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Garcia MA, Braun UK, Imam S, Poon I, Jackson L. Pancreatic Enzyme Supplementation for Patients with Pancreatic Cancer #500. J Palliat Med 2025. [PMID: 39984171 DOI: 10.1089/jpm.2025.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2025] Open
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Zhang Y, Wei X, Jiang S, Gao W, Wang K, Wang H, Wang H, Si N, Zhou Y, Luo K, Wang M, Liu Y, Chen L, Ni L, Zhao H. Jianwei Xiaoshi oral liquid attenuates high-calorie diet-induced dyspepsia in immature rats via regulating the pancreatic secretion pathway and maintaining the homeostasis of intestinal microbiota. Chin Med 2025; 20:6. [PMID: 39755683 DOI: 10.1186/s13020-024-01052-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 12/19/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear. METHODS To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC-Q-Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia. RESULTS A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body. CONCLUSION JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders.
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Affiliation(s)
- Yan Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Xiaolu Wei
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Shan Jiang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Wenya Gao
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Kun Wang
- Jichuan Pharmaceutical Group Co., Ltd., Jiangsu, 22544, China
| | - Hongjie Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Huijun Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Nan Si
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Yanyan Zhou
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Keke Luo
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Mengxiao Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Yuyang Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Lihua Chen
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Liqi Ni
- Jichuan Pharmaceutical Group Co., Ltd., Jiangsu, 22544, China.
| | - Haiyu Zhao
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
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Khatkov IE, Maev IV, Bordin DS, Kononenko IB, Kucheryavyy YA, Pokataev IA, Snegovoy AV, Tryakin AA, Feoktistova PS, Zhukova LG. Role of enzyme replacement therapy for exocrine and nutritional insufficiency in patients with malignancies: A review. JOURNAL OF MODERN ONCOLOGY 2024; 26:380-389. [DOI: 10.26442/18151434.2024.3.203007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Exocrine pancreatic insufficiency (EPI) is a condition in which the amount of secreted pancreatic enzymes is insufficient to maintain normal digestion. EPI is a frequent complication of pancreatic or other malignancies. The presence of EPI in a cancer patient may be suggested by symptoms of maldigestion, malabsorption, and alteration of nutritional markers; however, it is important to note that the EPI symptoms may be subtle. In the early stages, EPI may be latent and manifested by malnutrition. However, even in the later stages, the symptoms of EPI may be similar to those of cancer or be masked by the condition after chemoradiation therapy. Antitumor therapy itself may also cause EPI. Enzyme replacement therapy (ERT) is the standard of care for EPI, but it is rarely prescribed to cancer patients. However, supportive therapy plays an essential role in treating cancer patients because the quality of life and life expectancy of patients largely depend on the adequacy of the complex treatment. The review discusses the possible causes of EPI and its diagnosis and treatment in cancer patients. Special attention is paid to ERT regimens, including those for improving digestion and the drug's dosage form. It is shown that pancreatin in minimicrospheres is the drug of choice for ERT, since the minimum particle size facilitates the most physiological digestion process.
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Affiliation(s)
- Igor E. Khatkov
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
| | | | - Dmitry S. Bordin
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
- Tver State Medical University
| | - Inessa B. Kononenko
- Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of National Medical Research Radiological Centre
| | | | - Ilya A. Pokataev
- Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department
| | - Anton V. Snegovoy
- Russian University of Medicine
- Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of National Medical Research Radiological Centre
| | | | - Polina S. Feoktistova
- Loginov Moscow Clinical Scientific Center
- Central State Medical Academy of the President of the Russian Federation
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Garcia MAG, Imam S, Braun UK, Jackson LK. Rational Prescribing of Pancreatic Enzymes for Patients with Pancreatic Cancer. PHARMACY 2024; 12:47. [PMID: 38525727 PMCID: PMC10961774 DOI: 10.3390/pharmacy12020047] [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: 01/29/2024] [Revised: 02/26/2024] [Accepted: 03/01/2024] [Indexed: 03/26/2024] Open
Abstract
Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use of pancreatic enzyme replacement therapy. PERT is a key strategy in managing the symptoms of EPI and can improve quality of life, which is a central focus in palliative care. This treatment is profoundly underutilized in the palliative care of these patients. The objective of this review is to discuss the pharmacology, pharmacokinetics, side effects, available evidence of the effectiveness of pancreatic enzyme use for patients with pancreatic cancer, and challenges, along with proposed solutions regarding its use.
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Affiliation(s)
- Mary Acelle G. Garcia
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Syed Imam
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Ursula K. Braun
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Leanne K. Jackson
- Rehabilitation & Extended Care Line, Section of Palliative Medicine, Michael E DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA; (S.I.); (U.K.B.); (L.K.J.)
- Department of Medicine, Section of Geriatric and Palliative Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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Zhukova LG, Bordin DS, Dubtsova EA, Ilin MA, Kiriukova MA, Feoktistova PS, Egorov VI. How a significant increase in survival in pancreatic cancer is achieved. The role of nutritional status and supportive care: A review. JOURNAL OF MODERN ONCOLOGY 2024; 25. [DOI: 10.26442/18151434.2023.4.202541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.
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Estes-Doetsch H, Roberts K, Newkirk M, Parker A. Fat-soluble vitamin deficiency and exocrine pancreatic insufficiency among adults with chronic pancreatitis: Is routine monitoring necessary for all patients? Nutr Clin Pract 2024; 39:129-140. [PMID: 37840401 DOI: 10.1002/ncp.11082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 08/07/2023] [Accepted: 09/17/2023] [Indexed: 10/17/2023] Open
Abstract
Chronic pancreatitis (CP) is often associated with exocrine pancreatic insufficiency (EPI), which may increase risk for fat-soluble vitamin depletion. Although vitamin D deficiency is widespread among the general population, vitamins A, E, and K deficiencies may more uniquely present in patients with CP. Yet, it is unclear whether fat-soluble vitamin status should be routinely monitored in all patients with CP or limited to those with EPI. The purpose of this review is to describe the laboratory status of vitamins A, E, and K in adult patients with CP and their association with exocrine pancreatic function. Five primary, observational studies met the inclusion criteria for qualitative synthesis. Biochemical deficiencies in fat-soluble vitamins were observed across trials but results varied with respect to whether EPI increased risk. Challenges related to the diagnosis and treatment of EPI along with potential confounders may contribute to the heterogeneity among study results. Although more studies are needed to determine the influence of pancreatic enzyme replacement therapy on fat-soluble vitamin status as well as effective vitamin repletion strategies, clinicians should consider periodically screening for deficiencies in all patients with CP regardless of EPI to avoid associated health effects of vitamin depletion.
