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Gupta M, Midha S, Sachdeva V, Singh J, Pandey S, Mittal C, Teja V, Vajpai T, Dhooria A, Tandon N, Jagannath S, Garg PK. Subclinical pancreatic exocrine insufficiency is associated with osteopathy in patients with chronic pancreatitis: Implications for management. Pancreatology 2025; 25:193-199. [PMID: 39757054 DOI: 10.1016/j.pan.2024.12.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 12/22/2024] [Accepted: 12/24/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND AND AIMS Patients with chronic pancreatitis (CP) may develop pancreatic exocrine insufficiency (PEI) but data regarding subclinical PEI are scarce. Our objective was to detect subclinical PEI in patients with CP and its functional consequences. METHODS We prospectively included patients with CP from April 2018-December 2021. Mild PEI and severe PEI were diagnosed if fecal elastase (FE) was 100-200 μg/g and <100 μg/g stool respectively. Vitamin levels and DEXA scan were done to assess functional consequences of PEI. Presence of subclinical PEI in CP (low FE-1 but without steatorrhea) with consequent osteopathy was the primary outcome. RESULTS Of 120 patients with CP, subclinical PEI (low FE-1 but no steatorrhea) was present in 84/120(70%) patients: 6/8(75%) in early CP, 41/53(77%) in definite CP and 37/55(67.2%) in advanced CP. Overall, 72.1% patients had osteopathy including 53(62%) among patients with subclinical PEI. There was no difference in osteopathy between subclinical and severe PEI. Patients with severe PEI had lower vitamin A levels as compared to mild PEI and no PEI patients [1.3 ± 0.5 mg/ml vs. 1.7 ± 0.6 mg/ml vs. 1.8 ± 0.5 mg/ml; p = 0.04]. There was no difference in vitamin D levels. Osteopathy was present in 40/56 (71.4%) in advanced, 26/56 (46.4%) in definite and 2/8 (25%) in early CP patients (p = 0.09). On multivariable analysis, patients with advanced CP had the higher risk of osteopathy (odds ratio 7.6, 95% CI 1.9-29.7). CONCLUSIONS Subclinical PEI was present even in early CP with increased risk of osteopathy and fat-soluble vitamin deficiency.
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Affiliation(s)
- Mehul Gupta
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Shallu Midha
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Sachdeva
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Jairam Singh
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Shivam Pandey
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Chetanya Mittal
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Varun Teja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Tanmay Vajpai
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Anugrah Dhooria
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Nikhil Tandon
- Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
| | - Soumya Jagannath
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
| | - Pramod Kumar Garg
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
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Vanek P, Freeman ML. Updates in the Diagnosis of Chronic Pancreatitis: Current Approaches and New Possibilities. Gastroenterol Clin North Am 2025; 54:143-156. [PMID: 39880524 DOI: 10.1016/j.gtc.2024.08.007] [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] [Indexed: 01/31/2025]
Abstract
This review provides a comprehensive update on the diagnostic approaches to chronic pancreatitis (CP), emphasizing recent advancements in imaging techniques, biomarker research, and multivariable scoring systems. Despite substantial progress in these areas, current diagnostic algorithms have limitations, particularly for early and non-calcific CP. Traditional criteria have focused on classic diagnostic signs, but "minimal change" CP is increasingly recognized through advanced imaging and function tests. This article aims to guide clinicians in applying current methods and available strategies for CP diagnosis and outline research efforts in the field.
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Affiliation(s)
- Petr Vanek
- Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900 Olomouc, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 65653 Brno, Czech Republic
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
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Dominguez‐Muñoz JE, Vujasinovic M, de la Iglesia D, Cahen D, Capurso G, Gubergrits N, Hegyi P, Hungin P, Ockenga J, Paiella S, Perkhofer L, Rebours V, Rosendahl J, Salvia R, Scheers I, Szentesi A, Bonovas S, Piovani D, Löhr JM. European guidelines for the diagnosis and treatment of pancreatic exocrine insufficiency: UEG, EPC, EDS, ESPEN, ESPGHAN, ESDO, and ESPCG evidence-based recommendations. United European Gastroenterol J 2025; 13:125-172. [PMID: 39639485 PMCID: PMC11866322 DOI: 10.1002/ueg2.12674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/12/2024] [Indexed: 12/07/2024] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high-quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence-Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence-based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.
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Affiliation(s)
- J. Enrique Dominguez‐Muñoz
- Department of Gastroenterology and HepatologyUniversity Hospital of Santiago de CompostelaSantiago de CompostelaSpain
| | - Miroslav Vujasinovic
- Department of MedicineKarolinska Institutet and Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
| | | | - Djuna Cahen
- Department of Gastroenterology and HepatologyErasmus MC University Medical CenterRotterdamThe Netherlands
| | - Gabriele Capurso
- Department of GastroenterologySan Raffaele University HospitalMilanItaly
| | | | - Peter Hegyi
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
- Institute of Pancreatic DiseasesSemmelweis UniversityBudapestHungary
- Translational Pancreatology Research GroupInterdisciplinary Center of Excellence for Research and Development and InnovationUniversity of SzegedSzegedHungary
| | - Pali Hungin
- Faculty of Medical SciencesNewcastle UniversityNewcastle‐upon‐TyneUK
| | - Johann Ockenga
- Department of GastroenterologyEndocrinology and Clinical NutritionKlinikum Bremen MitteBremenGermany
| | - Salvatore Paiella
- Unit of Pancreatic SurgeryUniversity of Verona Hospital TrustVeronaItaly
| | - Lukas Perkhofer
- Department of Internal Medicine ISection of Interdisciplinary PancreatologyUlm University HospitalUlmGermany
| | - Vinciane Rebours
- Department of PancreatologyBeaujon HospitalDMU DigestAP‐HPClichyFrance
| | - Jonas Rosendahl
- Department of Internal Medicine IMartin Luther UniversityHalleGermany
| | - Roberto Salvia
- Unit of Pancreatic SurgeryUniversity of Verona Hospital TrustVeronaItaly
| | - Isabelle Scheers
- Pediatric GastroenterologyHepatology and Nutrition UnitCliniques Universitaires Saint‐LucUniversité Catholique de LouvainBrusselsBelgium
| | - Andrea Szentesi
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
| | - Stefanos Bonovas
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IRCCS Humanitas Research HospitalMilanItaly
| | - Daniele Piovani
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IRCCS Humanitas Research HospitalMilanItaly
| | - J. Matthias Löhr
- Department of Clinical SciencesKarolinska Institutet and Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
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Vijver MAT, Bomer N, Verdonk RC, van der Meer P, van Veldhuisen DJ, Dams OC. Micronutrient Deficiencies in Heart Failure and Relationship with Exocrine Pancreatic Insufficiency. Nutrients 2024; 17:56. [PMID: 39796492 PMCID: PMC11723028 DOI: 10.3390/nu17010056] [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: 11/24/2024] [Revised: 12/16/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Micronutrient deficiencies are common and play a significant role in the prognosis of many chronic diseases, including heart failure (HF), but their prevalence in HF is not well known. As studies have traditionally focused on causes originating within the intestines, exocrine pancreatic insufficiency (EPI) has been overlooked as a potential contributor. The exocrine pancreas enables the absorption of various (fat-soluble) micronutrients and may be insufficient in HF. We hypothesize that EPI contributes to micronutrient deficiencies in HF. OBJECTIVES To evaluate micronutrient concentrations in HF cases and their association with clinical characteristics and EPI. MATERIALS AND METHODS Plasma samples from 59 consecutive hospitalized patients with HF were analyzed for vitamins A, D, and E and the minerals selenium and zinc. EPI was defined as fecal elastase 1 level < 206 μg/g. RESULTS The mean age of patients was 59 ± 14 years, with 24 (41%) being women, and a median NT-proBNP concentration of 3726 [2104-6704] pg/mL was noted. Vitamin A deficiency occurred in eight (14%) of the patients, and 12 (20%) exceeded the upper limit. More than half (51%) were vitamin D-deficient. No patients showed vitamin E deficiency, but 14 (24%) had elevated levels. Selenium deficiency was common, affecting 36 (61%) patients, while zinc was below the normal range in seven patients (12%). Micronutrient levels did not differ significantly based on the presence of EPI. CONCLUSIONS This study provides novel insights into the micronutrient status of patients with HF. Deficiencies in vitamins A and D, selenium, and zinc are prevalent in HF, but these findings are not associated with exocrine pancreatic function.
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Affiliation(s)
- Marlene A. T. Vijver
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (M.A.T.V.); (N.B.); (P.v.d.M.); (O.C.D.)
| | - Nils Bomer
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (M.A.T.V.); (N.B.); (P.v.d.M.); (O.C.D.)
| | - Robert C. Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands;
| | - Peter van der Meer
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (M.A.T.V.); (N.B.); (P.v.d.M.); (O.C.D.)
| | - Dirk J. van Veldhuisen
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (M.A.T.V.); (N.B.); (P.v.d.M.); (O.C.D.)
| | - Olivier C. Dams
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (M.A.T.V.); (N.B.); (P.v.d.M.); (O.C.D.)
