|
1
|
Fu Y, Nguyen HN, Ponrartana S, Piester TL, Trout AT, Alharbi O, Abu-El-Haija M, Zheng Y. Endoscopic pancreatic function test and other modalities for exocrine pancreatic disease measures. J Pediatr Gastroenterol Nutr 2025; 80:847-854. [PMID: 39945045 DOI: 10.1002/jpn3.70006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 01/26/2025] [Indexed: 05/13/2025]
Abstract
OBJECTIVES Exocrine pancreatic insufficiency (EPI) reflects inadequate pancreatic enzyme(s) and/or bicarbonate secretion, leading to malabsorption. We aim to compare different assessment tools for exocrine pancreatic function and correlate them with the endoscopic pancreatic function test (ePFT) as a reference standard. METHODS Combined retrospective and prospective analysis of clinical data for children who underwent clinically indicated ePFTs. We compared ePFT against patient symptoms, laboratory results, magnetic resonance cholangiopancreatography with secretin 49/53 magnetic resonance imaging, among those, 35/49 with secretin enhanced magnetic resonance cholangiopancreatography (sMRCP), or endoscopic ultrasound (EUS 36/53) findings with the ePFT results. RESULTS A total of 53 patients who underwent ePFT between September 2018 and April 2023 were included. 30 were Female (57%). Median age when ePFT was performed was 14 years (range: 4-21 years). Primary indication for ePFT: Acute recurrent or chronic pancreatitis (74%), Pancreas atrophy (9%), Other (post- pancreatic surgery, malnutrition with low fecal elastase-1 (FE-1) (17%). Patients with high pancreatic enzyme activities had a higher volume of pancreatic fluid secretion on ePFT. They also had larger pancreatic anteroposterior diameter and pancreas parenchyma volume, as well as higher post-secretin enteric fluid volume increment on sMRCP compared to those with low enzyme activities. Our findings also underscore the importance of lipase in maintaining and promoting weight gain in pediatric patients. In our patient cohort, the FE-1 level was lower in patients with low pancreatic enzyme activities. Our study showed that steatorrhea is associated with low pancreatic enzyme activities, whereas abdominal pain and unintentional weight loss might be nonspecific to EPI. No significant correlations were observed from blood cell counts, blood electrolytes, lipase, albumin, bilirubin, alanine aminotransferase, serum lipids, fat-soluble vitamins, prothrombin time, hemoglobin A1C, and EUS with pancreatic enzymes or bicarbonate concentration. CONCLUSIONS sMRCP is a promising noninvasive modality in assessing exocrine pancreatic function in children.
Collapse
Affiliation(s)
- Yinan Fu
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| | - HaiThuy N Nguyen
- Department of Radiology, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| | - Skorn Ponrartana
- Department of Radiology, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| | - Travis L Piester
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| | - Andrew T Trout
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Pediatric Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Omar Alharbi
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| | - Maisam Abu-El-Haija
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Pediatric Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Yuhua Zheng
- Department of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California (USC), Los Angeles, California, USA
| |
Collapse
|
|
2
|
Gummadi VV, Gonska T. Serum Trypsin Is a Reliable Biomarker of Pancreas Function. Pancreas 2025; 54:e360-e368. [PMID: 39626172 DOI: 10.1097/mpa.0000000000002445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 11/12/2024] [Indexed: 04/24/2025]
Abstract
ABSTRACT Pancreatic diseases pose significant diagnostic and therapeutic challenges necessitating robust biomarkers for accurate diagnosis, management, and monitoring of pancreas function.Pancreas function can be measured with direct (invasive) and indirect tests. However, neither approach allows for continuous disease monitoring to identify disease progression or therapeutic response. We demonstrate literature evidence suggesting that trypsin, an important pancreatic digestive enzyme, holds promise as a continuous biomarker. On one hand, assessment of trypsin concentration in the serum sensitively and specifically detects pancreas inflammation; whereas on the other hand, declining trypsin levels in serum show good correlation with direct pancreatic function tests to identify exocrine pancreatic insufficiency. With this comprehensive review, we aimed to evaluate the existing evidence on the utility of trypsin as a continuous biomarker, spanning from acute to chronic pancreatitis and pancreas function, highlighting its potential in monitoring disease evolution on an individual patient level.
Collapse
Affiliation(s)
- Vybhav Venkatesh Gummadi
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Toronto
| | | |
Collapse
|
|
3
|
Shivakumar N, Morrison DJ, Hegde SG, Kurpad AV, Kelly P. Is there dietary macronutrient malabsorption in children with environmental enteropathy? Eur J Clin Nutr 2025; 79:181-194. [PMID: 39379550 PMCID: PMC11893463 DOI: 10.1038/s41430-024-01510-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 08/28/2024] [Accepted: 09/12/2024] [Indexed: 10/10/2024]
Abstract
Assessing the digestive and absorptive capacity of the gastro-intestinal tract (GIT) using minimally- or non-invasive methods, particularly in children, has been difficult owing to the complex physiology and variability in functional measurements. However, measuring GIT function is increasingly important with the emerging relevance of childhood environmental enteropathy (EE) as a mediating factor in linear growth faltering, severe acute malnutrition, poor oral vaccine uptake and impaired cognition. In EE, sub-optimal nutrient digestion and absorption (malabsorption) forms the critical link to the conditions mentioned above. The present narrative review discusses probable mechanisms that can cause malabsorption of macronutrients, along with mechanistic and experimental evidence, in children (if not, in adults) with EE. The strengths and limitations of the human experimental studies are examined in relation to a battery of existing and potential tests that are used to measure malabsorption. From the available studies conducted in children, lactose and fat malabsorption are more likely to occur in EE. Breath tests (non-invasive) measuring carbohydrate (13C-starch/sucrose/lactose), fat (13C-mixed triglyceride) and dipeptide (benzoyl-L-tyrosyl-L-1-13C-alanine) malabsorption with modifications to the existing protocols seem suitable for use in children with EE. Future research should focus on understanding the degree of macronutrient malabsorption using these tests, in different settings, and link them to functional outcomes (such as growth, muscle strength, cognition).
