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Dominguez‐Muñoz JE, Vujasinovic M, de la Iglesia D, Cahen D, Capurso G, Gubergrits N, Hegyi P, Hungin P, Ockenga J, Paiella S, Perkhofer L, Rebours V, Rosendahl J, Salvia R, Scheers I, Szentesi A, Bonovas S, Piovani D, Löhr JM. European guidelines for the diagnosis and treatment of pancreatic exocrine insufficiency: UEG, EPC, EDS, ESPEN, ESPGHAN, ESDO, and ESPCG evidence-based recommendations. United European Gastroenterol J 2025; 13:125-172. [PMID: 39639485 PMCID: PMC11866322 DOI: 10.1002/ueg2.12674] [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: 05/23/2024] [Accepted: 08/12/2024] [Indexed: 12/07/2024] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high-quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence-Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence-based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.
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Affiliation(s)
- J. Enrique Dominguez‐Muñoz
- Department of Gastroenterology and HepatologyUniversity Hospital of Santiago de CompostelaSantiago de CompostelaSpain
| | - Miroslav Vujasinovic
- Department of MedicineKarolinska Institutet and Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
| | | | - Djuna Cahen
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Gabriele Capurso
- Department of GastroenterologySan Raffaele University HospitalMilanItaly
| | | | - Peter Hegyi
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
- Institute of Pancreatic DiseasesSemmelweis UniversityBudapestHungary
- Translational Pancreatology Research GroupInterdisciplinary Center of Excellence for Research and Development and InnovationUniversity of SzegedSzegedHungary
| | - Pali Hungin
- Faculty of Medical SciencesNewcastle UniversityNewcastle‐upon‐TyneUK
| | - Johann Ockenga
- Department of GastroenterologyEndocrinology and Clinical NutritionKlinikum Bremen MitteBremenGermany
| | - Salvatore Paiella
- Unit of Pancreatic SurgeryUniversity of Verona Hospital TrustVeronaItaly
| | - Lukas Perkhofer
- Department of Internal Medicine ISection of Interdisciplinary PancreatologyUlm University HospitalUlmGermany
| | - Vinciane Rebours
- Department of PancreatologyBeaujon HospitalDMU DigestAP‐HPClichyFrance
| | - Jonas Rosendahl
- Department of Internal Medicine IMartin Luther UniversityHalleGermany
| | - Roberto Salvia
- Unit of Pancreatic SurgeryUniversity of Verona Hospital TrustVeronaItaly
| | - Isabelle Scheers
- Pediatric GastroenterologyHepatology and Nutrition UnitCliniques Universitaires Saint‐LucUniversité Catholique de LouvainBrusselsBelgium
| | - Andrea Szentesi
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
| | - Stefanos Bonovas
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IRCCS Humanitas Research HospitalMilanItaly
| | - Daniele Piovani
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IRCCS Humanitas Research HospitalMilanItaly
| | - J. Matthias Löhr
- Department of Clinical SciencesKarolinska Institutet and Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
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Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet 2021; 397:2195-2211. [PMID: 34090606 DOI: 10.1016/s0140-6736(20)32542-3] [Citation(s) in RCA: 363] [Impact Index Per Article: 90.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 10/03/2020] [Accepted: 11/20/2020] [Indexed: 12/11/2022]
Abstract
Cystic fibrosis is a monogenic disease considered to affect at least 100 000 people worldwide. Mutations in CFTR, the gene encoding the epithelial ion channel that normally transports chloride and bicarbonate, lead to impaired mucus hydration and clearance. Classical cystic fibrosis is thus characterised by chronic pulmonary infection and inflammation, pancreatic exocrine insufficiency, male infertility, and might include several comorbidities such as cystic fibrosis-related diabetes or cystic fibrosis liver disease. This autosomal recessive disease is diagnosed in many regions following newborn screening, whereas in other regions, diagnosis is based on a group of recognised multiorgan clinical manifestations, raised sweat chloride concentrations, or CFTR mutations. Disease that is less easily diagnosed, and in some cases affecting only one organ, can be seen in the context of gene variants leading to residual protein function. Management strategies, including augmenting mucociliary clearance and aggressively treating infections, have gradually improved life expectancy for people with cystic fibrosis. However, restoration of CFTR function via new small molecule modulator drugs is transforming the disease for many patients. Clinical trial pipelines are actively exploring many other approaches, which will be increasingly needed as survival improves and as the population of adults with cystic fibrosis increases. Here, we present the current understanding of CFTR mutations, protein function, and disease pathophysiology, consider strengths and limitations of current management strategies, and look to the future of multidisciplinary care for those with cystic fibrosis.
