreaticoduodenectomy”.Studies that analysed PEI and its complications in the setting of PD for malignant and benign disease were included.Studies reporting PEI in the setting of PD for chronic pancreatitis,conference abstracts and reviews were excluded.The incidence of PEI approached 100%following PD in some series.The pre-operative incidence varied depending on the characteristics of the patient cohort and it was higher(46%-93%)in series where pancreatic cancer was the predominant indication for surgery.Variability was also recorded with regards to the method used for the diagnosis and evaluation of pancreatic function and malabsorption.Pancreatic enzyme replacement therapy is the mainstay of the management.PEI is common and remains undertreated after PD.Future studies are required for the identification of a welltolerated,reliable and reproducible diagnostic test in this setting.

Pathological evaluation of pancreatic exocrine glands in experimental fluorosis

Objective:To monitor the pathological alterations in pancreas of rat during experimental fluorosis. Methods:Sixty Sprague Dawley albino rats of both sexes were divided into 12 experimental groups and one control group.The rats of control group were administered subcutaneously double distilled water 1 mL/kg bw daily.The experimental groups were injected with 30,45,and 75 mg NaF/kg bw/day.The experimental period was divided into 4 phases at interval of 15,22,30,and 36 days.Animals were sacrificed from each group at the end of 16,23,31,and 37 days.Results: The following changes were observed in this study:(1) Pathological examination of pancreas after 15 days of fluoride treatment revealed:hypertrophy of acini,leucocytes infilteration and pycnouc nuclei due to necrosis of acini in group 1;uremic alterations,invulsion and infoldings of reticular layer of islets of Langerhans in group 2;and a decrease in number of acini and interlobular connective tissues resulted in an increase in intercellular spaces in pancreas of rats in group 3.(2)Hyalinization and hypertrophy in the lobules of acini and hyperplasia and hypertrophy in intercalated duct with mucinous secretion in pancreas of rat of group 4;squamous metaplasia of pancreatic duct,adenoma of pancreas,hemorrhagic necrosis in group 5;and hyperplasia of acini and reduction in number of pancreatic islets in group 6.(3) Disorganization and atrophy of pancreatic lobules and presence of vacuoles in a group of six were visible in pancreas of rats in group 7;acute pancreatic and lamellated inflammatory cells in test rats of group 8;and islet adenoma and decrease in number of islets cells,and exudation in acini were noticed in experimental rats of group 9.(4) In the last phase of experimentation,atrophic alterations in pancreatic acini,invulsions,and necrosis was prominent in group 10,deep inflammation and proliferation of connective tissue of pancreas in experimental group 11,and periodical fibrosis, hyperplasia of acini,degenerative changes in pancreas of rats in group 12.Conclusion:The histopathological examination of pancreas of fluoridated rats exhibited structural alterations in the exocrine glands.The acini revealed hypertrophy,pyknotic nucleus,necrosis and uremic alterations.Acini became lobulated and reveal increased pigmentation.

Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine insufficiency

OBJECTIVE: To examine the feasibility and significance of 13C-Hiolein breath test in evaluating chronicpancreatitis-related exocrine insufficiency and efficacy of enzyme treatment.METHODS: The 13C-Hiolein breath test was used in 8 healthy volunteers （group 1）, 8 chronicpancreatitis （CP） patients without steatorrhea （group 2）, and 8 CP patients with steatorrhea （group 3）.To evaluate the function of pancreatic exocrine, 13CO2 was determined following 13C-Hiolein diet. The13C-Hiolein test was repeated in group 3 after enzyme supplement therapy.RESULTS: Administration of 13C-Hiolein diet resulted in significantly higher cumulative percent dose of13C recovery per 6 h （cPDR/6 h） and maximal PDR (PDRpeak) in the healthy controls （group 1） thanthe CP patients with steatorrhea （group 3） （11.22%±1.22% and 6.11%±0.59% vs. 2.87%±0.73%and 1.53%±0.36%, respectively, both P【0.01）. In the CP patients with steatorrhea （group 3）, arepeated test after enzyme supplementation therapy showed a significant elevation of both cPDR/6 h andPDRpeak （9.03%±0.84% and 2.33%±0.47%, both P【0.01 compared with those before enzymetreatment）, but cPDR/6 h remained significantly lower than that in the healthy volunteers （group 1, P【0.05）. Both cPDR and PDRpeak in the CP patients without steatorrhea （group 2） were similar to those inthe healthy controls （group 1, both P】0.05）.CONCLUSION: The results of 13C-Hiolein breath test well reflect fat metabolism status in CP patients,and the test can be used to monitor the efficacy of pancreatic enzymes therapy.

Study of nennatolysosomes in mouse hepatocytes and pancreatic exocrine acinar cells

Acid phosphatase(ACPase)-positive nematolysosomes in mouse hepatocytes and thepancreatic exocrine acinar cells were studied with ultracytoehemical method.The nematolyso-somes were 2～8μm in length,0.1～0.3μm in diameter.Some branched and some did notbranch,and most of them winded through the organelles.

Staging chronic pancreatitis with exocrine function tests: Are we better?

Chronic pancreatitis(CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1(EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.

