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Gastroenterology Research and Practice 2010Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic...
Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.
PubMed: 21197074
DOI: 10.1155/2010/898193 -
Journal of Diabetes Investigation Oct 2023It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is...
It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [ F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [ F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [ F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [ F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [ F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.
Topics: Humans; Positron Emission Tomography Computed Tomography; Exenatide; Pancrelipase; Peptides; Kidney Transplantation; Pancreas
PubMed: 37377043
DOI: 10.1111/jdi.14045 -
Fujita Medical Journal 2019Patients who have undergone pancreaticoduodenectomy (PD) may experience a long-term decrease in quality of life because of postoperative pancreatic dysfunction (such as...
OBJECTIVES
Patients who have undergone pancreaticoduodenectomy (PD) may experience a long-term decrease in quality of life because of postoperative pancreatic dysfunction (such as digestive and absorption disorders) and fatty liver as a result of combined resection of the duodenum, gallbladder, and bile duct. The present study investigated the usefulness of pancrelipase for the prevention of pancreatic dysfunction after PD.
METHODS
The data from 73 patients who underwent PD in a single institution were analyzed. Patients who underwent PD during 2007-2011 were administered the low-titer pancreatic enzyme preparations berizym and pancreatin (first period group), while patients who underwent PD during 2012-2017 were administered the high-titer pancreatic enzyme preparation pancrelipase (second period group). The following measures of the nutrition status were examined before and after PD: serum albumin concentration, total lymphocyte count, serum total cholesterol concentration, body mass index, controlling nutrition status (CONUT) index, Onodera's prognostic nutrition index (PNI), and liver computed tomography values.
RESULTS
The second period group had significantly higher serum albumin concentrations at 3 and 6 months postoperatively, serum total cholesterol concentrations at 1 month postoperatively, and Onodera's PNI values at 3 and 6 months postoperatively than the first period group. The CONUT index values at 6 months after PD were significantly lower in the second period group than in the first period group.
CONCLUSIONS
Pancrelipase is useful in improving the nutrition status and preventing fatty liver after PD.
PubMed: 35111504
DOI: 10.20407/fmj.2018-016 -
Journal of Magnetic Resonance Imaging :... Dec 2022The feasibility and reproducibility of multifrequency MR elastography (MRE) for diagnosing pancreatic ductal adenocarcinoma (PDAC) have not been reported.
BACKGROUND
The feasibility and reproducibility of multifrequency MR elastography (MRE) for diagnosing pancreatic ductal adenocarcinoma (PDAC) have not been reported.
PURPOSE
To determine the feasibility and reproducibility of multifrequency MRE for assessing pancreatic stiffness in healthy and diseased pancreases.
STUDY TYPE
Prospective.
SUBJECTS
A total of 40 healthy volunteers and 10 patients with PDAC were prospectively recruited between March 2018 and October 2021.
FIELD STRENGTH/SEQUENCE
A 3.0-T pancreatic MRE at frequencies in the order of 30, 40, 60, 80, and 100 Hz.
ASSESSMENT
Body mass index (BMI) and wave distance of the healthy pancreas and PDAC were measured. Image quality was assessed using the image quality score (IQS: 1-4, ≥3 were considered diagnostic quality). Three readers independently performed the pancreatic stiffness and IQS assessments to evaluate reproducibility.
STATISTICAL TESTS
Logistic regression analyses were performed to determine variables that influenced IQS. Statistical significance was set at P <0.05. Levels of inter- and intrarater agreement were assessed using intraclass correlation coefficients (ICC) and Cohen's kappa coefficient (κ). Good reproducibility was set at ICC and κ ≥ 0.8.
RESULTS
In logistic regression analysis, a diagnostic IQS in healthy volunteers was independently associated with a lower BMI (odds ratio [OR] = 0.89 kg/m ), shorter wave distance (OR = 0.70 cm ), and lower frequency (30 and 40 Hz: OR = 170.01 and 96.02). In PDAC, frequency was the only independent factor for diagnostic IQS (30-60 Hz: OR = 46.18, 46.18, and 17.20, respectively) with 100 Hz as a reference. In healthy volunteers, good reproducibility was observed at 30 and 40 Hz. In PDAC, good reproducibility was observed at 30-60 Hz.