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Affiliation(s)
- Michal Shteinberg
- Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel; Rappaport Faculty of Medicine, The Technion-Israel Institute of Technology, Haifa, Israel
| | - Iram J Haq
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | | | - Jane C Davies
- National Heart and Lung Institute, Imperial College London, London, UK; Royal Brompton and Harefield, Guy's and St Thomas' NHS Foundation Trust, London, UK.
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3
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Abstract
BACKGROUND Most people with cystic fibrosis (CF) (80% to 90%) need pancreatic enzyme replacement therapy (PERT) to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of PERT is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. OBJECTIVES To evaluate the efficacy and safety of PERT in children and adults with CF and to compare the efficacy and safety of different formulations of PERT and their appropriateness in different age groups. Also, to compare the effects of PERT in CF according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 07 November 2019. We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 26 December 2019. SELECTION CRITERIA Randomised and quasi-randomised controlled trials in people of any age, with CF and receiving PERT, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other PERT preparations. DATA COLLECTION AND ANALYSIS Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias and quality of the evidence (GRADE) of the trials included in the review. MAIN RESULTS 14 trials were included in the review (641 children and adults with CF), two of these were parallel trials and 12 were cross-over trials. Interventions included different enteric and non-enteric-coated preparations of varying formulations in comparison to each other. The number of participants in each trial varied between 14 and 129. 13 trials were for a duration of four weeks and one trial lasted seven weeks. The majority of the trials had an unclear risk of bias from the randomisation process as the details of this were not given; they also had a high risk of attrition bias and reporting bias. The quality of the evidence ranged from moderate to very low. We mostly could not combine data from the trials as they compared different formulations and the findings from individual trials provided insufficient evidence to determine the size and precision of the effects of different formulations. AUTHORS' CONCLUSIONS There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over trials is likely to underestimate the level of inconsistency between the results of the trials due to over-inflation of CIs from the individual trials.There is no evidence on the long-term effectiveness and risks associated with PERT. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.
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Affiliation(s)
| | - Arturo Solis-Moya
- Servicio de Neumología, Hospital Nacional de Niños, San José, Costa Rica
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Altman K, McDonald CM, Michel SH, Maguiness K. Nutrition in cystic fibrosis: From the past to the present and into the future. Pediatr Pulmonol 2019; 54 Suppl 3:S56-S73. [PMID: 31715089 DOI: 10.1002/ppul.24521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 08/19/2019] [Indexed: 12/13/2022]
Abstract
Nutritional management is an integral part of multidisciplinary care for persons with cystic fibrosis. This review will look at how nutrition care has evolved over time. In addition, we will look at how some newer therapies impact nutrition care.
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Affiliation(s)
- Kimberly Altman
- Gunnar Esiason Adult Cystic Fibrosis and Lung Center, New York Presbyterian/Columbia University Medical Center, New York, New York, United States
| | | | - Suzanne H Michel
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States
| | - Karen Maguiness
- Section of Pediatric Pulmonology, Allergy, and Sleep Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States
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Layer P, Kashirskaya N, Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J Gastroenterol 2019; 25:2430-2441. [PMID: 31171887 PMCID: PMC6543241 DOI: 10.3748/wjg.v25.i20.2430] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 04/02/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.
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Affiliation(s)
- Peter Layer
- Department of Internal Medicine, Israelitic Hospital, Hamburg 22297, Germany
| | - Nataliya Kashirskaya
- Department of Genetic Epidemiology (Cystic Fibrosis group), Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moscow 115522, Russia
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman 83001, Ukraine
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Colombo C, Nobili RM, Alicandro G. Challenges with optimizing nutrition in cystic fibrosis. Expert Rev Respir Med 2019; 13:533-544. [PMID: 31094240 DOI: 10.1080/17476348.2019.1614917] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction. Optimizing nutrition remains the cornerstone of therapy for patients with cystic fibrosis (CF) since it is associated with better pulmonary function and survival. However, a significant proportion of patients still fail to achieve normal growth and nutritional status. Areas covered. This review describes the current challenges in providing effective nutritional therapy in CF with a focus on the current issues related to energy imbalance, dietary composition, adherence to nutritional recommendations, pancreatic enzyme replacement therapy, and the effects of modulators of the CF transmembrane conductance regulator. Expert opinion. CF is a multisystemic disease that requires a personalized nutritional approach with accurate evaluation of energy balance. There is an urgent need for evidence-based recommendations on the dietary composition, in consideration of the increasing prevalence of overweight, diabetes and the potential effects of fatty acids on inflammation and immune response. More research into new pancreatic enzyme formulations is also required.
