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Launspach M, Mindermann A, Schulz J, Alasfar L, Cyrull S, Zirngibl F, Oevermann L, Künkele A, Deubzer HE, von Bernuth H, Pruß A, Lang P, Bufler P, Eggert A, von Stackelberg A, Schulte JH. High Incidence and Impact of Suspected Exocrine Pancreatic Insufficiency in Patients Post-Hematopoietic Stem Cell Transplantation: A Single-Center Prospective Observational Study. United European Gastroenterol J 2025; 13:257-267. [PMID: 39955611 PMCID: PMC11975613 DOI: 10.1002/ueg2.12769] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/18/2024] [Accepted: 11/27/2024] [Indexed: 02/17/2025] Open
Abstract
Exocrine pancreatic insufficiency (EPI) is suspected but remains understudied in immunosuppressed conditions such as post-hematopoietic stem cell transplantation (HSCT). This prospective observational study aimed to investigate the incidence, impact, and risk factors of EPI in a cohort of 83 pediatric and young adult patients who underwent allogeneic HSCT at Charité - Universitätsmedizin Berlin between 2020 and 2023. Fecal pancreatic elastase (PE) measurements and transabdominal ultrasound were utilized to evaluate pancreatic function over a one-year period. Secondary analysis explored the association of EPI with clinical complications and included a multivariable regression analysis of potential risk factors. Low PE levels significantly correlated with pathological pancreatic imaging findings, independent of concurrent diarrhea. EPI was suspected in 45% (32/71) of patients (95%CI: [34.1%, 56.6%]), with 29% (13/45) (95%CI: [17.7%, 43.4%]) showing signs of prolonged EPI (pEPI) lasting at least 8 weeks. After excluding cases with confounding factors such as missing enteral nutrition and diarrhea, the cumulative incidence of prolonged EPI was 20% (8/41) (95%CI: 10.2%-34.0%) in the overall cohort. EPI was associated with weight loss, prolonged dependence on parenteral nutrition, and extended hospitalizations. Adenovirus (ADV) infection emerged as a significant risk factor for EPI (hazard ratio 3.22 [95%CI:1.26-8.2], p = 0.014), along with additional factors such as higher BMI pre-HSCT, pre-existing pancreatic damage and early post-HSCT fasting. The persistence of pancreatic atrophy and EPI beyond two years post-HSCT in individual cases suggests a potential for permanent pancreatic damage. This study underscores that EPI is a common complication following HSCT, with ADV infection being an important risk factor. The findings support routine PE measurements and early initiation of pancreatic enzyme replacement therapy (PERT), alongside aggressive treatment of ADV infections. Further research is necessary to evaluate the effects of PERT in this population and to explore the applicability of these findings in other immunosuppressed groups.
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Affiliation(s)
- Michael Launspach
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- The German Cancer Consortium (DKTK)Partner Site BerlinBerlinGermany
- The German Cancer Research Center (DKFZ)HeidelbergGermany
| | - Aurika Mindermann
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Joachim Schulz
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Lina Alasfar
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Department of Internal Medicine VUniversity Hospital HeidelbergIm Neuenheimer Feld 672HeidelbergGermany
| | - Sandra Cyrull
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Felix Zirngibl
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Lena Oevermann
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Annette Künkele
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- The German Cancer Consortium (DKTK)Partner Site BerlinBerlinGermany
- The German Cancer Research Center (DKFZ)HeidelbergGermany
| | - Hedwig E. Deubzer
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- The German Cancer Consortium (DKTK)Partner Site BerlinBerlinGermany
- The German Cancer Research Center (DKFZ)HeidelbergGermany
- Experimental and Clinical Research CenterMax Delbrück Center for Molecular Medicine and Charité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Horst von Bernuth
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- Department of Pediatric Respiratory MedicineImmunology and Critical Care MedicineCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Department of ImmunologyLabor Berlin ‐ Charité Vivantes GmbHBerlinGermany
- Berlin‐Brandenburg Center for Regenerative Therapies (BCRT)Charité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Axel Pruß
- Institute of Transfusion MedicineCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Peter Lang
- Department of Hematology/Oncology and General PediatricsChildren’s University HospitalUniversity of TuebingenTuebingenGermany
| | - Philip Bufler
- Department of Pediatric Gastroenterology, Nephrology, and Metabolic DiseasesCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Angelika Eggert
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- The German Cancer Consortium (DKTK)Partner Site BerlinBerlinGermany
- The German Cancer Research Center (DKFZ)HeidelbergGermany
| | - Arend von Stackelberg
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Johannes H. Schulte
- Department of Pediatric Oncology and HematologyCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Berlin Institute of Health at Charité ‐ Universitätsmedizin BerlinBerlinGermany
- The German Cancer Consortium (DKTK)Partner Site BerlinBerlinGermany
- The German Cancer Research Center (DKFZ)HeidelbergGermany
- Department of Hematology/Oncology and General PediatricsChildren’s University HospitalUniversity of TuebingenTuebingenGermany
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Lee JM, Lee SH, Choi YH, Han SY, Jo JH, Choe JW, Kim EJ, Jang DK, Jung MK. Association between severity of pancreatic exocrine insufficiency and computed tomography-based morphological severity in patients with chronic pancreatitis. Medicine (Baltimore) 2024; 103:e40737. [PMID: 39612393 PMCID: PMC11608721 DOI: 10.1097/md.0000000000040737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 11/11/2024] [Indexed: 12/01/2024] Open
Abstract
The association between pancreatic exocrine insufficiency (PEI) and morphologic findings in chronic pancreatitis has not yet been fully studied. Thus, the aim of this study was to investigate the correlation between PEI severity and computed tomography (CT)-based morphological severity in patients with chronic pancreatitis. This nationwide survey included 180 Korean participants with chronic pancreatitis aged 18 years or older between January 2018 and December 2021. PEI severity was measured by the PEI questionnaire (PEI-Q). Morphological severity was measured using a CT-based scoring system, which included pancreatic duct caliber, pancreatic duct stricture or intraductal obstructing calculus, pancreatic atrophy, and pancreatic calcification. In addition, 35 patients who received pancreatic enzyme replacement therapy (PERT) were evaluated by PEI-Q to determine whether PEI improved after PERT. PEI severity was normal (n = 89), mild (n = 69), moderate (n = 14), or severe (n = 8). Severities of pancreatic duct caliber and pancreatic duct stricture or intraductal obstructing calculus had small but significant associations with PEI severity (Cramer V = 0.121 and 0.141, respectively). Severities of pancreatic atrophy and pancreatic calcification were not significantly associated with PEI severity. PEI severity showed a significant improvement after PERT (P < .001). In conclusion, PEI severity had significant associations with CT-based morphological severities, including severities of pancreatic duct caliber and pancreatic duct stricture or intraductal obstructing calculus. In addition, PEI-Q could be a useful indicator for evaluating the therapeutic effect of PERT in clinical practice.