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Affiliation(s)
- Holly Estes-Doetsch
- Medical Dietetics Division, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Kristen Roberts
- Medical Dietetics Division, College of Medicine, The Ohio State University, Columbus, Ohio, USA
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Melanie Newkirk
- Department of Clinical and Preventive Nutrition Sciences, School of Health Professions, Rutgers University, Newark, New Jersey, USA
| | - Anna Parker
- Department of Clinical and Preventive Nutrition Sciences, School of Health Professions, Rutgers University, Newark, New Jersey, USA
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Balzano G, Zerbi A, Aleotti F, Capretti G, Melzi R, Pecorelli N, Mercalli A, Nano R, Magistretti P, Gavazzi F, De Cobelli F, Poretti D, Scavini M, Molinari C, Partelli S, Crippa S, Maffi P, Falconi M, Piemonti L. Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial. Ann Surg 2023; 277:894-903. [PMID: 36177837 PMCID: PMC10174105 DOI: 10.1097/sla.0000000000005713] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). BACKGROUND Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. METHODS Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. RESULTS Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. CONCLUSIONS TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.
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Affiliation(s)
- Gianpaolo Balzano
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessandro Zerbi
- Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Francesca Aleotti
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Giovanni Capretti
- Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Raffella Melzi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Nicolò Pecorelli
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia Mercalli
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Rita Nano
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paola Magistretti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Francesca Gavazzi
- Department of Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Francesco De Cobelli
- Department of Radiology, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Dario Poretti
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Marina Scavini
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Chiara Molinari
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Stefano Partelli
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Crippa
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Paola Maffi
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Massimo Falconi
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Lorenzo Piemonti
- Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Shestakova MV, Maev IV, Ametov AS, Antsiferov MB, Bordin DS, Galstyan GR, Dzgoeva FK, Kucheryavyy YA, Mkrtumyan AM, Nikonova TV, Pashkova EY. Pancreatic exocrine insufficiency in diabetes mellitus. DIABETES MELLITUS 2023; 26. [DOI: 10.14341/dm13027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT).
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Affiliation(s)
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - A. S. Ametov
- Russian Medical Academy of Continuous Professional Education
| | - M. B. Antsiferov
- Endocrinological Dispensary of the Moscow City Health Department
| | - D. S. Bordin
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; A.S. Loginov Moscow Clinical Scientific Centre; Tver State Medical University
| | | | | | | | - A. M. Mkrtumyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; A.S. Loginov Moscow Clinical Scientific Centre
| | | | - E. Y. Pashkova
- Russian Medical Academy of Continuous Professional Education; Botkin Hospital
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Shestakova MV, Maev IV, Ametov AS, Antsiferov MB, Bordin DS, Galstyan GR, Dzgoeva FK, Kucheryavyy YA, Mkrtumyan AM, Nikonova TV, Pashkova EY. Pancreatic exocrine insufficiency in diabetes mellitus. DIABETES MELLITUS 2023; 26. [DOI: https:/doi.org/10.14341/dm13027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Diabetes is disease of both the endo- and exocrine parts of the pancreas. Pancreatic exocrine insufficiency (PEI) can occur in every 2–3 patients with diabetes and affect not only the quality, but also life expectancy. At the same time, the diagnosis and treatment of PEI is not getting enough attention. The endocrinologist, as the main specialist leading patients with diabetes, can diagnose and treat patients with pancreatic exocrine insufficiency and diabetes using adequate doses of pancreatic enzyme replacement therapy (PERT).
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Affiliation(s)
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - A. S. Ametov
- Russian Medical Academy of Continuous Professional Education
| | - M. B. Antsiferov
- Endocrinological Dispensary of the Moscow City Health Department
| | - D. S. Bordin
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; A.S. Loginov Moscow Clinical Scientific Centre; Tver State Medical University
| | | | | | | | - A. M. Mkrtumyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry; A.S. Loginov Moscow Clinical Scientific Centre
| | | | - E. Y. Pashkova
- Russian Medical Academy of Continuous Professional Education; Botkin Hospital
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Singh A, Aggarwal M, Garg R, Stevens T, Chahal P. Post-pancreatitis diabetes mellitus: insight on optimal management with nutrition and lifestyle approaches. Ann Med 2022; 54:1776-1786. [PMID: 35786076 PMCID: PMC9254994 DOI: 10.1080/07853890.2022.2090601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Pancreatitis is the leading gastrointestinal cause of hospitalizations. There are multiple short- and long-term complications associated with pancreatitis. Post-pancreatitis diabetes mellitus (PPDM) is one of the less explored complications of pancreatitis. Nonetheless, it has attracted considerable attention during the last decade. PPDM is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM. However, there exists a knowledge gap amongst practitioners regarding diagnosis, complications, and management of PPDM. In this narrative, we aim to provide a brief review regarding risks, diagnosis and management of PPDM with a special focus on dietary and lifestyle management strategies.KEY MESSAGESPost-pancreatitis diabetes mellitus (PPDM) is now the second most common cause of new-onset diabetes mellitus (DM) in adults after type II DM surpassing type 1 DM.New-onset diabetes in patients with pancreatitis could also be an early marker of occult pancreatic malignancy.Management of PPDM is complex and requires a team-based approach including gastroenterologists, endocrinologists, primary care physicians, nutritionists, and behavioural health specialists.
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Affiliation(s)
- Amandeep Singh
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Manik Aggarwal
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Rajat Garg
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tyler Stevens
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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Maehira H, Iida H, Mori H, Nitta N, Maekawa T, Tokuda A, Takebayashi K, Kaida S, Miyake T, Tani M. Aggressive Intervention of Pancrelipase After Pancreatectomy Prevents Deterioration of Postoperative Nutritional Status. Pancreas 2022; 51:394-398. [PMID: 35695803 DOI: 10.1097/mpa.0000000000002035] [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: 12/10/2022]
Abstract
OBJECTIVES This study aimed to investigate the effect of early administration of delayed-release high-titer pancrelipase. METHODS The medical records of 120 patients who had undergone pancreatectomy with computed tomography (CT) before and 6 months after surgery were retrospectively reviewed. Delayed-release high-titer pancrelipase were administered daily starting on postoperative day 3, which was defined as the EP group. The postoperative nutritional status and CT attenuation values of the liver were compared between the EP and control groups. RESULTS Thirty-three patients (28%) were categorized into the EP group. With regard to the postoperative nutritional status 6 months after surgery, the body mass index, total lymphocyte count, and Onodera's prognostic nutritional index were higher, and controlling nutritional status score was lower in the EP group than that in the control group. The CT attenuation values of the liver were not significantly different. After propensity score matching analysis, body mass index (20.7 vs 19.2, P = 0.049) and Onodera's prognostic nutritional index (47.9 vs 44.2, P = 0.045) were significantly higher, and controlling nutritional status score was significantly lower in the EP group than that in the control group (1 vs 3, P = 0.046). CONCLUSIONS The early administration of pancrelipase after pancreatectomy improved nutritional status after pancreatectomy.
