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Lee AA, Park WG. PPI and PERT for Exocrine Pancreatic Insufficiency-Pertinent or Problem? Dig Dis Sci 2025; 70:1288-1289. [PMID: 39984786 DOI: 10.1007/s10620-025-08932-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 02/14/2025] [Indexed: 02/23/2025]
Affiliation(s)
- Alice A Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, 300 Pasteur Drive Stanford M/C 5244, Stanford, CA, 94305, USA.
| | - Walter G Park
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, 300 Pasteur Drive Stanford M/C 5244, Stanford, CA, 94305, USA
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2
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Phillips AE, Brownell JN, Tindall A, Kiernan BD, Patel D, Gelfond D, Stallings VA. Proton-Pump Inhibitors and Fat Absorption in Cystic Fibrosis and Pancreatic Insufficiency: A Randomized Crossover Pilot Trial. Dig Dis Sci 2025; 70:968-977. [PMID: 39537890 PMCID: PMC11920344 DOI: 10.1007/s10620-024-08728-8] [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: 05/03/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Dietary fat malabsorption contributes to poor nutritional status in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton-pump inhibitors (PPI) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve dietary fat absorption has been accepted in clinical practice despite limited evidence. AIMS This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole to determine if PPI improved the efficacy of PERT as indicated by measures of dietary fat absorption. METHODS Fat malabsorption via stool coefficient of fat absorption (CFA) and malabsorption blood test (MBT), gastrointestinal pH (wireless motility capsule [WMC]), and quality of life (QOL) were assessed after 14 days on both placebo or PPI (omeprazole). RESULTS Total 19 subjects enrolled, 13 were randomized, and 9 provided paired results on placebo and PPI. The 3 subject results for CFA were as follows: 1 increased, 1 decreased, and 1 was within the reference range in both tests for fat absorption. For 9 MBT subjects, 7 decreased and 2 increased fat absorption. For the 4 WMC studies, no change in transit times, nor in pH profiles were noted. No differences were seen in the domains of the two QOL questionnaires comparing placebo and PPI. CONCLUSIONS These limited descriptive pilot study results in participants with CF and EPI on PERT evaluated by stool, blood, and QOL tests did not suggest improvement in fat absorption attributable to PPI.
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Affiliation(s)
- Anna Evans Phillips
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Jefferson N Brownell
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, 3500 Civic Center Blvd., Philadelphia, PA, 19104, USA.
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Alyssa Tindall
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, 3500 Civic Center Blvd., Philadelphia, PA, 19104, USA
| | - Bridget Dowd Kiernan
- Division of Gastroenterology, Hepatology, and Nutrition, New York University, New York, NY, USA
| | - Dhiren Patel
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cardinal Glennon Children's Medical Center, Saint Louis University School of Medicine, St. Louis, MO, USA
| | - Daniel Gelfond
- WNY Pediatric Gastroenterology and Nutrition, DGRD, Buffalo, NY, USA
| | - Virginia A Stallings
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, 3500 Civic Center Blvd., Philadelphia, PA, 19104, USA
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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3
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Morris-Stiff G. Exocrine pancreatic insufficiency and fat malabsorption related to pancreatectomy and other gastrointestinal surgery: A narrative review. Nutr Clin Pract 2024; 39 Suppl 1:S35-S45. [PMID: 38429966 DOI: 10.1002/ncp.11123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/08/2024] [Accepted: 01/08/2024] [Indexed: 03/03/2024] Open
Abstract
Surgical resection is the mainstay of treatment for patients with tumors of the pancreas. There are a number of well-recognized complications that account for the significant morbidity associated with the operation, including exocrine pancreatic insufficiency (EPI). Patients with pancreatic cancer commonly have evidence of EPI prior to surgery, and this is exacerbated by an operation, the extent of the insult being dependent on the indication for surgery and the operation performed. There are accumulating data to demonstrate that treatment of EPI with pancreatic enzyme replacement (PERT) enhances clinical outcomes after surgery by reducing critical complications; this in turn may enhance oncological outcomes. Data would indicate that quality of life (QoL) is also improved after surgery when enzymes are prescribed. To date, many surgeons and clinicians have not appreciated the need for PERT or the benefits it may bring to their patients; therefore, education of clinicians remains a significant opportunity. In turn, patient education about consumption of the correct dose of enzymes at the appropriate time is key to an optimal outcome. In addition, because of the complex nature of the regulation of pancreatic exocrine function, there is evidence to support the presence of EPI following operations performed on other gastrointestinal (GI) organs, including the esophagus, stomach, and small intestine. The aim of this review is to document the existing published evidence in relation to EPI and its treatment with PERT following GI surgery.
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Dutta AK, Jain A, Jearth V, Mahajan R, Panigrahi MK, Sharma V, Goenka MK, Kochhar R, Makharia G, Reddy DN, Kirubakaran R, Ahuja V, Berry N, Bhat N, Dutta U, Ghoshal UC, Jain A, Jalihal U, Jayanthi V, Kumar A, Nijhawan S, Poddar U, Ramesh GN, Singh SP, Zargar S, Bhatia S. Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship. Indian J Gastroenterol 2023; 42:601-628. [PMID: 37698821 DOI: 10.1007/s12664-023-01428-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College and Hospital, Vellore, 632 004, India.