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Orkin S, Holovach P, Thompson T, Farrell P, Nasr A, Vitale D, Ibrahim S, Kotha N, Estes J, Hornung L, Abu-El-Haija M. Nutritional parameters following first episode of pediatric acute pancreatitis. Clin Nutr ESPEN 2024; 63:409-416. [PMID: 38996062 PMCID: PMC11884237 DOI: 10.1016/j.clnesp.2024.06.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/18/2024] [Accepted: 06/27/2024] [Indexed: 07/14/2024]
Abstract
BACKGROUND AND OBJECTIVES Acute pancreatitis (AP) carries the risk of subsequent nutritional deficiencies. The prevalence of these deficiencies following a single episode of AP in children is unknown. We aimed to determine prevalence of anthropometric and laboratory-based measures of nutritional status in children following their first (index) admission for AP. METHODS Prospective observational cohort study of patients ≤21 years of age with first episode of confirmed AP. Anthropometric and laboratory values were obtained at time of AP onset and at follow up time points of 3 and 12 months (m) post AP. AP attack was classified as either: mild, moderately severe or severe (which were combined in one group (SAP)). RESULTS 181 patients met criteria and were followed prospectively with 52% male, a median age of 13.7 years (IQR 9.4-16.0) and median Body Mass Index (BMI) Z-score of 0.6 (IQR -0.5, 1.6). Most patients had mild AP (140, 77%), with 23% meeting criteria for moderate or severe (41/181). 6 (3%) had diabetes mellitus (DM) predating AP and were excluded from further analysis. BMI Z-score remained stable during the follow up period. 13% of patients developed pre-DM or DM at 3m or 12m. Nearly one third of patients had low ferritin at 3m (29%) or 12m (29%). At 12m, 8% of patients had Vitamin A deficiency. 6% of patients had low Vitamin E levels at 3m and 5% at 12m. Over half of patients at both 3m and 12m had 25 OH Vitamin D insufficiency or deficiency (56% and 56%). Prolonged International Normalized Ratio (INR) (>1.3) was seen in 9% of patients at 12m. Very low albumin (<3.5 g/dL) was found in 24% of patients at 3m and 18% at 12m (Table 1). Patients with very low albumin at 3m were younger (median 10.7 vs. 14.2 years, p = 0.04), however sex, BMI Z-score and AP severity were not associated with albumin level. Although BMI Z-score did not differ between the groups, those with SAP had a significant decrease in BMI Z-score from first attack compared to mild AP at 3m (-0.4 vs. 0.0, p = 0.0002, Figure 2). At 3m, Vitamin E deficiency in SAP versus mild AP was found in 20% vs 2% (p = 0.04) and SAP had a lower median hematocrit (35.8 vs. 37.6, p = 0.046). There were no other laboratory significant differences at 3m in mild versus SAP groups. At 12m, those with SAP were more likely to have pre-DM or DM compared to mild AP (31% vs. 7%, p = 0.002). No other significant laboratory differences occurred at 12m. CONCLUSIONS After the first AP attack patients experience nutritional deficiencies, including ferritin, all fat-soluble vitamins, and low albumin. SAP is associated with a decrease in BMI Z-score, increased prevalence of vitamin E deficiency at 3m, and an increase in pre-diabetes and diabetes at 12m. Serial monitoring of vitamin and mineral values post AP is warranted and further prospective studies are needed.
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Affiliation(s)
- Sarah Orkin
- Department of Pediatrics, College of Medicine, University of Cincinnati, USA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA.
| | - Phillip Holovach
- Department of Pediatrics, College of Medicine, University of Cincinnati, USA
| | - Tyler Thompson
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - Peter Farrell
- Department of Pediatrics, College of Medicine, University of Cincinnati, USA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - Alexander Nasr
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - David Vitale
- Department of Pediatrics, College of Medicine, University of Cincinnati, USA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - Sherif Ibrahim
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - Nicole Kotha
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - James Estes
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
| | - Lindsey Hornung
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, USA
| | - Maisam Abu-El-Haija
- Department of Pediatrics, College of Medicine, University of Cincinnati, USA; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, USA
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Hrabak P, Zelenkova M, Krechler T, Soupal J, Vocka M, Hanus T, Petruzelka L, Svacina S, Zak A, Zima T, Kalousova M. Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2024; 168:132-138. [PMID: 38058194 DOI: 10.5507/bp.2023.049] [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: 10/03/2023] [Accepted: 11/23/2023] [Indexed: 12/08/2023] Open
Abstract
AIMS Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. METHODS High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. RESULTS We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. CONCLUSION Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.
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Affiliation(s)
- Pavel Hrabak
- Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Miroslava Zelenkova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Tomas Krechler
- Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Jan Soupal
- 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Michal Vocka
- Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Tomas Hanus
- Department of Urology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Lubos Petruzelka
- Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Stepan Svacina
- 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Ales Zak
- Fourth Department of Internal Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Tomas Zima
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
| | - Marta Kalousova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
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Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
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Valente R, Coppola A, Scandavini CM, Halimi A, Magnusson A, Lauro A, Sotirova I, Arnelo U, Franklin O. Interactions between the Exocrine and the Endocrine Pancreas. J Clin Med 2024; 13:1179. [PMID: 38398492 PMCID: PMC10890016 DOI: 10.3390/jcm13041179] [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: 01/08/2024] [Revised: 02/07/2024] [Accepted: 02/19/2024] [Indexed: 02/25/2024] Open
Abstract
The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.
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Affiliation(s)
- Roberto Valente
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
- Department of Surgery, Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | | | - Chiara Maria Scandavini
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
| | - Asif Halimi
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
| | - Annelie Magnusson
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
| | - Augusto Lauro
- Department of Surgery, Sapienza University of Rome, 00161 Rome, Italy;
| | - Ira Sotirova
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
| | - Urban Arnelo
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
| | - Oskar Franklin
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185 Umeå, Sweden; (R.V.); (C.M.S.); (A.H.); (A.M.); (I.S.); (U.A.); (O.F.)
- Department of Surgery, Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
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Capurso G, Tacelli M, Vanella G, Ponz de Leon Pisani R, Dell'Anna G, Abati M, Mele R, Lauri G, Panaitescu A, Nunziata R, Zaccari P, Archibugi L, Arcidiacono PG. Managing complications of chronic pancreatitis: a guide for the gastroenterologist. Expert Rev Gastroenterol Hepatol 2023; 17:1267-1283. [PMID: 38093702 DOI: 10.1080/17474124.2023.2295498] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 12/08/2023] [Indexed: 12/19/2023]
Abstract
INTRODUCTION Chronic pancreatitis is a heterogeneous and complex syndrome that, in most cases, causes pain as a cardinal symptom and affects both the morphology and function of the pancreas, leading to several serious complications. AREAS COVERED The present review, based on a non-systematic PubMed search updated to June 2023, aims to present the current available evidence on the role of gastroenterologists in the diagnosis and treatment of both local and systemic complications by either endoscopic or medical treatments. EXPERT OPINION At diagnosis and during chronic pancreatitis follow-up, particular care is needed to consider not only the clinically manifest signs and symptoms of the disease, such as pain, jaundice, gastrointestinal obstruction, and pseudocysts, which require multidisciplinary discussion to establish the best treatment option (endoscopic or surgical), but also less evident systemic complications. Pancreatic exocrine and endocrine insufficiency, together with chronic inflammation, addiction, and dysbiosis, contribute to malnutrition, sarcopenia, and osteopathy. These complications, in turn, increase the risk of infection, thromboembolic events, and death. Patients with chronic pancreatitis also have an increased risk of psychiatric disorders and pancreatic cancer onset. Overall, patients with chronic pancreatitis should receive a holistic evaluation, considering all these aspects, possibly through multidisciplinary care in dedicated expert centers.
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Affiliation(s)
- Gabriele Capurso
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Tacelli
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Vanella
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Ruggero Ponz de Leon Pisani
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Dell'Anna
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Martina Abati
- Nutrition Service, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Mele
- Nutrition Service, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gaetano Lauri
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Afrodita Panaitescu
- Vita-Salute San Raffaele University, Milan, Italy
- Bucharest Clinical Emergency Hospital, Bucharest, Romania
| | - Rubino Nunziata
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Italy
| | - Piera Zaccari
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Livia Archibugi
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreatobiliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Whitcomb DC, Buchner AM, Forsmark CE. AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review. Gastroenterology 2023; 165:1292-1301. [PMID: 37737818 DOI: 10.1053/j.gastro.2023.07.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/18/2023] [Accepted: 07/04/2023] [Indexed: 09/23/2023]
Abstract
DESCRIPTION Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI. METHODS This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100-200 μg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.