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Affiliation(s)
| | - Hiroya Iida
- From the Department of Surgery, Shiga University of Medical Science
| | - Haruki Mori
- From the Department of Surgery, Shiga University of Medical Science
| | - Nobuhito Nitta
- From the Department of Surgery, Shiga University of Medical Science
| | - Takeru Maekawa
- From the Department of Surgery, Shiga University of Medical Science
| | - Aya Tokuda
- Cancer Center, Shiga University of Medical Science Hospital, Shiga, Japan
| | | | - Sachiko Kaida
- From the Department of Surgery, Shiga University of Medical Science
| | - Toru Miyake
- From the Department of Surgery, Shiga University of Medical Science
| | - Masaji Tani
- From the Department of Surgery, Shiga University of Medical Science
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Dos Anjos F, Wruck J, do Carmo TIT, Miranda Soares VE, de Resende E Silva DT, Bagatini MD, de Oliveira Maciel SFV. Pancreatic Insufficiency in a Child with p.Gly542* and c.2657+5G>A Heterozygote CFTR: A Case Report. Clin Med Res 2022; 20:46-51. [PMID: 35131845 PMCID: PMC9390849 DOI: 10.3121/cmr.2022.1618] [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: 09/03/2020] [Accepted: 01/25/2022] [Indexed: 11/18/2022]
Abstract
Cystic fibrosis is a monogenic and autosomal recessive disease. It is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene responsible for encoding the CFTR protein. Involvement of the gastrointestinal and respiratory systems is the main clinical manifestation. In this case, we report a heterozygous CFTR patient harboring class I (p.Gly542*) and class V (c.2657+5G>A) mutations. The importance of this case report lies in the clinical features because the patient, aged 3 years, presented with early exocrine pancreatic insufficiency, which can be considered atypical, as most individuals with this genotype are pancreatic sufficient or develop pancreatic insufficiency later in life. This report aims at presenting the tests requested that contributed to the patient's diagnosis, as well as at understanding the association between these mutations and their phenotypic presentation. Interpretation of the genotype-phenotype relationship represents a challenge, as genetic analysis alone is not sufficient to clearly predict severity of the disease. This is because the significant phenotypic heterogeneity existing among patients with the same genotype may exert socioeconomic and sociocultural influences, or by the action of CFTR modifiers, such as environmental and modifying genes, which can alter the protein's function and exert an impact on the individual's phenotype.
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Affiliation(s)
- Fernanda Dos Anjos
- Medicial student, Federal University of Fronteira Sul, Chapecó, SC, Brazil
| | - Jonatha Wruck
- Medicial student, Federal University of Fronteira Sul, Chapecó, SC, Brazil
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13
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Abstract
BACKGROUND Chronic pancreatitis (CP) is defined according to the recently proposed mechanistic definition as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. METHODS The clinical practice guidelines for CP in Japan were revised in 2021 based on the 2019 Japanese clinical diagnostic criteria for CP, which incorporate the concept of a pathogenic fibro-inflammatory syndrome in the pancreas. In this third edition, clinical questions are reclassified into clinical questions, background questions, and future research questions. RESULTS Based on analysis of newly accumulated evidence, the strength of evidence and recommendations for each clinical question is described in terms of treatment selection, lifestyle guidance, pain control, treatment of exocrine and endocrine insufficiency, and treatment of complications. A flowchart outlining indications, treatment selection, and policies for cases in which treatment is ineffective is provided. For pain control, pharmacological treatment and the indications and timing for endoscopic and surgical treatment have been updated in the revised edition. CONCLUSIONS These updated guidelines provide clinicians with useful information to assist in the diagnosis and treatment of CP.
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14
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Hammer HF. Management of Chronic Diarrhea in Primary Care: The Gastroenterologists' Advice. Dig Dis 2021; 39:615-621. [PMID: 33588424 DOI: 10.1159/000515219] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/10/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Chronic diarrhea is defined as more than 3 bowel movements per day, or loose stools, or stool weight >200 g/day for at least 4 weeks. Accompanying symptoms may include urgency, abdominal pain, or cramps. SUMMARY A number of causes have to be considered, including inflammatory, neoplastic, malabsorptive, infective, vascular, and functional gastrointestinal diseases. Other causes include food intolerances, side effects of drugs, or postsurgical conditions. Diarrhea may also be symptom of a systemic disease, like diabetes or hyperthyroidism. Special patient groups, like the very elderly and immunocompromised patients, pose special challenges. This review follows a question-answer style and addresses questions raised on the intersection of primary and secondary care. What do you mean by diarrhea? Why is it important to distinguish between acute or chronic diarrhea? How shall the patient with chronic diarrhea be approached? How can history and physical exam help? How can routine laboratory tests help in categorizing diarrhea? Which additional laboratory tests may be helpful? How to proceed in undiagnosed or intractable diarrhea? What are the treatment options in patients with chronic diarrhea? Key Messages: Acute diarrhea is usually of infectious origin with the main treatment goal of preventing water and electrolyte disturbances. Chronic diarrhea is usually not of infectious origin and may be the symptom of a large number of gastrointestinal and general diseases or drug side effects. In undiagnosed or intractable diarrhea, the question shall be raised whether the appropriate tests have been performed and interpreted correctly.
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Affiliation(s)
- Heinz F Hammer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Graz, Austria
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15
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Diéguez-Castillo C, Jiménez-Luna C, Martín-Ruiz JL, Martínez-Galán J, Prados J, Torres C, González-Ramírez AR, Caba O. Role of Exocrine and Endocrine Insufficiency in the Management of Patients with Chronic Pancreatitis. J Clin Med 2020; 9:jcm9062014. [PMID: 32604940 PMCID: PMC7356684 DOI: 10.3390/jcm9062014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/22/2020] [Accepted: 06/25/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Exocrine pancreatic insufficiency results from the destruction of the pancreatic parenchyma and is diagnosed by using direct or indirect tests, both of which have shortcomings. Chronic pancreatitis is the most frequent cause of this pathology in adults. Methods: Patients meeting radiological or histological diagnostic criteria of chronic pancreatitis are enrolled and the stool elastase test is conducted, considering fecal elastase levels >200 µg/g to represent normal pancreatic function, and levels <200 μg/g to indicate the presence of exocrine pancreatic insufficiency. Additionally, we determine the body mass index of the patients and study their nutritional status and main biochemical and hematological variables, including their glucose and hemoglobin A1c (HbA1c) levels. Results: Exocrine pancreatic insufficiency is detected in 60% of the patients. Among these, 83.3% are severe cases, and 72% of the latter also are diagnosed with endocrine pancreatic insufficiency (diabetes mellitus). During the nutritional status study, HbA1c levels are significantly higher, and magnesium and prealbumin levels are significantly lower in patients with exocrine pancreatic insufficiency than in those without this disease. Conclusions: Exocrine and endocrine pancreatic insufficiency are highly prevalent among patients with chronic pancreatitis and an early diagnosis of these diseases is vital to improve the clinical management of these patients and reduce their risk of mortality.