| | | | - Vaneet Jearth
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ramit Mahajan
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | - Govind Makharia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | | | - Richard Kirubakaran
- Center of Biostatistics and Evidence Based Medicine, Vellore, 632 004, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Neha Berry
- BLK Institute of Digestive and Liver Disease, New Delhi, 201 012, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Uday Chand Ghoshal
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Jain
- Choithram Hospital and Research Center, Indore, 452 014, India
| | | | - V Jayanthi
- Sri Ramachandra Medical College, Chennai, 600 116, India
| | - Ajay Kumar
- Institute of Digestive and Liver Diseases, BLK - Max Superspeciality Hospital, New Delhi, 201 012, India
| | | | - Ujjal Poddar
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Shivram P Singh
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Showkat Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Kashmir, 190 011, India
| | - Shobna Bhatia
- Sir H N Reliance Foundation Hospital, Mumbai, 400 004, India
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Digestive enzyme supplementation in prescription drugs, over-the-counter drugs, and enzyme foods. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2022. [DOI: 10.1007/s40005-022-00605-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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Cañamares-Orbis P, Bernal-Monterde V, Sierra-Gabarda O, Casas-Deza D, Garcia-Rayado G, Cortes L, Lué A. Impact of Liver and Pancreas Diseases on Nutritional Status. Nutrients 2021; 13:1650. [PMID: 34068295 PMCID: PMC8153270 DOI: 10.3390/nu13051650] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/02/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022] Open
Abstract
Liver and pancreatic diseases have significant consequences on nutritional status, with direct effects on clinical outcomes, survival, and quality of life. Maintaining and preserving an adequate nutritional status is crucial and should be one of the goals of patients with liver or pancreatic disease. Thus, the nutritional status of such patients should be systematically assessed at follow-up. Recently, great progress has been made in this direction, and the relevant pathophysiological mechanisms have been better established. While the spectrum of these diseases is wide, and the mechanisms of the onset of malnutrition are numerous and interrelated, clinical and nutritional manifestations are common. The main consequences include an impaired dietary intake, altered macro and micronutrient metabolism, energy metabolism disturbances, an increase in energy expenditure, nutrient malabsorption, sarcopenia, and osteopathy. In this review, we summarize the factors contributing to malnutrition, and the effects on nutritional status and clinical outcomes of liver and pancreatic diseases. We explain the current knowledge on how to assess malnutrition and the efficacy of nutritional interventions in these settings.
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Affiliation(s)
- Pablo Cañamares-Orbis
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge, 22004 Huesca, Spain;
| | - Vanesa Bernal-Monterde
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Olivia Sierra-Gabarda
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Diego Casas-Deza
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain; (V.B.-M.); (O.S.-G.); (D.C.-D.)
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
| | - Guillermo Garcia-Rayado
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
- Service of Digestive Diseases, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Luis Cortes
- Instituto de Investigación Sanitaria (IIS) Aragón, 50009 Zaragoza, Spain; (G.G.-R.); (L.C.)
- Service of Digestive Diseases, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
| | - Alberto Lué
- Unidad de Gastroenterología, Hepatología y Nutrición, Hospital Universitario San Jorge, 22004 Huesca, Spain;
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Ng SM, Moore HS. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev 2021; 4:CD003424. [PMID: 33905540 PMCID: PMC8079129 DOI: 10.1002/14651858.cd003424.pub5] [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: 11/09/2022]
Abstract
BACKGROUND Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review. OBJECTIVES To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals, abstract books and conference proceedings. Both authors double checked the reference lists of the searches Most recent search of the Group's Trials Register: 26 April 2021. On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic. SELECTION CRITERIA All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS The searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. AUTHORS' CONCLUSIONS Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
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Affiliation(s)
- Sze May Ng
- Department of Paediatrics, Southport & Ormskirk NHS Trust, Ormskirk District General Hospital, Ormskirk, UK
| | - Helen S Moore
- Department of Paediatrics, Southport & Ormskirk NHS Trust, Ormskirk District General Hospital, Ormskirk, UK
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Abstract
Chronic pancreatitis is a complex and irreversible disease of the pancreas and is associated with significant morbidity and mortality. Nutrition deficiencies in chronic pancreatitis are common and can be atypical in nature. As such, the management of these deficiencies can be individualized for patients. The aim of this review is to discuss the components of nutrition deficiencies in chronic pancreatitis, their management, and the current areas of research that are being explored. The clinical guidelines of major national and international societies were analyzed for recommendations on the nutrition management of chronic pancreatitis. The etiology of nutrition deficiencies in chronic pancreatitis is multifactorial and includes aspects of exocrine and/or endocrine dysfunction, significant abdominal pain, often persistent alcohol consumption, and increased metabolic activity. A large number of patients with nutrition deficiencies are underrecognized and undertreated. Although the majority of these patients can be managed by oral and pancreatic enzyme supplementation, some patients may require enteral tube feeding and, in rare cases, parenteral feeding. Current areas of research include the accurate identification of patients at risk for nutrition deficiencies, optimization of feeding regimens, and research into islet cell autotransplantation.
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Affiliation(s)
- Stephen J O'Brien
- Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Endashaw Omer
- Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, Kentucky, USA
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10
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Exocrine Pancreatic Insufficiency and Nutritional Complications. Respir Med 2020. [DOI: 10.1007/978-3-030-42382-7_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Rational Use of Pancreatic Enzymes for Pancreatic Insufficiency and Pancreatic Pain. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1148:323-343. [PMID: 31482505 DOI: 10.1007/978-981-13-7709-9_14] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
We describe the rational use of enteric coated and unprotected replacement pancreatic enzymes for treatment of malabsorption due to pancreatic insufficiency and for pancreatic pain. Enteric coated formulations mix poorly with food allowing separation of enzymes and nutrients when emptying from the stomach. The site of dissolution of the enteric coating in the intestine is also unpredictable and enzymes may not be released until the distal intestine. Together, these barriers result in the lack of dose-response such that the strategy of increasing the dosage following a suboptimal effect is often ineffective. The ability to maintain the intragastric pH ≥4 with the combination of proton pump inhibitors and antacids suggests that it should be possible to reliably obtain a good response with uncoated enzymes. We also discuss the recognition, treatment and prevention of nutritional deficiencies associated with pancreatic insufficiency and recommend a test and treat strategy to identify and resolve nutritional deficits. Finally, we focus on mechanisms causing pain that may be amenable to therapy with pancreatic enzymes. Pain due to malabsorbed digestive contents can be prevented by successful therapy of malabsorption. Feedback inhibition of endogenous pancreatic secretion can prevent pain associated with pancreatic secretion but requires use of non-enteric coated formulations.
