Pancreatin Microspheres Research Articles

PWE-217 Pancreatic enzyme replacement therapy in chronic pancreatitis and pancreatic cancer – are we getting it right?: Abstract PWE-217 Table 1

<h3>Introduction</h3> Pancreatic enzyme insufficiency (PEI) is a well recognised cause of malnutrition in chronic pancreatitis and pancreatic cancer. Pancreatic enzyme replacement therapy (PERT) in the form of enteric coated pancreatin microspheres is recommended in both these groups of patients with symptoms of PEI to prevent weight loss and malnutrition and improve quality of life. Given that the probability of PEI is high in PC (80–90%), PERT is recommended without the use of formal diagnostic tests. The optimal starting dose of PERT is 40–50000 lipase units per main meal. The aim of this study was to evaluate the use of PERT including appropriate dosing in chronic pancreatitis (CP) and pancreatic cancer (PC) and to ascertain if there was a difference in prescribing practice between these groups. <h3>Method</h3> A single centre retrospective analysis of patients diagnosed with CP and PC since 2010 in a large North London district general hospital was performed using local upper gastrointestinal cancer multidisciplinary team records and clinical coding. We identified 149 patients with PC and 110 with CP though 32 patients from the PC group and 4 from CP were excluded from the study due to poor documentation in the records leading to insufficient information surrounding enzyme supplementation and dosages. Information was collected from electronic patient records on the patients’ symptoms, evidence of PERT and the dose prescribed. <h3>Results</h3> Symptoms of pancreatic enzyme insufficiency (abdominal pain, weight loss or steatorrhoea) were recorded in 72/117 (61.5%) of PC patients compared with 75/106 (70.8%) of CP patients. PERT was prescribed in 14/72 (19.5%) patients with PC versus 53/75 (70.7%) with CP. The Table 1shows the enzyme formulation and dosages used in both groups. <h3>Conclusion</h3> In our study we demonstrate that the majority of patients with PEI in CP are prescribed PERT, a stark contrast with a mere 20% in PC. However in both groups, most patients were not prescribed optimal doses of PERT though again, this figure was better in the CP group (14/53 or 26.4%) compared to the PC group (2/14 or 14.3%). This study highlights the missed opportunity to reduce symptoms and improve quality of life in CP and PC patients with a simple intervention. Increased awareness of the availability and appropriate dosing of PERT in conditions resulting in PEI is required. <h3>Disclosure of interest</h3> None Declared.

PWE-206 Pancreatic enzyme replacement therapy in pancreatic cancer- a role for the dietician

<h3>Introduction</h3> Pancreatic enzyme insufficiency (PEI) is a well-recognised cause of malnutrition in pancreatic cancer (PC). Pancreatic enzyme replacement therapy (PERT) in the form of enteric coated pancreatin microspheres is recommended in these patients with symptoms of PEI to prevent weight loss and malnutrition and improve quality of life. Given that the probability of PEI is high in PC (80–90%), PERT is recommended without the use of formal diagnostic tests. The optimal starting dose of PERT is 40–50000 lipase units per main meal. The aim of this study was to evaluate the use of PERT in PC patients, to ascertain if these patients were given the appropriate PERT dose and to determine whether dietician review was associated with more and better PERT use. <h3>Method</h3> A single centre retrospective analysis of patients diagnosed with PC in 2014 in a tertiary hospital specialising in the treatment of patients with hepato-pancreato-biliary (HPB) diseases. We identified 80 patients with PC. Information was collected from electronic patient records regarding the patients’ symptoms of PEI, evidence of PERT use, the dose prescribed and whether the patients were seen by a dietician. Fisher’s exact test was used to calculate whether (a) dietician review was associated with higher rate of PERT use and (b) dietician review was associated with higher rate of appropriate PERT dosing. <h3>Results</h3> Symptoms of PEI (abdominal pain, weight loss or steatorrhoea) were recorded in 57.5% of PC patients (46/80). PERT was prescribed in the minority of patients [41.3% (33/80)] with appropriate dosing given to the majority of patients when prescribed [66.7% (22/33)]. A dietician was involved in the care of less than half [43.8% (35/80)] of patients. However, referral to a dietician was strongly associated with PERT use with 60% (21/35) of patients being referred given PERT compared to only 26.7% (12/45) of patients who were not (p = 0.003). Dietician involvement was also associated with more appropriate PERT use with 85% (17/20) of patients given appropriate doses compared to 45.5% (5/11); (p = 0.038) when started without dietician review. <h3>Conclusion</h3> In this audit, we demonstrated that while symptoms of PEI were present in the majority of patients, the minority of patients were given PERT. The minority of patients were seen by a dietician but when assessed were more likely to receive PERT at the appropriate dosage, which may account for the low rate of PERT in the cohort as a whole. This study highlights the lack of awareness of the problem of PEI in PC patients amongst managing physicians. This could lead to a missed opportunity to reduce symptoms and improve quality of life in patients with a simple intervention. A referral to the dietician was shown to benefit these patients. <h3>Disclosure of interest</h3> None Declared.