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Affiliation(s)
- Carmelo Diéguez-Castillo
- Department of Gastroenterology, San Cecilio University Hospital, 18012 Granada, Spain; (C.D.-C.); (J.L.M.-R.)
| | - Cristina Jiménez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain; (C.J.-L.); (J.P.)
| | - Jose Luis Martín-Ruiz
- Department of Gastroenterology, San Cecilio University Hospital, 18012 Granada, Spain; (C.D.-C.); (J.L.M.-R.)
| | - Joaquina Martínez-Galán
- Department of Medical Oncology, Virgen de las Nieves University Hospital, 18014 Granada, Spain;
| | - José Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain; (C.J.-L.); (J.P.)
| | - Carolina Torres
- Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, 18071 Granada, Spain;
| | | | - Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain; (C.J.-L.); (J.P.)
- Correspondence: ; Tel.: +34-958-243-534
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16
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Omega-3 fatty acid exposure with a low-fat diet in patients with past hypertriglyceridemia-induced acute pancreatitis; an exploratory, randomized, open-label crossover study. Lipids Health Dis 2020; 19:117. [PMID: 32473640 PMCID: PMC7260759 DOI: 10.1186/s12944-020-01295-7] [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: 05/23/2019] [Accepted: 05/21/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Omega-3 fatty acids (OM3-FAs) are recommended with a low-fat diet for severe hypertriglyceridemia (SHTG), to reduce triglycerides and acute pancreatitis (AP) risk. A low-fat diet may reduce pancreatic lipase secretion, which is required to absorb OM3-ethyl esters (OM3-EEs), but not OM3-carboxylic acids (OM3-CAs). METHODS In this exploratory, randomized, open-label, crossover study, 15 patients with SHTG and previous AP were instructed to take OM3-CA (2 g or 4 g) and OM3-EE 4 g once daily for 4 weeks, while adhering to a low-fat diet. On day 28 of each treatment phase, a single dose was administered in the clinic with a liquid low-fat meal, to assess 24-h plasma exposure. Geometric least-squares mean ratios were used for between-treatment comparisons of baseline (day 0)-adjusted area under the plasma concentration versus time curves (AUC0-24) and maximum plasma concentrations (Cmax) for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). RESULTS Before initiating OM3-FA treatment, mean baseline fasting plasma EPA + DHA concentrations (nmol/mL) were 723 for OM3-CA 2 g, 465 for OM3-CA 4 g and 522 for OM3-EE 4 g. At week 4, mean pre-dose fasting plasma EPA + DHA concentrations increased by similar amounts (+ 735 - + 768 nmol/mL) for each treatment. During the 24-h exposure assessment (day 28), mean plasma EPA + DHA increased from pre-dose to the maximum achieved concentration by + 32.7%, + 45.8% and + 3.1% with single doses of OM3-CA 2 g, OM3-CA 4 g and OM3-EE 4 g, respectively. Baseline-adjusted AUC0-24 was 60% higher for OM3-CA 4 g than for OM3-EE 4 g and baseline-adjusted Cmax was 94% higher (both non-significant). CONCLUSIONS Greater 24-h exposure of OM3-CA versus OM3-EE was observed for some parameters when administered with a low-fat meal at the clinic on day 28. However, increases in pre-dose fasting plasma EPA + DHA over the preceding 4-week dosing period were similar between treatments, leading overall to non-significant differences in baseline (day 0)-adjusted AUC0-24 and Cmax EPA + DHA values. It is not clear why the greater 24-h exposure of OM3-CA versus OM3-EE observed with a low-fat meal did not translate into significantly higher pre-dose fasting levels of DHA + EPA with longer-term use. TRIAL REGISTRATION ClinicalTrials.gov, NCT02189252, Registered 23 June 2014.
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17
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Abstract
PURPOSE OF REVIEW Type 1 and type 2 diabetes are often accompanied by mostly mild forms of exocrine pancreatic insufficiency. Despite high prevalence, little is known about the clinical consequences of exocrine pancreatic insufficiency and its optimal (nutritional) treatment. Even less is known if and to what extent exocrine pancreas insufficiency also affects glycemic control in diabetes. This article aims for summarizing current clinical knowledge on screening, diagnosis, and treatment and gives an overview on the pathophysiology of exocrine pancreatic insufficiency in diabetes. RECENT FINDINGS Recent studies reveal novel insights into the close interaction of acinar, ductal, and endocrine cells and the gut-pancreas axis. Exocrine pancreatic insufficiency is a clinically relevant, frequent but poorly understood disorder in both type 1 and type 2 diabetes.
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Affiliation(s)
- Bernhard Radlinger
- Department of Internal Medicine 1, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - Gabriele Ramoser
- Department of Pediatrics II, Medical University Innsbruck, Innsbruck, Austria
| | - Susanne Kaser
- Department of Internal Medicine 1, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
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18
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Prasanna T, McNeil CM, Nielsen T, Parkin D. Isolated immune-related pancreatic exocrine insufficiency associated with pembrolizumab therapy. Immunotherapy 2019; 10:171-175. [PMID: 29370723 DOI: 10.2217/imt-2017-0126] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.
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Affiliation(s)
- Thiru Prasanna
- Chris O'Brien Lifehouse, Medical Oncology Department, Camperdown, NSW, Australia.,Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Catriona M McNeil
- Chris O'Brien Lifehouse, Medical Oncology Department, Camperdown, NSW, Australia.,Royal Prince Alfred Hospital, Camperdown, NSW, Australia.,Sydney Medical School, University of Sydney, NSW, Australia
| | | | - David Parkin
- Wyong Public Hospital, Gastroenterology Department, NSW, Australia
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19
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Widodo AD, Timan IS, Bardosono S, Siagian M, Winarta W, Prasetyo D, Firmansyah A. Poor diagnostic values of stool analysis and steatocrit test in detecting exocrine pancreatic insufficiency. MEDICAL JOURNAL OF INDONESIA 2019. [DOI: 10.13181/mji.v28i2.1690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Exocrine pancreatic insufficiency (EPI) is one of the most challenging cases to be diagnosed accurately in Indonesia because of the unavailability of the fecal elastase-1 (FE-1) test, which is the primary indirect diagnostic tool till date. Stool analysis and steatocrit test are feasible alternatives as they can detect nutrient malabsorption, a consistent feature in EPI. Despite the common practice of using both tests, no study has ever been conducted in Indonesia to evaluate their accuracy.
METHODS This cross-sectional diagnostic study was conducted in 182 children aged 6–60 months. Study subjects were divided into children with persistent diarrhea (PD), those with malnutrition, and healthy children. Children with PD and malnutrition were selected on the basis of clinical criteria and the WHO z-score. FE-1 test was used as the gold standard to detect EPI. Primary endpoints of this study were sensitivity and specificity of the stool analysis and the steatocrit test. The accuracy of both tests, represented by area under the curve (AUC) values, was also evaluated individually and in combination.