Collapse
Affiliation(s)
- Nirupama Shivakumar
- Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences (A Unit of CBCI Society for Medical Education), Bangalore, India
- Center for Doctoral Studies, Manipal Academy of Higher Education, Manipal, India
| | - Douglas J Morrison
- Scottish Universities Environmental Research Centre (SUERC), University of Glasgow, Glasgow, UK
| | - Shalini G Hegde
- Department of Pediatric Surgery, St. John's Medical College Hospital, St. John's National Academy of Health Sciences, Bangalore, India
| | - Anura V Kurpad
- Department of Physiology, St. John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India
| | - Paul Kelly
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.
| |
Collapse
|
|
4
|
Pandey A, Mehta D, Horvath K. A Review of Exocrine Pancreatic Insufficiency in Children beyond Cystic Fibrosis and the Role of Endoscopic Direct Pancreatic Function Testing. Curr Gastroenterol Rep 2025; 27:14. [PMID: 39971805 DOI: 10.1007/s11894-025-00959-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2025] [Indexed: 02/21/2025]
Abstract
PURPOSE OF REVIEW Common indications to evaluate exocrine pancreatic function in children include chronic diarrhea, steatorrhea, failure to thrive, cystic fibrosis and those with chronic abdominal pain due to chronic pancreatitis where imaging studies are normal [1]. Exocrine Pancreatic Insufficiency (EPI) has a spectrum of severity. In children often remains an underdiagnosed condition, particularly in its mild, partial, and isolated enzyme deficiency forms. The purpose of this review is to help understand the different varieties of EPI including isolated pancreatic enzyme deficiencies as possible causes of malnutrition and growth failure in pediatric patients. RECENT FINDINGS Among the indirect diagnostic methods, the fecal elastase-1 (FE-1) testing is the most widely used one. While it has good sensitivity and specificity in severe pancreatic damage, like cystic fibrosis in children, its performance in the diagnosis of mild, partial, and isolated enzyme deficiencies is poor. Direct pancreatic function testing performed during endoscopy (ePFT), has emerged as a more sensitive and specific method for assessing all forms of exocrine pancreatic function. Notably, recent guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) emphasize the importance of ePFT in pediatric patients. Most of the pediatric practitioners taught that the pancreas has only two diseases, cystic fibrosis and pancreatitis. They are missing the fact that pancreas, like other digestive organs, can have different, many times secondary, dysfunctions that influence the growth of children. Most pediatric gastroenterologists still use the fecal elastase-1 (FE-1) test, however, this lacks sufficient specificity and sensitivity [2-5] especially in patients with mild or early pancreatic disease or those with isolated enzyme deficiencies [5]. The most accurate diagnostic modality to explore these conditions is ePFT. In this review we highlighted the critical importance of direct pancreatic function testing. Enhancing clinical awareness and incorporating direct testing methods can ultimately improve outcomes for affected children.
Collapse
Affiliation(s)
- Akash Pandey
- Pediatric Center for Digestive Health and Nutrition Arnold Palmer Hospital for Children, Orlando Health, 60 W. Gore St., MP 373, Orlando, FL, 32806, USA.
- Arnold Palmer Hospital for children, 65 N Gore Street, Orlando, FL, 32806, USA.
| | - Devendra Mehta
- Pediatric Center for Digestive Health and Nutrition Arnold Palmer Hospital for Children, Orlando Health, 60 W. Gore St., MP 373, Orlando, FL, 32806, USA
| | - Karoly Horvath
- Pediatric Center for Digestive Health and Nutrition Arnold Palmer Hospital for Children, Orlando Health, 60 W. Gore St., MP 373, Orlando, FL, 32806, USA
| |
Collapse
|
|
5
|
Fernandez J, Hopson P, Patel SB, Horvath K, Pandey A. Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2023; 76:475-479. [PMID: 36720112 DOI: 10.1097/mpg.0000000000003725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD. METHODS Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed. RESULTS Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013). CONCLUSIONS This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT.
Collapse
Affiliation(s)
- Jenelle Fernandez
- From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL
- the Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of South Florida, Morsani College of Medicine, Tampa, FL
| | - Puanani Hopson
- From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL
- the Department of Pediatric and Adolescent Medicine, Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Samit B Patel
- From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL
- Pediatric Gastroenterology and Nutrition of Tampa Bay, Tampa, FL
| | - Karoly Horvath
- From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL
| | - Akash Pandey
- From the Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL
| |
Collapse
|
|
6
|
Yuzyuk TN, Nelson HA, Johnson LM. Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing. Crit Rev Clin Lab Sci 2023:1-16. [PMID: 36876586 DOI: 10.1080/10408363.2023.2179968] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
Pediatric patients with exocrine pancreatic insufficiency (EPI) have symptoms that include abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea. This condition can be present at birth or develop during childhood for certain genetic disorders. Cystic fibrosis (CF) is the most prevalent disorder in which patients are screened for EPI; other disorders also are associated with pancreatic dysfunction, such as hereditary pancreatitis, Pearson syndrome, and Shwachman-Diamond syndrome. Understanding the clinical presentation and proposed pathophysiology of the pancreatic dysfunction of these disorders aids in diagnosis and treatment. Testing pancreatic function is challenging. Directly testing aspirates produced from the pancreas after stimulation is considered the gold standard, but the procedures are not standardized or widely available. Instead, indirect tests are often used in diagnosis and monitoring. Although indirect tests are more widely available and easier to perform, they have inherent limitations due to a lack of sensitivity and/or specificity for EPI.