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de la Iglesia-García D, Huang W, Szatmary P, Baston-Rey I, Gonzalez-Lopez J, Prada-Ramallal G, Mukherjee R, Nunes QM, Domínguez-Muñoz JE, Sutton R, NIHR Pancreas Biomedical Research Unit Patient Advisory Group. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut 2017; 66:1354-1355. [PMID: 27941156 PMCID: PMC5530474 DOI: 10.1136/gutjnl-2016-312529] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 11/06/2016] [Accepted: 11/18/2016] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. DESIGN Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. RESULTS A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. CONCLUSIONS PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
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Affiliation(s)
- Daniel de la Iglesia-García
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK,Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain
| | - Wei Huang
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK,Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Peter Szatmary
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
| | - Iria Baston-Rey
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain
| | - Jaime Gonzalez-Lopez
- Department of Pharmacy, University Hospital of Santiago de Compostela, Compostela, Spain
| | - Guillermo Prada-Ramallal
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Compostela, Spain
| | - Rajarshi Mukherjee
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
| | - Quentin M Nunes
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
| | - J Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Compostela, Spain
| | - Robert Sutton
- NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, University of Liverpool, Liverpool, UK
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Khatkov IE, Maev IV, Bordin DS, Kucheryavyi YA, Abdulkhakov SR, Alekseenko SA, Alieva EI, Alikhanov RB, Bakulin IG, Baranovsky AY, Beloborodova EV, Belousova EA, Buriev IM, Bystrovskaya EV, Vertyankin SV, Vinokurova LV, Galperin EI, Gorelov AV, Grinevich VB, Danilov MV, Darvin VV, Dubtsova EA, Dyuzheva TG, Egorov VI, Efanov MG, Zakharova NV, Zagainov VE, Ivashkin VT, Izrailov RE, Korochanskaya NV, Kornienko EA, Korobka VL, Kokhanenko NY, Livzan MA, Loranskaya ID, Nikolskaya KA, Osipenko MF, Okhlobystin AV, Pasechnikov VD, Plotnikova EY, Polyakova SI, Sablin OA, Simanenkov VI, Ursova NI, Tsvirkun VV, Tsukanov VV, Shabunin AV. [The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy]. TERAPEVT ARKH 2017; 89:80-87. [PMID: 28914856 DOI: 10.17116/terarkh201789880-87] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Pancreatology Club Professional Medical Community, 1A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Kazan State Medical University, Ministry of Health of Russia, Kazan; 4Kazan (Volga) Federal University, Kazan; 5Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk; 6Morozov City Children's Clinical Hospital, Moscow Healthcare Department, Moscow; 7I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 8Siberian State Medical University, Ministry of Health of Russia, Tomsk; 9M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 10Maimonides State Classical Academy, Moscow; 11V.I. Razumovsky State Medical University, Ministry of Health of Russia, Saratov; 12I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 13S.M. Kirov Military Medical Academy, Ministry of Defense of Russia, Saint Petersburg; 14Surgut State Medical University, Ministry of Health of Russia, Surgut; 15City Clinical Hospital Five, Moscow Healthcare Department, Moscow; 16Nizhny Novgorod Medical Academy, Ministry of Health of Russia, Nizhny Novgorod; 17Territorial Clinical Hospital Two, Ministry of Health of the Krasnodar Territory, Krasnodar; 18Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg; 19Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don; 20Omsk Medical University, Ministry of Health of Russia, Omsk; 21Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 22Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk; 23Stavropol State Medical University, Ministry of Health of Russia, Stavropol; 24Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo; 25N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Russian Ministry for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint Petersburg; 27Research Institute for Medical Problems of the North, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy.