RESULTS Each component of stool analysis and steatocrit test in each subgroup of patients generally had higher specificity than sensitivity. The specificity of both tests among healthy and malnourished children was good (≥70%), but among children with PD, the specificity of some components was <70%. The individual and combined AUC values of both tests in each subgroup of subjects were poor (<0.7).
CONCLUSIONS Stool analysis and steatocrit test cannot be used as alternative methods for FE-1 to detect EPI.
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20
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Yamamoto A, Ito K, Yasokawa K, Kanki A, Tanimoto D, Hayashida M, Tamada T. Symptoms that are associated with decreased pancreatic enzyme flow: MRCP assessment. J Magn Reson Imaging 2019; 50:417-423. [PMID: 30637845 DOI: 10.1002/jmri.26619] [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: 10/29/2018] [Revised: 12/03/2018] [Accepted: 12/03/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pancreatic exocrine insufficiency is one of the causes of malabsorption syndrome. In many cases of malabsorption syndrome, pancreatic exocrine insufficiency can be treated with pancreatic enzyme replacement therapy. Therefore, it is important to detect pancreatic endocrine insufficiency as early and accurately as possible. Recent studies have shown that cine-dynamic MR cholangiopancreatography (MRCP) may be useful to evaluate pancreatic exocrine function PURPOSE: To identify abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion for which cine-dynamic MRCP should be performed to diagnose pancreatic exocrine insufficiency. STUDY TYPE Prospective. POPULATION In all, 111 patients with various types of abdominal symptoms. FIELD STRENGTH/SEQUENCE 5 T or 3 T, MRCP with spatially selective inversion recovery pulse (cine-dynamic MRCP). ASSESSMENT Cine-dynamic MRCP was performed and an 18-question clinical questionnaire on abdominal symptoms was administered. The secretion grade derived from cine-dynamic MRCP was compared between those answering "yes" and "no" for all 18 items STATISTICAL TESTS: Univariate analysis and further analyzed using multiple regression analysis. The associations between the secretion grade and the items in the clinical questionnaire were analyzed by univariate analysis and further analyzed using multiple regression analysis. RESULTS The following three items showed significantly negative correlations with secretion grade: Q9, Does your rectal gas smell foul? (β = -0.44, P = 0.001); Q13, Is stool quantity large? (β = -0.41, P = 0.001); and Q18, Are your stools soft? (β = -0.53, P < 0.001). No significant correlations with exocrine pancreatic function measured by cine-dynamic MRCP were seen for the remaining 15 abdominal symptom items. DATA CONCLUSION Abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion were foul rectal gas, large stool, and soft stool. Pancreatic exocrine insufficiency due to decreased pancreatic enzyme flow may be suspected in patients with these abdominal symptoms. LEVEL OF EVIDENCE 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:417-423.
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Affiliation(s)
- Akira Yamamoto
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
| | - Katsuyoshi Ito
- Department of Radiology, Yamaguchi University, Ube, Japan
| | - Kazuya Yasokawa
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
| | - Akihiko Kanki
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
| | - Daigo Tanimoto
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
| | - Minoru Hayashida
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
| | - Tsutomu Tamada
- Department of Radiology, Kawasaki Medical School, Kurashiki, Japan
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21
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Leerhøy B, Shabanzadeh DM, Nordholm-Carstensen A, Novovic S, Hansen MB, Jørgensen LN. Pancreatic function following post-endoscopic retrograde cholangiopancreatography pancreatitis: A controlled cohort study with long-term follow-up. United European Gastroenterol J 2018; 6:586-594. [PMID: 29881614 DOI: 10.1177/2050640617742498] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/17/2017] [Indexed: 12/21/2022] Open
Abstract
Background Acute pancreatitis is one of the most common causes of gastrointestinal-related hospitalization and the incidence is increasing. Endo- and exocrine pancreatic function can be compromised after acute pancreatitis. Objective The purpose of this study was to explore the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on pancreatic function. Methods A follow-up study was carried out with prospective assessment of endo- and exocrine pancreatic function among cases with previous PEP and matched controls from a Danish cohort consisting of 772 patients undergoing first-time ERCP. Pancreatic function was evaluated by faecal-elastase-1 test, blood levels of haemoglobin A1c, C-peptide, vitamin B12, vitamin D and indirectly by changes in body weight. Results Twenty-nine cases and 49 controls participated in the study. Mean follow-up time (standard deviation) was 58 (21) months. Twelve (41%), eight (28%) and nine (31%) patients had mild, moderate and severe PEP, respectively. There was no difference between cases and controls with regard to pancreatic function parameters and PEP severity was not associated with pancreatic function. Factors associated with pancreatic function impairment included body mass index, alcohol consumption, age and smoking. Conclusion This study suggests that long-term pancreatic function following PEP is similar to the pancreatic function of other patients with comparable gallstone-related morbidity.
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Affiliation(s)
- Bonna Leerhøy
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Denmark
| | - Daniel M Shabanzadeh
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Denmark
| | | | - Srdan Novovic
- 2Department of Gastroenterology and Gastrointestinal Surgery, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Mark B Hansen
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Denmark.,Zealand Pharma, Research and Development, Glostrup, Denmark
| | - Lars N Jørgensen
- Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Denmark
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Othman MO, Harb D, Barkin JA. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. Int J Clin Pract 2018; 72:e13066. [PMID: 29405509 PMCID: PMC5873407 DOI: 10.1111/ijcp.13066] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 01/08/2018] [Indexed: 12/14/2022] Open
Abstract
AIMS In exocrine pancreatic insufficiency (EPI), the quantity and/or activity of pancreatic digestive enzymes are below the levels required for normal digestion, leading to maldigestion and malabsorption. Diagnosis of EPI is often challenging because the characteristic signs and symptoms overlap with those of other gastrointestinal conditions. Additionally, there is no single convenient, or specific diagnostic test for EPI. The aim of this review is to provide a framework for differential diagnosis of EPI vs other malabsorptive conditions. METHODS This is a non-systematic narrative review summarising information pertaining to the aetiology, diagnosis and management of EPI. RESULTS Exocrine pancreatic insufficiency may be caused by pancreatic disorders, including chronic pancreatitis, cystic fibrosis, pancreatic resection and pancreatic cancer. EPI may also result from extra-pancreatic conditions, including coeliac disease, Zollinger-Ellison syndrome and gastric surgery. Timely and accurate diagnosis of EPI is important, as delays in treatment prolong maldigestion and malabsorption, with potentially serious consequences for malnutrition, overall health and quality of life. Symptoms of EPI are non-specific; therefore, a high index of clinical suspicion is required to make a correct diagnosis.