Collapse
Affiliation(s)
- Tatiana N Yuzyuk
- Department of Pathology, University of Utah/ARUP Laboratories, Salt Lake City, UT, USA
| | - Heather A Nelson
- Department of Pathology, University of Utah/ARUP Laboratories, Salt Lake City, UT, USA
| | - Lisa M Johnson
- Department of Laboratories, Seattle Children's Hospital, Seattle, WA, USA
| |
Collapse
|
|
7
|
Terlizzi V, Parisi GF, Ferrari B, Castellani C, Manti S, Leonardi S, Taccetti G. Effect of Dornase Alfa on the Lung Clearance Index in Children with Cystic Fibrosis: A Lesson from a Case Series. CHILDREN (BASEL, SWITZERLAND) 2022; 9:1625. [PMID: 36360353 PMCID: PMC9688561 DOI: 10.3390/children9111625] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/15/2022] [Accepted: 10/24/2022] [Indexed: 09/12/2023]
Abstract
BACKGROUND Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy. METHODS This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3-6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy. RESULTS DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0). CONCLUSIONS This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.
Collapse
Affiliation(s)
- Vito Terlizzi
- Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Giuseppe Fabio Parisi
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, 95121 Catania, Italy
| | - Beatrice Ferrari
- Rehabilitation Unit, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Chiara Castellani
- Rehabilitation Unit, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Sara Manti
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, 95121 Catania, Italy
- Pediatric Unit, Department of Human and Pediatric Pathology “Gaetano Barresi”, AOUP G. Martino, University of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy
| | - Salvatore Leonardi
- Pediatric Respiratory and Cystic Fibrosis Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, 95121 Catania, Italy
| | - Giovanni Taccetti
- Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Meyer Children’s Hospital, 50139 Florence, Italy
| |
Collapse
|
|
8
|
Terlizzi V, Centrone C, Ferrari B, Castellani C, Gunawardena TNA, Taccetti G, Laselva O. Modulator Therapy in Cystic Fibrosis Patients with cis Variants in F508del Complex Allele: A Short-Term Observational Case Series. J Pers Med 2022; 12:jpm12091421. [PMID: 36143206 PMCID: PMC9504164 DOI: 10.3390/jpm12091421] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 11/16/2022] Open
Abstract
Previous studies reported the influence of cis variants in F508del cystic fibrosis (CF) patients in their responses to CFTR modulators. The current study is a prospective, observational study involving three patients with CF and pancreatic insufficiency, carrying a complex allele including F508del with A238V, I1027T, or L467F. We report clinical data before and after 4 weeks of treatment with tezacaftor (TEZ)/ivacaftor (IVA), elexacaftor (ELX)/TEZ/IVA, and lumacaftor (LUM)/IVA for patients with complex alleles A238V, I1027T, and L467F, respectively. The 50-year-old patient bearing F508del;A238V/D1152H showed a normal sweat test (13 mEq/L) and improvements in forced expiratory volume in the first second (FEV1) (+7 points), body mass index (BMI) (+0.85), and respiratory CF Questionnaire-Revised (CFQ-R) domain (+22.2 points). The 12-year-old patient bearing F508del;I1027T/R709X showed an improvement in a sweat test (−40 mEq/l), FEV1 (+9 points) and the respiratory CFQ-R domain (+16.7 points). No changes in outcomes were observed for the 6-year-old patient F508del;L467F/F508del. Our data highlight that the reported variants do not modify the phenotypic expression of F508del. Searching L467F is crucial in CF patients with F508del nonresponsive to ELX/TEZ/IVA. Further data are needed to evaluate the clinical effect of these variants after a longer follow up.
Collapse
Affiliation(s)
- Vito Terlizzi
- Department of Paediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children’s Hospital, 50139 Florence, Italy
- Correspondence: (V.T.); (O.L.); Tel.: +39-0881588074 (O.L.)
| | - Claudia Centrone
- Diagnostic Genetics Unit, Careggi University Hospital, 50134 Florence, Italy
| | - Beatrice Ferrari
- Rehabilitation Unit, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Chiara Castellani
- Department of Radiology, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Tarini N. A. Gunawardena
- Programme in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 8X4, Canada
- Programme in Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 8X4, Canada
| | - Giovanni Taccetti
- Department of Paediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children’s Hospital, 50139 Florence, Italy
| | - Onofrio Laselva
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
- Correspondence: (V.T.); (O.L.); Tel.: +39-0881588074 (O.L.)
| |
Collapse
|
|
9
|
Abstract
Feeding intolerance is ubiquitous in neonatal intensive care units with as many signs and symptoms as possible diagnoses. Optimizing nutrition is paramount in both preterm and term infants. Determining the cause of feeding intolerance and adjusting nutrition interventions is an important part of the daily care of newborns. This review discusses the role of malabsorption and food intolerance as possible causes of nutrition difficulties in the newborn.