Su1888 Pancreatic Enzyme Replacement Therapy in Chronic Pancreatitis and Pancreatic Cancer- Are We Getting It Right?

Introduction Pancreatic enzyme insufficiency (PEI) is a well recognised cause of malnutrition in chronic pancreatitis and pancreatic cancer. Pancreatic enzyme replacement therapy (PERT) in the form of enteric coated pancreatin microspheres is recommended in both these groups of patients with symptoms of PEI to prevent weight loss and malnutrition and improve quality of life. Given that the probability of PEI is high in PC (80–90%), PERT is recommended without the use of formal diagnostic tests. The optimal starting dose of PERT is 40–50000 lipase units per main meal. The aim of this study was to evaluate the use of PERT including appropriate dosing in chronic pancreatitis (CP) and pancreatic cancer (PC) and to ascertain if there was a difference in prescribing practice between these groups. Method A single centre retrospective analysis of patients diagnosed with CP and PC since 2010 in a large North London district general hospital was performed using local upper gastrointestinal cancer multidisciplinary team records and clinical coding. We identified 149 patients with PC and 110 with CP though 32 patients from the PC group and 4 from CP were excluded from the study due to poor documentation in the records leading to insufficient information surrounding enzyme supplementation and dosages. Information was collected from electronic patient records on the patients’ symptoms, evidence of PERT and the dose prescribed. Results Symptoms of pancreatic enzyme insufficiency (abdominal pain, weight loss or steatorrhoea) were recorded in 72/117 (61.5%) of PC patients compared with 75/106 (70.8%) of CP patients. PERT was prescribed in 14/72 (19.5%) patients with PC versus 53/75 (70.7%) with CP. The Table 1shows the enzyme formulation and dosages used in both groups. Conclusion In our study we demonstrate that the majority of patients with PEI in CP are prescribed PERT, a stark contrast with a mere 20% in PC. However in both groups, most patients were not prescribed optimal doses of PERT though again, this figure was better in the CP group (14/53 or 26.4%) compared to the PC group (2/14 or 14.3%). This study highlights the missed opportunity to reduce symptoms and improve quality of life in CP and PC patients with a simple intervention. Increased awareness of the availability and appropriate dosing of PERT in conditions resulting in PEI is required. Disclosure of interest None Declared.