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Affiliation(s)
- David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Anna M Buchner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Chris E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida
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Vujasinovic M, Nikolic S, Gordon Achour A, Löhr JM. Autoimmune pancreatitis and micronutrients. Dig Liver Dis 2023; 55:1375-1381. [PMID: 37121818 DOI: 10.1016/j.dld.2023.04.009] [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: 01/25/2023] [Revised: 04/06/2023] [Accepted: 04/06/2023] [Indexed: 05/02/2023]
Abstract
INTRODUCTION Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but have yet to be assessed in autoimmune pancreatitis (AIP). The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. PATIENTS AND METHODS We retrospectively analysed medical records of patients treated for AIP. Demographic and clinical data were collected. RESULTS One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). Relapse was observed in 37% of the AIP patients. Initial analysis showed that AIP relapse was associated with any micronutrient deficiency as well as zinc and vitamin D deficiency, but after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, the association ceased to be statistically significant. CONCLUSION Zinc and vitamin D deficiencies may be common in patients with AIP, indicating that these micronutrients might play a role in the natural course of AIP. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI, which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients.
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Affiliation(s)
- Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm 141 86, Sweden; Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden.
| | - Sara Nikolic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm 141 86, Sweden; Department of Gastroenterology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
| | - Alina Gordon Achour
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm 141 86, Sweden
| | - J Matthias Löhr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm 141 86, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
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12
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Ramsey ML, Hart PA, Forsmark CE. Evaluation and management of exocrine pancreatic insufficiency: pearls and pitfalls. Curr Opin Gastroenterol 2023; 39:428-435. [PMID: 37530731 PMCID: PMC10403264 DOI: 10.1097/mog.0000000000000951] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
PURPOSE OF REVIEW The diagnosis and management of exocrine pancreatic dysfunction (EPD) can be challenging. EPD classically results from conditions that cause loss of pancreatic acinar cell function and decreased digestive enzyme production. However, several conditions may contribute to signs or symptoms of EPD with otherwise normal pancreatic exocrine function. A thoughtful approach to considering these conditions, along with their specific therapies, can guide a tailored management approach. RECENT FINDINGS An EPD severity classification schema has been proposed, which emphasizes a shift towards a more restrictive prescription of pancreas enzyme replacement therapy (PERT) for patients with milder EPD. In contrast, PERT use has been associated with a measurable survival benefit among individuals with EPD and pancreatic cancer, so the prescription of PERT may be more liberal in this population. Recent publications in the cystic fibrosis population offer pearls guiding the titration and optimization of PERT. SUMMARY Among individuals with severe EPD, PERT is an effective therapy. Among individuals with milder EPD, although PERT is effective, there may be opportunities to provide additional and potentially more effective therapies.
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Affiliation(s)
- Mitchell L Ramsey
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Christopher E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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Kumar V, Barkoudah E, Jin DX, Banks P, McNabb-Baltar J. Hospital Frailty Risk Score (HFRS) Predicts Adverse Outcomes Among Hospitalized Patients with Chronic Pancreatitis. Dig Dis Sci 2023:10.1007/s10620-023-07946-w. [PMID: 37140839 DOI: 10.1007/s10620-023-07946-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 04/04/2023] [Indexed: 05/05/2023]
Abstract
INTRODUCTION The prevalence of frailty among patients with chronic pancreatitis (CP) and its impact on clinical outcomes is unclear. We report the impact of frailty on mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the United States. METHODS We extracted data on patients hospitalized with a primary or secondary diagnosis of CP from the Nationwide Readmissions Database 2019. We applied a previously validated hospital frailty risk scoring system to classify CP patients into frail and non-frail on index hospitalization and compared the characteristics of frail and non-frail patients. We studied the impact of frailty on mortality, readmission, and healthcare utilization. RESULTS Of 56,072 patients with CP, 40.78% of patients were classified as frail. Frail patients experienced a higher rate of unplanned and preventable hospitalizations. Almost two-thirds of frail patients were younger than 65, and one-third had no or only single comorbidity. On multivariate analysis, frailty was independently associated with two times higher mortality risk (adjusted hazard ratio [aHR], 2.05; 95% CI 1.7-2.5). Frailty was also associated with a higher risk of all-cause readmission with an aHR of 1.07; (95% CI 1.03-1.1). Frail patients experienced a longer length of stay, higher hospitalization costs, and hospitalization charges. Infectious causes were the most common cause of readmission among frail patients compared to acute pancreatitis among non-frail patients. CONCLUSIONS Frailty is independently associated with higher mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the US.
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Affiliation(s)
- Vivek Kumar
- Department of General Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Ebrahim Barkoudah
- Department of General Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - David X Jin
- Division of Gastroenterology, Hepatology, and Endoscopy, Center for Pancreatic Disease, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - Peter Banks
- Division of Gastroenterology, Hepatology, and Endoscopy, Center for Pancreatic Disease, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
| | - Julia McNabb-Baltar
- Division of Gastroenterology, Hepatology, and Endoscopy, Center for Pancreatic Disease, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
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14
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Chhoda A, Hernandez-Woodbine MJ, Addo NAA, Nasir SA, Grimshaw A, Gunderson C, Ahmed A, Freedman SD, Sheth SG. Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:1374-1394. [PMID: 36925454 PMCID: PMC10011962 DOI: 10.3748/wjg.v29.i8.1374] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/15/2023] [Accepted: 02/15/2023] [Indexed: 02/28/2023] Open
Abstract
BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.
AIM To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes.
METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.
RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis.
CONCLUSION This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.
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Affiliation(s)
- Ankit Chhoda
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | | | - Nana Afua Akkya Addo
- Department of Medicine, Norwalk Hospital, Yale School of Medicine, Norwalk, CT 06850, United States
| | - Syed Alishan Nasir
- Department of Medicine, Norwalk Hospital, Yale School of Medicine, Norwalk, CT 06850, United States
| | - Alyssa Grimshaw
- Cushing/Whitney Medical Library, Yale University, New Haven, CT 06510, United States
| | - Craig Gunderson
- General Internal Medicine, Yale School of Medicine, New Haven, CT 06510, United States
| | - Awais Ahmed
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Steven D. Freedman
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Sunil G. Sheth
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
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Borel P, Dangles O, Kopec RE. Fat-soluble vitamin and phytochemical metabolites: Production, gastrointestinal absorption, and health effects. Prog Lipid Res 2023; 90:101220. [PMID: 36657621 DOI: 10.1016/j.plipres.2023.101220] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 12/12/2022] [Accepted: 01/12/2023] [Indexed: 01/18/2023]
Abstract
Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.
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Affiliation(s)
- Patrick Borel
- C2VN, INRAE, INSERM, Aix-Marseille Univ, Marseille, France.
| | | | - Rachel E Kopec
- Human Nutrition Program, Department of Human Sciences, Foods for Health Discovery Theme, The Ohio State University, Columbus, OH 43210, USA.
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Zhang J, Fan H, Gross M, Liu N, Carlson H, Wood A, Hoffman K, Petrosino J, Pankratz N, Thyagarajan B, Fisher W. Progressive reduction in circulating levels of carotenoids and other micronutrients in patients with chronic pancreatitis. Pancreatology 2022; 22:1126-1133. [PMID: 36198488 DOI: 10.1016/j.pan.2022.09.243] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/26/2022] [Accepted: 09/21/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although micronutrients modulate immunity and inflammation, it remains elusive whether they are implicated in the development and progression of chronic pancreatitis (CP). This study aimed to investigate differences in the circulating levels of selected carotenoids and vitamins between CP and controls and trends in the levels of these micronutrients across controls, early CP, and definite CP. METHODS Demographic and lifestyle data were extracted from medical records for 53 patients with CP (13 early and 38 definite) and obtained using a questionnaire for 52 controls. Plasma β-carotene, lycopene, cryptoxanthin, zeaxanthin, and α-tocopherol and serum 25(OH)D, folate, IL-6, TNF-α, and MCP-1 were measured with state-of-the-art methods. RESULTS The levels of all micronutrients (except folate) were significantly lower in CP than in controls. There was a progressive decrease in the levels of these micronutrients across controls, early CP, and definite CP (all p values for trend: ≤0.0012); e.g., plasma lycopene was 36.6, 21.5, and 14.5 μg/dL for controls, early CP, and definite CP, respectively. After adjustment for confounders, there were strong, inverse associations between the levels of all micronutrients (except folate) and CP (e.g., OR (95% CI) for ≥ median vs. <median: 0.10 (0.04, 0.27) for lycopene, 0.15 (0.05, 0.38) for α-tocopherol, and 0.24 (0.09, 0.64) for 25(OH)D). These associations became weaker after additional adjustment for inflammation markers (IL-6, TNF-α, and MCP-1). CONCLUSIONS The circulating levels of some carotenoids, α-tocopherol, and vitamin D were reduced in CP patients compared with controls and this reduction was more pronounced in definite CP than in early CP.