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Affiliation(s)
- Carla Colombo
- a Department of Pathophysiology and Transplantation , Università degli Studi di Milano , Milan , Italy.,b Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan , Italy
| | - Rita Maria Nobili
- b Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Centre , Milan , Italy
| | - Gianfranco Alicandro
- c Department of Clinical Sciences and Community Health , Università degli Studi di Milano , Milano , Italy
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Shandro BM, Nagarajah R, Poullis A. Challenges in the management of pancreatic exocrine insufficiency. World J Gastrointest Pharmacol Ther 2018; 9:39-46. [PMID: 30397535 PMCID: PMC6212541 DOI: 10.4292/wjgpt.v9.i5.39] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/06/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic exocrine insufficiency (PEI) occurs when the insufficient secretion or function of pancreatic enzymes leads to maldigestion, most commonly as a result of chronic pancreatitis and pancreatic cancer. The condition is associated with significant morbidity and reductions in quality of life, even in milder forms. The challenges in approaching this condition include the non-specific presentation of mild to moderate PEI, and the lack of a convenient, accurate diagnostic test in this cohort. Classical symptoms appear late in the disease, and the diagnosis should be considered before steatorrhoea develops. Direct pancreatic function tests are the reference standard for diagnosis, but are invasive and not widely available. The faecal elastase-1 (FE-1) stool test is widely available and has been shown to be as effective as the 13C-mixed triglyceride breath test in more advanced disease. We recommend a pragmatic diagnostic approach that combines clinical history, assessment of nutritional status and measurement of FE-1. The critical first step is to consider the diagnosis. Once the diagnosis is confirmed, pancreatic enzyme replacement therapy should be initiated. The variety of enzyme preparations and recommended dosing regimens can present a challenge when selecting an adequate initial dose. Non-response should be actively sought and addressed in a systematic manner. This article discusses these challenges, and presents a practical approach to the diagnosis and management of PEI.
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Affiliation(s)
- Benjamin Myles Shandro
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
| | - Rani Nagarajah
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
| | - Andrew Poullis
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
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Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in Cystic Fibrosis. J Cyst Fibros 2017; 16 Suppl 2:S70-S78. [DOI: 10.1016/j.jcf.2017.06.011] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/30/2017] [Accepted: 06/30/2017] [Indexed: 12/19/2022]
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Chin M, Aaron SD, Bell SC. The treatment of the pulmonary and extrapulmonary manifestations of cystic fibrosis. Presse Med 2017; 46:e139-e164. [PMID: 28576636 DOI: 10.1016/j.lpm.2016.11.030] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 10/12/2016] [Accepted: 11/06/2016] [Indexed: 12/26/2022] Open
Abstract
Cystic fibrosis (CF) is a complex multisystem disease with considerable between patient variability in its manifestations and severity. In the past several decades, the range of treatments and the evidence to support their use for the pulmonary and extrapulmonary manifestations of CF have increased dramatically, contributing to the improved median survival of patients. As therapy for CF has evolved, new challenges including treatment adherence, medication intolerance and allergy, medical complications and coping with the burden of disease in the context of having a family and managing employment have arisen. While the majority of current therapy focuses primarily on improving symptoms, new therapies (CFTR modulators) target the underlying genetic defect.
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Affiliation(s)
- Melanie Chin
- Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Rode Road, Chermside, Brisbane, QLD 4032, Australia
| | - Shawn D Aaron
- The Ottawa Hospital Research Institute, University of Ottawa, 501, Smyth Road, K1H 8L6 Ottawa, Canada
| | - Scott C Bell
- Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Rode Road, Chermside, Brisbane, QLD 4032, Australia; QIMR Berghofer Medical Research Institute, 300, Herston Road, Herston, QLD 4006, Australia; School of Medicine, The University of Queensland, Brisbane, QLD 4006, Australia.
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Kessler L, Abély M. Atteinte pancréatique exocrine et endocrine dans la mucoviscidose. Arch Pediatr 2016; 23:12S21-12S32. [DOI: 10.1016/s0929-693x(17)30059-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Abstract
BACKGROUND Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. OBJECTIVES To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. SELECTION CRITERIA Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. DATA COLLECTION AND ANALYSIS Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. MAIN RESULTS One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001). AUTHORS' CONCLUSIONS There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.