DATA CONCLUSION
MRE at 30 and 40 Hz provides diagnostic wave images and reliable measurements of pancreatic stiffness in healthy volunteers. MRE at 30-60 Hz is acceptable for PDACs (IQS ≥ 3, ICC and κ ≥ 0.80).
EVIDENCE LEVEL
1 TECHNICAL EFFICACY: Stage 2.
Topics: Humans; Elasticity Imaging Techniques; Pancrelipase; Reproducibility of Results; Prospective Studies; Feasibility Studies; Pancreas; Magnetic Resonance Imaging; Pancreatic Neoplasms
PubMed: 35332973
DOI: 10.1002/jmri.28158 -
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 -
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 -
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 -
Alimentary Pharmacology & Therapeutics May 2011Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI)... (Randomized Controlled Trial)
Randomized Controlled Trial
A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery.
BACKGROUND
Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS).
AIM
To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population.
METHODS
This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules).
RESULTS
Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed.
CONCLUSIONS
Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.
Topics: Adult; Capsules; Delayed-Action Preparations; Double-Blind Method; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Pancreas; Pancreatitis, Chronic; Pancrelipase; Time Factors; Treatment Outcome; Weight Gain
PubMed: 21418260
DOI: 10.1111/j.1365-2036.2011.04631.x -
Surgical Case Reports Apr 2022Solid pseudopapillary neoplasms of the pancreas are rare. Moreover, pancreatoduodenectomy (PD) and postoperative care are not common in pediatric surgery. Herein, we...
BACKGROUND
Solid pseudopapillary neoplasms of the pancreas are rare. Moreover, pancreatoduodenectomy (PD) and postoperative care are not common in pediatric surgery. Herein, we report a case of PD and nonalcoholic fatty liver disease (NAFLD) after PD and present a literature review.
CASE PRESENTATION
A 10-year-old girl with a suspected liver tumor was referred to our hospital. Echography, enhanced computed tomography and magnetic resonance imaging showed that the tumor coexisted with the solid and cystic parts of the pancreatic head. Since the patient was a young woman and the imaging findings were consistent with that of pancreatic solid pseudopapillary neoplasms (SPNs), we diagnosed her with pancreatic SPN. Thereafter, PD was performed, and she was discharged 10 days after the operation. Although her postoperative course was mostly uneventful, she experienced few episodes of abdominal pain and diarrhea before hospital discharge. These symptoms subsequently became more frequent and severe. The patient was urgently readmitted to the hospital for watery steatorrhea and lower abdominal colic pain. Her serum aspartate aminotransferase and alanine aminotransferase levels were elevated, and a fatty liver was detected on echography. The patient was diagnosed with steatorrhea, peristaltic pain, and NAFLD after PD. Pancrelipase (containing pancreatic digestive enzymes), antidiarrheal agents, and probiotics were started. Dosage increase of these drugs reduced the defecation frequency and abdominal pain and switched diarrhea to loose stools. However, more lipids in meals or more meals caused diarrhea and abdominal pain. Therefore, the doses of these drugs were further increased, and another antidiarrheal agent, loperamide hydrochloride, was added. Exocrine pancreatic enzymes supplementation and careful follow-up should prevent NAFLD progression after PD. At present, the patient has occasional abdominal pain, but has tangible soft stools once or twice a day. Although echography still shows a mottled fatty liver, her hepatic enzymes are only mildly elevated.
CONCLUSIONS
Pediatric PD is rare, and residual pancreatic function is usually sufficient, unlike in adult cases. However, we experienced a case of NAFLD after PD for a pediatric pancreatic SPN, in which pancreatic enzyme supplementation effectively improved this condition. Further attention must be paid to worsening of NAFLD that can develop nonalcoholic steatohepatitis.
PubMed: 35381910
DOI: 10.1186/s40792-022-01414-9 -
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