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Affiliation(s)
- Jianjun Zhang
- Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA.
| | - Hao Fan
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN, USA
| | - Myron Gross
- Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Nianjun Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN, USA
| | - Hannah Carlson
- Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Amy Wood
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Kristi Hoffman
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Joseph Petrosino
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Nathan Pankratz
- Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - William Fisher
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
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Cañamares-Orbís P, García-Rayado G, Alfaro-Almajano E. Nutritional Support in Pancreatic Diseases. Nutrients 2022; 14:4570. [PMID: 36364832 PMCID: PMC9656643 DOI: 10.3390/nu14214570] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/23/2022] [Accepted: 10/24/2022] [Indexed: 08/13/2023] Open
Abstract
This review summarizes the main pancreatic diseases from a nutritional approach. Nutrition is a cornerstone of pancreatic disease and is sometimes undervalued. An early identification of malnutrition is the first step in maintaining an adequate nutritional status in acute pancreatitis, chronic pancreatitis and pancreatic cancer. Following a proper diet is a pillar in the treatment of pancreatic diseases and, often, nutritional counseling becomes essential. In addition, some patients will require oral nutritional supplements and fat-soluble vitamins to combat certain deficiencies. Other patients will require enteral nutrition by nasoenteric tube or total parenteral nutrition in order to maintain the requirements, depending on the pathology and its consequences. Pancreatic exocrine insufficiency, defined as a significant decrease in pancreatic enzymes or bicarbonate until the digestive function is impaired, is common in pancreatic diseases and is the main cause of malnutrition. Pancreatic enzymes therapy allows for the management of these patients. Nutrition can improve the nutritional status and quality of life of these patients and may even improve life expectancy in patients with pancreatic cancer. For this reason, nutrition must maintain the importance it deserves.
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Affiliation(s)
- Pablo Cañamares-Orbís
- Gastroenterology, Hepatology and Nutrition Unit, San Jorge University Hospital, Martínez de Velasco Avenue 36, 22004 Huesca, Spain
| | - Guillermo García-Rayado
- Digestive Disease Department, Lozano Blesa University Clinic Hospital, San Juan Bosco Avenue 15, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco Avenue 13, 50009 Zaragoza, Spain
| | - Enrique Alfaro-Almajano
- Digestive Disease Department, Lozano Blesa University Clinic Hospital, San Juan Bosco Avenue 15, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), San Juan Bosco Avenue 13, 50009 Zaragoza, Spain
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Maev IV, Levchenko AI, Andreev DN. Changes in the Intestinal Microbiota in Patients with Chronic Pancreatitis: Systematizing Literature Data. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:17-26. [DOI: 10.22416/1382-4376-2022-32-4-17-26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
The purpose of the review. To systematize literature data on changes in the structure of the intestinal microbiota in patients with chronic pancreatitis (CP).Key findings. The human intestinal microbiota is a dynamically changing system that is constantly undergoing qualitative and quantitative changes, especially in several pathological conditions of the digestive system. At present, the differences in the intestinal microbiota in pancreatic diseases are poorly understood. The severe CP is associated with impaired synthesis of antimicrobial peptides, bicarbonates, and digestive enzymes by the pancreas, which is a risk factor for dysbiotic changes in the intestinal microbiota, consisting in the development of small intestinal bacterial overgrowth (SIBO) and gut dysbiosis. The results of two large meta-analyses show that about a third of CP patients have SIBO. The colonic microbiota in patients with CP is also characterized by dysbiotic disorders, primarily in the reduction of alpha-diversity. Some studies have shown that these patients have an increase in Firmicutes, while Bacteroides and Faecalibacterium are reduced. In addition, as a rule, in patients with CP, the growth of Escherichia, Shigella and Streptococcus is recorded.Conclusion. In general, scientific papers have revealed significant heterogeneity in the profiles of the intestinal microbiota in patients with CP. Thus, several questions remain open, prioritizing the further study of the intestinal microbiota in patients with CP for identifying the specifics of its structure that can personalize the selection of enzyme replacement therapy and restrict the unreasonable prescription of additional pharmacotherapy (the use of proton pump inhibitors and / or antibacterial drugs).
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Affiliation(s)
- I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - A. I. Levchenko
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
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Abstract
PURPOSE OF REVIEW This review aims to discuss recent developments in the nutritional management in chronic pancreatitis. RECENT FINDINGS Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6-12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed. SUMMARY Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.
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Erchinger F, Tjora E, Nordaas IK, Dimcevski G, Olesen SS, Jensen N, Dahl EE, Borch A, Nøjgaard C, Novovic S, Barauskas G, Ignatavicius P, Vujasinovic M, Lőhr M, Laukkarinen J, Parhiala M, Drewes AM, Engjom T. Pancreatic enzyme treatment in chronic pancreatitis: Quality of management and adherence to guidelines-A cross-sectional observational study. United European Gastroenterol J 2022; 10:844-853. [PMID: 35981311 PMCID: PMC9557959 DOI: 10.1002/ueg2.12276] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/17/2022] [Indexed: 12/01/2022] Open
Abstract
Objectives Pancreatic exocrine insufficiency (PEI) is a common complication in patients with chronic pancreatitis (CP), leading to increased morbidity and mortality if not treated adequately. Pancreatic enzyme replacement therapy|pancreas enzyme replacement therapy (PERT) is the cornerstone in treatment of patients with PEI. In the present study, we use data from the Scandinavian Baltic Pancreatic Club database to examine adherence of PERT according to United European Gastroenterology evidence‐based guidelines treatment of CP. Patients and methods Patients with definitive or probable CP according to M‐ANNHEIM diagnostic criteria were included. We collected information on exposures, exocrine function, intake of pancreatic enzymes, and markers of nutrition. Fecal elastase <200 μg/g was defined as a marker for PEI. Enzyme replacement therapy of 100,000 lipase units or more was defined as adequate treatment. Results We included 1006 patients from 8 centers in five countries. Sixty‐four percent of the patients were correctly treated. Twenty‐five per cent of PEI patients were not taking enzymes at all, and 20% of PEI patients were undertreated with insufficient PERT doses according to the guidelines. Fourteen percent of patients with sufficient pancreatic function were receiving enzymes despite normal exocrine pancreatic function. There were center differences. Current smoking was associated with lack of treatment and alcohol abuse was associated with under‐treatment. There were no associations between “no treatment” or “under‐treatment” for underweight or vitamin D deficiency. Conclusion In our CP expert centers, the adherence to guidelines for enzyme treatment is insufficient. Both patient factors and center differences have influence on treatment adherence.
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Affiliation(s)
| | - Erling Tjora
- Pediatric Department, Haukeland University Hospital, Bergen, Norway
| | | | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Søren Schou Olesen
- Department of Gastroenterology and Hepatology, Centre of Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Nanna Jensen
- Department of Gastroenterology, Bispebjerg University Hospital, Copenhagen, Denmark
| | - Eva Efsen Dahl
- Department of Gastroenterology, Bispebjerg University Hospital, Copenhagen, Denmark
| | - Anders Borch
- Department of Gastroenterology, Herlev University Hospital, Herlev, Denmark
| | - Camilla Nøjgaard
- Department of Gastroenterology, Hvidovre University Hospital, Herlev, Denmark
| | - Srdan Novovic
- Department of Gastroenterology, Hvidovre University Hospital, Herlev, Denmark
| | - Giedrus Barauskas
- Department of Gastrointestinal Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Povilas Ignatavicius
- Department of Gastrointestinal Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden
| | - Matthias Lőhr
- Department of Gastroenterology, Karolinska University Hospital, Stockholm, Sweden
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, University Hospital, Tampere, Finland
| | - Mikael Parhiala
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, University Hospital, Tampere, Finland
| | - Asbjørn Mohr Drewes
- Department of Gastroenterology and Hepatology, Centre of Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Trond Engjom
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
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21
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Zheng M, Gao R. Vitamin D: A Potential Star for Treating Chronic Pancreatitis. Front Pharmacol 2022; 13:902639. [PMID: 35734414 PMCID: PMC9207250 DOI: 10.3389/fphar.2022.902639] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/13/2022] [Indexed: 11/13/2022] Open
Abstract
Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas. The incidence of CP is increasing worldwide but the effective therapies are lacking. Hence, it is necessary to identify economical and effective agents for the treatment of CP patients. Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy. Clinical studies show that VD deficiency is prevalent in CP patients. However, the correlation between VD level and the risk of CP remains controversial. VD and its analogues have been demonstrated to inhibit pancreatic fibrosis by suppressing the activation of pancreatic stellate cells and the production of extracellular matrix. Limited clinical trials have shown that the supplement of VD can improve VD deficiency in patients with CP, suggesting a potential therapeutic value of VD in CP. However, the mechanisms by which VD and its analogues inhibit pancreatic fibrosis have not been fully elucidated. We are reviewing the current literature concerning the risk factors for developing CP, prevalence of VD deficiency in CP, mechanisms of VD action in PSC-mediated fibrogenesis during the development of CP and potential therapeutic applications of VD and its analogues in the treatment of CP.