Collapse
|
|
10
|
Hopson P, Smadi Y, Mehta V, Patel S, Mehta D, Horvath K. Assessment of exocrine pancreatic function in children and adolescents with direct and indirect testing. Front Pediatr 2022; 10:908542. [PMID: 36452348 PMCID: PMC9704773 DOI: 10.3389/fped.2022.908542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 10/19/2022] [Indexed: 11/15/2022] Open
Abstract
The exocrine pancreas plays an important role in digestion. Understanding of the physiology and regulation of exocrine function provides insight into disease processes and basis of functional testing. Specifically, exocrine pancreatic insufficiency (EPI) can cause maldigestion and thus a proper assessment of exocrine pancreatic function is important. There are indirect and direct methods for evaluating pancreatic function. Indirect methods are varied and include stool, serum, urine, and breath tests. Fecal elastase is a commonly used indirect test today. Direct methods involve stimulated release of pancreatic fluid that is collected from the duodenum and analyzed for enzyme activity. The most used direct test today is the endoscopic pancreatic function test. Indirect pancreatic function testing is limited in identifying cases of mild to moderate EPI, and as such in these cases, direct testing has higher sensitivity and specificity in diagnosing EPI. This review provides a comprehensive guide to indirect and direct pancreatic function tests as well as an in-depth look at exocrine pancreatic function including anatomy, physiology, and regulatory mechanisms.
Collapse
Affiliation(s)
- Puanani Hopson
- Department of Children Center, Pediatric and Adolescent Medicine, Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Yamen Smadi
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Vijay Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Samit Patel
- Pediatric Gastroenterology & Nutrition of Tampa Bay, Tampa Bay, FL, United States
| | - Devendra Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Karoly Horvath
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| |
Collapse
|
|
11
|
Higashiguchi T, Kato H, Yasuoka H, Ito M, Asano Y, Kawabe N, Arakawa S, Shimura M, Koike D, Hayashi C, Ochi T, Kamio K, Kawai T, Utsumi T, Nagata H, Kondo Y, Tochii D, Horiguchi A. A preserved pancreatic exocrine function after pancreatectomy may be a crucial cause of pancreatic fistula: paradoxical results of the 13C-trioctanoin breath test in the perioperative period. Surg Today 2021; 52:580-586. [PMID: 34529132 DOI: 10.1007/s00595-021-02371-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/08/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE The aim of this study was to elucidate the association between pancreatic fistula (PF) and the sequential changes in the perioperative exocrine function after pancreatectomy. METHODS The subjects were 96 patients who underwent a 13C-trioctanoin breath test before and 1 month after pancreatectomy, between 2006 and 2018. We retrospectively compared the pre- and postoperative fat absorption levels between patients with PF (PF group; n = 17) and without PF (non-PF group; n = 79) using the breath test. RESULTS The preoperative level of 13C-trioctanoin absorption (%dose/h) was comparable between the non-PF and PF groups (36.5 vs. 36.9). In the non-PF group, 13C-trioctanoin absorption was significantly decreased after surgery in comparison to the preoperative setting (post-operative 28.5; pre-operative 36.5; p < 0.0001), whereas these values were comparable (post-operative 36.9; pre-operative 34.5; p = 0.129) in the PF group. Moreover, postoperative absorption in the PF group was significantly better than that in the non-PF group (34.5 vs. 28.5%, p = 0.0003). The maximum drain amylase level was significantly higher in patients with a 13C-trioctanoin absorption level (%dose/h) of ≥ 30 in comparison to patients with levels of < 30 (2502 vs. 398 U/L, p = 0.001). CONCLUSION PF did not exacerbate the pancreatic exocrine function in the early postoperative period, and the acceleration or preservation of the exocrine function after surgery may be an important cause of PF.
Collapse
Affiliation(s)
- Takahiko Higashiguchi
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Hiroyuki Kato
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan.
| | - Hironobu Yasuoka
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Masahiro Ito
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Yukio Asano
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Norihiko Kawabe
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Satoshi Arakawa
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Masahiro Shimura
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Daisuke Koike
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Chihiro Hayashi
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Takayuki Ochi
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Kenshiro Kamio
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Toki Kawai
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Toshiaki Utsumi
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Hidetoshi Nagata
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Yuka Kondo
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Daisuke Tochii
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Akihiko Horiguchi
- Department of Gastroenterological Surgery, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| |
Collapse
|
|
12
|
Suzuki M, Minowa K, Isayama H, Shimizu T. Acute recurrent and chronic pancreatitis in children. Pediatr Int 2021; 63:137-149. [PMID: 32745358 DOI: 10.1111/ped.14415] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 06/27/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022]
Abstract
Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.
Collapse
Affiliation(s)
- Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kei Minowa
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| |
Collapse
|
|
13
|
Endoscopic Pancreatic Function Testing (ePFT) in Children: A Position Paper From the NASPGHAN Pancreas Committee. J Pediatr Gastroenterol Nutr 2021; 72:144-150. [PMID: 32910088 DOI: 10.1097/mpg.0000000000002931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Endoscopic pancreatic function testing (ePFT) is one of the few ways to directly diagnose exocrine pancreatic insufficiency, and considerable confusion regarding indications, utility, and interpretation of the test remains. This position paper of the Pancreas Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reviews the history and indications for ePFT in children. We compare various methods in current practice and determine their strengths and limitations, and based on data from children and adults we provide guidance on a protocol on how to perform ePFT in children. Lastly, we pose areas in need of further research relating to ePFT in children.
Collapse
|
|
14
|
Abstract
OBJECTIVES Endoscopic pancreatic function test (ePFT) has been in use for exocrine function testing since the 1990s. In patients, short ePFT assesses acinar function, unlike the longer version for ductal function in adults. The present study summarizes characteristics of 1913 short ePFTs (S-ePFT) performed at 2 centers since 2001. METHODS The main indications in patients presenting at ages infancy to 24.3 years, for the S-ePFT were failure to thrive, weight loss, diarrhea, and abdominal pain with bloating. Secretin was administered as bolus, and 4 aliquots of fluid were collected between 4 and 10 minutes after administration. Amylase, lipase, trypsin, and chymotrypsin activities were measured in the laboratory. RESULTS The pH of consecutive samples increased by 0.3 to 0.7. Overall, 36.7% had abnormal S-ePFT with selective amylase deficiency (9.5%) and generalized enzyme deficiency (8.9%) being the most frequent. Retest reproducibility, repeatability, and clinical validity were high. By adding S-ePFT to endoscopy for the suspicion of malabsorption, the abnormal findings increased by 36.9%. CONCLUSIONS Short ePFT assesses pancreatic acinar function in a reliable and clinically meaningful way in patients. Diagnostic yield of endoscopy increased substantially albeit with increased sedation time. By S-ePFT ductal function, cytokines and proteomics can also be assessed.