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Affiliation(s)
- Usha Rani Somaraju
- Malla Reddy Medical College for WomenDepartment of BiochemistrySuraram Main RoadJeedimetla Qutbullapur MunicipalityHyderabadIndia500 055
| | - Arturo Solis‐Moya
- Hospital Nacional de NiñosServicio de NeumologíaCaja Costarricense del Seguro SocialPO Box 220 ‐ 1017San JoséCosta Rica
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Smith RC, Smith SF, Wilson J, Pearce C, Wray N, Vo R, Chen J, Ooi CY, Oliver M, Katz T, Turner R, Nikfarjam M, Rayner C, Horowitz M, Holtmann G, Talley N, Windsor J, Pirola R, Neale R. Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency. Pancreatology 2016; 16:164-80. [PMID: 26775768 DOI: 10.1016/j.pan.2015.12.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 12/01/2015] [Accepted: 12/10/2015] [Indexed: 02/06/2023]
Abstract
AIM Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). METHODS A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. RESULTS AND CONCLUSIONS Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy.
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Affiliation(s)
| | - Ross C Smith
- Department of Surgery, University of Sydney, NSW, Australia; Australasian Pancreatic Club, Australia.
| | | | | | - Callum Pearce
- Institute for Immunology and Infectious Diseases, Murdoch University, WA, Australia; Fremantle Hospital, WA, Australia
| | - Nick Wray
- Nutrition & Dietetics, School of Health Sciences, Flinders University, Adelaide, SA, Australia
| | - Ruth Vo
- Liverpool Hospital, University of NSW, Australia
| | - John Chen
- South Australian Liver Transplant & HPB Unit, RAH & Flinders Medical Centre, SA, Australia
| | - Chee Y Ooi
- School of Women's and Children's Health, Dept. of Medicine, University of NSW, Australia; Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW, Australia
| | - Mark Oliver
- Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, VIC, Australia
| | - Tamarah Katz
- Sydney Children's Hospital, Randwick, NSW, Australia
| | - Richard Turner
- Hobart Clinical School and Dept. Surgery, University of Tasmania, Australia
| | - Mehrdad Nikfarjam
- Dept. Surgery, University of Melbourne, VIC, Australia; Australasian Pancreatic Club, Australia
| | - Christopher Rayner
- School of Medicine, University of Adelaide, SA, Australia; Centre for Digestive Diseases, Royal Adelaide Hospital, SA, Australia
| | - Michael Horowitz
- Endocrine and Metabolic Unit, University of Adelaide and Royal Adelaide Hospital, SA, Australia
| | - Gerald Holtmann
- Faculty of Medicine and Biomedical Sciences, University of Queensland, Australia; Translational Research Institute, Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Qld, Australia
| | - Nick Talley
- Faculty of Health and Medicine, University of Newcastle, NSW, Australia; Royal Australasian College of Physicians, Australia
| | - John Windsor
- Dept. of Surgery, University of Auckland, New Zealand
| | - Ron Pirola
- Faculty of Medicine, SW Sydney Clinical School, University of NSW, Australia
| | - Rachel Neale
- Cancer Control Laboratory, Queensland Institute of Medical Research, Qld, Australia
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Lowe ME, Whitcomb DC. Next Generation of Pancreatic Enzyme Replacement Therapy: Recombinant Microbial Enzymes and Finding the Perfect Lipase. Gastroenterology 2015; 149:1678-81. [PMID: 26505819 DOI: 10.1053/j.gastro.2015.10.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Mark E Lowe
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh/UPMC, Pittsburgh, Pennsylvania
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Lindkvist B, Phillips ME, Domínguez-Muñoz JE. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: Prevalence and diagnostic use. Pancreatology 2015; 15:589-97. [PMID: 26243045 DOI: 10.1016/j.pan.2015.07.001] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/06/2015] [Accepted: 07/07/2015] [Indexed: 12/11/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) frequently occurs secondary to exocrine pancreatic disease (e.g. chronic pancreatitis, cystic fibrosis, cancer) or pancreatic/gastrointestinal surgery, resulting in the maldigestion of nutrients and consequently malnutrition. Pancreatic enzyme replacement therapy (PERT) is the cornerstone of PEI management. Despite its clinical relevance, the diagnosis of PEI in clinical practice is challenging, as the current gold standard test is cumbersome, and alternatives have limited availability or accuracy. There is a need for accurate and easily applicable diagnostic modalities. We review the prevalence of clinical symptoms and changes in anthropometric measurements and laboratory nutritional markers indicative of malnutrition in patients with PEI, and the relevance of these findings in diagnosing PEI and monitoring PERT efficacy. Based on limited available evidence, assessment of clinical symptoms, body weight, body mass index and other anthropometric parameters are not sensitive methods for PEI diagnosis, owing to high variability and multiple confounding factors, but appear useful in monitoring PERT efficacy. Limited evidence precludes strong recommendations but suggests that serum levels of vitamin E, magnesium, and plasma proteins, notably retinol binding protein, albumin, and prealbumin, may have diagnostic utility in PEI. Studies show that assessment of changes in these and other nutritional parameters is helpful in monitoring PERT efficacy. Further research is needed to confirm the diagnostic accuracy of these parameters for PEI. Until such data are available, a nutritional evaluation including circulating vitamin E, magnesium, retinol binding protein, albumin, and prealbumin may be used to evaluate the probability of PEI in clinical practice when reliable pancreatic function tests are not available.