Considerations on pancreatic exocrine function after pancreaticoduodenectomy

The pancreaticoduodenectomy(PD) procedure may lead to pancreatic exocrine and endocrine insufficiency.There are several types of reconstruction for this kind of operation.Pancreaticogastrostomy(PG) was introduced to reduce the rate of postoperative pancreatic fistula.Although some randomized control trials have shown no differences regarding pancreatic leakage between PG and pancreaticojejunostomy(PJ),recently some reports reveal benefits from the PG over the PJ.Some surgeons concern about the performing of the PG and inactivation of pancreatic enzymes being in contact with the gastric juice,and the detrimental results over the exocrine pancreatic function.The pancreatic exocrine function can be measured with direct and indirect tests.Direct tests have the highest sensitivity and specificity for detection of exocrine insufficiency but require tube placement.Among the tubeless indirect tests,the van de Kamer stool fat analysis remains the standard to diagnose fat malabsorption.The patient compliance and time consuming makes it not so suitable for its clinical use.Fecal immunoreactive elastase test is employed for screening of exocrine insufficiency,is not cumbersome,and has been used to study pancreatic function after resection.We analyze the FE1 levels in our patients after the PD with two types of reconstruction,PG and PJ,and we discuss some considerations about the pancreaticointestinal drainage method after pancreaticoduodenectomy.

Yield of testing for micronutrient deficiencies associated with pancreatic exocrine insufficiency in a clinical setting: An observational study

BACKGROUND Pancreatic exocrine insufficiency(PEI)can be difficult to diagnose and causes maldigestion symptoms and malabsorption.There has been a number of studies that have identified PEI associated micronutrient deficiencies(PEI-MD),however there is variation in both the frequency and type of PEI-MD reported,with the majority of studies including patients with PEI due to chronic pancreatitis(CP)or CP without PEI.There is a paucity of information regarding the prevalence of PEIMD in patients with PEI without CP and the yield of testing for PEI-MD in a clinical setting in patients with suspected benign pancreatic diseases.AIM To prospectively assess the yield and type of PEI–MD in patients with and without PEI secondary to benign pancreatic disease.METHODS Patients investigated for maldigestion symptoms with Faecal Elastase-1(FEL-1)and suspected or proven benign pancreatic disease were prospectively identified.At the time of FEL-1 testing,serum samples were taken for micronutrients identified by previous studies as PEI-MD:prealbumin,retinol binding protein,copper,zinc,selenium,magnesium and later in the study lipid adjusted vitamin E.FEL-1 was recorded,with a result<200μg/g considered diagnostic of PEI.Patients underwent computed tomography(CT)imaging when there was a clinical suspicion of CP,a new diagnosis of PEI recurrent,pancreatic type pain(epigastric abdominal pain radiating to back with or without previous acute pancreatitis attacks)or weight loss.RESULTS After exclusions,112 patients were recruited that underwent testing for FEL-1 and PEI-MD.PEI was identified in 41/112(36.6%)patients and a pancreatic CT was performed in 82 patients.Overall a PEI-MD was identified in 21/112(18.8%)patients.The yield of PEI-MD was 17/41(41.5%)if PEI was present which was significantly higher than those without 4/71(5.6%)(P=0.0001).The yield of PEI–MD was significantly higher when PEI and CP were seen together 13/22(59.1%)compared to CP without PEI and PEI without CP(P<0.03).Individual micronutrient assessment showed a more frequent occurrence of prealbumin 8/41(19.5%),selenium 6/41(14.6%)and magnesium 5/41(12.2%)deficiency when PEI was present(<0.02).The accuracy of using the significant micronutrients identified in our cohort as a predictor of PEI showed a positive predictive value of 80%-85.7%[95%confidence interval(CI):38%-100%]and a low sensitivity of 9.8%-19.5%[95%CI:3.3%-34.9%].CONCLUSION Testing for PEI-MD in patients with suspected pancreatic disease has a high yield,specifically when PEI and CP are found together.PEI-MD testing should include selenium,magnesium and prealbumin.

Associations with pancreatic exocrine insufficiency:An United Kingdom single-centre study

BACKGROUND Pancreatic exocrine insufficiency(PEI)is said to be associated with numerous conditions both within and outside the gastrointestinal(GI)system.The majority of research has been concerned with conditions that reduce the volume of functioning pancreatic tissue or prevent adequate drainage to the small bowel,such as chronic pancreatitis,cystic fibrosis,pancreatic cancer and pancreatic resection.However,the evidence base supporting an association with extrapancreatic conditions,such as coeliac disease,diabetes mellitus and congestive cardiac failure,is heterogeneous.AIM To strengthen the evidence base by studying all previously reported associations with PEI in a large cohort of outpatients.METHODS A single-centre retrospective study was performed.General gastroenterology outpatients tested for PEI with faecal elastase-1(FE1)were identified and information retrieved from the electronic patient record.PEI was defined as FE1<200μg/g.Patients already taking pancreatic enzyme replacement therapy were excluded.Multiple imputation was used to handle missing data.Univariable logistic regression was used to study which presenting symptoms predicted PEI.Multivariable logistic regression was used to explore the relationship between all previously reported associations and PEI.RESULTS Of 1027 patients were included.182 patients(17.7%)were diagnosed with PEI.Steatorrhoea[odds ratios(OR):2.51,95%confidence intervals(CI):1.58-3.98]and weight loss(OR:1.49,95%CI:1.08-2.06)were the only presenting symptoms that predicted PEI.Chronic pancreatitis(OR:7.98,95%CI:3.95-16.15),pancreatic cancer(OR:6.58,95%CI:1.67-25.98),upper GI surgery(OR:2.62,95%CI:1.32-5.19),type 2 diabetes(OR:1.84,95%CI:1.18-2.87),proton pump inhibitor therapy(OR:1.87,95%CI:1.25-2.80)and Asian ethnicity(OR:2.11,95%CI:1.30-3.42)were significantly associated with PEI in the multivariable analysis.None of the other historically reported associations with PEI were significant after adjustment for the other variables included in our multivariable analysis.CONCLUSION PEI is common in patients with chronic pancreatitis,pancreatic cancer,upper GI surgery and type 2 diabetes.Proton pump inhibitor therapy may also be associated with PEI or a false positive FE1.

Impacts of pancreatic exocrine insufficiency on gut microbiota

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal p H as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.