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22
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Cai F, Hu C, Chen CJ, Han YP, Lin ZQ, Deng LH, Xia Q. Vitamin D and Pancreatitis: A Narrative Review of Current Evidence. Nutrients 2022; 14:nu14102113. [PMID: 35631254 PMCID: PMC9143310 DOI: 10.3390/nu14102113] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/12/2022] [Accepted: 05/13/2022] [Indexed: 12/10/2022] Open
Abstract
Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.
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Affiliation(s)
- Fei Cai
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Cheng Hu
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Chan-Juan Chen
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Yuan-Ping Han
- The Center for Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu 610017, China;
| | - Zi-Qi Lin
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
| | - Li-Hui Deng
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
- Correspondence:
| | - Qing Xia
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; (F.C.); (C.H.); (C.-J.C.); (Z.-Q.L.); (Q.X.)
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23
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de Rijk FEM, van Veldhuisen CL, Besselink MG, van Hooft JE, van Santvoort HC, van Geenen EJM, Hegyi P, Löhr JM, Dominguez-Munoz JE, de Jonge PJF, Bruno MJ, Verdonk RC, Zou WB, Engjom T, Ooi CY, Sutton R, Frulloni L, Neoptolemos J, Wilcox C, Miroslav V, Trikudanathan G, Liao Z, Hauge T, Mössner J, Hoge C, Fockens P, Mieog S, Capurso G, Cui Y, de Madaria E, Distler M, Aghdassi A, Whitcomb DC, Russell K, Beyer G, Kunovsky L, Kwanten W, Nava AK, Conlon K, Siriwardena A, Paiella S, Alconchel F, Marino MV, de Meijer VE, Domingo C, Kleeff J, Lakshmanan A, Lie Chu MJ, Bouwense S, Nashidengo PR, Konstantinos P, Muttillo EM, Umar GI, Castro Santiago MJ, Lopez-Lopez V, Torri F, Schmelzle M, Ignatavicius P, Wicherts D, Gomes A, Machairas NA, Dorovinis PI, Serrablo A, Soreide K, Rahbari M, Jie Chu MJ, Ptasnuka M, Petrulionis M, Noel CB, Castro E, Di Martino M, Recordare A, Stättner S, Ausania F, Hartman V, Roeyen G, Egorov V, Vanagas T, Ebrahim M, Arabadzhieva E, Malleo G, Li L, Adams D, Oracz G, Nageshwar RD, Waldthaler A, Masamune A, Drewes AM, Amodio A, Tirkes T, Srivastava A, Beilman GJ, Berger Z, Lindkvist B, Cavestro GM, Gariepy C, Czakó L, Di Leo M, Sharma V, Lakhtakia S, Rana SS, Duggan SN, Kwon CI, Phillips AE, Forsmark CE, Gleeson FC, Lehman GA, Greenhalf W, Costamagna G, Halloran CM, Friess H, Rasmussen HH, Ikeura T, Haldorsen IS, Itoi T, Izbicki JR, Windsor J, Poulsen JL, Frokjaer JB, Larino-Noia J, Wang D, Garcia JI, Kalaitzakis E, Wertheim-Tysarowska K, Kubota K, Larusch J, Lerch MM, Hu LH, Frulloni L, Erkan M, Machicado JD, Arvanitakis M, Buchler MW, Levy MF, Heyman MB, Nojgaard C, Khashab MA, Delhaye M, Ogura T, Okazaki K, Ghaneh P, Banks PA, Gupta P, Papachristou GI, Michl P, Levy P, Pukitis A, Pezzilli R, Baron RD, Amann ST, Schwarzenberg SJ, Isaji S, Olesen SS, Novovic S, Hughes SJ, Werlin SL, Gonska T, Gardner TB, Topazian MD, Trikudanathan G, Weiss FU, Akshintala VS, Morinville VD, Rebours V, Vincze A, Singh VK, Cui N, Zhang H, Li ZS, Liao Z. Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study. Pancreatology 2022; 22:457-465. [PMID: 35346599 DOI: 10.1016/j.pan.2022.03.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.
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Affiliation(s)
- Florence E M de Rijk
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands.
| | - Charlotte L van Veldhuisen
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Erwin J M van Geenen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Peter Hegyi
- Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - J-Matthias Löhr
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Juan E Dominguez-Munoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Pieter Jan F de Jonge
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, the Netherlands
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Karpińska M, Czauderna M. Pancreas-Its Functions, Disorders, and Physiological Impact on the Mammals' Organism. Front Physiol 2022; 13:807632. [PMID: 35431983 PMCID: PMC9005876 DOI: 10.3389/fphys.2022.807632] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 02/04/2022] [Indexed: 12/15/2022] Open
Abstract
This review aimed to analyze the scientific literature on pancreatic diseases (especially exocrine pancreatic insufficiency). This review also describes the correlation between the physiological fitness of the pancreas and obesity. The influence of the pancreatic exocrine function on the development of the organism of adults and adolescents was also described. The results of piglet studies available in the literature were cited as an established model used to optimize treatments for pancreatic diseases in humans. The pancreas has an exocrine and hormonal function. Consequently, it is one of the key internal organs in animals and humans. Pancreatic diseases are usually severe and particularly troublesome. A properly composed diet and taken dietary supplements significantly improve the patient's well-being, as well as the course of the disease. Therefore, a diet and a healthy lifestyle positively affect maintaining the optimal physiological efficiency of the pancreas.
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Affiliation(s)
- Monika Karpińska
- The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Warsaw, Poland
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25
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Abstract
IgG4-related conditions affecting the digestive tract are part of a multi-organ fibro-inflammatory disorder termed IgG4-related disease (IgG4-RD), with autoimmune pancreatitis and IgG4-related cholangitis being the most prominent manifestations. Gastrointestinal symptoms include jaundice, weight loss, abdominal pain, biliary strictures, and pancreatic and hepatic masses that mimic malignant diseases. IgG4-RD manifestations occur less frequently elsewhere in the digestive tract, namely in the oesophagus, retroperitoneum or intestine. Evidence-based European guidelines frame the current state-of-the-art in the diagnosis and management of IgG4-related digestive tract disease. Diagnosis is based on histology (if available), imaging, serology, other organ involvement and response to therapy (HISORt criteria). Few biomarkers beyond serum IgG4 concentrations are reliable. The first-line therapy (glucocorticoids) is swiftly effective but disease flares are common at low doses or after tapering. Second-line therapy might consist of other immunosuppressive drugs such as thiopurines or rituximab. Further trials, for example, of anti-CD19 drugs, are ongoing. Although an association between IgG4-RD and the development of malignancies has been postulated, the true nature of this relationship remains uncertain at this time.
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26
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Kucheryavyy YA, Bordin DS. A brief review of clinical guidelines for the diagnosis and treatment of exocrine pancreatic insufficiency. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:5-14. [DOI: 10.31146/1682-8658-ecg-195-11-5-14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
In recent years, several consensus and guidelines for the diagnosis and treatment of chronic pancreatitis have been published. In 2017, the Russian and Pan-European (HaPanEU) consensus was published, in 2018 — the international consensus on minimal change pancreatitis, in 2020 — the clinical guidelines of the American College of Gastroenterology, in 2021 — the British clinical guidelines. Many of their provisions overlap. This review article analyzed the main provisions of the latest recommendations, taking into account the possibility of their adaptation to Russian clinical practice.
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Affiliation(s)
| | - D. S. Bordin
- A.S. Loginov Moscow clinical scientific center; A.I. Yevdokimov Moscow State University of Medicine and Dentistry; Tver State Medical University
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27
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Srivoleti P, Dolan RD, Yang AL, Jin DX, Banks PA, McNabb-Baltar J. Provider Differences in Monitoring and Management of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis. Pancreas 2022; 51:25-27. [PMID: 35195591 DOI: 10.1097/mpa.0000000000001967] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Chronic pancreatitis (CP) is a common cause of exocrine pancreatic insufficiency (EPI). Regular monitoring and treatment are recommended to decrease morbidity. This study evaluates whether provider type impacts EPI monitoring and management in CP. METHODS Fecal elastase 1 (FE-1) testing and pancreatic enzyme replacement therapy (PERT) utilization were retrospectively compared between primary care providers (PCPs), gastroenterologists and pancreas specialists using pairwise comparisons. Multivariate analysis was conducted to study the association between adequate PERT and age, sex, race, insurance status, provider type, and etiology. RESULTS Among 256 patients, FE-1 was measured in 115 (44.9%) and of 143 (55.9%) patients who received PERT, 100 (69.9%) received adequate dosage. Fecal elastase 1 testing was performed in 7/57 (12.3%) by PCP, 11/38 (28.9%) by gastroenterologists, and 97/161 (60.2%) by pancreas specialists (P < 0.0001). Adequate PERT was prescribed in 7/24 (29.2%) patients by PCPs, 11/20 (55.0%) by gastroenterologists, and 82/99 (82.8%) by pancreas specialists (P < 0.0001). On multivariate analysis, pancreas specialists were significantly more likely to prescribe adequate PERT compared with PCP (odds ratio, 11.3; 95% confidence interval, 3.3-38.2; P < 0.001). CONCLUSIONS Many patients with CP receive inadequate surveillance and EPI treatment. Pancreas specialists are more likely to surveil and treat EPI adequately.
