-
JOP : Journal of the Pancreas Sep 2018Drug-induced exanthems are commonly associated with NSAIDs, antibiotics, and anti-epileptics. Pancrelipase is frequently used for conditions resulting in pancreatic...
INTRODUCTION
Drug-induced exanthems are commonly associated with NSAIDs, antibiotics, and anti-epileptics. Pancrelipase is frequently used for conditions resulting in pancreatic exocrine insufficiency. Published case reports of pancrelipase hypersensitivity focus on the respiratory manifestations.
CASE REPORT
Here we report a case of skin hypersensitivity resulting from pancrelipase use. To further assess this association, we used a Naranjo nomogram, which determines the likelihood that an adverse drug reaction is the result of the drug itself. Our patient had a score of seven, suggesting our patient had a probably adverse drug reaction.
DISCUSSION
As pancrelipase is a commonly prescribed drug, clinicians should be aware of the potential hypersensitivity skin reactions associated with pancrelipase.
PubMed: 30405325
DOI: No ID Found -
Journal of Veterinary Internal Medicine Sep 2018Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be...
Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency.
BACKGROUND
Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be advantageous.
HYPOTHESIS/OBJECTIVES
Enteric coated enzyme supplements are superior to uncoated supplements in dogs with clinical EPI.
ANIMALS
Eleven dogs with naturally occurring EPI that were apparently free from other diseases.
METHODS
Randomized, blinded, controlled cross-over clinical trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a commercially available uncoated product in dogs with clinical EPI. Search of serum canine serum trypsin-like immunoreactivity concentration ≤ 2.5 µg/L in the Gastrointestinal Laboratory database was used to identify dogs with EPI.
RESULTS
There was no difference -4.46% (95% CI: -7.97%--0.96%; P = .15) in the % acid hydrolysis fecal fat (primary outcome) between the enteric coated formulation (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the study. Other variables did not differ between treatments.
CONCLUSIONS AND CLINICAL IMPORTANCE
This study, which had low statistical power, did not detect a difference between formulations.
Topics: Animals; Cross-Over Studies; Dog Diseases; Dogs; Dosage Forms; Exocrine Pancreatic Insufficiency; Pancrelipase; Random Allocation
PubMed: 30221800
DOI: 10.1111/jvim.15235 -
BMC Cancer May 2018Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can... (Comparative Study)
Comparative Study
BACKGROUND
Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer.
METHODS
A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan-Meier and Cox regression; groups were compared using the log-rank test.
RESULTS
Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28-100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19-9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0-211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4-114.6 days) (HR 2.117, 95% CI 1.493-3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55-4.11; P < 0.001).
CONCLUSIONS
In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Malnutrition; Middle Aged; Palliative Care; Pancreas; Pancreatic Neoplasms; Pancrelipase; Retrospective Studies; Survival Analysis; Treatment Outcome; Weight Loss
PubMed: 29728096
DOI: 10.1186/s12885-018-4439-x -
Caco-2 Cell Conditions Enabling Studies of Drug Absorption from Digestible Lipid-Based Formulations.Pharmaceutical Research Feb 2018To identify conditions allowing the use of cell-based models for studies of drug absorption during in vitro lipolysis of lipid-based formulations (LBFs).
PURPOSE
To identify conditions allowing the use of cell-based models for studies of drug absorption during in vitro lipolysis of lipid-based formulations (LBFs).
METHODS
Caco-2 was selected as the cell-based model system. Monolayer integrity was evaluated by measuring mannitol permeability after incubating Caco-2 cells in the presence of components available during lipolysis. Pure excipients and formulations representing the lipid formulation classification system (LFCS) were evaluated before and after digestion. Porcine mucin was evaluated for its capacity to protect the cell monolayer.
RESULTS
Most undigested formulations were compatible with the cells (II-LC, IIIB-LC, and IV) although some needed mucin to protect against damaging effects (II-MC, IIIB-MC, I-LC, and IIIA-LC). The pancreatic extract commonly used in digestion studies was incompatible with the cells but the Caco-2 monolayers could withstand immobilized recombinant lipase. Upon digestion, long chain formulations caused more damage to Caco-2 cells than their undigested counterparts whereas medium chain formulations showed better tolerability after digestion.
CONCLUSIONS
Most LBFs and components thereof (undigested and digested) are compatible with Caco-2 cells. Pancreatic enzyme is not tolerated by the cells but immobilized lipase can be used in combination with the cell monolayer. Mucin is beneficial for critical formulations and digestion products.
Topics: Administration, Oral; Caco-2 Cells; Drug Evaluation, Preclinical; Drug Liberation; Enzymes, Immobilized; Excipients; Fungal Proteins; Gastrointestinal Absorption; Humans; Lipase; Lipids; Lipolysis; Mucins; Pancrelipase; Pharmaceutical Preparations; Recombinant Proteins
PubMed: 29484506
DOI: 10.1007/s11095-017-2327-8 -
Diabetologia Apr 2018Direct in vivo assessment of pancreatic islet-cells for the study of the pathophysiology of diabetes in humans is hampered by anatomical and technological hurdles. To...