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Affiliation(s)
- Mohamed O. Othman
- Division of GastroenterologyDepartment of MedicineBaylor College of MedicineHoustonTXUSA
| | - Diala Harb
- Global Medical AffairsAbbVie Inc.MettawaILUSA
| | - Jodie A. Barkin
- Division of GastroenterologyDepartment of MedicineLeonard M. Miller School of MedicineUniversity of MiamiMiamiFLUSA
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Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study. GASTROENTEROLOGIA Y HEPATOLOGIA 2017; 41:77-86. [PMID: 28935122 DOI: 10.1016/j.gastrohep.2017.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 06/20/2017] [Accepted: 08/08/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL). METHODS This was a cross-sectional, multicenter Spanish study. CP patients without follow-up by a gastroenterologist or surgeon in at least 2 years were included. EPI was defined as fecal elastase test <200mcg/g. For nutritional assessment, laboratory and anthropometric data were obtained. QoL was investigated using the EORTC QLQ-C30 questionnaire. RESULTS 64 patients (mean age 58.8±10.3 years, 85.9% men) from 10 centers were included. Median time since diagnosis of CP was 58.7 months [37.7-95.4]. Forty-one patients (64.1%) had EPI. Regarding nutritional status, the following differences were observed (EPI vs. Non-EPI): BMI (23.9±3.5kg/m2 vs. 25.7±2.5, p=0.03); glucose (121 [96-189] mg/dL vs. 98 [90-116], p=0.006); HbA1c 6.6% [6.0-8.4] vs. 5.5 [5.3-6.0], p=0.0005); Vitamin A (0.44mg/L [0.35-0.57] vs. 0.53 [0.47-0.63], p=0.048) and Vitamin E (11.2±5.0μg/ml vs. 14.4±4.3, p=0.03). EPI group showed a worse EORTC QLQ-C30 score on physical (93.3 [66.7-100] vs. 100 [93.3-100], p=0.048) and cognitive function (100 [83.3-100] vs. 100 [100-100], p=0.04). CONCLUSIONS Prevalence of EPI is high in patients with CP without follow-up. EPI group had higher levels of glucose, lower levels of vitamins A and E and worse QoL.
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24
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Bio-Inspired Polymer Membrane Surface Cleaning. Polymers (Basel) 2017; 9:polym9030097. [PMID: 30970776 PMCID: PMC6432259 DOI: 10.3390/polym9030097] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 03/02/2017] [Accepted: 03/05/2017] [Indexed: 11/24/2022] Open
Abstract
To generate polyethersulfone membranes with a biocatalytically active surface, pancreatin was covalently immobilized. Pancreatin is a mixture of digestive enzymes such as protease, lipase, and amylase. The resulting membranes exhibit self-cleaning properties after “switching on” the respective enzyme by adjusting pH and temperature. Thus, the membrane surface can actively degrade a fouling layer on its surface and regain initial permeability. Fouling tests with solutions of protein, oil, and mixtures of both, were performed, and the membrane’s ability to self-clean the fouled surface was characterized. Membrane characterization was conducted by investigation of the immobilized enzyme concentration, enzyme activity, water permeation flux, fouling tests, porosimetry, X-ray photoelectron spectroscopy, and scanning electron microscopy.
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25
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Smits MM, Tonneijck L, Muskiet MHA, Kramer MHH, Pieters-van den Bos IC, Vendrik KEW, Hoekstra T, Bruno MJ, Diamant M, van Raalte DH, Cahen DL. Pancreatic Effects of Liraglutide or Sitagliptin in Overweight Patients With Type 2 Diabetes: A 12-Week Randomized, Placebo-Controlled Trial. Diabetes Care 2017; 40:301-308. [PMID: 27998910 DOI: 10.2337/dc16-0836] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 11/22/2016] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology. RESEARCH DESIGN AND METHODS For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n = 19), sitagliptin 100 mg (n = 19), or matching placebos (n = 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI). RESULTS No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3 to 32.9; P = 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipase/amylase levels after 12 weeks. However, liraglutide increased lipase levels after 6 weeks (23.5 U/L [95% CI 2.1-44.8]; P = 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9]; P = 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2], P = 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9], P = 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm3 [95% CI -1.2 to 16.6]; P = 0.09). Treatment-induced volume expansion was associated with increased amylase levels. CONCLUSIONS A 12-week treatment with liraglutide or sitagliptin only resulted in a brief and modest increase of plasma pancreatic enzyme concentrations in patients with type 2 diabetes. Apart from a minimal sitagliptin-induced increase in intraduodenal fluid secretion, pancreatic exocrine function was unaffected. The long-term clinical consequences of these discrete changes require further study.
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Affiliation(s)
- Mark M Smits
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Lennart Tonneijck
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Marcel H A Muskiet
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Mark H H Kramer
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | | | - Karuna E W Vendrik
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Trynke Hoekstra
- Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands.,Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Michaela Diamant
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Daniël H van Raalte
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Djuna L Cahen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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Heubi JE, Schaeffer D, Ahrens RC, Sollo N, Strausbaugh S, Graff G, Jain R, Witte S, Forssmann K. Safety and Efficacy of a Novel Microbial Lipase in Patients with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis: A Randomized Controlled Clinical Trial. J Pediatr 2016; 176:156-161.e1. [PMID: 27297209 DOI: 10.1016/j.jpeds.2016.05.049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 04/12/2016] [Accepted: 05/12/2016] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To evaluate the safety and efficacy of a novel microbial lipase (NM-BL) in a liquid formulation for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF) in a phase IIa proof-of-concept study. STUDY DESIGN We conducted a double-blind, randomized, placebo controlled crossover study in patients with cystic fibrosis and exocrine pancreatic insufficiency. Adolescent and adult patients with CF were randomized to receive NM-BL or placebo for 1 week as replacement for their usual pancreatic enzyme formulation. They were subsequently crossed-over to the alternate study treatment. The coefficient of fat absorption was evaluated as the primary endpoint. Symptoms and adverse events were evaluated as secondary endpoints. RESULTS A total of 35 patients were randomized into the study and 22 patients completed both treatment periods. During treatment with NM-BL, the coefficient of fat absorption was significantly greater (72.7%) compared with placebo (53.8%) with a difference between groups of 18.8% (P < .001). Subjective assessment of stool fat and stool consistency also improved under treatment with NM-BL. Adverse events were mostly gastrointestinal in nature and were more common in the group receiving NM-BL. CONCLUSIONS Currently available pancreatic enzyme products are limited because of the lack of liquid formulations and being largely porcine based. The novel microbial lipase NM-BL was safe and effective in this short term trial. The trial provided clinical proof-of-concept for this novel microbial lipase as a treatment for EPI in CF. A larger phase 2 dose ranging trial is warranted. TRIAL REGISTRATION ClinicalTrials.gov: NCT01710644.
