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The Oncologist Dec 2023Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk...
BACKGROUND
Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI.
PATIENTS AND METHODS
A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start.
RESULTS
Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01).
CONCLUSION
ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
Topics: Humans; Pancrelipase; Immune Checkpoint Inhibitors; Steatorrhea; Retrospective Studies; Case-Control Studies; Acute Disease; Pancreatitis; Exocrine Pancreatic Insufficiency; Hyperglycemia; Weight Loss
PubMed: 37285223
DOI: 10.1093/oncolo/oyad150 -
PloS One 2023The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess...
INTRODUCTION
The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption.
METHODS
We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase.
RESULTS
The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase.
CONCLUSION
The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.
Topics: Humans; Swine; Animals; Pancrelipase; Lipolysis; Intestinal Absorption; Lipase; Exocrine Pancreatic Insufficiency; Fatty Acids, Omega-3
PubMed: 37155649
DOI: 10.1371/journal.pone.0284651 -
PancreasThis retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated...
A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States.
OBJECTIVES
This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D).
METHODS
Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline.
RESULTS
A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959).
CONCLUSIONS
Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.
Topics: Humans; United States; Pancrelipase; Gastrointestinal Agents; Diabetes Mellitus, Type 2; Retrospective Studies; Exocrine Pancreatic Insufficiency; Pancreatitis, Chronic; Abdominal Pain
PubMed: 37099771
DOI: 10.1097/MPA.0000000000002203 -
Internal Medicine (Tokyo, Japan) Sep 2023We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and...
We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and 72 years old, with no history of abdominal surgery presented to our hospital with severe anorexia and nausea persisting for one week. Examinations revealed progressive, marked FL disease with hepatomegaly and PEI, for which pancreatic enzyme replacement therapy was effective. Commonly known causes of PEI include chronic pancreatitis, abdominal surgery (e.g. pancreaticoduodenectomy), pancreatic cancer, and obstruction of the pancreatic duct, none of which were present in either of these two cases.
Topics: Humans; Female; Middle Aged; Aged; Exocrine Pancreatic Insufficiency; Pancreas; Non-alcoholic Fatty Liver Disease; Pancreatitis, Chronic; Pancreatic Neoplasms; Enzyme Replacement Therapy
PubMed: 36754408
DOI: 10.2169/internalmedicine.0775-22 -
Frontiers in Medicine 2022Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to...
BACKGROUND
Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD.
METHODS
Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015.
RESULTS
Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (-0.03 versus -0.26; = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, = 0.004), abdominal pain (2.92 versus 2.42, = 0.009), and diarrhea sub-scores (3.44 versus 2.92, = 0.037) during the run-in period with omeprazole.
CONCLUSION
In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.
PubMed: 36687454
DOI: 10.3389/fmed.2022.1001879 -
Molecules (Basel, Switzerland) Dec 2022Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous...
(L.) DC. and L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies.
Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous (L.) DC. and L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The -hexane and dichloromethane fractions from , as well as the -hexane fraction from , were effective in protecting the protein from heat-induced denaturation (IC = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 μg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC values equal to 2.23 ± 0.02 mg/mL (for sample), and 2.05 ± 0.02 mg/mL (. Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.
Topics: Antioxidants; Methylene Chloride; Phytochemicals; Plant Extracts; Tropaeolum; Valerianaceae; Pancrelipase; Protein Denaturation; Anti-Obesity Agents
PubMed: 36615228
DOI: 10.3390/molecules28010032 -
International Journal of Pharmaceutics Jan 2023The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as...
In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model.
The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.
Topics: Humans; Pancrelipase; Capsules; Caffeine; Gastrointestinal Agents; Exocrine Pancreatic Insufficiency; Duodenum; Gelatin
PubMed: 36442722
DOI: 10.1016/j.ijpharm.2022.122441 -
Frontiers in Physiology 2022Pancreatin secretion is dramatically decreased over time after weaning, thus affecting the utilization of nutrients in piglets. Therefore, exogenous pancreatin is...