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Affiliation(s)
- Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Young Hoon Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Yong Han
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Jung Hyun Jo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Wan Choe
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Eui Joo Kim
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Dong Kee Jang
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Min Kyu Jung
- Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
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Stornello C, Deli C, Dell'Anna G, Lauri G, Ponz de Leon Pisani R, Tacelli M, Archibugi L, Vanella G, Apadula L, Rossi G, Zaccari P, Mariani A, Petrone MC, Cammà C, Arcidiacono PG, Capurso G. Correlation between endoscopic ultrasound features and exocrine pancreatic function in chronic pancreatitis. Pancreatology 2024; 24:834-839. [PMID: 39138091 DOI: 10.1016/j.pan.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 06/07/2024] [Accepted: 08/07/2024] [Indexed: 08/15/2024]
Abstract
BACKGROUND Endoscopic ultrasound (EUS) is the most sensitive method for diagnosing chronic pancreatitis (CP) in its early stages, and Rosemont Classification (RC) is used for its evaluation. Data on the correlation between EUS features and pancreatic exocrine insufficiency (PEI) are limited. We investigated the correlation between the EUS findings and PEI. METHODS This was a retrospective, monocentric cohort study involving patients prospectively enrolled from 2018 to 2022, with definite or probable CP according to the M-ANNHEIM criteria. All the patients underwent EUS and exocrine function investigations within 12 months of diagnosis. PEI was diagnosed using fecal elastase (FE) or when overt steatorrhea was reversed by pancreatic enzyme replacement therapy. Logistic regression analyses, rank correlation, ROC curve, and area under the curve (AUROC) were performed to evaluate the association between EUS features and PEI, and the accuracy of RC in predicting PEI. RESULTS Among 128 patients examined (63.3 % male; mean age, 47 years), 69.5 % were diagnosed with PEI. In multivariate logistic regression among all the RC criteria, only lithiasis in the main pancreatic duct (MPD) was associated with increased risk of PEI (OR 2.92, 95 % CI 1.29-6.61; p = 0.01). Rank analysis showed a weak inverse correlation between RC and FE (Spearman's rho = -0.02; p = 0.03). The accuracy of RC was moderate (AUROC 0.62, p = 0.014). CONCLUSIONS Among RC EUS features, lithiasis in the MPD is helpful for predicting the risk of PEI, while other findings are of limited utility in evaluating exocrine function.
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Affiliation(s)
- Caterina Stornello
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy; Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Italy
| | - Chiara Deli
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Dell'Anna
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Gaetano Lauri
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Ruggero Ponz de Leon Pisani
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Tacelli
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Livia Archibugi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Vanella
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Laura Apadula
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Gemma Rossi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Piera Zaccari
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Alberto Mariani
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Calogero Cammà
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
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Chu P, Mioc J, Henry O, O’Donovan P. The clinical, economic, and humanistic burden of treatments for exocrine pancreatic insufficiency and cost-effectiveness of treatments: A systematic literature review. Medicine (Baltimore) 2024; 103:e39224. [PMID: 39151540 PMCID: PMC11332733 DOI: 10.1097/md.0000000000039224] [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: 02/16/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND To examine the burden of exocrine pancreatic insufficiency (EPI), specifically the clinical impact of EPI on patients, their quality of life (QoL) and the cost-effectiveness of existing treatments. METHODS A systematic literature review was conducted using key search terms for the clinical, economic, and humanistic burden. Databases were searched from 2010 to 2022, with articles screened independently by 2 reviewers at abstract and full-text stage against pre-defined eligibility criteria. RESULTS Seventy-one publications were identified that reported relevant clinical, humanistic, and economic data. Prevalence and incidence of EPI varied across identified studies; EPI appears to be especially prevalent as a comorbid condition in patients with cystic fibrosis. EPI has a large impact on QoL, with lower QoL scores in patients with EPI compared with those without EPI. The instruments used to assess QoL, however, were inconsistent across studies. Where reported, economic burden studies highlighted that patients with EPI have higher healthcare resource utilization compared with those without, with costs increasing with disease severity. CONCLUSION This systematic literature review highlights that patients with EPI have higher treatment costs and lower QoL scores than patients without EPI. The prevalence of EPI as a comorbid condition is high, particularly in patients with cystic fibrosis.
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Affiliation(s)
- Paula Chu
- Organon International GmbH, Lucerne, Switzerland
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Ambrosetti MC, Grecchi A, Ambrosetti A, Amodio A, Mansueto G, Montemezzi S, Zamboni GA. Quantitative Edge Analysis of Pancreatic Margins in Patients with Chronic Pancreatitis: A Correlation with Exocrine Function. Diagnostics (Basel) 2023; 13:2272. [PMID: 37443666 DOI: 10.3390/diagnostics13132272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/23/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Many efforts have been made to improve accuracy and sensitivity in diagnosing chronic pancreatitis (CP), obtaining quantitative assessments related to functional data. Our purpose was to correlate a computer-assisted analysis of pancreatic morphology, focusing on glandular margins, with exocrine function-measured by fecal elastase values-in chronic pancreatitis patients. METHODS We retrospectively reviewed chronic pancreatitis patients who underwent fecal elastase assessment and abdominal MRI in our institute within 1 year. We identified 123 patients divided into three groups based on the fecal elastase value: group A with fecal elastase > 200 μg/g; group B with fecal elastase between 100 and 200 μg/g; and group C with fecal elastase < 100 μg/g. Computer-assisted quantitative edge analysis of pancreatic margins was made on non-contrast-enhanced water-only Dixon T1-weighted images, obtaining the pancreatic margin score (PMS). PMS values were compared across groups using a Kruskal-Wallis test and the correlation between PMS and fecal elastase values was tested with the Spearman's test. RESULTS A significant difference in PMS was observed between the three groups (p < 0.0001), with a significant correlation between PMS and elastase values (r = 0.6080). CONCLUSIONS Quantitative edge analysis may stratify chronic pancreatitis patients according to the degree of exocrine insufficiency, potentially contributing to the morphological and functional staging of this pathology.