Collapse
|
|
15
|
Abstract
OBJECTIVES Among the 3 lines of pancreatic enzymes, amylase secretion develops last and it is not detected in duodenal aspirates of infants in the first month after birth. The aim of this study was to assess the prevalence and symptoms of isolated amylase deficiency in children. METHODS During a 6-year period, we performed endoscopic pancreatic function tests (ePFT) in 712 children. Isolated amylase deficiency was defined as activity that was below the third percentile of our referenced population with normal lipase and protease activities. RESULTS Seventy-two children between age 0.21 and 15.7 years (boys, n = 35) had isolated amylase deficiency. The highest prevalence of isolated amylase deficiency was found in patients less than 6 months of age (52.9%). From 6 months to 1 year of age, the prevalence was 40%. The prevalence gradually decreased until 18 months. Failure to thrive, poor weight gain, diarrhea, and abdominal bloating were the most frequent indications for ePFT. Eleven children had repeat ePFT after initial diagnosis and 6 had normal enzyme activity, whereas 5 had remained amylase-deficient an average of 1.65 years later. CONCLUSIONS The prevalence of selective amylase deficiency was 10.1% in the 712 children who underwent ePFT with the suspicion of malabsorption. Low amylase activity is "physiologic" in infants <6 months of age, however, this study supports that it should be considered in the differential diagnosis in children older than 6 months of age.
Collapse
|
|
16
|
Abstract
This article will review briefly the physiology of pancreatic enzyme secretion and the role of stimulated endoscopic testing for assessing exocrine pancreatic function. Published studies in both the pediatric and adult literature are reviewed. The technique and utility of endoscopic pancreatic function testing as the method of choice in the differential diagnosis of pancreatic disorders in childhood is described. Finally, emerging, clinically useful markers that can be measured in the pancreatic fluid will be described.
Collapse
|
|
17
|
Abstract
OBJECTIVES Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman-Diamond syndrome, or chronic pancreatitis. Fecal elastase-1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea. METHODS We followed 43 children (age range 1 month-18 years) with low fecal elastase-1 in our institution between the years 2009 and 2017. We followed growth and laboratory results (particularly, complete blood count, albumin, transaminases, celiac serology, sweat test, and fat-soluble vitamins). Elastase levels <200 mg/g were considered as pancreatic insufficiency. RESULTS Twenty-six were excluded due to missing data, a comorbidity or being syndromatic. Enrolled children (17) were all otherwise healthy.The median age at diagnosis was 3 years (range 0.2-15 years), 11 girls and 6 boys. Their main presenting symptoms were failure to thrive and/or diarrhea. Median fecal elastase-1 levels were 71 mg/g (range 18-160). Median time for normalization was 6 months (range 1-48 months). Abdominal sonography, celiac serology, and sweat test were normal for all patients. Most patients were treated with pancreatic enzymes until resolution. CONCLUSIONS Transient EPI without clear etiology should be in the differential diagnosis of EPI after ruling out known etiologies. The resolving course pattern may be attributed to an unidentified infectious agent. Further studies to assess the etiology are mandated.
Collapse
|
|
18
|
Abu-El-Haija M, Conwell DL. Pancreatic Insufficiency: What Is the Gold Standard? Gastrointest Endosc Clin N Am 2018; 28:521-528. [PMID: 30241641 DOI: 10.1016/j.giec.2018.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Endoscopic pancreatic function testing assesses exocrine insufficiency and chronic pancreatitis. Indirect pancreatic function tests have limited sensitivity and specificity in early disease stages. Magnetic resonance cholangiopancreatography shows promise in detecting early changes as a direct measure of pancreatic function. This article summarizes the evolution of pancreatic function testing and highlights areas for future research, such as development of diagnostic biomarkers to stratify disease severity and targeted therapies to retard disease progression.
Collapse
Affiliation(s)
- Maisam Abu-El-Haija
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, USA.
| | - Darwin L Conwell
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Ohio State University Wexner Medical Center, Columbus, OH, USA
| |
Collapse
|
|
19
|
Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16:1220-1228.e4. [PMID: 29374614 PMCID: PMC6402774 DOI: 10.1016/j.cgh.2018.01.027] [Citation(s) in RCA: 132] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 01/13/2018] [Accepted: 01/16/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI. METHODS We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis. RESULTS We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives). CONCLUSIONS In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.