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Affiliation(s)
- Padmavathi Srivoleti
- From the Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Russell D Dolan
- From the Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Allison L Yang
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
| | - David X Jin
- From the Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Peter A Banks
- From the Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Julia McNabb-Baltar
- From the Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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28
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Adam MG, Beyer G, Christiansen N, Kamlage B, Pilarsky C, Distler M, Fahlbusch T, Chromik A, Klein F, Bahra M, Uhl W, Grützmann R, Mahajan UM, Weiss FU, Mayerle J, Lerch MM. Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects. Gut 2021; 70:2150-2158. [PMID: 33541865 PMCID: PMC8515121 DOI: 10.1136/gutjnl-2020-320723] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 12/01/2020] [Accepted: 12/01/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management. DESIGN We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts. RESULTS A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)). CONCLUSIONS This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.
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Affiliation(s)
| | - Georg Beyer
- Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
| | | | | | - Christian Pilarsky
- Department of Surgery, Erlangen University Hospital, Erlangen, Bayern, Germany
| | - Marius Distler
- Clinic and Outpatient Clinic for Visceral-, Thorax- and Vascular Surgery, Dresden University Hospital, Dresden, Sachsen, Germany
| | - Tim Fahlbusch
- St. Josef Hospital, Department of Surgery, Ruhr University Bochum, Bochum, Nordrhein-Westfalen, Germany
| | - Ansgar Chromik
- Askleipios Clinic Harburg, Department for General and Visceral Surgery, Asklepios Hospital Group, Hamburg, Hamburg, Germany
| | - Fritz Klein
- Department of Surgery, Charité Universitätsmedizin Berlin Campus Charite Mitte, Berlin, Berlin, Germany
| | - Marcus Bahra
- Department of Surgery, Charité Universitätsmedizin Berlin Campus Charite Mitte, Berlin, Berlin, Germany
| | - Waldemar Uhl
- St. Josef Hospital, Department of Surgery, Ruhr University Bochum, Bochum, Nordrhein-Westfalen, Germany
| | - Robert Grützmann
- Department of Surgery, Erlangen University Hospital, Erlangen, Bayern, Germany
| | - Ujjwal M Mahajan
- Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
| | - Frank U Weiss
- Department of Medicine A, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
| | - Julia Mayerle
- Department of Medicine II, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
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Ul Ain Q, Bashir Y, Kelleher L, Bourne DM, Egan SM, McMahon J, Keaskin L, Griffin OM, Conlon KC, Duggan SN. Dietary intake in patients with chronic pancreatitis: A systematic review and meta-analysis. World J Gastroenterol 2021; 27:5775-5792. [PMID: 34629801 PMCID: PMC8473599 DOI: 10.3748/wjg.v27.i34.5775] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/26/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis (CP) results in malabsorption and ultimate malnutrition. However, the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation, alcohol excess and poor dietary intake all contribute. Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain. Whilst up to half of patients with chronic pancreatitis are reportedly malnourished, the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date.
AIM To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls, and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP.
METHODS A systematic literature search was performed using EMBASE, MEDLINE, and Cochrane review on studies published between 1946 and August 30th, 2019. Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review (qualitative analysis). Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included. Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis (quantitative analysis). Meta-analysis was performed using Review Manager 5.3. Newcastle Ottawa Scale (NOS) was used to assess quality of studies.
RESULTS Of 6715 studies retrieved in the search, 23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis. In the meta-analysis, the total energy (calorie) intake of patients with CP was similar to that of healthy controls [mean difference (MD): 171.3; 95% confidence interval (CI): -226.01, 568.5; P = 0.4], however patients with CP consumed significantly fewer non-alcohol calories than controls [MD: -694.1; 95%CI: -1256.1, (-132.1); P = 0.02]. CP patients consumed more protein, but carbohydrate and fat intakes did not differ significantly. Those with alcohol-related CP consumed more mean (standard deviation) calories than CP patients with a non-alcohol aetiology [2642 (1090) kcal and 1372 (394) kcal, respectively, P = 0.046], as well as more protein, fat, but not carbohydrate.
CONCLUSION Although patients with CP had similar calorie intake to controls, studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls. A high calorie intake, made up to a large degree by alcohol, may in part contribute to poor nutritional status in CP.
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Affiliation(s)
- Qurat Ul Ain
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
| | - Yasir Bashir
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
| | - Linda Kelleher
- Department of Nutrition and Dietetics, Tallaght University Hospital, Dublin 24 D24 NR0A, Ireland
| | - David M Bourne
- Department of Newcastle Nutrition, Freeman Hospital, Newcastle Upon Tyne NE77DN, United Kingdom
| | - Suzanne M Egan
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
| | - Jean McMahon
- Library and Information Services Tallaght, Tallaght University Hospital, Dublin 24 D24 NR0A, Ireland
| | - Laura Keaskin
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
| | - Oonagh M Griffin
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
- Department of Nutrition and Dietetics, St. Vincent’s University Hospital, Dublin 4 D04 T6F4, Ireland
| | - Kevin C Conlon
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
| | - Sinead N Duggan
- Professorial Surgical Unit, Department of Surgery, Trinity College Dublin, Dublin 24 D24 NR0A, Ireland
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Influences of dietary oils and fats, and the accompanied minor content of components on the gut microbiota and gut inflammation: A review. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.05.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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Huang C, Iovanna J, Santofimia-Castaño P. Targeting Fibrosis: The Bridge That Connects Pancreatitis and Pancreatic Cancer. Int J Mol Sci 2021; 22:4970. [PMID: 34067040 PMCID: PMC8124541 DOI: 10.3390/ijms22094970] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/04/2021] [Accepted: 05/05/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic fibrosis is caused by the excessive deposits of extracellular matrix (ECM) and collagen fibers during repeated necrosis to repair damaged pancreatic tissue. Pancreatic fibrosis is frequently present in chronic pancreatitis (CP) and pancreatic cancer (PC). Clinically, pancreatic fibrosis is a pathological feature of pancreatitis and pancreatic cancer. However, many new studies have found that pancreatic fibrosis is involved in the transformation from pancreatitis to pancreatic cancer. Thus, the role of fibrosis in the crosstalk between pancreatitis and pancreatic cancer is critical and still elusive; therefore, it deserves more attention. Here, we review the development of pancreatic fibrosis in inflammation and cancer, and we discuss the therapeutic strategies for alleviating pancreatic fibrosis. We further propose that cellular stress response might be a key driver that links fibrosis to cancer initiation and progression. Therefore, targeting stress proteins, such as nuclear protein 1 (NUPR1), could be an interesting strategy for pancreatic fibrosis and PC treatment.
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Affiliation(s)
| | | | - Patricia Santofimia-Castaño
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13288 Marseille, France; (C.H.); (J.I.)
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Maev IV, Kucheryavyy YA, Andreev DN. Exocrine pancreas insufficiency: clinical significance and approaches to correction from evidence medicine. TERAPEVT ARKH 2021; 93:509-515. [PMID: 36286789 DOI: 10.26442/00403660.2021.04.200800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022]
Abstract
Exocrine pancreatic insufficiency (EPI) is a common complication of both benign and malignant diseases of the pancreas, as well as a consequence of radical surgical operations on the pancreas and a whole range of other variable extra-pancreatic causes. In clinical practice in the adult population, most cases of EPI are associated with chronic pancreatitis, while in the pediatric population with cystic fibrosis. The regression of the production of digestive enzymes in EPI mediates the development of the syndrome of maldigestion and malabsorption, leading to the progressive development of malnutrition, the importance of which is often underestimated by practitioners. At the same time, the development of nutritional deficiency is not just a complication of EPI, but also has an important effect on the course of the underlying causative disease, worsening the prognosis and quality of life of the patient, and is also a proven risk factor for osteoporosis and sarcopenia. To date, compensation for the absolute deficiency of pancreatic enzymes using enzyme replacement therapy is the only possible way to correct the EPI and prevent nutritional deficiency.