Preparation and In Vivo Efficacy Study of Pancreatin Microparticles as an Enzyme Replacement Therapy for Pancreatitis

Deficiency manifestations because of pancreatic insufficiency are treated by oral administration of pancreatic enzymes. As pancreatic enzymes get denatured in hostile acidic conditions of stomach, this investigation was aimed at formulating multiparticulates of pancreatic enzymes coated with enteric polymers such as eudragit L100, cellulose acetate phthalate, and hydroxyl propyl methyl cellulose phthalate, which will circumvent gastric inactivation in addition to providing optimal mixing with chyme. Pancreatin microspheres were prepared by emulsification phase separation by nonsolvent addition and solvent evaporation techniques. This process was optimized for core : coat ratio (1:0.5), stirrer speed (350–400 rpm), dispersant concentration, and amount of nonsolvent added to precipitate microspheres. Optimized formulations were assessed for % enzyme content, acid resistance, flow properties, particle size, particle morphology (by standard electron microscopy), compatibility of drug and polymer in formulation (by differential scanning calorimetry), in vitro release kinetics, and in vivo efficacy study in pancreatitis-induced animal model. Capsules containing enteric-coated pancreatin microspheres offered adequate protection to enzymes and prevented their denaturation in acidic environment. Developed multiparticulate dosage forms promoted effective mixing, instant and complete in vitro release compared with marketed tablets.

Pancreatic Enzyme Supplementation Therapy.

Effective treatment of malabsorption due to severe pancreatic exocrine insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. To achieve this, modern therapeutic concepts recommend administration of 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres. In case of treatment failure, dosage should be increased two to three times. If this still is not successful, compliance may be checked by measurement of fecal chymotrypsin, although this is not a standardized procedure. In the compliant patient, diagnosis of pancreatic exocrine insufficiency needs to be reviewed, particularly cases of celiac disease, (concomitant) bacterial overgrowth, and blind loop syndrome, as well as giardiasis, which need to be excluded or otherwise be treated specifically. Finally, additional acid suppression with application of unprotected pancreatin and/or reduced fat intake may help to control malabsorption. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy. On the one hand, this leads to loss of energy that may only partly be compensated for by increased nutrient intake. On the other hand, increased nutrient exposition of distal intestinal sites may release excessive amounts of mostly inhibitory distal intestinal neurohumoral mediators, and thereby disturb gastrointestinal secretory and motor functions. Consequently, future developments are needed for optimizing treatment.

Lipase supplementation therapy: standards, alternatives, and perspectives.

Treatment of steatorrhea by lipase supplementation therapy has become more successful in the last decade due to better understanding of the physiology and pathophysiology of the digestive process. Porcine lipase has been the therapeutic standard for several decades and will continue to be the treatment of choice in pancreatic exocrine insufficiency. Modern therapeutic concepts recommend administration of 25,000-40,000 units of porcine lipase per meal using pH-sensitive pancreatin microspheres. In case of treatment failure, the dose should be increased, compliance should be checked, and other reasons for malabsorption should be excluded. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed for optimizing treatment. In this article, pathophysiologic characteristics of pancreatic exocrine insufficiency, prerequisites for use of alternative lipase sources as well as currently available lipases of nonporcine origin, and new developments are discussed. Current literature suggests that bovine lipase products present a theoretical alternative but play no major role in the western world. Fungal lipase has inferior properties compared with conventional products. Bacterial lipase products show promising potential and offer future therapeutic alternatives. Moreover, human pancreatic lipase gene transfer and application of bioengineered human gastric lipase appear on the horizon.

Pancreatic enzyme replacement therapy.

Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

What to Do when a Patient with Exocrine Pancreatic Insufficiency Does Not Respond to Pancreatic Enzyme Substitution

In the majority of patients, pancreatin microsphere preparations containing 25,000–40,000 FIP units of lipase will lead to a clinical improvement and reduction of steatorrhea in patients with exocrine pancreatic insufficiency. In patients failing to respond, the following stepwise procedure is recommended: increasing enzyme dosage; checking the patient’s compliance; reevaluating the diagnosis; and as a last resort to decrease fat intake or adding H₂-blockers or proton pump inhibitors. Although this stepwise procedure is time-consuming, it is necessary to prevent in patients not responding to pancreatic enzyme substitution the development of late complications of exocrine pancreatic insufficiency.

Colonic wall thickening is related to age and not dose of high strength pancreatin microspheres in children with cystic fibrosis.