Collapse
Affiliation(s)
- Rohini R Vanga
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Aylin Tansel
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | | | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Mohamed O Othman
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
| |
Collapse
|
|
20
|
Sanctuary MR, Kain JN, Angkustsiri K, German JB. Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis. Front Nutr 2018; 5:40. [PMID: 29868601 PMCID: PMC5968124 DOI: 10.3389/fnut.2018.00040] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/30/2018] [Indexed: 12/13/2022] Open
Abstract
Children with autism spectrum disorders (ASD), characterized by a range of behavioral abnormalities and social deficits, display high incidence of gastrointestinal (GI) co-morbidities including chronic constipation and diarrhea. Research is now increasingly able to characterize the “fragile gut” in these children and understand the role that impairment of specific GI functions plays in the GI symptoms associated with ASD. This mechanistic understanding is extending to the interactions between diet and ASD, including food structure and protein digestive capacity in exacerbating autistic symptoms. Children with ASD and gut co-morbidities exhibit low digestive enzyme activity, impaired gut barrier integrity and the presence of antibodies specific for dietary proteins in the peripheral circulation. These findings support the hypothesis that entry of dietary peptides from the gut lumen into the vasculature are associated with an aberrant immune response. Furthermore, a subset of children with ASD exhibit high concentrations of metabolites originating from microbial activity on proteinaceous substrates. Taken together, the combination of specific protein intakes poor digestion, gut barrier integrity, microbiota composition and function all on a background of ASD represents a phenotypic pattern. A potential consequence of this pattern of conditions is that the fragile gut of some children with ASD is at risk for GI symptoms that may be amenable to improvement with specific dietary changes. There is growing evidence that shows an association between gut dysfunction and dysbiosis and ASD symptoms. It is therefore urgent to perform more experimental and clinical research on the “fragile gut” in children with ASD in order to move toward advancements in clinical practice. Identifying those factors that are of clinical value will provide an evidence-based path to individual management and targeted solutions; from real time sensing to the design of diets with personalized protein source/processing, all to improve GI function in children with ASD.
Collapse
Affiliation(s)
- Megan R Sanctuary
- Department of Nutrition, University of California, Davis, Davis, CA, United States
| | - Jennifer N Kain
- Department of Neurobiology, Physiology and Behavior Department, University of California, Davis, Davis, CA, United States
| | - Kathleen Angkustsiri
- School of Medicine, Department of Pediatrics, University of California, Davis, Sacramento, CA, United States.,Department of Pediatrics, UC Davis MIND Institute, Sacramento, CA, United States
| | - J Bruce German
- Department of Food Science and Technology, University of California, Davis, Davis, CA, United States.,Foods for Health Institute, University of California, Davis, Davis, CA, United States
| |
Collapse
|
|
21
|
Abstract
OBJECTIVE The aim of this study was to compare the hemodynamic parameters from the anesthesia records of children who underwent upper gastrointestinal endoscopy (esophagogastroduodenoscopy [EGD]) with and without secretin pancreatic function tests (sPFTs). METHODS The hemodynamic parameters were retrieved from an electronic anesthesia database. The secretin group consisted of 186 children, and the age- and sex-matched control group included 136 patients who did not have sPFTs. RESULTS There was no difference in the demographic parameters (age and sex) between the 2 groups. The secretin group had a lower height and body mass index. The sPFT resulted in an average 3-minute extension of the endoscopic procedure. The heart rate increased during the EGD in both groups and was higher (averaged 7 beats per minute) in the secretin group than the EGD-only group. There were mild elevations on the systolic and diastolic blood pressures. None of these changes were clinically significant. There were no complications reported during the anesthesia and procedures in the 2 groups. CONCLUSIONS Secretin PFT is a safe procedure. It only slightly prolongs the total procedure and anesthesia time. There were no clinically significant changes in the vital parameters in the secretin group, and there were no adverse effects recorded.
Collapse
|
|
22
|
Abstract
Cystic Fibrosis (CF) is a rare, multisystem disease leading to significant morbidity and mortality. CF is caused by defects in the cystic fibrosis transmembrane conductance regulator protein (CFTR), a chloride and bicarbonate transporter. Early diagnosis and access to therapies provides benefits in nutrition, pulmonary health, and cognitive ability. Several screening and diagnostic tests are available to support a diagnosis. We discuss the characteristics of screening and diagnostic tests for CF and guideline-based algorithms using these tools to establish a diagnosis. We discuss classification and management of common "diagnostic dilemmas," including the CFTR-related metabolic syndrome and other CFTR-associated diseases.
Collapse
Affiliation(s)
- John Brewington
- Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC 2021, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
| | - J P Clancy
- Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC 2021, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
| |
Collapse
|
|
23
|
ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children. J Pediatr Gastroenterol Nutr 2015; 61:144-53. [PMID: 25915425 DOI: 10.1097/mpg.0000000000000830] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis.
Collapse
|
|
24
|
Terlizzi V, Carnovale V, Castaldo G, Castellani C, Cirilli N, Colombo C, Corti F, Cresta F, D'Adda A, Lucarelli M, Lucidi V, Macchiaroli A, Madarena E, Padoan R, Quattrucci S, Salvatore D, Zarrilli F, Raia V. Clinical expression of patients with the D1152H CFTR mutation. J Cyst Fibros 2015; 14:447-52. [PMID: 25583415 DOI: 10.1016/j.jcf.2014.12.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 12/17/2014] [Accepted: 12/18/2014] [Indexed: 01/30/2023]
Abstract
BACKGROUND Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. METHODS A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. RESULTS 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. CONCLUSIONS The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans.