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Affiliation(s)
- Björn Lindkvist
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Mary E Phillips
- Department of Nutrition and Dietetics, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
| | - J Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
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Abstract
PURPOSE OF REVIEW The article reviews advances in gastrointestinal aspects of cystic fibrosis (CF) published in the literature over the past year, and highlights new and interesting research. RECENT FINDINGS Animal models can be used to understand the pathophysiology of gastrointestinal complications in CF. The CF mouse is useful for studying distal intestinal obstruction, dysmotility and dysbiosis, and the CF pig model has helped us better understand meconium ileus and pancreatic and hepatobiliary secretory problems. Studies in humans help elucidate the evolution of pancreatic insufficiency, how reflux may lead to lung disease, problems with intestinal dysmotility, mechanisms leading to pancreatitis and the increased prevalence of gastrointestinal cancer. Biomarkers are shedding light on CF-related liver disease. Rectal biopsies can help in diagnosis and in studying new drugs for CF. SUMMARY Gastrointestinal complications of CF are likely to be seen with increasing frequency as patients with CF lead longer lives. CF animal models and modern research techniques are providing new insights into extrapulmonary complications. CF clinicians should be familiar with diagnosis and management of common gastrointestinal complications and should build bridges with specialists so that referrals can be made when needed.
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Lima TRL, Guimarães FS, Sá Ferreira A, Penafortes JTS, Almeida VP, Lopes AJ. Correlation between posture, balance control, and peripheral muscle function in adults with cystic fibrosis. Physiother Theory Pract 2013; 30:79-84. [DOI: 10.3109/09593985.2013.820246] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Butler CA, Bell SC. New insights into gene-specific management in cystic fibrosis from the 2012 European Cystic Fibrosis Conference. Expert Rev Respir Med 2012; 6:499-501. [PMID: 23134242 DOI: 10.1586/ers.12.52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
35th European Cystic Fibrosis Conference The Convention Centre, Dublin, Ireland, 6-9 June 2012 More than 2400 delegates attended the 35th European Cystic Fibrosis Conference held in Dublin between 6 and 9 June 2012. More than 525 abstracts were presented at the conference. There were 30 symposia with four speakers at each, in addition to numerous workshops where researchers had the opportunity to present their work into scientific, clinical and psychological aspects of cystic fibrosis care. Keynote speakers provided state of the art lectures in two plenary sessions. This report highlights two important areas in the field of molecular genetics and the need for new and validated clinical trial end points.
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Affiliation(s)
- Claire Ann Butler
- Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, UK
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Rowe SM, Borowitz DS, Burns JL, Clancy JP, Donaldson SH, Retsch-Bogart G, Sagel SD, Ramsey BW. Progress in cystic fibrosis and the CF Therapeutics Development Network. Thorax 2012; 67:882-90. [PMID: 22960984 PMCID: PMC3787701 DOI: 10.1136/thoraxjnl-2012-202550] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.
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Affiliation(s)
- Steven M Rowe
- Department of Medicine, University of Alabama at Birmingham, 1819 University Boulevard (MCLM 768), Birmingham, AL 35294, USA.
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Kalnins D, Wilschanski M. Maintenance of nutritional status in patients with cystic fibrosis: new and emerging therapies. DRUG DESIGN DEVELOPMENT AND THERAPY 2012; 6:151-61. [PMID: 22787388 PMCID: PMC3392141 DOI: 10.2147/dddt.s9258] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health.
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Affiliation(s)
- Daina Kalnins
- Clinical Dietetics, Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
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