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Gavioli EM, Pao K, Harrington M. A retrospective evaluation of vitamin K for hemoptysis in adult cystic fibrosis patients. Hosp Pract (1995) 2021; 49:262-265. [PMID: 33726579 DOI: 10.1080/21548331.2021.1905413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVES Hemoptysis is a complication in cystic fibrosis (CF) patients, and is associated with pulmonary exacerbations and hospitalizations. Pancreatic insufficiency is common in CF patients, and therefore these patients may benefit from the use of vitamin K therapy. METHODS This was an observational study conducted in adult CF patients aiming to describe the utilization of vitamin K therapy in the setting of hemoptysis during an acute CF pulmonary exacerbation. An evaluation of hospital length of stay, time until the next pulmonary exacerbation, and 30-day re-admission rates were evaluated in CF patients who presented with hemoptysis and received vitamin K therapy. RESULTS The average dose of vitamin K therapy was 10 mg for an average duration of 4.9 ± 0.55 days for 38 adult CF patients included in this cohort. The median length of stay among patients who received vitamin K therapy was 8 days (IQR: 6-12 days). The median time until next hospital admission was 127 days (95% CI: 71.4 to 182.6 days), and the 30-day readmission rates were 7.89%. Two patients developed a thromboembolism after receiving vitamin K therapy. CONCLUSIONS Evidence for the use of vitamin K therapy in the setting of CF-related hemoptysis remains unclear, and warrants further safety and efficacy evaluation. Further prospective studies are needed to determine the appropriateness of dosing and duration of vitamin K therapy, as well as determining its role in the setting of the varying levels of hemoptysis during a pulmonary CF exacerbation.
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Affiliation(s)
- Elizabeth Marie Gavioli
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, 1 University Plaza, Brooklyn, New York, United States.,Mount Sinai Beth Israel Hospital, New York, United States
| | - Kevin Pao
- Mount Sinai Beth Israel Hospital, New York, United States
| | - Matthew Harrington
- Mount Sinai Beth Israel Hospital, New York, United States.,Icahn School of Medicine at Mount Sinai, New York, United States
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Andreev DN, Maev IV, Kucheryavyy YA. Prevalence and risk of bone fractures in patients with chronic pancreatitis: meta-analysis. RHEUMATOLOGY SCIENCE AND PRACTICE 2021; 59:56-61. [DOI: 10.47360/1995-4484-2021-56-61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Affiliation(s)
- D. N. Andreev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - I. V. Maev
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
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Katagiri N, Hitomi H, Mae SI, Kotaka M, Lei L, Yamamoto T, Nishiyama A, Osafune K. Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells. Sci Rep 2021; 11:3936. [PMID: 33594180 PMCID: PMC7887226 DOI: 10.1038/s41598-021-83431-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 02/03/2021] [Indexed: 12/13/2022] Open
Abstract
Erythropoietin (EPO) is a crucial hormone for erythropoiesis and produced by adult kidneys. Insufficient EPO production in chronic kidney disease (CKD) can cause renal anemia. Although hypoxia-inducible factors (HIFs) are known as a main regulator, the mechanisms of EPO production have not been fully elucidated. In this study, we aimed to examine the roles of retinoic acid (RA) in EPO production using EPO-producing cells derived from human induced pluripotent stem cells (hiPSC-EPO cells) that we previously established. RA augmented EPO production by hiPSC-EPO cells under hypoxia or by treatment with prolyl hydroxylase domain-containing protein (PHD) inhibitors that upregulate HIF signals. Combination treatment with RA and a PHD inhibitor improved renal anemia in vitamin A-depleted CKD model mice. Our findings using hiPSC-EPO cells and CKD model mice may contribute to clarifying the EPO production mechanism and developing efficient therapies for renal anemia.
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Affiliation(s)
- Naoko Katagiri
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan
| | - Hirofumi Hitomi
- Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Osaka, 573-1010, Japan
| | - Shin-Ichi Mae
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan
| | - Maki Kotaka
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan
| | - Li Lei
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan
| | - Takuya Yamamoto
- Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto, 606-8507, Japan
- Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, 606-8501, Japan
- AMED-CREST, AMED 1-7-1 Otemachi, Chiyodaku, Tokyo, 100-0004, Japan
- Medical-Risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, 606-8507, Japan
| | - Akira Nishiyama
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan
| | - Kenji Osafune
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
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Srivastava A, Saini N, Mathias A, Arya A, Jain S, Yachha SK. Prevalence and predictive factors of undernutrition and low bone mineral density in children with chronic pancreatitis. Pancreatology 2021; 21:74-80. [PMID: 33262050 DOI: 10.1016/j.pan.2020.11.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/19/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Malnutrition and bone disease are common in adults with chronic pancreatitis (CP). We studied the nutritional status and bone mineral density (BMD) of children with CP and the factors predicting them. METHODS CP children were prospectively evaluated with a detailed questionnaire, anthropometry, 25-hydroxy vitamin D, fecal elastase and BMD [total body less head (TBLH), spine and hip] by dual energy x-ray absorptiometry. Body mass index (BMI) Z score of -1 to -1.9, -2 to -2.9 and <-3 was taken as mild, moderate and severe malnutrition respectively. Low BMD and osteoporosis were defined as per International Society for Clinical Densitometry. RESULTS 83 children (46 boys, 14[4.3-21]years) with CP were enrolled. Majority had Cambridge IV (51,62.2%) or III (15,18.3%) changes. 34(41%) had undernutrition (mild-37.3%, moderate-2.4%, severe-1.2%). Overweight and obesity were present in 3.6% and 1.2% cases. BMI had a significant correlation with haemoglobin, serum albumin, percentage body fat and BMD. A majority had low fecal elastase (69 [84.1%], <100 μg/g) and vitamin D deficiency (70[84.3%],<20 ng/ml). 9 cases had a history of fractures. 14/75(18.6%) cases had low TBLH-BMD and this group had a lower BMI (-1.3[-1.9 to 0.34] vs 0.8 [-2.1 to 5.50; p = 0.03) than patients with normal BMD. There was no difference in age, disease duration, vitamin D, fecal elastase and Cambridge grade between normal and low BMD. CONCLUSIONS 41% CP children have undernutrition with a majority having mild undernutrition. Nearly 20% have low BMD, with osteoporosis in none. Subjects with low BMI have lower BMD and percentage body fat.
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Affiliation(s)
- Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Nidhi Saini
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amrita Mathias
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Asmita Arya
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sunil Jain
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - S K Yachha
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Electrochemical vitamin sensors: A critical review. Talanta 2021; 222:121645. [DOI: 10.1016/j.talanta.2020.121645] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/04/2020] [Accepted: 09/05/2020] [Indexed: 02/06/2023]
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Siener R, Machaka I, Alteheld B, Bitterlich N, Metzner C. Effect of Fat-Soluble Vitamins A, D, E and K on Vitamin Status and Metabolic Profile in Patients with Fat Malabsorption with and without Urolithiasis. Nutrients 2020; 12:nu12103110. [PMID: 33053816 PMCID: PMC7601514 DOI: 10.3390/nu12103110] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/06/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022] Open
Abstract
Patients with intestinal fat malabsorption and urolithiasis are particularly at risk of acquiring fat-soluble vitamin deficiencies. The aim of the study was to evaluate the vitamin status and metabolic profile before and after the supplementation of fat-soluble vitamins A, D, E and K (ADEK) in 51 patients with fat malabsorption due to different intestinal diseases both with and without urolithiasis. Anthropometric, clinical, blood and 24-h urinary parameters and dietary intake were assessed at baseline and after ADEK supplementation for two weeks. At baseline, serum aspartate aminotransferase (AST) activity was higher in stone formers (SF; n = 10) than in non-stone formers (NSF; n = 41) but decreased significantly in SF patients after supplementation. Plasma vitamin D and E concentrations increased significantly and to a similar extent in both groups during intervention. While plasma vitamin D concentrations did not differ between the groups, vitamin E concentrations were significantly lower in the SF group than the NSF group before and after ADEK supplementation. Although vitamin D concentration increased significantly in both groups, urinary calcium excretion was not affected by ADEK supplementation. The decline in plasma AST activity in patients with urolithiasis might be attributed to the supplementation of ADEK. Patients with fat malabsorption may benefit from the supplementation of fat-soluble vitamins ADEK.