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Affiliation(s)
- James E Heubi
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
| | | | - Richard C Ahrens
- Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA
| | - Natalie Sollo
- University of Kansas School of Medicine-Wichita/Via Christi Research, Wichita, KS
| | | | - Gavin Graff
- Penn State Milton S. Hershey Medical Center, Hershey, PA
| | - Raksha Jain
- The University of Texas Southwestern Medical Center, Dallas, TX
| | - Stephan Witte
- Nordmark Arzneimittel GmbH & Co. KG, Uetersen, Germany
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27
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Efficacy and Safety of Pancrelipase/Pancreatin in Patients With Exocrine Pancreatic Insufficiency and a Medical History of Diabetes Mellitus. Pancreas 2016; 45:679-86. [PMID: 26495784 DOI: 10.1097/mpa.0000000000000514] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES The aim of this study was to perform exploratory analyses of the efficacy and safety of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency (EPI) with (n = 36) and without (n = 18) concurrent diabetes mellitus (DM). METHODS This was a retrospective, post hoc, subgroup (±DM) analysis of a double-blind, randomized, placebo-controlled trial of pancrelipase in patients with EPI due to chronic pancreatitis or pancreatectomy (total or partial). After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units/meal, 36,000/snack) or placebo for 7 days. Outcomes included changes in coefficients of fat absorption (CFA) and nitrogen absorption (CNA) from baseline to the end of the double-blind period. RESULTS Mean changes in nutrient absorption were greater with pancrelipase versus placebo in patients with DM (CFA, 36.0% vs 7.5%, P < 0.0001; CNA, 33.4% vs 3.7%, P = 0.0002) and without DM (CFA, 25.2% vs 12.3%, P = 0.0326; CNA, 39.1% vs 17.6%, P = 0.1187). Diabetes mellitus was not significantly associated with outcomes for CFA (P = 0.0802) and CNA (P = 0.2934). Incidences of adverse events, including hypoglycemia and hyperglycemia, were similar in the pancrelipase and placebo arms. CONCLUSIONS Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.
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28
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Aronson JK. Defining 'nutraceuticals': neither nutritious nor pharmaceutical. Br J Clin Pharmacol 2016; 83:8-19. [PMID: 26991455 DOI: 10.1111/bcp.12935] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Accepted: 03/09/2016] [Indexed: 12/19/2022] Open
Abstract
There are widespread inconsistencies and contradictions in the many published definitions of 'nutraceuticals' and 'functional foods', demonstrating wholesale uncertainty about what they actually are. Furthermore, in a 2014 lecture, the inventor of the term 'nutraceutical', confessing that nutraceuticals do not work, said that 'the quest to demonstrate whether … long-term supplementation [with nutraceuticals] can prevent serious diseases … has come to an end'. Definitions of 'nutraceuticals' and related terms, still widely used, should therefore be explored systematically. There are no internationally agreed definitions of 'nutraceuticals' and 'functional foods', or of similar terms, such as 'health foods', or of terms related to herbal products, which are sometimes referred to as 'nutraceuticals', compounding the confusion. 'Nutraceuticals' and 'functional foods' are vague, nondiscriminatory, unhelpful terms; the evidence suggests that they should be abandoned in favour of more precise terms. The term 'dietary supplement' is widely used to designate formulations that are also called 'nutraceuticals' but it would be better restricted to individual compounds used to treat or prevent deficiencies. 'Fortified foods', sometimes called 'designer foods', are foods to which compounds of proven therapeutic or preventive efficacy (e.g. folic acid) have been added. Other terms, such as 'food', 'foodstuffs', 'eat', 'drink', and 'nutrition', are well defined, as are 'medicinal products' and 'pharmaceutical formulations'. Dietary regimens, such as Mediterranean or nitrate-rich diets or vegetarianism, can affect health. A dietary regimen of this kind can be defined as a programme of food, of a defined kind and/or quantity, prescribed or adopted for the restoration or preservation of health.
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Affiliation(s)
- Jeffrey K Aronson
- Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Oxford, OX26GG, UK
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29
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Tseng DSJ, Molenaar IQ, Besselink MG, van Eijck CH, Borel Rinkes IH, van Santvoort HC. Pancreatic Exocrine Insufficiency in Patients With Pancreatic or Periampullary Cancer: A Systematic Review. Pancreas 2016; 45:325-30. [PMID: 26495777 DOI: 10.1097/mpa.0000000000000473] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The aim of this study was to determine the prevalence of pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer, both before and after resection. METHODS Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines). We included studies reporting on pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer. Data on patient demographics, type of pancreatic resection, diagnostic test, and occurrence of pancreatic exocrine insufficiency were extracted. Prevalence of pancreatic exocrine insufficiency was calculated before and after pancreatic resections and in patients with locally advanced pancreatic cancer. RESULTS Nine observational cohort studies with 693 patients were included. Median preoperative prevalence of pancreatic exocrine insufficiency was 44% (range, 42%-47%) before pancreatoduodenectomy, 20% (range, 16%-67%) before distal pancreatectomy, 63% before total pancreatectomy, and 25% to 50% in patients with locally advanced pancreatic cancer. The median prevalence of pancreatic exocrine insufficiency at least 6 months after pancreatoduodenectomy was 74% (range, 36%-100%) and 67% to 80% after distal pancreatectomy. CONCLUSION Pancreatic exocrine insufficiency is diagnosed in approximately half of all patients scheduled to undergo resection for pancreatic or periampullary cancer. The prevalence increases markedly after resection. These data highlight the need of pancreatic enzyme suppletion in these patients.
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Affiliation(s)
- Dorine S J Tseng
- From the *Department of Surgery, University Medical Center Utrecht, Utrecht; †Department of Surgery, Academic Medical Center, Amsterdam; and ‡Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
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30
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Lévy P, Domínguez-Muñoz E, Imrie C, Löhr M, Maisonneuve P. Epidemiology of chronic pancreatitis: burden of the disease and consequences. United European Gastroenterol J 2014; 2:345-54. [PMID: 25360312 DOI: 10.1177/2050640614548208] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Accepted: 07/23/2014] [Indexed: 12/13/2022] Open
Abstract
The epidemiology of chronic pancreatitis (CP) is incompletely understood. A number of difficulties exist in estimating the prevalence and incidence of CP. Long-term follow-up is often problematic, especially in chronic alcoholics, and obtaining a formal and standardised diagnosis can take years. The available studies are reasonably consistent in their estimation of the incidence of CP but few studies have attempted to estimate prevalence. Although life expectancy in CP is diminished compared with control populations, median survival lies in the range of 15-20 years. Such a survival would suggest a prevalence of CP rather higher than that determined from the survey studies. A recent epidemiological study in France found an annual incidence of 7.8 per 100,000. Assuming a survival of 15-20 years, the annual prevalence should be between 120 to 143 per 100,000. Overall, our understanding of the epidemiology of CP is poor compared with other illnesses. We consider that both prevalence and the rate of pancreatic insufficiency and of CP are currently underestimated. There is a distinct need for more studies to remedy this lack of knowledge.