Collapse
Affiliation(s)
- Vito Terlizzi
- Dipartimento di Scienze Mediche Traslazionali, Sezione di Pediatria, Università di Napoli Federico II, Naples, Italy
| | - Vincenzo Carnovale
- Centro Fibrosi Cistica Adulti, Dipartimento di Scienze Traslazionali, Università di Napoli Federico II, Naples, Italy
| | - Giuseppe Castaldo
- CEINGE-Biotecnologie avanzate, Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy
| | - Carlo Castellani
- Centro Fibrosi Cistica, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Natalia Cirilli
- Centro Regionale Fibrosi Cistica, Dipartimento Materno-Infantile, Ospedali Riuniti Ancona, Ancona, Italy
| | - Carla Colombo
- Centro Fibrosi Cistica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Fabiola Corti
- Centro Fibrosi Cistica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Federico Cresta
- Centro Fibrosi Cistica, Dipartimento di Pediatria, IRCCS G. Gaslini, Genova, Italy
| | - Alice D'Adda
- Centro Fibrosi Cistica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Marco Lucarelli
- Dipartimento di Biotecnologie Cellulari ed Ematologia, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza Università e Policlinico Umberto I, Rome, Italy
| | - Vincenzina Lucidi
- Unità di Fibrosi Cistica, IRCCS Ospedale Pediatrico Bambin Gesù, Rome, Italy
| | | | - Elisa Madarena
- Centro Fibrosi Cistica, Ospedale Giovanni Paolo II, Lamezia, Italy
| | - Rita Padoan
- Centro di supporto Fibrosi Cistica, Dipartimento di Pediatria, Università di Brescia, Brescia, Italy
| | - Serena Quattrucci
- Dipartimento di Pediatria, Centro Fibrosi Cistica, Sapienza Università e Policlinico Umberto I, Rome, Italy
| | - Donatello Salvatore
- Centro Fibrosi Cistica, Centro Pediatrico Bambino Gesù Basilicata, AOR San Carlo, Potenza, Italy
| | - Federica Zarrilli
- Dipartimento di Bioscienze e Territorio, Università del Molise, Isernia, Italy
| | - Valeria Raia
- Dipartimento di Scienze Mediche Traslazionali, Sezione di Pediatria, Università di Napoli Federico II, Naples, Italy.
| |
Collapse
|
|
25
|
Sun X, Olivier AK, Yi Y, Pope CE, Hayden HS, Liang B, Sui H, Zhou W, Hager KR, Zhang Y, Liu X, Yan Z, Fisher JT, Keiser NW, Song Y, Tyler SR, Goeken JA, Kinyon JM, Radey MC, Fligg D, Wang X, Xie W, Lynch TJ, Kaminsky PM, Brittnacher MJ, Miller SI, Parekh K, Meyerholz DK, Hoffman LR, Frana T, Stewart ZA, Engelhardt JF. Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets. THE AMERICAN JOURNAL OF PATHOLOGY 2014; 184:1309-1322. [PMID: 24637292 PMCID: PMC4005986 DOI: 10.1016/j.ajpath.2014.01.035] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 01/27/2014] [Accepted: 01/30/2014] [Indexed: 02/07/2023]
Abstract
Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients.
Collapse
Affiliation(s)
- Xingshen Sun
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | | | - Yaling Yi
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Christopher E Pope
- Department of Pediatrics, University of Washington, Seattle, Washington; Department of Microbiology, University of Washington, Seattle, Washington
| | - Hillary S Hayden
- Department of Microbiology, University of Washington, Seattle, Washington
| | - Bo Liang
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Hongshu Sui
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Weihong Zhou
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Kyle R Hager
- Department of Microbiology, University of Washington, Seattle, Washington
| | - Yulong Zhang
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Xiaoming Liu
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Ziying Yan
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - John T Fisher
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Nicholas W Keiser
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Yi Song
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Scott R Tyler
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - J Adam Goeken
- Department of Pathology, University of Iowa, Iowa City, Iowa
| | - Joann M Kinyon
- Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa
| | - Matthew C Radey
- Department of Microbiology, University of Washington, Seattle, Washington
| | - Danielle Fligg
- Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa
| | - Xiaoyan Wang
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Weiliang Xie
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Thomas J Lynch
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | - Paul M Kaminsky
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa
| | | | - Samuel I Miller
- Department of Microbiology, University of Washington, Seattle, Washington; Department of Genome Sciences, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington
| | - Kalpaj Parekh
- Department of Cardiothoracic Surgery, University of Iowa, Iowa City, Iowa
| | | | - Lucas R Hoffman
- Department of Pediatrics, University of Washington, Seattle, Washington; Department of Microbiology, University of Washington, Seattle, Washington
| | - Timothy Frana
- Department of Veterinary Diagnostic & Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa
| | - Zoe A Stewart
- Department of Surgery, University of Iowa, Iowa City, Iowa
| | - John F Engelhardt
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa.
| |
Collapse
|
|
26
|
Terlizzi V, Tosco A, Tomaiuolo R, Sepe A, Amato N, Casale A, Mercogliano C, De Gregorio F, Improta F, Elce A, Castaldo G, Raia V. Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis. J Cyst Fibros 2014; 13:579-84. [PMID: 24525081 DOI: 10.1016/j.jcf.2014.01.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Revised: 01/14/2014] [Accepted: 01/15/2014] [Indexed: 11/25/2022]
Abstract
BACKGROUND Currently no tools to predict risk of acute (AP) and recurrent pancreatitis (ARP) in children with cystic fibrosis (CF) are available. We assessed the prevalence of AP/ARP and tested the potential role of Pancreatic Insufficiency Prevalence (PIP) score in a cohort of children with CF. METHODS We identified two groups of children, on the basis of presence/absence of AP/ARP, who were compared for age at diagnosis, clinical features, genotypes and sweat chloride level. PIP score was calculated for each patient. RESULTS 10/167 (5.9%) experienced at least one episode of AP during follow up; 10/10 were pancreatic sufficient (PS). Patients with AP/ARP showed a PIP score ≤0.25 more frequently (6/10) than patients without AP/ARP. The odds ratio (95% CI) of developing pancreatitis was 4.54 (1.22-16.92) for patients with PIP <0.25 when compared with those who have a PIP score >0.25 (p 0.0151). PIP score was correlated with sweat chloride test (p < 0.01). CONCLUSION PIP score, PS status and normal/borderline sweat chloride levels could be applied to predict pancreatitis development in children with CF. ARP could lead to pancreatic insufficiency.