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Affiliation(s)
- I E Khatkov
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy; FGBOU VO 'Moskovskij gosudarstvennyj mediko-stomatologicheskij universitet im. A.I. Evdokimova' Minzdrava Rossii, Moskva
| | - I V Maev
- FGBOU VO 'Moskovskij gosudarstvennyj mediko-stomatologicheskij universitet im. A.I. Evdokimova' Minzdrava Rossii, Moskva
| | - D S Bordin
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy; GBOU VPO 'Tverskoj gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Tver'
| | - Yu A Kucheryavyi
- FGBOU VO 'Moskovskij gosudarstvennyj mediko-stomatologicheskij universitet im. A.I. Evdokimova' Minzdrava Rossii, Moskva
| | - S R Abdulkhakov
- FGBOU VO 'Kazanskij gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Kazan'; FGAOU VO 'Kazanskij federal'nyj universitet', Kazan'
| | - S A Alekseenko
- FGBOU VO 'Dal'nevostochnyj gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Habarovsk
| | | | - R B Alikhanov
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - I G Bakulin
- GBOU VPO 'Severo-Zapadnyj gosudarstvennyj meditsinskij universitet im. I.I. Mechnikova' Minzdrava Rossii, Sankt-Peterburg
| | - A Yu Baranovsky
- GBOU VPO 'Severo-Zapadnyj gosudarstvennyj meditsinskij universitet im. I.I. Mechnikova' Minzdrava Rossii, Sankt-Peterburg
| | | | - E A Belousova
- FUV GBUZ MO 'Moskovskij oblastnoj nauchno-issledovatel'skij klinicheskij institut im. M.F. Vladimirskogo', Moskva
| | - I M Buriev
- GOU VPO 'Gosudarstvennaja klassicheskaja akademija im. Majmonida', Moskva
| | - E V Bystrovskaya
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - S V Vertyankin
- FGBOU VO 'Gosudarstvennyj meditsinskij universitet im. V.I. Razumovskogo' Minzdrava Rossii, Saratov
| | - L V Vinokurova
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - E I Galperin
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - A V Gorelov
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - V B Grinevich
- FGBVOU VO 'Voenno-meditsinskaja akademija im. S.M. Kirova' Ministerstva oborony, Sankt-Peterburg
| | - M V Danilov
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - V V Darvin
- FGBOU VO 'Surgutskij gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Surgut
| | - E A Dubtsova
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - T G Dyuzheva
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - V I Egorov
- GBUZ 'Gorodskaja klinicheskaja bol'nitsa #5' DZM, Moskva
| | - M G Efanov
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - N V Zakharova
- GBOU VPO 'Severo-Zapadnyj gosudarstvennyj meditsinskij universitet im. I.I. Mechnikova' Minzdrava Rossii, Sankt-Peterburg
| | - V E Zagainov
- FGBOU VO 'Nizhegorodskaja meditsinskaja akademija' Minzdrava Rossii, Nizhnij Novgorod
| | - V T Ivashkin
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - R E Izrailov
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - N V Korochanskaya
- GBOU 'Kraevaja klinicheskaja bol'nitsa #2' MZ Krasnodarskogo kraja, Krasnodar
| | - E A Kornienko
- FGBOU VO 'Sankt-Peterburgskij gosudarstvennyj pediatricheskij meditsinskij universitet' Minzdrava Rossii, Sankt-Peterburg
| | - V L Korobka
- FGBOU VO 'Rostovskij gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Rostov na Donu
| | - N Yu Kokhanenko
- FGBOU VO 'Sankt-Peterburgskij gosudarstvennyj pediatricheskij meditsinskij universitet' Minzdrava Rossii, Sankt-Peterburg
| | - M A Livzan
- FGBOU VPO 'Omskij meditsinskij universitet' Minzdrava Rossii, Omsk
| | - I D Loranskaya
- FGBOU DPO 'Rossijskaja meditsinskaja akademija poslediplomnogo obrazovanija' Minzdrava Rossii, Moskva
| | - K A Nikolskaya
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - M F Osipenko
- GBOU VPO 'Novosibirskij gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Novosibirsk
| | - A V Okhlobystin
- FGBOU VO 'Pervyj moskovskij gosudarstvennyj meditsinskij universitet im. I.M. Sechenova' Minzdrava Rossii, Moskva
| | - V D Pasechnikov
- FGBOU VO 'Stavropol'skij gosudarstvennyj meditsinskij universitet' Minzdrava Rossii, Stavropol'
| | - E Yu Plotnikova
- FGBOU VO Kemerovskij gosudarstvennyj meditsinskij universitet Minzdrava Rossii, Kemerovo
| | - S I Polyakova
- FGBOU VO 'Rossijskij nauchno-issledovatel'skij meditsinskij universitet im. N.I. Pirogova' Minzdrava Rossii, Moskva
| | - O A Sablin
- FGBU 'Vserossijskij tsentr ekstrennoj i radiatsionnoj meditsiny imeni A.M. Nikiforova' MChS Rossii, Sankt-Peterburg
| | - V I Simanenkov
- GBOU VPO 'Severo-Zapadnyj gosudarstvennyj meditsinskij universitet im. I.I. Mechnikova' Minzdrava Rossii, Sankt-Peterburg
| | - N I Ursova
- FUV GBUZ MO 'Moskovskij oblastnoj nauchno-issledovatel'skij klinicheskij institut im. M.F. Vladimirskogo', Moskva
| | - V V Tsvirkun
- Professional'noe meditsinskoe soobschestvo 'Pankreatologicheskij klub', GBUZ 'Moskovskij klinicheskij nauchno-prakticheskij tsentr im. A.S. Loginova' DZ Moskvy
| | - V V Tsukanov
- FITs KNTs SO RAN, NII meditsinskih problem Severa, Krasnojarsk
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14
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Ng SM, Moore HS, Cochrane Cystic Fibrosis and Genetic Disorders Group. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev 2016; 2016:CD003424. [PMID: 27546383 PMCID: PMC7170416 DOI: 10.1002/14651858.cd003424.pub4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review. OBJECTIVES To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016. SELECTION CRITERIA All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. AUTHORS' CONCLUSIONS Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
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Affiliation(s)
- Sze May Ng
- Southport & Ormskirk NHS Trust, Ormskirk District General HospitalDepartment of PaediatricsWigan RoadOrmskirkLancashireUKL39 2AZ
| | - Helen S Moore
- Southport & Ormskirk NHS Trust, Ormskirk District General HospitalDepartment of PaediatricsWigan RoadOrmskirkLancashireUKL39 2AZ
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15
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Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21 st century. World J Gastroenterol 2014; 20:11467-11485. [PMID: 25206255 PMCID: PMC4155341 DOI: 10.3748/wjg.v20.i33.11467] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 07/18/2014] [Accepted: 07/30/2014] [Indexed: 02/07/2023] Open
Abstract
Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.