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Affiliation(s)
- Maria Chiara Ambrosetti
- Radiology Unit, Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy
| | - Annamaria Grecchi
- Institute of Radiology, Department of Diagnostics and Public Health, Policlinico GB Rossi, University of Verona, 37134 Verona, Italy
| | - Alberto Ambrosetti
- Department of Physics and Astronomy "Galileo Galilei", University of Padova, 35131 Padova, Italy
| | - Antonio Amodio
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, Department of Medicine, G.B. Rossi University Hospital, 37134 Verona, Italy
| | - Giancarlo Mansueto
- Institute of Radiology, Department of Diagnostics and Public Health, Policlinico GB Rossi, University of Verona, 37134 Verona, Italy
| | - Stefania Montemezzi
- Radiology Unit, Department of Pathology and Diagnostics, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy
| | - Giulia A Zamboni
- Institute of Radiology, Department of Diagnostics and Public Health, Policlinico GB Rossi, University of Verona, 37134 Verona, Italy
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Brenner DM, Domínguez-Muñoz JE. Differential Diagnosis of Chronic Diarrhea: An Algorithm to Distinguish Irritable Bowel Syndrome With Diarrhea From Other Organic Gastrointestinal Diseases, With Special Focus on Exocrine Pancreatic Insufficiency. J Clin Gastroenterol 2023:00004836-990000000-00152. [PMID: 37115854 DOI: 10.1097/mcg.0000000000001855] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
Chronic diarrhea, defined as diarrhea persisting for more than 4 weeks, affects up to 5% of the population regardless of patient age, sex, race, or socioeconomic status. The impact on patient health and quality of life is substantial, and diagnosis and management of these patients have significant economic consequences for health care services. The differential diagnosis of chronic diarrhea is broad, with etiologies including infections, endocrinopathies, maldigestive/malabsorptive conditions, and disorders of gut-brain interaction. The considerable overlap of symptoms across this spectrum makes accurate diagnosis problematic and may lead to delays in diagnosis or misdiagnosis. In this narrative review, we consider the differential diagnosis of chronic diarrhea, focusing on irritable bowel syndrome with diarrhea and exocrine pancreatic insufficiency, two conditions that may present similarly but have very different underlying causes and require significantly different management strategies. We outline a 4-step diagnostic strategy and propose a straightforward algorithm to assist in efficiently differentiating irritable bowel syndrome from exocrine pancreatic insufficiency and other causes of chronic diarrhea. We anticipate that these aids will improve diagnostic accuracy, which ultimately should lead to improvements in patients' health-related quality of life and reduce the societal burden on health care services.
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Affiliation(s)
- Darren M Brenner
- Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, IL
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Powell-Brett S, Hall L, Edwards M, Roberts K. A systematic review and meta-analysis of the accuracy and methodology of the 13C mixed triglyceride breath test for the evaluation of pancreatic function. Pancreatology 2023; 23:283-293. [PMID: 36805050 DOI: 10.1016/j.pan.2023.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 01/31/2023] [Accepted: 02/13/2023] [Indexed: 02/23/2023]
Abstract
INTRODUCTION The diagnosis of pancreatic exocrine insufficiency (PEI) is challenging. The 13C mixed triglyceride breath test (13C MTGT) has emerged as a promising diagnostic method. However, there is need to assimilate high quality evidence to understand its accuracy and address variation in the conduct of the test. This systematic review aims to appraise the existing literature on the methodology and accuracy of the 13C MTGT. METHODS A systematic literature search of PUBMED, MEDLINE, and EMBASE databases identified articles describing the use of the 13C MTGT in the analysis of pancreatic function in adults. Data extraction addressed each methodological step in detail. These were combined in a narrative synthesis. For quantitative analysis, those studies within this search that assessed the accuracy of the 13C MTGT were selected. RESULTS 37 studies were included for qualitative review, 6 assessed sensitivity and specificity of the 13C MTGT against another measure of PEI and were included in quantitative synthesis. Areas with a majority consensus were pre-test overnight fasting, a test meal with a lipid load of at least 10 g, within-test control of exercise and dietary intake, breath sampling every 30 min and the preference of isotope ratio mass spectrometry (IRMS) for analysis. Good evidence suggests there is no benefit to extend the total timeframe of breath sampling beyond 6 h. Areas of uncertainty are a) Duration of PERT cessation b) the addition of metoclopramide, c) the ideal test meal and d) if the time frame can be shortened. Quantitative analysis among 6 studies demonstrated a pooled sensitivity and specificity of the 13C MTGT for diagnosing PEI of 0.84 (95% CI: 0.73-0.91) and 0.87 (95% CI: 0.79-0.93) respectively. CONCLUSION There is yet to emerge a clear standard of breath test methodology that is validated for all causes of PEI and suitable for routine use. The accuracy of the 13C MTGT for diagnosing PEI is encouraging when compared to other measures. We present a suggested set protocol based on the current literature and identify areas that need further, high quality evidence. With refinement, the 13C MTGT could become a valuable, non-invasive PEI diagnostic tool that could be used outside of specialist centres.
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Affiliation(s)
- Sarah Powell-Brett
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
| | - Lewis Hall
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Michael Edwards
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Keith Roberts
- Department of Hepatobiliary, Pancreatic and Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Conti CB, Mulinacci G, Salerno R, Dinelli ME, Grassia R. Applications of endoscopic ultrasound elastography in pancreatic diseases: From literature to real life. World J Gastroenterol 2022; 28:909-917. [PMID: 35317053 PMCID: PMC8908282 DOI: 10.3748/wjg.v28.i9.909] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 11/11/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
Elastography is a non-invasive method widely used to measure the stiffness of the tissues, and it is available in most endoscopic ultrasound machines, using either qualitative or quantitative techniques. Endoscopic ultrasound elastography is a tool that should be applied to obtain a complementary evaluation of pancreatic diseases, together with other imaging tests and clinical data. Elastography can be informative, especially when studying pancreatic masses and help the clinician in the differential diagnosis between benign or malignant lesions. However, further studies are necessary to standardize the method, increase the reproducibility and establish definitive cut-offs to distinguish between benign and malignant pancreatic masses. Moreover, even if promising, elastography still provides little information in the evaluation of benign conditions.
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Affiliation(s)
| | - Giacomo Mulinacci
- Interventional Endoscopy Unit, ASST Monza, Ospedale San Gerardo, Monza 20900, Italy
| | - Raffaele Salerno
- Gastroenterology and Endoscopy Unit, ASST Fatebenefratelli-Sacco, Milan 20121, Italy
| | - Marco Emilio Dinelli
- Interventional Endoscopy Unit, ASST Monza, Ospedale San Gerardo, Monza 20900, Italy
| | - Roberto Grassia
- Gastroenterology and Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
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Hopson P, Smadi Y, Mehta V, Patel S, Mehta D, Horvath K. Assessment of exocrine pancreatic function in children and adolescents with direct and indirect testing. Front Pediatr 2022; 10:908542. [PMID: 36452348 PMCID: PMC9704773 DOI: 10.3389/fped.2022.908542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 10/19/2022] [Indexed: 11/15/2022] Open
Abstract
The exocrine pancreas plays an important role in digestion. Understanding of the physiology and regulation of exocrine function provides insight into disease processes and basis of functional testing. Specifically, exocrine pancreatic insufficiency (EPI) can cause maldigestion and thus a proper assessment of exocrine pancreatic function is important. There are indirect and direct methods for evaluating pancreatic function. Indirect methods are varied and include stool, serum, urine, and breath tests. Fecal elastase is a commonly used indirect test today. Direct methods involve stimulated release of pancreatic fluid that is collected from the duodenum and analyzed for enzyme activity. The most used direct test today is the endoscopic pancreatic function test. Indirect pancreatic function testing is limited in identifying cases of mild to moderate EPI, and as such in these cases, direct testing has higher sensitivity and specificity in diagnosing EPI. This review provides a comprehensive guide to indirect and direct pancreatic function tests as well as an in-depth look at exocrine pancreatic function including anatomy, physiology, and regulatory mechanisms.
