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Pancreas Aug 2018Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients.
METHODS
Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival.
RESULTS
A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070).
CONCLUSIONS
In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Nutritional Status; Pancreatic Neoplasms; Pancrelipase; Treatment Outcome
PubMed: 29851751
DOI: 10.1097/MPA.0000000000001079 -
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 -
Nutrition in Clinical Practice :... Apr 2018This clinical observation describes the enteral nutrition (EN) management of 2 toddlers at high nutrition risk due to cystic fibrosis (CF), exocrine pancreatic...
This clinical observation describes the enteral nutrition (EN) management of 2 toddlers at high nutrition risk due to cystic fibrosis (CF), exocrine pancreatic insufficiency, and comorbid medical conditions. The first case report describes a boy with severe malabsorption after intestinal resection. The second case report reviews a boy with CF and neuroblastoma. When pancreatic enzyme replacement therapy with EN was not effective or appropriate, use of an in-line digestive cartridge was initiated. While using the digestive cartridge, both children showed improvements in their anthropometric measures. This observation reviews the nutrition management throughout their clinical course and describes the use of a digestive cartridge with EN.
Topics: Child Nutritional Physiological Phenomena; Child, Preschool; Cystic Fibrosis; Digestion; Enteral Nutrition; Enzymes, Immobilized; Exocrine Pancreatic Insufficiency; Growth Charts; Humans; Lipolysis; Malabsorption Syndromes; Male; Malnutrition; Microspheres; Neuroblastoma; Pancrelipase; Severity of Illness Index; Steatorrhea; Treatment Outcome; Weight Gain
PubMed: 29658186
DOI: 10.1002/ncp.10080 -
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 -
Immunotherapy Mar 2018We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented...
We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Exocrine Pancreatic Insufficiency; Feces; Gastrointestinal Agents; Humans; Immunotherapy; Male; Melanoma; Pancreatic Elastase; Pancrelipase; Skin Neoplasms; Treatment Outcome
PubMed: 29370723
DOI: 10.2217/imt-2017-0126 -
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 -
Zhen Ci Yan Jiu = Acupuncture Research Apr 2017To observe the effect of electroacupuncture (EA) on pancreatic glucagon-like peptide-1 receptor (GLP-1 R), pancreatic and duodenal homeobox 1 (PDX-1) protein expression...
OBJECTIVE
To observe the effect of electroacupuncture (EA) on pancreatic glucagon-like peptide-1 receptor (GLP-1 R), pancreatic and duodenal homeobox 1 (PDX-1) protein expression and blood glucose in type 2 diabetes rats, so as to explore the underlying mechanism of EA treatment in improving type 2 diabetes.
METHODS
Sprague-Dawley rats were randomly divided into blank control group, model group, "Weiwanxiashu" (EX-B 3) group, "Xinshu" (BL 15) group, and "Shenshu" (BL 23) group, 12 rats in each group. Diabetes model was established by feeding the rat with high fat and high sugar diet combined with intraperitoneal injection of streptozotocin (35 mg/kg). All the EA groups received 2 Hz, 2 mA continuous wave treatment for 20 min everyday, 6 times per week lasting for 4 weeks. Fasting blood glucose was measured by Roche glucometer before and after treatment. Hematoxylin and eosin (HE) staining and Masson staining were used to detect pancreas morphology. GLP-1 R and PDX-1 protein expressions in the pancreas were detected by Western blot.
RESULTS
Compared to the blank control group, fasting blood glucose was significantly increased in the model group(<0.01), accompanied with shrunken islet area, reduced nucleus counts of islet β cells, and compensatorily enlarged β cell nucleus. Compared to the model group, EA intervention significantly reduced fasting blood glucose level only in the EX-B 3 group (<0.05), partly restored pancreas morphology and nucleus counts of islet β cells in the EX-B 3, BL 15, and BL 23 groups. Compared to the blank control group, GLP-1 R and PDX-1 expressions were decreased in the model group (<0.01), while EA treatment could obviously increase GLP-1 R expression in the EX-B 3(<0.01), BL 15 (<0.01) and BL 23 (<0.05) groups compared with the model group. The expression of GLP-1 R in the BL 15 group was the highest among the three EA groups (<0.05,<0.01), and that in the EX-B 3 group was higher than in the BL 23 group (<0.05).There were no signifincant differences in the expression of PDX-1 protein among the three EA groups (>0.05).
CONCLUSIONS
EA treatment at EX-B 3 can reduce blood glucose via regulating pancreas function, increasing pancreatic GLP-1 R expression, and partly restoring the morphology of pancreas.
Topics: Acupuncture Points; Animals; Diabetes Mellitus, Type 2; Electroacupuncture; Glucagon; Glucagon-Like Peptide-1 Receptor; Humans; Islets of Langerhans; Male; Pancrelipase; Rats; Rats, Sprague-Dawley
PubMed: 29071956
DOI: No ID Found