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MESH Headings
- Animals
- Antacids/therapeutic use
- Chemistry, Pharmaceutical
- Drug Therapy, Combination
- Enzyme Replacement Therapy/history
- Enzyme Replacement Therapy/trends
- Exocrine Pancreatic Insufficiency/diagnosis
- Exocrine Pancreatic Insufficiency/drug therapy
- Exocrine Pancreatic Insufficiency/enzymology
- Exocrine Pancreatic Insufficiency/history
- Exocrine Pancreatic Insufficiency/physiopathology
- Gastric Emptying/drug effects
- History, 20th Century
- History, 21st Century
- Humans
- Hydrogen-Ion Concentration
- Intestinal Absorption
- Intestine, Small/drug effects
- Intestine, Small/metabolism
- Lipid Metabolism/drug effects
- Pancreas, Exocrine/drug effects
- Pancreas, Exocrine/enzymology
- Pancreas, Exocrine/physiopathology
- Tablets, Enteric-Coated
- Treatment Outcome
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Abstract
BACKGROUND Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. OBJECTIVES To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 17 March 2014. SELECTION CRITERIA All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. AUTHORS' CONCLUSIONS Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
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Affiliation(s)
- Sze May Ng
- Department of Paediatrics, Southport & Ormskirk NHS Trust, Ormskirk District General Hospital, Wigan Road, Ormskirk, Lancashire, UK, L39 2AZ
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17
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Abstract
BACKGROUND Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. OBJECTIVES To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 15 February 2012. SELECTION CRITERIA All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS Both authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS Thirty-eight trials were identified from the searches. Sixteen trials, with 256 participants, were suitable for inclusion. Seven trials were limited to children and three trials enrolled only adults. Meta-analysis was not performed. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. AUTHORS' CONCLUSIONS Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
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Affiliation(s)
- Sze May Ng
- Department of Paediatrics, Southport & Ormskirk NHS Trust, Ormskirk District General Hospital, Ormskirk, UK.
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18
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Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin Exp Gastroenterol 2011; 4:55-73. [PMID: 21753892 PMCID: PMC3132852 DOI: 10.2147/ceg.s17634] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Indexed: 12/14/2022] Open
Abstract
Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.
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Affiliation(s)
- Aaron Fieker
- Division of Digestive Diseases, University of Oklahoma, OKC, OK, USA
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CREON (Pancrelipase Delayed-Release Capsules) for the treatment of exocrine pancreatic insufficiency. Adv Ther 2010; 27:895-916. [PMID: 21086085 DOI: 10.1007/s12325-010-0085-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2010] [Indexed: 12/12/2022]
Abstract
Exocrine pancreatic insufficiency (EPI) is associated with conditions including cystic fibrosis (CF), chronic pancreatitis (CP), and pancreatic surgery (PS). The symptoms include maldigestion, malnutrition, weight loss, flatulence, and steatorrhea. Pancreatic enzyme replacement therapy (PERT) is the standard treatment for EPI; it is regulated in many countries and most recently in the USA following a US FDA mandate for all PERT manufacturers to submit new drug applications. Pancrelipase delayed-release capsules (CREON®, Abbott, Marietta, GA, USA) have been available in Europe since 1984 and in the USA since 1987; a new formulation was the first PERT to gain approval in the USA in 2009. The efficacy and safety of CREON have been demonstrated in double-blind, randomized, placebo-controlled trials in patients with CF aged ≥7 years and in patients with CP or post-PS. The data consistently demonstrate significantly better fat and nitrogen absorption with CREON versus placebo, and improvements in clinical symptoms, stool frequency, and body weight. Additionally, efficacy and safety of CREON have been shown in open-label studies in young children with CF (aged 1 month to 6 years), with control of fat malabsorption and control of clinical symptoms. The most commonly reported adverse events (AEs) with PERT are gastrointestinal disorders and allergic skin reactions. In clinical studies, CREON was well tolerated with very few withdrawals due to AEs and a low frequency of AEs judged treatment related, regardless of patient age. To further support the known safety profile of PERT, all manufacturers are required to investigate risk factors for fibrosing colonopathy, a rare gastrointestinal complication of CF, and the theoretical risk of viral transmission from porcine-derived PERT products. Together, the clinical study data and wealth of clinical experience suggest that CREON is effective and safe in patients with EPI regardless of etiology, with a very favorable risk-benefit profile.
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20
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Krishnamurty DM, Rabiee A, Jagannath SB, Andersen DK. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis. Ther Clin Risk Manag 2009; 5:507-20. [PMID: 19707261 PMCID: PMC2710383 DOI: 10.2147/tcrm.s3196] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Pancreatic enzyme supplements (PES) are used in chronic pancreatitis (CP) for correction of pancreatic exocrine insufficiency (PEI) as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated) and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.
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Abstract
PURPOSE OF REVIEW As in previous reviews in this journal, this review is focused on the most important new observations in chronic pancreatitis made in the past year and the beginning of this year. RECENT FINDINGS Important observations include the following: first, the natural history and course of chronic pancreatitis; second, that smoking enhances the risk of chronic pancreatitis; third, possible new function tests in combination with imaging procedures; fourth, the superiority of surgery compared with endotherapy for long-term pain relief; fifth, new insights in autoimmune pancreatitis. SUMMARY All in all, little progress has recently been made in the field of diagnosis and therapy of chronic pancreatitis. There are some studies in the field of endotherapy and autoimmune pancreatitis that are promising however.
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Abstract
Pancreatic exocrine insufficiency with steatorrhea is a major consequence of pancreatic diseases (eg, chronic pancreatitis, cystic fibrosis, severe acute necrotizing pancreatitis, pancreatic cancer), extrapancreatic diseases such as celiac disease and Crohn's disease, and gastrointestinal and pancreatic surgical resection. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. Therapy for pancreatic exocrine insufficiency is based on the oral administration of pancreatic enzymes aiming at providing the duodenal lumen with sufficient active lipase at the time of gastric emptying of nutrients. Administration of enzymes in the form of enteric-coated minimicrospheres avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. Nevertheless, such factors as acidic intestinal pH and bacterial overgrowth may prevent normalization of fat digestion even in compliant patients. The present article critically reviews current therapeutic approaches to pancreatic exocrine insufficiency.