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Affiliation(s)
- Puanani Hopson
- Department of Children Center, Pediatric and Adolescent Medicine, Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Yamen Smadi
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Vijay Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Samit Patel
- Pediatric Gastroenterology & Nutrition of Tampa Bay, Tampa Bay, FL, United States
| | - Devendra Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Karoly Horvath
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
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10
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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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11
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Endoscopic Ultrasonography Findings of Early and Suspected Early Chronic Pancreatitis. Diagnostics (Basel) 2020; 10:diagnostics10121018. [PMID: 33261170 PMCID: PMC7760161 DOI: 10.3390/diagnostics10121018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/19/2020] [Accepted: 11/24/2020] [Indexed: 02/07/2023] Open
Abstract
Chronic pancreatitis (CP) is associated with a risk of pancreatic cancer and is characterized by irreversible morphological changes, fibrosis, calcification, and exocrine and endocrine insufficiency. CP is a progressive disease with a poor prognosis and is typically diagnosed at an advanced stage. The Japan Pancreas Society proposed criteria for early CP in 2009, and their usefulness has been reported. Recently, a mechanism definition was proposed by the International Consensus Guidelines and early CP was defined as a disease state that is not based on disease duration. CP is diagnosed by computed tomography, magnetic resonance imaging, and endoscopic cholangiopancreatography, which can detect calcification and dilation of the pancreatic ducts; however, detecting early CP with these modalities is difficult because subtle changes in early CP occur before established CP or end-stage CP. Endoscopic ultrasonography (EUS) is useful in the diagnosis of early CP because it allows high-resolution, close-up observation of the pancreas. In addition to imaging findings, EUS with elastography enables measurement of the stiffness of the pancreas, an objective diagnostic measure. Understanding the EUS findings of early CP is important because a histological diagnosis is problematic, and other modalities are not capable of detecting subtle changes in early CP.
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12
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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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13
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Carnie LE, Lamarca A, McNamara MG, Bibby N, O'Reilly DA, Valle JW. The assessment of pancreatic exocrine function in patients with inoperable pancreatic cancer: In need of a new gold-standard. Pancreatology 2020; 20:668-675. [PMID: 32284260 DOI: 10.1016/j.pan.2020.03.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 01/17/2020] [Accepted: 03/30/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency is commonplace in patients with pancreatic cancer, adversely impacting on quality of life and survival. Whilst the management of exocrine insufficiency is well established, diagnosis remains challenging in clinical practice. A plethora of diagnostic tests exist. Nevertheless, a lack of consensus remains about the optimal diagnostic method, specifically in patients with pancreatic cancer. Research, to date, has primarily been undertaken in patients with chronic pancreatitis and cystic fibrosis. This manuscript will review the current literature and will examine the evidence around the diagnostic tests available for pancreatic exocrine insufficiency and whether any exists specifically for pancreatic cancer cohorts. FINDINGS Evidence to recommend an individual test for the diagnosis of pancreatic exocrine insufficiency in clinical practice is lacking. Direct testing (by direct sampling of pancreatic secretions) has the highest specificity and sensitivity but is no longer routinely deployed or feasible in practice. Indirect testing, such as faecal elastase, is less accurate with high false-positive rates, but is routinely available in clinical practice. The 13C-mixed triglyceride breath test and the gold-standard 72-h faecal fat test have high specificity for indirect tests, but are not routinely available and cumbersome to undertake. A combination approach including nutritional markers and faecal elastase has more recently been proposed. CONCLUSION Further research is required to identify the most optimal and accurate diagnostic tool to diagnose pancreatic exocrine insufficiency in patients with pancreatic cancer in clinical practice.
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Affiliation(s)
- Lindsay E Carnie
- Nutrition & Dietetics, The Christie NHS Foundation Trust, Manchester, UK
| | - Angela Lamarca
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK
| | - Mairéad G McNamara
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK
| | - Neil Bibby
- Dietetics, Manchester Royal Infirmary, Manchester, UK
| | | | - Juan W Valle
- Medical Oncology Department, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, UK.
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14
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Pathanki AM, Attard JA, Bradley E, Powell-Brett S, Dasari BVM, Isaac JR, Roberts KJ, Chatzizacharias NA. Pancreatic exocrine insufficiency after pancreaticoduodenectomy: Current evidence and management. World J Gastrointest Pathophysiol 2020; 11:20-31. [PMID: 32318312 PMCID: PMC7156847 DOI: 10.4291/wjgp.v11.i2.20] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 03/13/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreaticoduodenectomy (PD) is the commonest procedure performed for pancreatic cancer. Pancreatic exocrine insufficiency (PEI) may be caused or exacerbated by surgery and remains underdiagnosed and undertreated. The aim of this review was to ascertain the incidence of PEI, its consequences and management in the setting of PD for indications other than chronic pancreatitis. A literature search of databases (MEDLINE, EMBASE, Cochrane and Scopus) was carried out with the MeSH terms "pancreatic exocrine insufficiency" and "Pancreaticoduodenectomy". Studies that analysed PEI and its complications in the setting of PD for malignant and benign disease were included. Studies reporting PEI in the setting of PD for chronic pancreatitis, conference abstracts and reviews were excluded. The incidence of PEI approached 100% following PD in some series. The pre-operative incidence varied depending on the characteristics of the patient cohort and it was higher (46%-93%) in series where pancreatic cancer was the predominant indication for surgery. Variability was also recorded with regards to the method used for the diagnosis and evaluation of pancreatic function and malabsorption. Pancreatic enzyme replacement therapy is the mainstay of the management. PEI is common and remains undertreated after PD. Future studies are required for the identification of a well-tolerated, reliable and reproducible diagnostic test in this setting.
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Affiliation(s)
- Adithya M Pathanki
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Joseph A Attard
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Elizabeth Bradley
- Department of Nutrition and Dietetics, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Sarah Powell-Brett
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Bobby V M Dasari
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - John R Isaac
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Keith J Roberts
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
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Narita M, Hata H, Matsusue R, Yamaguchi T, Otani T, Ikai I. Is the remnant pancreas still working over a year after surgery in patients undergoing pancreaticoduodenectomy with reconstruction by pancreaticogastrostomy? Pancreatology 2020; 20:217-222. [PMID: 31862231 DOI: 10.1016/j.pan.2019.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 12/11/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreaticogastrostomy (PG) has been widely used as an alternative to pancreatojejunostomy (PJ) in patients undergoing pancreaticoduodenectomy (PD), but its long-term exocrine function remains unclear. The present study aimed to measure the secretion of pancreatic α-amylase (p-AMY) into the gastric cavity in patients who underwent PG reconstruction after PD over 1 year after surgery and to evaluate the relationship between gastric p-AMY level and clinically available indirect tests. METHODS Clinical records of 39 patients who underwent PG reconstruction after PD were reviewed. Pancreatic exocrine function was evaluated over 1 year after surgery using the following methods: 1) Measurement of p-AMY level in gastric fluids (gastric p-AMY level) during routine gastrointestinal endoscopy, 2) Qualitative faecal fat determination by Sudan III staining on faeces and 3) Pancreatic function diagnostic (PFD) test using oral administration of N-benzoyl-l-tyrosyl-p-aminobenzoic acid. RESULTS Gastric p-AMY level was detectable in 31 of 39 patients (79%), and 12 patients (30.8%) had steatorrhea over a year after surgery. Patients with steatorrhea had significantly lower gastric p-AMY level, larger diameter of remnant main pancreatic duct (MPD) and larger pancreatic duct to parenchymal thickness ratio than those without steatorrhea (84 IU/L vs 7979 IU/L, respectively; P < 0.001, 5.3 mm vs 3.2 mm, respectively; P = 0.001, and 0.38 vs 0.23, respectively; P = 0.007). Receiver operating characteristic analysis showed that the cut-off value of the diameter of the remnant MPD to predict steatorrhea was 3.5 mm (sensitivity, 92.3%; specificity, 70.4%). PFD test was not associated with any clinical data. CONCLUSIONS Pancreatic enzyme was detected in 79% of patients having PG reconstruction. Diameter of remnant MPD >3.5 mm and pancreatic parenchymal atrophy may be surrogate markers of postoperative exocrine insufficiency following PD.