Direct in vivo assessment of pancreatic islet-cells for the study of the pathophysiology of diabetes in humans is hampered by anatomical and technological hurdles. To date, most of the information that has been generated is derived from histological studies performed on pancreatic tissue from autopsy, surgery, in vivo biopsy or organ donation. Each approach has its advantages and disadvantages (as summarised in this commentary); however, in this edition of Diabetologia, Kusmartseva et al ( https://doi.org/10.1007/s00125-017-4494-x ) provide further evidence to support the use of organ donor pancreases for the study of human diabetes. They show that length of terminal hospitalisation of organ donors prior to death does not seem to influence the frequency of inflammatory cells infiltrating the pancreas and the replication of beta cells. These findings are reassuring, demonstrating the reliability of this precious and valuable resource for human islet cells research.
Topics: Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Pancreas; Pancrelipase; Reproducibility of Results
PubMed: 29354869
DOI: 10.1007/s00125-018-4546-x -
Biochemical and Biophysical Research... Jan 2018Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with...
Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.
Topics: Administration, Oral; Animals; Bacteria; Dietary Supplements; Enzyme Replacement Therapy; Gastrointestinal Agents; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Pancreas; Pancrelipase
PubMed: 29106956
DOI: 10.1016/j.bbrc.2017.10.130 -
BioMed Research International 2017The present paper proposed an interactive segmentation method of pancreases in abdominal computed tomography (CT) images based on the anatomical knowledge of medical...
The present paper proposed an interactive segmentation method of pancreases in abdominal computed tomography (CT) images based on the anatomical knowledge of medical doctors and the statistical information of pancreas shapes. This segmentation method consisted of two phases: training and testing. In the training phase, pancreas regions were manually extracted from sample CT images for training, and then a probabilistic atlas (PA) was constructed from the extracted regions. In the testing phase, a medical doctor selected seed voxels for a pancreas and background in a CT image for testing by use of our graphical user interface system. The homography transformation was used to fit the PA to the seeds. The graph cut technique whose data term was weighted by the transformed PA was applied to the test image. The seed selection, the atlas transformation, and the graph cut were executed iteratively. This doctor-in-the-loop segmentation method was applied to actual abdominal CT images of fifteen cases. The experimental results demonstrated that the proposed method was more accurate and effective than the conventional graph cut.
Topics: Abdomen; Algorithms; Humans; Liver; Models, Theoretical; Pancreas; Pancrelipase; Pattern Recognition, Automated; Radiographic Image Enhancement; Radiographic Image Interpretation, Computer-Assisted; Tomography, X-Ray Computed
PubMed: 29082247
DOI: 10.1155/2017/5094592 -
American Journal of Physiology.... Feb 2018The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate...
The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by PEI, an effect that was counteracted with the enzymes at level B. The total recovery of N in urinary urea and plasma proteins was 14 ± 5.1% in the control group and decreased to 5.5 ± 2.1% by PEI. It was dose dependently restored by the treatment. Both N recovery in plasma and urine were correlated to protein digestibility. We confirm that the N transfer in those pools is a sensitive marker of protein malabsorption. Nevertheless, an optimization of the test meal conditions would be necessary in the view of implementing a clinical test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of ileal protein digestibility in minipigs with pancreatic exocrine insufficiency and to validate reliable metabolic markers using a N oral meal test. N recovery in plasma proteins and to a higher extent in urine was sensitive to protein malabsorption. This test is minimally invasive and could be used to reveal protein malabsorption in patients.
Topics: Animals; Biomarkers; Blood Glucose; Caseins; Digestion; Disease Models, Animal; Energy Metabolism; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Gastric Inhibitory Polypeptide; Ileum; Insulin; Malabsorption Syndromes; Pancrelipase; Postprandial Period; Swine; Swine, Miniature; Time Factors; Urea
PubMed: 29074486
DOI: 10.1152/ajpgi.00218.2017 -
Gastric Cancer : Official Journal of... May 2018Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out.
METHODS
After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI).
RESULTS
BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy.
CONCLUSIONS
PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.
Topics: Adenocarcinoma; Aged; Exocrine Pancreatic Insufficiency; Female; Gastrectomy; Gastrointestinal Agents; Humans; Male; Middle Aged; Nutritional Status; Pancrelipase; Stomach Neoplasms
PubMed: 28804801
DOI: 10.1007/s10120-017-0757-y -
International Medical Case Reports... 2017Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at...
Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.
PubMed: 28769592
DOI: 10.2147/IMCRJ.S139022