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Affiliation(s)
- J Enrique Domínguez-Muñoz
- Department of Gastroenterology, University Hospital of Santiago de Compostela, C/ Choupana, s/n, E-15706-Santiago de Compostela, Spain.
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Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, Iglesias-Rey M. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2007; 5:484-8. [PMID: 17445754 DOI: 10.1016/j.cgh.2007.01.004] [Citation(s) in RCA: 120] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Malnutrition persists in most patients with chronic pancreatitis despite an adequate clinical response to oral pancreatic enzyme substitution therapy. Our aims were to analyze the accuracy of the 13C-mixed triglyceride breath test as a tool for evaluating the effect of enzyme therapy on fat digestion in chronic pancreatitis, and to analyze the impact of modifying the therapy according to the breath test on patients' nutritional status. METHODS The accuracy of the breath test for monitoring the effect of therapy was evaluated prospectively in 29 patients with maldigestion secondary to chronic pancreatitis by using the coefficient of fat absorption as the gold standard. Therapy was modified to obtain a normal breath test result in a further 20 chronic pancreatitis patients with malnutrition despite an adequate clinical response to the enzyme therapy; the impact of this therapeutic modification on patients' nutritional status was evaluated. RESULTS The coefficient of fat absorption and breath test results were similar when assessing fat absorption before and during treatment. Modification of the enzyme therapy to normalize fat absorption as assessed by the breath test in the second group of 20 patients was associated with a significant increase of body weight (P < .001), and serum concentrations of retinol binding protein (P < .001) and prealbumin (P < .001). CONCLUSIONS The 13C-mixed triglyceride breath test is an accurate method to evaluate the effect of enzyme therapy on fat digestion. This method is simpler than the standard fecal fat test to assess therapy in patients with pancreatic exocrine insufficiency. Normalizing fat absorption improves nutrition in these patients.
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Affiliation(s)
- J Enrique Domínguez-Muñoz
- Department of Gastroenterology and Foundation for Research in Digestive Diseases, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
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Vecht J, Symersky T, Lamers CBHW, Masclee AAM. Efficacy of lower than standard doses of pancreatic enzyme supplementation therapy during acid inhibition in patients with pancreatic exocrine insufficiency. J Clin Gastroenterol 2006; 40:721-5. [PMID: 16940886 DOI: 10.1097/00004836-200609000-00012] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
GOAL To compare, during strong acid inhibition with omeprazole, the effect of 2 different doses of an enteric-coated pancreatic enzyme preparation on fecal fat excretion and abdominal symptoms in patients with exocrine insufficiency due to chronic pancreatitis (CP). BACKGROUND Treatment with pancreatic enzymes reduces fecal fat excretion in patients with CP but is rather unsuccessful due to irreversible lipase inactivation at pH below 4. STUDY Sixteen patients with CP (3 women, 13 men; age 53+/-3 y) participated in this randomized double blind 2-way cross over study. Fecal fat excretion and fat intake were measured and abdominal symptoms (visual analog scales) were scored during a 2 weeks control period, during omeprazole 60 mg+pancreatic enzymes 10,000 Fédération Internationale Pharmaceutique IU lipase tid (treatment A) for 2 weeks and during omeprazole 60 mg+pancreatic enzymes, 20,000 Fédération Internationale Pharmaceutique IU lipase tid (treatment B) for 2 weeks. RESULTS During acid inhibition with enzyme supplementation fecal fat excretion was significantly (P<0.01) reduced compared with control: 18+/-7 and 18+/-5 g/24 h versus 36+/-8 g/24 h for treatment A, B, and control, respectively. Abdominal symptom score and general well being improved significantly (P<0.05) during treatments A and B versus control. No differences in fat excretion or symptoms scores between treatments A and B were observed. CONCLUSIONS During strong acid inhibition, lower than recommended oral doses of pancreatic enzymes are therapeutically effective with respect to fat absorption and symptom reduction.
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Affiliation(s)
- Juda Vecht
- Department of Gastroenterology-Hepatology, Leiden University Medical Center, The Netherlands
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Johnson CD, Howse F, Fitzsimmons D, Harris S, Pickering R, George SL. Quality of life and functional long-term outcome after partial pancreatoduodenectomy: pancreatogastrostomy versus pancreatojejunostomy. Ann Surg Oncol 2005; 14:750-1. [PMID: 17151790 DOI: 10.1245/s10434-006-9173-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2006] [Accepted: 04/18/2006] [Indexed: 11/18/2022]
Abstract
BACKGROUND To determine the effects of pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) as types of reconstruction after partial pancreatoduodenectomy on postoperative quality of life and long-term gastrointestinal morbidity, the outcomes of 104 patients (PG, n = 63; PJ, n = 41) were evaluated. METHODS To compare the two groups, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-PAN 26) standard and an additional self-developed questionnaire were used. The mean time after surgery was 6.4 +/- 3.4 years. RESULTS In the PG group, there was a significant reduction of gastric acid reflux, gastroduodenal ulcers, and pain compared with before surgery. However, a significant increase in steatorrhea, intolerance toward larger meals, and aversion against certain foods were observed. In the PJ group, no significant change of preoperative symptoms was present except for jaundice. The incidence of diabetes mellitus and the need for pancreatic enzyme substitution had increased significantly but similarly in both groups. The global quality of life was identical in both groups of patients. CONCLUSIONS This analysis demonstrates that the global quality of life was not affected by the type of reconstruction after partial pancreatoduodenectomy. Patients who underwent PG had a significant reduction of gastric reflux, pain, and abdominal discomfort compared with before surgery. Patients in both groups showed an impaired exocrine and endocrine pancreatic function of a similar extent.