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Affiliation(s)
- Masato Narita
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan.
| | - Hiroaki Hata
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan
| | - Ryo Matsusue
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan
| | - Takashi Yamaguchi
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan
| | - Tetsushi Otani
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan
| | - Iwao Ikai
- Department of Surgery, National Hospital Organisation, Kyoto Medical Centre,1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8555, Japan
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Domínguez-Muñoz JE. Pancreatic Insufficiency, Exocrine. ENCYCLOPEDIA OF GASTROENTEROLOGY 2020:79-87. [DOI: 10.1016/b978-0-12-801238-3.65869-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Abstract
PURPOSE OF REVIEW Pancreatic exocrine insufficiency (PEI) is one of the well known causes of malabsorption syndrome. An insufficient secretion of pancreatic enzymes and bicarbonate secondary to different pancreatic diseases and upper gastrointestinal and pancreatic surgery leads to maldigestion and malabsorption of nutrients. Patients with PEI may present with symptoms of malabsorption and different nutritional deficiencies. Recent data support the high clinical relevance of PEI and its treatment. RECENT FINDINGS Deficiencies of fat-soluble vitamins, proteins, micronutrients and antioxidants in patients with PEI are associated not only with an increased risk of osteoporosis and sarcopenia but also of cardiovascular events and mortality. Pancreatic enzyme replacement therapy (PERT) allows improving fat and protein digestion, relieving maldigestion-related symptoms, normalizing the nutritional status, and improving quality of life of patients with PEI. Recent data support the efficacy of PERT on survival in patients with pancreatic cancer. Dose of oral pancreatic enzymes should be adequate to normalize the nutritional status of PEI patients. SUMMARY Increasing evidence supports the relevance of PEI management by dietary advice and appropriate PERT. Well designed and powered randomized, placebo-controlled clinical trials are needed to further evaluate the clinical impact of PEI and its treatment in clinical practice.
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Abstract
Chronic pancreatitis (CP) is an important gastrointestinal cause of morbidity worldwide. It can severely impair the quality of life besides life-threatening acute and long-term complications. Pain and pancreatic exocrine insufficiency (leading to malnutrition) impact the quality of life. Acute complications include pseudocysts, pancreatic ascites, and vascular complications. Long-term complications are diabetes mellitus and pancreatic cancer. Early diagnosis of CP is crucial to alter the natural course of the disease. However, majority of the cases are diagnosed in the advanced stage. The role of various imaging techniques in the diagnosis of CP is discussed in this review.
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Affiliation(s)
- Rohan Kamat
- Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India
| | - Pankaj Gupta
- Department of Gastroenterology, PGIMER, Chandigarh, India
| | - Surinder Rana
- Department of Gastroenterology, PGIMER, Chandigarh, India
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Abstract
PURPOSE OF REVIEW Pancreatic exocrine insufficiency (PEI), defined as a secretion of pancreatic enzymes and bicarbonate insufficient to maintain a normal digestion, is a frequent but frequently underdiagnosed and undertreated condition. PEI may be secondary to different pancreatic diseases and extrapancreatic conditions. Recent data support the high clinical relevance of PEI and its treatment. RECENT FINDINGS Together with symptoms of maldigestion, PEI is associated with nutritional deficiencies leading to osteoporosis, low-trauma fractures, sarcopenia and increased mortality. No single widely available test allows to diagnose PEI accurately. Diagnosis of PEI requires the evaluation of symptoms, nutritional markers and a noninvasive pancreatic function test in the appropriate clinical context. Pancreatic enzyme replacement therapy (PERT) improves digestion, symptoms, nutritional status and quality of life of patients with PEI. In addition, PERT is associated with a longer survival in patients with unresectable pancreatic cancer and after surgery for pancreatic cancer or chronic pancreatitis. SUMMARY Awareness of PEI in different clinical conditions is required. Nutritional advice and appropriate PERT are mandatory to reduce the morbidity and mortality associated with PEI. Further studies on the clinical impact of PEI and its treatment are needed, especially in diseases other than chronic pancreatitis and cystic fibrosis.
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Increased Risk of Mortality Associated With Pancreatic Exocrine Insufficiency in Patients With Chronic Pancreatitis. J Clin Gastroenterol 2018; 52:e63-e72. [PMID: 28858943 DOI: 10.1097/mcg.0000000000000917] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) is a common serious complication in chronic pancreatitis (CP); however, little is known about its effect on mortality in these patients. In this study, we assessed the mortality risk of PEI in patients with CP. STUDY A prospective, longitudinal cohort study conducted in patients with CP under long-term follow-up. CP and PEI were diagnosed using pancreatic imaging and the C-labeled mixed triglyceride breath test, respectively. Multivariate analysis was performed to evaluate the impact of PEI and other clinical features on mortality risk. RESULTS Patients (N=430) were analyzed (79.1% male; mean age, 47.8 y) during a mean follow-up of 8.6±4.6 years. PEI prevalence was 29.3% and mortality was 10.9%. Most frequent causes of death were cancer (40.4%), infection (21.3%), and acute cardiovascular event (14.9%). Multivariate analyses showed associations between increased mortality and presence of PEI [hazard ratio (HR), 2.59; 95% confidence interval (CI), 1.42-4.71; P<0.003], liver cirrhosis (HR, 3.87; 95% CI, 1.95-7.69; P<0.001), age at diagnosis (HR, 1.05; 95% CI, 1.03-1.09; P<0.001), toxic etiology of CP (HR, 3.11; 95% CI, 1.11-8.70; P<0.05) and respiratory comorbidity (HR, 2.19; 95% CI, 1.12-4.31; P<0.03). Nutritional markers were significantly lower in patients with PEI versus those without PEI (P<0.001) and in those who died versus survivors (P<0.001). CONCLUSIONS PEI was a significant independent risk factor for mortality in patients with CP. These results support further research into the optimal treatment of PEI to reduce mortality in this population.
