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pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21^(st) century

World Journal of Gastroenterology 2014年第33期20卷 11467-11485页

作者： Tony Trang Johanna Chan David Y Graham Department of Medicine Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 United States

Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes,(e.g., giving unprotected enzymes at the start of the mealand acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

关键词： pancreatic insufficiency pancreatic enzyme replacement therapy Lipase Clinical trials Steator-rhea Fat malabsorption Chronic pancreatitis

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Natural history,clinical characteristics,outcomes,and long-term follow-up of pain-free chronic pancreatitis

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Gastroenterology Report 2023年第1期11卷 309-315页

作者： Awais Ahmed Ishani Shah Rachel Bocchino Steven D.Freedman Darshan J.Kothari Sunil G.Sheth Department of Medicine Division of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of Internal MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of GastroenterologyDuke UniversityDurhamNCUSA

Background:Chronic pancreatitis(CP)is characterized by chronic abdominal pain and functional ***,a small subset of patients with prior acute pancreatitis(AP)and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical *** aimed to compare the clinical characteristics,outcomes,and healthcare utilization between CP patients with and without ***:Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April *** without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded,so as tominimize confounding factors of pancreatopathy unrelated to *** were divided into painful and pain-free groups to analyze differences in demographics,outcomes,and healthcare ***:Of 368 CP patients,49(13.3%)were pain-free at diagnosis and had remained so for>9 *** were no significant differences in body mass index,race,sex,or co-morbidities between the two ***-free patients were older at diagnosis(53.9 vs 45.7,P=0.004)and had less recurrent AP(RAP)(43.8%vs 72.5%,Ppancreatic insufficiency(EPI)(34.7%vs 65.7%,P<0.001).Pain-free patients had less disability(2.2%vs 22.0%,P=0.003),mental illness(20.4%vs 61.0%,P<0.001),surgery(0.0%vs 15.0%,P=0.059),and therapeutic interventions(0.0%vs 16.4%,P=0.005)for ***:We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were painfree at *** were older at diagnosis,had less EPI and RAP,and overall favorable outcomes with minimal resource utilization.

关键词： chronic pancreatitis pain-free pancreatic insufficiency diabetes

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De novo non-alcoholic fatty liver disease after pancreatectomy:A systematic review

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World Journal of Clinical Cases 2022年第35期10卷 12946-12958页

作者： Parth Shah Vanisha Patel Motaz Ashkar Gastroenterology Washington University in Saint LouisSaint LouisMO 63110United States Internal Medicine Washington University in Saint LouisSaint LouisMO 63110United States

BACKGROUND As operative techniques and mortality rates of pancreatectomy have improved,there has been a shift in focus to maintaining and improving the nutritional status of these patients as we continue to learn more about post-operative *** pancreatic endocrine and exocrine insufficiencies are known complications of pancreatectomy,increased longevity of these patients has also led to a higher incidence of de novo fatty liver disease which differs from traditional fatty liver disease given the lack of metabolic *** To identify and summarize patterns and risk factors of post-pancreatectomy de novo fatty liver disease to guide future *** We performed a database search on PubMed selecting papers published between 2001 and 2022 in the English *** was last accessed 1 June *** Various factors influence the development of de novo fatty liver including indication for surgery(benign vs malignant),type of pancreatectomy,amount of pancreas remnant,and peri-operative nutritional *** an incidence rate up to 75%,de novo non-alcoholic fatty liver disease(NAFLD)can develop within 12 mo after pancreatectomy and various risk factors have been established including pancreatic resection line and remnant pancreas volume,peri-operative malnutrition and weight loss,pancreatic exocrine insufficiency(EPI),malignancy as the indication for surgery,and postmenopausal *** Since majority of risk factors leads to EPI and malnutrition,peri-operative focus on nutrition and enzymes replacement is key in preventing and treating de novo NAFLD after pancreatectomy.