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26
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Abstract
Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. The majority of cases in the Western world are related to alcohol consumption. Treatment of alcoholic chronic pancreatitis has been difficult, since the mechanisms of disease progression and the causes of pain are poorly understood. The conservative management of chronic pancreatitis focuses on (a) avoidance of precipitating factors such as alcohol and smoking; (b) treatment of pain, and (c) replacement of exocrine and endocrine function. There is a lack of good controlled, randomized treatment trials in alcoholic pancreatitis. However, there is good evidence that lifestyle changes, such as alcohol cessation, hamper progression of the disease. Conservative treatment of pain should be based on a stepwise approach; however, underlying causes such as pseudocysts may require endoscopic or surgical therapy. Treatment of exocrine insufficiency requires pancreatic enzyme supplementation and adjustment to several smaller meals per day, while treatment of endocrine insufficiency requires insulin treatment.
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Affiliation(s)
- Roland H Pfutzer
- Department of Medicine II (Gastroenterology, Hepatology, Infectious Diseases), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
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Proesmans M, De Boeck K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur J Pediatr 2003; 162:760-3. [PMID: 13680386 DOI: 10.1007/s00431-003-1309-5] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2003] [Revised: 08/11/2003] [Accepted: 08/12/2003] [Indexed: 12/16/2022]
Abstract
UNLABELLED Despite treatment with supra-physiological doses of pancreatic enzyme supplements, residual steatorrhoea is a common problem in patients with cystic fibrosis (CF) and pancreatic insufficiency. Strategies to enhance the activity of pancreatic enzymes include decreasing duodenal acidity. The aim of this study was to evaluate the effect of omeprazole (Losec), a proton-pump inhibitor, on fat absorption in CF patients with residual steatorrhoea despite high dose pancreatic enzyme supplements (> or =10,000 U lipase/kg per day). A random cross-over design was chosen. Fat digestion was evaluated with and without omeprazole by means of chemical fat measurements in 3-day stool collections together with 3-day weighed food records for calculation of fat absorption. The results of 15 patients (3 girls and 12 boys) with confirmed steatorrhoea during the control evaluation were analysed. Median age was 8.7 years (range 3.5-15.9 years). Median daily lipase intake was 13,500 U/kg per day (range 10,000-22,000 U/kg per day). During treatment with omeprazole, median faecal fat loss (g fat/day) decreased from 13 g (quartiles 11.5-16.5 g/day) to 5.5 g (quartiles 4.9-8.1 g/day) (P<0.01). The same improvement was noted when fat absorption was calculated: 87% (quartiles 81-89%) without versus 94% (quartiles 90-96%) with omeprazole (P<0.001). CONCLUSION Omeprazole improves fat digestion and absorption in cystic fibrosis patients with residual faecal fat loss despite maximal pancreatic enzyme substitution.
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Affiliation(s)
- Marijke Proesmans
- Department of Paediatrics, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
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Abstract
BACKGROUND Malabsorption of fat and protein contributes to the poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic replacement therapy. The administration of gastric reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve nutritional status, fat malabsorption and gastro-intestinal symptoms in people with cystic fibrosis. It is thus important to establish the current level of evidence regarding potential benefits of drug therapies that reduce gastric acidity in people with cystic fibrosis. OBJECTIVES To assess the effect of drug therapies for reducing gastric acidity: in improving nutritional status; on symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH STRATEGY We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books and conference proceedings. Most recent search of the Group's register: April 2002. SELECTION CRITERIA All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS Both reviewers independently selected trials and assessed trial quality. MAIN RESULTS Thirty-six trials were identified from the initial search. Eleven trials with 172 participants were suitable for inclusion. Five trials were limited to children and three trials enrolled only adults. One trial found that drug therapies which reduce gastric acidity improve gastro-intestinal symptoms such as abdominal pain. Five trials reported significant improvement in measures of fat malabsorption. Two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified which assess the effectiveness of agents that reduce gastric acidity in improving quality of life, the complications of increased gastric acidity, or survival. REVIEWER'S CONCLUSIONS Trials have shown limited evidence that the agents which reduce gastric acidity in people with cystic fibrosis are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. We therefore recommend large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
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Affiliation(s)
- S M Ng
- Woodleigh, High Street, Woolton, Liverpool, UK, L25 7TD.
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29
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DiMagno EP. Gastric acid suppression and treatment of severe exocrine pancreatic insufficiency. Best Pract Res Clin Gastroenterol 2001; 15:477-86. [PMID: 11403540 DOI: 10.1053/bega.2001.0195] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Adding either H(2)-receptor antagonists (cimetidine or ranitidine) or proton pump inhibitors to an adequate amount of lipolytic activity improves fat malabsorption in most cases and abolishes steatorrhoea in up to 40% of children and adults with cystic fibrosis and in adults with chronic pancreatitis. Acid suppression improves fat absorption because the resultant increase in pH within the upper gastrointestinal tract improves the survival of lipolytic activity, reduces duodenal volume flow and prevents the precipitation of bile acids. These effects increase the concentration of intraduodenal lipolytic activity and promote the aggregation of bile acids and the micellar solubilization of lipid. The amount of lipase that should be recommended is controversial, but we interpret our studies as indicating that at least 90 000 United States Pharmacopeia (USP) units should be ingested with meals. This amount of lipolytic activity taken with an agent that suppresses gastric acid secretion improves fat absorption in most patients and may even abolish steatorrhoea.