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Scimeca M, Bischetti S, Lamsira HK, Bonfiglio R, Bonanno E. Energy Dispersive X-ray (EDX) microanalysis: A powerful tool in biomedical research and diagnosis. Eur J Histochem 2018; 62:2841. [PMID: 29569878 PMCID: PMC5907194 DOI: 10.4081/ejh.2018.2841] [Citation(s) in RCA: 122] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Revised: 01/15/2018] [Accepted: 01/17/2018] [Indexed: 02/06/2023] Open
Abstract
The Energy Dispersive X-ray (EDX) microanalysis is a technique of elemental analysis associated to electron microscopy based on the generation of characteristic Xrays that reveals the presence of elements present in the specimens. The EDX microanalysis is used in different biomedical fields by many researchers and clinicians. Nevertheless, most of the scientific community is not fully aware of its possible applications. The spectrum of EDX microanalysis contains both semi-qualitative and semi-quantitative information. EDX technique is made useful in the study of drugs, such as in the study of drugs delivery in which the EDX is an important tool to detect nanoparticles (generally, used to improve the therapeutic performance of some chemotherapeutic agents). EDX is also used in the study of environmental pollution and in the characterization of mineral bioaccumulated in the tissues. In conclusion, the EDX can be considered as a useful tool in all works that require element determination, endogenous or exogenous, in the tissue, cell or any other sample.
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Affiliation(s)
- Manuel Scimeca
- University of Rome "Tor Vergata", Department of Biomedicine and Prevention.
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Abstract
Malnutrition is a frequent complication in patients with chronic pancreatitis. Maldigestion as a consequence of pancreatic exocrine insufficiency is the major cause of malnutrition in these patients. Together with that, toxic habits and alterations of the gastroduodenal transit may play a relevant role. Malnutrition in chronic pancreatitis is associated with osteoporosis, sarcopenia, poor quality of life, and increased mortality. An adequate nutritional evaluation including anthropometric, biochemical, and morphologic parameters is recommended in these patients. Nutritional advice and support together with an adequate pancreatic enzyme replacement therapy are indicated.
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Abstract
Imaging of the endocrine pancreas is dominated by neuroendocrine tumors, a diverse category of neoplasms that may or may not cause symptoms from hormone hypersecretion. These tumors may also be evidence of several different genetic syndromes. Understanding the usefulness of different imaging modalities and entities that simulate neuroendocrine tumors is key for both radiologists and referring physicians.
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Affiliation(s)
- Mark Masciocchi
- Department of Radiology, UMass Memorial Medical Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
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Tirkes T, Fogel EL, Sherman S, Lin C, Swensson J, Akisik F, Sandrasegaran K. Detection of exocrine dysfunction by MRI in patients with early chronic pancreatitis. Abdom Radiol (NY) 2017; 42:544-551. [PMID: 27660281 DOI: 10.1007/s00261-016-0917-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE To determine if T1-weighted MR signal of the pancreas can be used to detect early CP. METHODS A retrospective analysis was performed on 51 suspected CP patients, who had both secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) and an intraductal secretin stimulation test (IDST). There were 29 patients in normal and 22 patients in the low bicarbonate group. Bicarbonate level, total pancreatic juice volume, and excretory flow rate were recorded during IDST. Signal intensity ratio of pancreas (SIR), fat signal fraction, pancreatograms findings, and grade of duodenal filling were recorded on S-MRCP by two blinded radiologists. RESULTS There was a significant difference in the signal intensity ratio of the pancreas to spleen (SIRp/s) between the normal and low bicarbonate groups (p < 0.0001). A significant positive correlation was found between pancreatic fluid bicarbonate level and SIRp/s (p < 0.0001). SIRp/s of 1.2 yielded sensitivity of 77% and specificity of 83% for detection of pancreatic exocrine dysfunction (AUC: 0.89). CONCLUSION T1-weighted MR signal of the pancreas has a high sensitivity and specificity for the detection of parenchymal abnormalities related to exocrine dysfunction and can therefore be helpful in evaluation of suspected early CP.
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Affiliation(s)
- Temel Tirkes
- Department of Radiology and Clinical Sciences, Indiana University School of Medicine, 550 N. University Blvd. Suite 0663, Indianapolis, IN, 46202, USA.
| | - Evan L Fogel
- Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Stuart Sherman
- Division of Gastroenterology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chen Lin
- Department of Radiology and Clinical Sciences, Indiana University School of Medicine, 550 N. University Blvd. Suite 0663, Indianapolis, IN, 46202, USA
| | - Jordan Swensson
- Department of Radiology and Clinical Sciences, Indiana University School of Medicine, 550 N. University Blvd. Suite 0663, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology and Clinical Sciences, Indiana University School of Medicine, 550 N. University Blvd. Suite 0663, Indianapolis, IN, 46202, USA
| | - Kumaresan Sandrasegaran
- Department of Radiology and Clinical Sciences, Indiana University School of Medicine, 550 N. University Blvd. Suite 0663, Indianapolis, IN, 46202, USA
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Chronic Pancreatitis-Like Changes Detected by Endoscopic Ultrasound in Type 1 Diabetics Are Not Associated With Gastrointestinal Symptoms or Nutritional Deficiencies. Pancreas 2017; 46:102-105. [PMID: 27984488 DOI: 10.1097/mpa.0000000000000671] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Previous studies have shown changes in the pancreas of type 1 diabetic (T1-DM) patients, similar to those present in patients with chronic pancreatitis. Our aim was to analyze the prevalence of endoscopic ultrasound (EUS) criteria for chronic pancreatitis in T1-DM, to determine the association with factors related to the diabetes and to define its clinical significance. METHODS Eighty-six T1-DM patients were prospectively included. All of them underwent EUS. Standard criteria were used. Patients were divided into 3 groups according to the number of EUS criteria they met: group A, 0 to 2 criteria; group B, 3 to 4; and group C, more than 4. Association between EUS findings and demographic or clinical factors was studied as well as the relationship between EUS abnormalities and the presence of gastrointestinal symptoms or nutritional deficiencies. RESULTS Fifty-three patients (61.6%) showed at least 1 morphologic abnormality. Fifty-eight patients were included in group A, 21 in group B, and 7 in Group C. No significant differences were found when comparing the 3 groups. CONCLUSIONS Chronic pancreatitis-like changes are frequent in the pancreas of T1-DM patients. These changes are not associated with demographic or clinical data. Therefore, the clinical relevance seems to be scarce.
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Kawada N, Tanaka S. Elastography for the pancreas: Current status and future perspective. World J Gastroenterol 2016; 22:3712-3724. [PMID: 27076756 PMCID: PMC4814734 DOI: 10.3748/wjg.v22.i14.3712] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2015] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Elastography for the pancreas can be performed by either ultrasound or endoscopic ultrasound (EUS). There are two types of pancreatic elastographies based on different principles, which are strain elastography and shear wave elastography. The stiffness of tissue is estimated by measuring the grade of strain generated by external pressure in the former, whereas it is estimated by measuring propagation speed of shear wave, the transverse wave, generated by acoustic radiation impulse (ARFI) in the latter. Strain elastography is difficult to perform when the probe, the pancreas and the aorta are not located in line. Accordingly, a fine elastogram can be easily obtained in the pancreatic body but not in the pancreatic head and tail. In contrast, shear wave elastography can be easily performed in the entire pancreas because ARFI can be emitted to wherever desired. However, shear wave elastography cannot be performed by EUS to date. Recently, clinical guidelines for elastography specialized in the pancreas were published from Japanese Society of Medical Ultrasonics. The guidelines show us technical knacks of performing elastography for the pancreas.