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Affiliation(s)
- Philippe Lévy
- Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l'Appareil Digestif, DHU UNITY, Hôpital Beaujon, Faculté Denis Diderot, Clichy Cedex, France
| | | | - Clem Imrie
- University of Glasgow, Glasgow, United Kingdom
| | - Matthias Löhr
- Karolinska University Hospital & Karolinska Institutet, Stockholm, Sweden
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31
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Afghani E, Sinha A, Singh VK. An overview of the diagnosis and management of nutrition in chronic pancreatitis. Nutr Clin Pract 2014; 29:295-311. [PMID: 24743046 DOI: 10.1177/0884533614529996] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic pancreatitis is characterized by long-standing inflammation of the pancreas, which results in fibrosis and the gradual loss of pancreatic function. The loss of islets and acinar cells results in diabetes and exocrine insufficiency, respectively. Exocrine insufficiency can result in maldigestion of fat, protein, and carbohydrate as well as vitamins and minerals. Patients may present with variable severity of disease, from mild to severe. The diagnosis of chronic pancreatitis can be challenging, especially in patients with early or mild disease who have few to no morphologic abnormalities on standard abdominal imaging studies. A number of imaging modalities and tests have evolved to aid in the diagnosis of chronic pancreatitis based on changes in structure or function. Clinicians typically focus on treating pain in chronic pancreatitis as opposed to exocrine insufficiency, despite the fact that maldigestion and malabsorption can result in nutrition deficiencies. The aims of this review are to describe the various modalities used to diagnose chronic pancreatitis, to illustrate the nutrition deficiencies associated with exocrine insufficiency, and to provide an overview of nutrition assessment and treatment in these patients.
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Affiliation(s)
- Elham Afghani
- Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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32
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Hammer HF. An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?). Wien Med Wochenschr 2014; 164:57-62. [PMID: 24468827 DOI: 10.1007/s10354-013-0260-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 12/25/2013] [Indexed: 12/13/2022]
Abstract
This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.
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Affiliation(s)
- Heinz F Hammer
- Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universitätsklinik, Auenbruggerplatz 15, 8036, Graz, Austria,
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33
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Olesen AE, Brokjaer A, Fisher IW, Larsen IM. Pharmacological challenges in chronic pancreatitis. World J Gastroenterol 2013; 19:7302-7307. [PMID: 24259961 PMCID: PMC3831212 DOI: 10.3748/wjg.v19.i42.7302] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 10/02/2013] [Accepted: 10/22/2013] [Indexed: 02/06/2023] Open
Abstract
Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids are often prescribed as pain treatment. Opioids have intrinsic effects on gastrointestinal motility and hence can modify the absorption of other drugs taken at the same time. Furthermore, the increased fluid absorption caused by opioids will decrease water available for drug dissolution and may hereby affect absorption of the drug. As stated above many factors can influence drug absorption and metabolism in patients with chronic pancreatitis. The factors may not have clinical relevance, but may explain inter-individual variations in responses to a given drug, in patients with chronic pancreatitis.
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34
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Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. CORE EVIDENCE 2012; 7:77-91. [PMID: 22936895 PMCID: PMC3426252 DOI: 10.2147/ce.s26705] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.
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Affiliation(s)
- Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
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35
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Olesen AE, Olofsen E, Olesen SS, Staahl C, Andresen T, Dahan A, Drewes AM. The absorption profile of pregabalin in chronic pancreatitis. Basic Clin Pharmacol Toxicol 2012; 111:385-90. [PMID: 22716224 DOI: 10.1111/j.1742-7843.2012.00914.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 06/13/2012] [Indexed: 12/29/2022]
Abstract
It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. The pharmacokinetics of pregabalin has never been investigated in patients suffering from chronic pancreatitis. The aim of this study was to develop a population pharmacokinetic model of pregabalin administered to patients with chronic pancreatitis. The pregabalin population pharmacokinetic analysis was conducted on data from fifteen patients with chronic pancreatitis. Each patient received 75 mg of pregabalin (oral capsule). Pregabalin concentrations were measured using a validated liquid chromatographic method. Data analysis was performed using non-linear mixed effects modelling methodology as implemented by NONMEM. A one-compartment model with first-order absorption and elimination adequately described pregabalin pharmacokinetics. Time to maximum observed plasma concentration (T(max) ) was 1.53 (95% CI 1.09-2.05). The maximum plasma concentration (C(max) ) was 1.98 μg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 μg*hr/ml (95% CI 14.7-26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.
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Affiliation(s)
- Anne E Olesen
- Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
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36
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Muneyuki T, Nakajima K, Aoki A, Yoshida M, Fuchigami H, Munakata H, Ishikawa SE, Sugawara H, Kawakami M, Momomura SI, Kakei M. Latent associations of low serum amylase with decreased plasma insulin levels and insulin resistance in asymptomatic middle-aged adults. Cardiovasc Diabetol 2012; 11:80. [PMID: 22748134 PMCID: PMC3439247 DOI: 10.1186/1475-2840-11-80] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 06/15/2012] [Indexed: 12/16/2022] Open
Abstract
Background Low serum amylase is likely to be associated with obesity and metabolic abnormalities, which are often accompanied by impaired insulin action. However, it is unclear whether low serum amylase is associated with impaired insulin action in clinical settings. Therefore, we investigated the associations of low serum amylase with plasma insulin levels, and obesity-related parameters, including leptin. Research design and methods We measured serum amylase, plasma insulin, obesity-related parameters such as leptin, cardiometabolic risk factors, and anthropometric parameters in a cross-sectional study of 54 asymptomatic subjects (mean age 48.6 ± 7.6 years) who were not being treated for diabetes. Results Body mass index (BMI) and plasma glucose at 120 min after a 75-g oral glucose tolerance test (OGTT) were significantly higher in subjects with low serum amylase (< 60 IU/l, n = 21) than in those with normal-to-high serum amylase (n = 33) (P = 0.04 and P = 0.004, respectively). In univariate correlation analysis, serum amylase was significantly correlated with BMI alone (r = –0.39, P = 0.004). By contrast, multivariate logistic analysis showed that each 1-SD increase in quantitative insulin sensitivity check index, and each 1-SD decrease in plasma insulin OGTT at 0 and 60 min, homeostasis model assessment of insulin resistance (HOMA)-R, and HOMA-β were significantly associated with low serum amylase, particularly after adjusting for BMI. When subjects were divided into three groups according to HOMA-R, serum amylase levels were significantly lower in subjects with HOMA-R > 2.5 (n = 23) compared with subjects with HOMA-R 1.6–2.5 (n = 10) (61.1 ± 13.6 U/ml versus 76.9 ± 20.5 U/ml, Bonferroni test, P = 0.02), but not compared with subjects with HOMA-R<1.6 (n = 21; 62.7 ± 17.6 U/ml). Similar trends were observed when subjects were divided according to plasma leptin and fasting plasma insulin levels. Conclusions These results suggest that after adjusting for BMI, low serum amylase is associated with decreased basal insulin levels and insulin secretion, as well as high insulin resistance. The nature of these associations remains to be elucidated in further studies.
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Affiliation(s)
- Toshitaka Muneyuki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, 1-847 Amanuma, Omiya, Saitama 330-8503, Japan
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