关键词： Pancreatectomy De novo fatty liver pancreatic insufficiency Malnutrition

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Exocrine pancreatic function assessed by secretin cholangio-Wirsung magnetic resonance imaging

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Hepatobiliary & pancreatic Diseases International 2008年第2期7卷 192-195页

作者： Lucia Calculli Raffaele Pezzilli Marta Fiscaletti Riccardo Casadei Carla Brindisi Giampaolo Gavelli Departments of Radiology Digestive Diseases and Internal Medicineand General SurgerySant'Orsola-Malpighi Hospital Bologna Italy

BACKGROUND:Magnetic resonance cholangiopancreato-graphy (MRCP) is useful to assess exocrine pancreatic function by combining rapid imaging acquisition with the administration of secretin, a gastrointestinal hormone that stimulates the secretion of bile and pancreatic juice. However, extensive data on this method are lacking. This study aimed to determine whether MRCP with secretin administration is able to simultaneously detect alterations of both the pancreatic ducts and exocrine pancreatic function. METHODS:All subjects older than 18 years who underwent magnetic resonance imaging (MRI) and cholangio-Wirsung magnetic resonance imaging (CWMRI) for suspicion of benign or malignant pancreatic diseases from January 2006 to December 2006 were enrolled in the study. MRI and CWMRI were carried out using a dedicated apparatus. RESULTS:Eighty-seven patients (46 males, 41 females, mean age 59.7±14.6, range 27-87 years) were enrolled. Of the 87 patients, 39 had a normal pancreas on imaging, 20 had an intrapapillary mucinous tumor (IPMT), and the rest had chronic pancreatitis (7), serous cystadenoma (6), a previous attack of acute biliary pancreatitis (5), congenital ductal abnormalities (5), mucinous cystadenoma (3), previous pancreatic head resection for autoimmune pancreatitis (1), or cholangiocarcinoma (1). Morphologically, we found two pseudocysts (one of the 7 patients with chronic pancreatitis, and one of the 5 patients after an attack of acute pancreatitis;the latter pseudocyst communicated with the main pancreatic duct). Calcifications were found in 3 of the 7 patients with chronic pancreatitis. All patients with IPMT and mucinous cystadenoma and 3 patients with serous cystadenoma were histologically confirmed. The remaining patients were followed up adequately to confirm the diagnosis by imaging. According to the Matos criteria, 73 patients (83.9%) were of grade 3, 8 grade 2, 4 grade 1, and 2 grade 0. The only pancreatic diseases which impaired the exocrine pancreati

关键词： chronic pancreatitis magnetic resonance cholangiopancreatography pancreatic neoplasms pancreatic insufficiency

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Johanson-Blizzard syndrome with mild phenotypic features confirmed by UBR1 gene testing

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World Journal of Gastroenterology 2008年第44期14卷 6863-6866页

作者： Naim Alkhouri Barbara Kaplan Marsha Kay Amy Shealy Carol Crowe Susanne Bauhuber Martin Zenker Department of Pediatric Gastroenterology and Nutrition Cleveland ClinicClevelandOH 44195United States Genomic Medicine Institute Cleveland ClinicClevelandOH 44195United States Department of Genetics MetroHealth Medical CenterClevelandOH 44195United States Institute of Human Genetics 91054 ErlangenGermany

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition associated with exocrine pancreatic insufficiency,and is characterized by hypoplastic nasal alae,mental retardation,sensorineural hearing loss,short stature,scalp defects,dental abnormalities and abnormal hair patterns. Growth hormone deficiency,hypopituitarism,and impaired glucagon secretion response to insulin-induced hypoglycemia have been reported. Congenital heart defects have also been described in this condition. Mental retardation is typically moderate to severe in patients with JBS; however,normal intelligence can occur. In the pancreas,there is a selective defect of acinar tissue,whereas the islets of Langerhans and ducts are preserved. Diabetes has been reported in older children,suggesting the progressive nature of pancreatic disease. The molecular basis of JBS has recently been mapped to chromosome 15q15-q21 with identified mutations in the UBR1 gene. We report the case of a 7-year-old female with pancreatic insufficiency and mild phenotypic features,in whom the diagnosis of JBS was established using recently described molecular testing for the UBR1 gene.

关键词： Johanson-Blizzard syndrome pancreatic insufficiency Sensorineural hearing loss UBR1 gene

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