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Development and Diagnostic Accuracy of a Breath Test for Pancreatic Exocrine Insufficiency in Chronic Pancreatitis. Pancreas 2016; 45:241-7. [PMID: 26390420 DOI: 10.1097/mpa.0000000000000434] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To develop a ¹³C-labeled substrate breath test by defining the optimal ¹³C-labeled substrate, substrate dose, test meal, and duration of the test and evaluating its accuracy for the diagnosis of pancreatic exocrine insufficiency (PEI) in chronic pancreatitis (CP). METHODS Five consecutive prospective comparative studies in patients with known advanced CP and healthy controls were performed to develop the optimal breath test. Coefficient of fat absorption was used as the reference method. The diagnostic accuracy of the optimized breath test was prospectively further evaluated in patients with advanced CP using coefficient of fat absorption as the reference method. RESULTS The optimal breath test protocol was that using 250 mg of ¹³C-mixed triglyceride as substrate together with a test meal containing 16 g of fat. Coefficient of fat absorption and breath test results correlated significantly (r = 0.736, P < 0.001). The test has sensitivity, specificity, and overall accuracy of 92.9%, 91.7%, and 92.3%, respectively, for the diagnosis of PEI. CONCLUSIONS The optimized ¹³C-mixed triglyceride breath test is an accurate and simple breath test for the diagnosis of PEI in patients with CP, easily applicable to the clinical routine.
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Abstract
Pancreatic exocrine insufficiency is a well-documented complication of chronic pancreatitis; however, study results of pancreatic exocrine insufficiency in pancreatic cancer are less consistent. This applies for patients who are treated non-surgically and those who undergo curative pancreatic cancer resection. This review article summarizes relevant studies addressing pancreatic exocrine insufficiency in pancreatic cancer, with particular differentiation between non-surgically and surgically treated patients, as well as between the different surgeries. We also summarize studies addressing pancreatic enzyme replacement therapy in pancreatic cancer.
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Phillips ME. Pancreatic exocrine insufficiency following pancreatic resection. Pancreatology 2015; 15:449-455. [PMID: 26145836 DOI: 10.1016/j.pan.2015.06.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 05/06/2015] [Accepted: 06/10/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Untreated pancreatic exocrine dysfunction is associated with poor quality of life and reduced survival, but is difficult to diagnose following pancreatic resection. Many factors including the extent of the surgery, the health of the residual pancreas and the type of reconstruction must be considered. Patients remain undertreated, and consequently there is much debate to whether or not pancreatic enzyme replacement therapy should be routinely prescribed following pancreatic resection. METHODS A review of the literature was undertaken to establish the incidence of PEI and factors identifying treatment. RESULTS Forty two to forty five percent of patients undergoing pancreatico-duodenectomy (PD) experience pancreatic exocrine insufficiency pre-operatively, whilst the post-operative incidence is 56-98% in PD, and 12-80% following distal and central pancreatectomy. CONCLUSIONS Routine use of pancreatic enzyme replacement should be considered at a starting dose of 50 to 75,000 units lipase with meals and 25,000 to 50,000 units with snacks in this patient group. Patients who have had a central or distal pancreatectomy should be individually assessed for pancreatic exocrine insufficiency in the post operative period, with those undergoing extensive resection most likely to experience insufficiency. Patients who fail to respond to pancreatic enzyme replacement therapy should be referred to a specialist dietitian, be advised on dose adjustment, and undergo investigation to exclude other gastro-intestinal pathology, including small bowel bacterial overgrowth and bile acid malabsorption.
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Affiliation(s)
- Mary E Phillips
- Royal Surrey County Hospital, Regional HPB Unit, Egerton Road, Guildford GU2 7XX, United Kingdom.
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Dominguez-Muñoz JE, Iglesias-Garcia J, Castiñeira Alvariño M, Luaces Regueira M, Lariño-Noia J. EUS elastography to predict pancreatic exocrine insufficiency in patients with chronic pancreatitis. Gastrointest Endosc 2015; 81:136-42. [PMID: 25088920 DOI: 10.1016/j.gie.2014.06.040] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 06/26/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Diagnosis of pancreatic exocrine insufficiency (PEI) is hindered by methodological difficulties of pancreatic function tests. The probability of PEI in chronic pancreatitis (CP) increases as pancreatic fibrosis develops. Pancreatic fibrosis in CP may be quantified by EUS elastography. OBJECTIVE To evaluate whether EUS-elastography can predict PEI in patients with CP. DESIGN Prospective, observational study. SETTING Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain. PATIENTS Patients diagnosed with CP based on EUS and magnetic resonance imaging and MRCP findings. INTERVENTIONS Diagnosis of PEI was based on the (13)C-mixed triglyceride breath test. EUS-elastography was performed with PENTAX echoendoscopes and Hitachi-Preirus US platform. Two areas were selected for elastographic evaluation: area A corresponds to the pancreatic parenchyma and area B to a soft peripancreatic reference area. The quotient B/A (strain ratio [SR]) was considered the elastographic result. MAIN OUTCOME MEASUREMENTS Pancreatic SR in CP patients with and without PEI. RESULTS A total of 115 patients with CP (mean age, 50.2 years, range, 21-81; 92 male) of different etiologies were included; 35 patients (30.4%) had PEI. Pancreatic SR was higher in patients with PEI (4.89; 95% confidence interval, 4.36-5.41) than in those with a normal breath test result (2.99; 95% confidence interval, 2.82-3.16) (P < .001). A direct relationship was found between the SR and the probability of PEI, which increases from 4.2% in patients with an SR less than 2.5 to 92.8% in those with an SR greater than >5.5. LIMITATIONS Single-center study. CONCLUSIONS The degree of pancreatic fibrosis as measured by EUS-guided elastography allows quantification of the probability of PEI in patients with CP.
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Affiliation(s)
- J Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Margarita Castiñeira Alvariño
- Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Maria Luaces Regueira
- Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Jose Lariño-Noia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; Foundation for Research in Digestive Diseases (FIENAD), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
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Abstract
OBJECTIVES Several recent studies have demonstrated the association between smoking and chronic pancreatitis (CP). However, less is known about the role of smoking in the development of CP-related complications. Our aim was to investigate the impact of smoking and alcohol consumption on age of onset and complications at CP diagnosis. METHODS A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Alcohol consumption and smoking habits were assessed using a standardized questionnaire. Morphologic severity was defined based on endoscopic ultrasound criteria for CP and classified as mild (3-4 criteria), moderate (5-6 criteria), and severe (≥7 criteria or calcifications). Pancreatic exocrine insufficiency (PEI) was diagnosed using the C-mixed triglyceride breath test. Odds ratios (OR) with 95% confidence intervals (CI) for CP-related complications were calculated using a case-case design. RESULTS A total of 241 patients were included. Smoking was associated with PEI (OR [95% CI], 2.4 [1.17-5.16]), calcifications (OR [95% CI], 2.33 [1.10-4.95]), and severe morphologic changes (OR [95% CI], 3.41 [1.31-8.85]) but not with pseudocysts or diabetes. Neither smoking nor alcohol consumption was associated with age of onset. CONCLUSIONS Tobacco, but not alcohol, is associated with PEI, calcifications, and severe morphologic (≥7 criteria or calcifications) CP at diagnosis. Smoking cessation should be encouraged in patients with CP.