Collapse
Affiliation(s)
- V Terlizzi
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - A Tosco
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - R Tomaiuolo
- CEINGE-Advanced Biotechnology, Naples, Italy; Department of Biochemistry and Biotechnology, University of Naples Federico II, Italy
| | - A Sepe
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - N Amato
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - A Casale
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - C Mercogliano
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - F De Gregorio
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - F Improta
- Department of Translational Medical Sciences, University of Naples Federico II, Italy
| | - A Elce
- CEINGE-Advanced Biotechnology, Naples, Italy; Department of Biochemistry and Biotechnology, University of Naples Federico II, Italy
| | - G Castaldo
- CEINGE-Advanced Biotechnology, Naples, Italy; Department of Biochemistry and Biotechnology, University of Naples Federico II, Italy
| | - V Raia
- Department of Translational Medical Sciences, University of Naples Federico II, Italy.
| |
Collapse
|
|
27
|
Bian Y, Wang L, Chen C, Lu JP, Fan JB, Chen SY, Zhao BH. Quantification of pancreatic exocrine function of chronic pancreatitis with secretin-enhanced MRCP. World J Gastroenterol 2013; 19:7177-7182. [PMID: 24222963 PMCID: PMC3819555 DOI: 10.3748/wjg.v19.i41.7177] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2013] [Revised: 09/04/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To obtain reference values for pancreatic flow output rate (PFR) and peak time (PT) in healthy volunteers and chronic pancreatitis (CP); to correlate quantification of secretin enhanced magnetic resonance cholangiopancreatography (SMRCP) of pancreatic fluid output following secretin with fecal elastase-1 (FE-1) tests.
METHODS: The present study includes 53 subjects comprised of 17 healthy individuals and 36 patients with CP from April 2011 to January 2013. The 36 patients with CP were divided into three groups of mild CP (n = 14), moderate CP (n = 19) and advanced CP (n = 3) by M-ANNHEIM classification for CP.. Fifty-three cases underwent FE-1 test and magnetic resonance imaging using 3.0 T-device (Signa EXCITE, GE Healthcare). Coronal T2-weighted single-shot turbo spin-echo, spiratory triggered, covering the papillae, duodenum and small bowel. MRCP was performed with a heavily T2-weighted fat-suppressed long TE HASTE sequence (thick slab 2D MRCP sequence), repeated every 2 min up to 11 min after 0.1 mL/kg secretin injection (Secrelux, Sanochemia®, Germany). FE-1 test used sandwich enzyme-linked immunosorbent assay (ELISA) test (ScheBo. Tech®, Germany).
RESULTS: A good linear correlation showed between the calculated volume and the actual volume by Phantom experiments. Fifty-three paired Quantification of secretin enhanced magnetic resonance cholangiopancreatography (MRCPQ) and FE-1 data sets were analyzed. The mean FE-1 of 53 cases was 525.41 ± 94.44 μg/g for 17 healthy volunteers, 464.95 ± 136.13 μg/g for mild CP, 301.55 ± 181.55 μg/g for moderate CP, 229.30 ± 146.60 μg/g for advanced CP. Also, there was statistically significant difference in FE-1 (P = 0.0001) between health and CP. The mean values of PFR and PT were 8.18 ± 1.11 mL/min, 5.76 ± 1.71 min for normal; 7.27 ± 2.04 mL/min, 7.71 ± 2.55 min for mild CP; 4.98 ± 2.57 mL/min, 9.10 ± 3.00 min for moderate CP; 4.13 ± 1.83 mL/min, 12.33 ± 1.55 min for advanced CP. Further, statistically significant difference in PFR (P = 0.0001) and PT (P = 0.0001) was observed between health and CP. Besides, there was correlation (r = 0.79) and consistency (K = 0.6) between MRCPQ and ELISA Test. It was related between M-ANNHEIM classification and PFR (r = 0.55), FE-1 (r = 0.57).
CONCLUSION: SMRCP can provide a safe, non-invasive and efficient method to evaluate the exocrine function of the pancreas.
Collapse
|
|
28
|
Wang S, Ma L, Zhuang Y, Jiang B, Zhang X. Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2013; 17:R171. [PMID: 23924602 PMCID: PMC4057406 DOI: 10.1186/cc12850] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2013] [Accepted: 08/07/2013] [Indexed: 12/16/2022]
Abstract
Introduction Malnutrition is a frequent problem associated with detrimental clinical outcomes in critically ill patients. To avoid malnutrition, most studies focus on the prevention of inadequate nutrition delivery, whereas little attention is paid to the potential role of exocrine pancreatic insufficiency (EPI). In this trial, we aim to evaluate the prevalence of EPI and identify its potential risk factors in critically ill adult patients without preexisting pancreatic diseases. Methods In this prospective cross-sectional study, we recruited 563 adult patients with critical illnesses. All details of the patients were documented, stool samples were collected three to five days following the initiation of enteral nutrition, and faecal elastase 1 (FE-1) concentrations were assayed using an enzyme-linked immunosorbent assay kit. Blood samples were also taken to determine serum amylase and lipase activity. Results The percentages of recruited patients with EPI (FE-1 concentration <200 μg/g) and severe EPI (FE-1 concentration <100 μg/g) were 52.2% and 18.3%, respectively. The incidences of steatorrhea were significantly different (P < 0.05) among the patients without EPI, with moderate EPI (FE-1 concentration = 100 to 200 μg/g) and severe EPI (FE-1 concentration < 100 μg/g). Both multivariate logistic regression analysis and z-tests indicated that the occurrence of EPI was closely associated with shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Conclusions More than 50% of critically ill adult patients without primary pancreatic diseases had EPI, and nearly one-fifth of them had severe EPI. The risk factors for EPI included shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. Trial registration NCT01753024
Collapse
|