Colonic fibrosis causing stricture is a recently described complication in cystic fibrosis (CF). Studies have suggested that ultrasound evidence of bowel thickening predicts this complication and that it is prevalent among children receiving large doses of high-strength pancreatin preparations. We performed ultrasound studies on our patients to look for evidence of bowel wall thickening or early stricture. Detailed colonic ultrasounds were carried out in 33 children with CF including 25 who had been receiving high-strength pancreatin (Creon 25,000) continuously for 3 years at the time of study. Median lipase intake was 19 330 U/kg/day (range 0-59 880 U/kg/day) and median protease intake was 387 U/kg/day (range 0-1170 U/kg/day). The combined thickness of mucosa, sub-mucosa and muscle layers was measured in ascending, transverse and descending colon using a 7.5 MHz transducer. Measurements were also made in nine healthy controls. There was no relationship between enzyme dosage and colon thickness but simple regression identified a significant relationship (P < 0.001) between age and maximum colon thickness in all three areas. The colon of CF children was up to 50% thicker than in controls. Thickening of the order described elsewhere did not occur among any of the children studied. The results suggest that the most important factor determining the thickness of the CF colon is age.

Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease.

Severe pancreatic exocrine insufficiency leading to malabsorption of nutrients is one of the most important late features of chronic pancreatitis. In contrast to other key enzymes, pancreatic synthesis and secretion of lipase is impaired more rapidly, its intraluminal survival is shorter due to its higher susceptibility against acidic and proteolytic denaturation, and its luminal digestive action is hardly compensated by nonpancreatic mechanisms. As a consequence, steatorrhea is in general more severe and occurs several years before clinical malabsorption of protein or starch. Apart from the detrimental effects of nutrient deficiency, profound alterations of upper gastrointestinal secretory and motor functions may be an additional and hitherto underestimated consequence of increased nutrient delivery to distal intestinal sites. Effective reduction of nutrient malabsorption in pancreatic insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. Modern enteric-coated pancreatin microsphere preparations attempt to achieve this by optimizing the size of individual microspheres and chemical properties of the coating. However, lipid digestion cannot be completely normalized in most patients by current standard therapy. In the future, acid and protease stable bacterial and fungal lipases with additional pH optima in the acidic milieu or animal or bioengineered human gastric lipase preparations may offer superior therapeutic alternatives. This review first summarizes current knowledge about secretion and luminal fate of pancreatic enzymes and their effects on nutrient digestion in health and chronic pancreatitis. Second, rationale, current standards, options, and future aspects of enzyme replacement therapy are discussed.

Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region

Background—Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea....

Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.

It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.

A double-blind, placebo-controlled randomized trial evaluating the efficacy of enteric-coated pancreatin microsphere therapy in patients with non-resectable malignant tumours of the pancreatic head region

A double-blind, placebo-controlled randomized trial evaluating the efficacy of enteric-coated pancreatin microsphere therapy in patients with non-resectable malignant tumours of the pancreatic head region

Simultaneous assessments of gastric emptying and pharmacodynamics of 2 millimeter enteric coated pancreatin microspheres in patients with chronic pancreatitis: [formula omitted]1, J.J.J. Borm 2, F.J. Hoek 1,3, B. Delzenne 3, A.F. Hofmann 4, J.J.M. de Goeij 5, E.A. van Royen 2, D.J. van Leeuwen 6, G.N.J. Tytgat 1. 1Dept. of Gastroenterology, 2Dept. of Nuclear Medicine and 3Dept. of Clinical Chemistry,

Simultaneous assessments of gastric emptying and pharmacodynamics of 2 millimeter enteric coated pancreatin microspheres in patients with chronic pancreatitis: [formula omitted]1, J.J.J. Borm 2, F.J. Hoek 1,3, B. Delzenne 3, A.F. Hofmann 4, J.J.M. de Goeij 5, E.A. van Royen 2, D.J. van Leeuwen 6, G.N.J. Tytgat 1. 1Dept. of Gastroenterology, 2Dept. of Nuclear Medicine and 3Dept. of Clinical Chemistry,