Pancreatin secretion is dramatically decreased over time after weaning, thus affecting the utilization of nutrients in piglets. Therefore, exogenous pancreatin is expected to alleviate this situation. This experiment was conducted to investigate the effects of exogenous pancreatin on the growth performance, nutrient digestion and absorption, and intestinal microbiota of piglets. One hundred eighty piglets (Duroc × Landrace × Yorkshire, 40 days) were randomly allotted to three treatments (basal diets supplemented with 0, 250, or 500 mg/kg pancreatin) with three replicate pens per treatment and 20 piglets per pen. Compared with the control diet, dietary 500 mg/kg pancreatin significantly increased ( < 0.05) the average daily gain (ADG) and the apparent digestibility of crude protein and crude fat of piglets. Regarding endogenous enzymes, pancrelipase activity in the pancreas, duodenal mucosa, and small intestinal digesta as well as trypsin activity in the jejunal digesta were increased in piglets fed a diet supplemented with 500 mg/kg pancreatin ( < 0.05). Moreover, amylopsin activity was significantly strengthened in the pancreas, duodenal mucosa, and digesta in piglets fed a diet with 500 mg/kg pancreatin ( < 0.05). The mRNA expression of nutrient transporters, including oligopeptide transporter-1 (PepT1), excitatory amino acid transporter-1 (EAAC1), cationic amino acid transporter-1 (CAT1), sodium glucose cotransporter-1 (SGLT1), glucose transporter-2 (GLUT2), and fatty acid transporter-4 (FATP4), in the jejunum significantly increased after dietary supplementation with 500 mg/kg pancreatin ( < 0.05). An increased villus height-to-crypt depth ratio of the ileum was observed in the 500 mg/kg pancreatin-treated group ( < 0.05). The composition of the colonic microbiota modulated by the addition of 500 mg/kg pancreatin was characterized by an increased relative abundance of ( < 0.05), and the predicted functions revealed that 500 mg/kg pancreatin supplementation enhanced the functional abundance of genetic information processing in colonic microorganisms and environmental information processing. Our findings suggested that the addition of 500 mg/kg pancreatin improved the growth performance of piglets, improved intestinal structure, and modulated the colon microbiota, thereby increasing nutrient digestibility.
PubMed: 36017338
DOI: 10.3389/fphys.2022.906522 -
The American Journal of Case Reports Aug 2022BACKGROUND Major findings of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome is a rare...
BACKGROUND Major findings of myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy (MIRAGE) syndrome is a rare genetic condition caused by a gain-of-function mutation in the SAMD9 gene. It acts as a growth repressor expressed in the endothelial cells. Pathogenic variants in the SAMD9 gene lead to profound growth-restricting activity intrinsic to the protein, which further reduces cellular proliferation and instigates this growth-limiting condition. Gastrointestinal features include chronic diarrhea, severe diaper rash, and colonic dilatation. Until now, there has been no description of exocrine pancreatic insufficiency as a possible cause of enteropathy in MIRAGE syndrome. CASE REPORT We report a case of MIRAGE syndrome affecting multiple systems in an infant who had severe enteropathy which responded well to porcine-derived pancreatic enzyme supplements despite normal pancreatic fecal elastase level. The infant is being followed up by multidisciplinary teams in our outpatient department. CONCLUSIONS Porcine-derived pancreatic enzyme is beneficial in enteropathy due to MIRAGE syndrome and is worth considering.
Topics: Adrenal Insufficiency; Animals; Endothelial Cells; Feces; Humans; Intracellular Signaling Peptides and Proteins; Pancreatic Elastase; Pancrelipase; Swine
PubMed: 35994417
DOI: 10.12659/AJCR.937057 -
Transplant International : Official... 2022
Topics: Abdomen; Humans; Pancreas; Pancrelipase; Reperfusion; Research Design
PubMed: 35497885
DOI: 10.3389/ti.2022.10038