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Sze KCP, Pirola RC, Apte MV, Wilson JS. Current options for the diagnosis of chronic pancreatitis. Expert Rev Mol Diagn 2014; 14:199-215. [PMID: 24512138 DOI: 10.1586/14737159.2014.883277] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The diagnostic options for chronic pancreatitis have evolved over recent years. The previous gold standard references for structural imaging and exocrine pancreatic function testing have both been supplanted and redesigned. Endoscopic retrograde pancreatography has now been overtaken by endoscopic ultrasound and magnetic resonance cholangiopancreatography, whilst the old technique for Dreiling tube pancreatic function testing has now been replaced by the endoscopic pancreatic function test. New advances in endoscopic ultrasound elastography have also extended the options for evaluating pancreatic masses to differentiate mass-forming chronic pancreatitis from malignancy. Genetic contribution to chronic pancreatitis is also now more widely recognized than ever before.
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Affiliation(s)
- Kenny Ching Pan Sze
- South Western Sydney Clinical School, University of New South Wales, Liverpool Hospital, Liverpool, NSW 2170, Australia
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Pongprasobchai S. Maldigestion from pancreatic exocrine insufficiency. J Gastroenterol Hepatol 2013; 28 Suppl 4:99-102. [PMID: 24251713 DOI: 10.1111/jgh.12406] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2013] [Indexed: 12/13/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) is one of the long-term consequences of chronic pancreatitis (CP). Majority of patients with PEI were undiagnosed or undertreated. Inadequately treated or subclinical severe PEI causes malnutrition and may pose the patients at risk of premature atherosclerosis and cardiovascular events. Indication of pancreatic enzyme replacement therapy (PERT) is patients with severe PEI, as indicated by the presence of steatorrhea, diarrhea, weight loss, fecal fat > 7 g/day, (13) C-mixed triglyceride breath test < 29%, fecal elastase < 100 ug/g stool, imaging or endoscopic findings of pancreatic ductal dilatation or calculi, and eight endosonographic criteria of CP. The mainstay treatment of PEI is PERT. Dietary fat restriction is unnecessary. PERT with lipase > 40,000 U per meal is recommended. Enteric-coating may be preferred to conventional enzymes because of the availability of high-dose preparations and no need of acid suppression co-therapy. Administration of enzymes with meals is proven to be the most effective regimen. Response to PERT should be measured by the improvement of patients' symptoms, nutritional status, and, in selected cases, by fecal fat or (13) C-mixed triglyceride breath test. Patients unresponsive to PERT should be checked for compliance, increase the dose of lipase to 90,000 units/meal or co-therapy with proton pump inhibitor. In patient with previous gastrointestinal surgery that may interfere enzyme-food mixing, opening the capsules and administering the enzyme granules with meals. Finally, search for small intestinal bacterial overgrowth syndrome and other causes of small bowel malabsorption.
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Affiliation(s)
- Supot Pongprasobchai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Lindkvist B. Diagnosis and treatment of pancreatic exocrine insufficiency. World J Gastroenterol 2013; 19:7258-7266. [PMID: 24259956 PMCID: PMC3831207 DOI: 10.3748/wjg.v19.i42.7258] [Citation(s) in RCA: 142] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 08/22/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis. Normal digestion requires adequate stimulation of pancreatic secretion, sufficient production of digestive enzymes by pancreatic acinar cells, a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food. Failure in any of these steps may result in pancreatic exocrine insufficiency, which leads to steatorrhea, weight loss and malnutrition-related complications, such as osteoporosis. Methods evaluating digestion, such as fecal fat quantification and the 13C-mixed triglycerides test, are the most accurate tests for pancreatic exocrine insufficiency, but the probability of the diagnosis can also be estimated based on symptoms, signs of malnutrition in blood tests, fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging. Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption, dietary consultation, enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment. Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicrospheres during meals. The dose should be in proportion to the fat content of the meal, usually 40-50000 lipase units per main meal, and half the dose is required for a snack. In cases that do not respond to initial treatment, the doses can be doubled, and proton inhibitors can be added to the treatment. This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency.
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Response to Talukdar et al. Pancreatology 2012. [DOI: 10.1016/j.pan.2012.09.005] [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: 08/30/2023]
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Lindkvist B, Domínguez-Muñoz JE, Luaces-Regueira M, Castiñeiras-Alvariño M, Nieto-Garcia L, Iglesias-Garcia J. Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis. Pancreatology 2012; 12:305-10. [PMID: 22898630 DOI: 10.1016/j.pan.2012.04.006] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2012] [Revised: 04/25/2012] [Accepted: 04/26/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Methods for evaluation of pancreatic exocrine insufficiency (PEI) are expensive, labor intensive, and not available at many institutions. The aim of this study was to investigate if PEI in chronic pancreatitis (CP) can by predicted by nutritional markers in blood. METHODS A retrospective analysis of a prospectively collected database of CP patients was performed. Diagnosis of CP was based on endoscopic ultrasonography or magnetic resonance imaging. PEI was investigated by the (13)C-mixed triglyceride breath test. Hemoglobin, mean corpuscular volume, lymphocytes, prothrombin time, and serum levels of total protein, albumin, prealbumin, retinol binding protein, cholesterol, triglycerides, amylase, folic acid, vitamin B12, HbA1C, transferrin, ferritin, magnesium and zinc were analyzed. RESULTS 114 patients were included in the study (97 males, mean age 48.1 years, 54 with alcohol etiology), 38 (33%) suffered from PEI. Magnesium below 2.05 mg/dL, hemoglobin, albumin, prealbumin and retinol binding protein below lower limit of normal and HbA1C above upper limit of normal were associated with PEI in univariate analysis. Magnesium below 2.05 mg/dL detected PEI with a sensitivity, specificity and positive and negative predictive values of 0.88 (95% confidence interval, 0.66-0.97), 0.66 (0.48-0.80), 0.58 (0.39-0.75) and 0.91 (0.73-0.98), respectively. The corresponding values were 1.00 (0.80-1.00), 0.55 (0.38-0.71), 0.52 (0.34-0.69) and 1.00 (0.82-1.00)) if one or more pathological tests among parameters significantly associated with PEI in was used as a positive test for PEI. CONCLUSION Serum nutritional markers can be used to predict the probability of PEI in CP and provide guidance in decisions on enzyme replacement therapy.
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Affiliation(s)
- Björn Lindkvist
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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