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Affiliation(s)
- E P DiMagno
- Department of Internal Medicine, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA
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30
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Evenepoel P. Alteration in digestion and absorption of nutrients during profound acid suppression. Best Pract Res Clin Gastroenterol 2001; 15:539-51. [PMID: 11403545 DOI: 10.1053/bega.2000.0197] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastric acid suppression therapy has for many years been the cornerstone of the treatment of peptic disease. The availability of more potent inhibitors of gastric acid secretion and the increasing demand for maintenance therapy has renewed interest in the potential side-effects of profound and/or long-lasting therapy. This chapter focuses on the potential interference of gastric acid suppression therapy with the process of the digestion and absorption of nutrients. The theoretical mechanisms by which hypochlorhydria resulting from gastric acid suppression therapy may hamper digestion and absorption are multiple and well documented. Clinical studies evaluating the effect of gastric acid suppression therapy on the assimilation of nutrients are, on the other hand, scarce and have, moreover, yielded conflicting results. The reason for the latter may be related, at least in part, to elements of study design. Data indicating overt malabsorption or clear deficiencies in patients on long-term gastric acid suppression therapy are currently lacking. Nevertheless, it seems prudent, while awaiting the results of additional long-term studies, regularly to monitor these patients, especially those with increased nutrient demand, poor intake or suboptimal stores.
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Affiliation(s)
- P Evenepoel
- Department of Medicine, University Hospital Leuven, Leuven, B-3000, Belgium
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Raia V, Maiuri L, de Ritis G, de Vizia B, Vacca L, Conte R, Auricchio S, Londei M. Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. Pediatr Res 2000; 47:344-50. [PMID: 10709733 DOI: 10.1203/00006450-200003000-00010] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator gene and characteristically leads to prominent lung and pancreatic malfunctions. Although an inflammatory reaction is normally observed in the CF airways, no studies have been performed to establish whether a chronic inflammatory response is also present in the CF intestine. We have investigated whether immunologic alterations and signs of inflammation are observed in CF small intestine. Fourteen CF, 20 negative, and four disease controls underwent duodenal endoscopy for diagnostic purposes. Two CF patients were rebiopsied, one after 3 mo of an elemental diet and the other after 2 wk of pancreatic enzyme withdrawal. In three CF and 10 controls, in vitro small intestine organ cultures were also performed. Expression of ICAM-1, IL-2 receptor, IL-2, IFN-gamma, CD80, and transferrin receptor was studied by immunohistochemistry before and after in vitro organ culture. In CF small intestine, an increased number of lamina propria mononuclear cells express ICAM-1 [mean 114 (SD 82.8), p < 0.001 versus controls], CD25 [20.2 (18.7), p < 0.01], IL-2 [23.6 (13.7), p < 0.05], and IFN-gamma [19 (15.9), p < 0.05], whereas villus enterocytes highly express transferrin receptor. Reduced expression of immunologic markers was observed after 24 h of in vitro culture in all three CF patients as well as in the patient kept on elemental diet for 3 mo. These results indicate that chronic inflammation is observed in CF duodenum and suggest that the perturbation of local mucosal immune response may contribute to the overall clinical picture in CF patients.
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Affiliation(s)
- V Raia
- Department of Pediatrics, University Federico II of Naples, Italy
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Abstract
I reviewed the literature (1966-1994) concerning gastrointestinal (GI) pH, motility/transit, and permeability in cystic fibrosis (CF). Most studies reported were performed with very small numbers of patients, but even when considered together the published data do not confirm some generally expressed views on these topics. The only clear findings were a high incidence of gastroesophageal reflux in CF; pre- and postprandial duodenal pH is 1-2 U lower in patients with CF than in healthy controls; and small intestinal paracellular permeability is 4-10 times greater than normal in CF. Some patients showed abnormalities of lower esophageal sphincter pressure and of esophageal motility, but apart from one case study other disturbances of GI motility have not been reported. The results of hydrogen breath tests strongly suggest that oro-cecal transit is slowed in CF, but these results must be confirmed by an alternative test. Measurements of colonic transit and colonic permeability have not been reported. The few studies of gastric emptying reported are controversial. Whether GI pH, apart from duodenal pH, is normal in CF or whether a subset of patients has exceptionally acid intestinal contents requiring specialized pancreatic enzyme supplementation to normalize digestion is not clear. Finally, I briefly discuss the findings in relation to their possible impact on the pathogenesis of fibrosing colonopathy.
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Affiliation(s)
- P C Gregory
- Department of Gastrointestinal Pharmacology, Solvay Pharma Deutschland, Hannover, Germany
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Cucchiara S, Raia V, Minella R, Frezza T, De Vizia B, De Ritis G. Ultrasound measurement of gastric emptying time in patients with cystic fibrosis and effect of ranitidine on delayed gastric emptying. J Pediatr 1996; 128:485-8. [PMID: 8618181 DOI: 10.1016/s0022-3476(96)70358-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Intestinal dysmotility is commonly reported in patients with cystic fibrosis (CF); however, gastric motor activity has rarely been investigated. We measured with real-time ultrasonography the antral distention and gastric emptying time of a solid-liquid meal in 29 patients with CF (age range, 5 to 17 years). A significantly prolonged gastric emptying time was present in 26 patients compared with 13 healthy control subjects (age range, 5 to 16 years); an exaggerated antral distention in the fed period was also detected. The patients with CF and delayed gastric emptying were randomly allocated to receive cisapride or ranitidine for 4 weeks. Twelve patients treated with ranitidine and 11 with cisapride completed the trial. There was a marked decrease in gastric emptying time, antral distention, and dyspeptic symptomatic score in patients receiving ranitidine but not in patients treated with cisapride. We conclude that gastric dysmotility is commonly detected in patients with CF and that H2 receptor blockers are more effective than prokinetics in improving dyspeptic symptoms and gastric emptying and distention.
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Affiliation(s)
- S Cucchiara
- Department of Pediatrics, University of Naples "Federico II," Naples, Italy
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