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Affiliation(s)
- Roswitha Siener
- Department of Urology, University Stone Center, University Hospital Bonn, 53127 Bonn, Germany;
- Correspondence: ; Tel.: +49-228-2871-9034
| | - Ihsan Machaka
- Department of Urology, University Stone Center, University Hospital Bonn, 53127 Bonn, Germany;
| | - Birgit Alteheld
- Department of Nutrition and Food Sciences, Nutritional Physiology, University of Bonn, 53115 Bonn, Germany;
| | - Norman Bitterlich
- Department of Biostatistics, Medicine and Service Ltd., 09117 Chemnitz, Germany;
| | - Christine Metzner
- Bonn Education Association for Dietetics r. A., 50935 Cologne, Germany; or
- Clinic for Gastroenterology, Metabolic Disorders and Internal Intensive Medicine (Medical Clinic III), RWTH Aachen, 52074 Aachen, Germany
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40
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Micronutrient deficits in patients with chronic pancreatitis: prevalence, risk factors and pitfalls. Eur J Gastroenterol Hepatol 2020; 32:1328-1334. [PMID: 32732813 DOI: 10.1097/meg.0000000000001866] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE We investigated the prevalence of micronutrient deficiencies and associated patient and disease-related risk factors in patients with chronic pancreatitis (CP). METHODS We enrolled 115 consecutive CP outpatients. Micro-nutritional assessments included plasma levels of fat-soluble vitamins (A, D and E) and trace elements (magnesium and zinc). Bioelectrical impedance and muscle function tests were used to characterize the macro-nutritional status (sarcopenia and phase angle). Prevalence of micro-nutritional deficiencies was estimated and associated with a number of patient and disease characteristics including presence of exocrine pancreatic insufficiency (EPI) and diabetes mellitus. In an additional analysis, we explored the association between micronutrient levels and macro-nutritional status. RESULTS The mean age of patients was 57.9 ± 13.0 years, 71% were men and 50% had an alcoholic aetiology. Vitamin D deficiency (22%) was the most common micronutrient deficit followed by zinc deficiency (20%) and magnesium deficiency (17%). Vitamin A deficiency (10%) and vitamin E deficiency (7%) were only seen in patients with EPI (P ≤ 0.03), while the presence of trace element deficits was associated with plasma albumin levels (P ≤ 0.006). Plasma zinc levels were decreased in sarcopenic patients (P < 0.001) and positively correlated to phase angle (coefficient 0.28; P < 0.001). CONCLUSION Various micronutrient deficits were observed in CP outpatients, and associated risk factors were diverse and distinct for the individual nutrients. Taken together, our findings highlight the complexity of micronutrient assessment in patients with CP and emphasise the importance of simultaneous evaluation of plasma protein levels, inflammatory activity and macro-nutritional status.
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Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J. Chronic pancreatitis. Lancet 2020; 396:499-512. [PMID: 32798493 DOI: 10.1016/s0140-6736(20)31318-0] [Citation(s) in RCA: 280] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/02/2020] [Accepted: 05/07/2020] [Indexed: 12/15/2022]
Abstract
Chronic pancreatitis is a multifactorial, fibroinflammatory syndrome in which repetitive episodes of pancreatic inflammation lead to extensive fibrotic tissue replacement, resulting in chronic pain, exocrine and endocrine pancreatic insufficiency, reduced quality of life, and a shorter life expectancy. The incidence and prevalence of chronic pancreatitis is rising and no curative treatment is available. Using novel diagnostic algorithms, definitive chronic pancreatitis can be diagnosed by imaging criteria alone, whereas probable chronic pancreatitis requires clinical features and imaging criteria. Criteria for the diagnosis of early chronic pancreatitis are still under discussion and need prospective validation in clinical trials. Cross-sectional imaging should be used first; endoscopic ultrasound is needed only when CT or MRI are inconclusive or to plan therapeutic interventions. Management of chronic pancreatitis requires an interdisciplinary approach including primary care practitioners, gastroenterologists, surgeons, radiologists, pain specialists, and nutritional therapists. Patients with chronic pancreatitis should be seen at least once a year and re-evaluated for causal risk factors, symptom control, and complications such as malnutrition, pancreatic exocrine insufficiency, and diabetes; refer to a specialised centre if symptoms are poorly controlled or there is risk of deterioration. Scoring systems to monitor disease progression have been developed and validated internationally. Interventional treatments for pain or cholestasis should be done by specialists only, and early discussion of treatment approaches should include all medical disciplines involved in care. Throughout this Seminar, we address research needs such as staging of pancreatitis, aspects of malnutrition and pain, and cancer surveillance, to help improve the care of patients.
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Affiliation(s)
- Georg Beyer
- Medical Department II, University Hospital, LMU Munich, Munich, Germany
| | - Aida Habtezion
- Division of Gastroenterology and Hepatology, Stanford Medicine, Stanford University, Stanford, CA, USA
| | - Jens Werner
- Department of General, Visceral and Transplant Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine, University of Greifswald, Greifswald, Germany
| | - Julia Mayerle
- Medical Department II, University Hospital, LMU Munich, Munich, Germany.
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Terlikowska KM, Dobrzycka B, Kinalski M, Terlikowski SJ. Serum Concentrations of Carotenoids and Fat-Soluble Vitamins in Relation to Nutritional Status of Patients with Ovarian Cancer. Nutr Cancer 2020; 73:1480-1488. [PMID: 32748660 DOI: 10.1080/01635581.2020.1801779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
In this study, we aimed to determine serum concentrations of carotenoids and fat-soluble vitamins (FSVs) in ovarian cancer (OC) patients categorized by clinical and nutritional status and to compare obtained results with healthy controls. We used single-step extraction methods throughout the study. Serum concentrations of the bioactive compounds were measured using HPLC. The evaluation of the nutritional status of patients was performed with scored PG-SGA questionnaire.The serum bioactive compound levels were significantly lower in early-stage OC patients (FIGO I/II) when compared to healthy controls for all-trans-retinoic acid, 25-hydroxycholecalciferol, all-trans-retinol, astaxanthin, zeaxanthin, lycopene and α-carotene, respectively. In patients with advanced-stage of OC (FIGO III/IV) the mean serum concentrations of carotenoids and FSVs were significantly lower than in healthy controls, excluding lutein and β + γ-tocopherol levels. Patients with OC and concomitant moderate or severe malnourishment showed significantly lower levels of 25-hydroxycholecalciferol and all-trans-retinol. It seems that our extraction and measurement methods for the bioactive compounds could be used in both, clinical and nutritional studies. The obtained results confirm that the PG-SGA assessment might be considered not only as a malnutrition assessment tool, but also for planning early nutritional intervention in patients with OC.
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Affiliation(s)
| | - Bozena Dobrzycka
- Department of Gynecology and Obstetrics, Medical University of Bialystok, Bialystok, Poland
| | - Maciej Kinalski
- Department of Gynecology and Obstetrics, Independent Public Healthcare Facility Regional Complex Jan Sniadecki Hospital, Bialystok, Poland
| | - Slawomir J Terlikowski
- Department of Obstetrics, Gynecology and Maternity Care, Medical University of Bialystok, Bialystok, Poland
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43
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Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, Capurso G, Culver EL, de-Madaria E, Della-Torre E, Detlefsen S, Dominguez-Muñoz E, Czubkowski P, Ewald N, Frulloni L, Gubergrits N, Duman DG, Hackert T, Iglesias-Garcia J, Kartalis N, Laghi A, Lammert F, Lindgren F, Okhlobystin A, Oracz G, Parniczky A, Mucelli RMP, Rebours V, Rosendahl J, Schleinitz N, Schneider A, van Bommel EF, Verbeke CS, Vullierme MP, Witt H. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8:637-666. [PMID: 32552502 DOI: 10.1177/2050640620934911] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
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Affiliation(s)
- J-Matthias Löhr
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
| | - Miroslav Vujasinovic
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Frank Buttgereit
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research Center IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain
| | - Emanuel Della-Torre
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Disease (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Nils Ewald
- Institute of Endocrinology, Diabetology and Metabolism, Johannes Wesling University hospital, Minden, Germany and Justus Liebig University Giessen, Giessen, Germany
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman, Ukraine
| | - Deniz Guney Duman
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fredrik Lindgren
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | | | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Andrea Parniczky
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Insitute of Pediatrics, Budapest, Hungary
| | | | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Clichy, Université de Paris, France
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Nicolas Schleinitz
- Département de Médicine Interne Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
| | - Alexander Schneider
- Department of Gastroenterology and Hepatology, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
| | - Eric Fh van Bommel
- Department of Internal Medicine, Dutch National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer hospital, Dordrecht, the Netherlands
| | | | | | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
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- See list at the end of this article
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Ahmed A, Deep A, Kothari DJ, Sheth SG. Bone disease in chronic pancreatitis. World J Clin Cases 2020; 8:1574-1579. [PMID: 32432135 PMCID: PMC7211537 DOI: 10.12998/wjcc.v8.i9.1574] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 03/26/2020] [Accepted: 04/18/2020] [Indexed: 02/05/2023] Open
Abstract
Bone disease (osteopenia or osteoporosis) is a highly prevalent condition in society and presents a tremendous, preventable public health burden. Screening procedures, such as, dual-energy X-ray absorptiometry scans, have allowed early identification and intervention to improve bone health, and reduce the risk of osteoporotic fractures, which carry significant morbidity and mortality. The association of bone disease has been recognized in several diseases of the gastrointestinal tract, resulting in established guidelines for screening in patients with malabsorptive disorders such as inflammatory bowel disease and celiac disease. Increasingly, the risk of bone disease has been recognized in patients with chronic pancreatitis (CP), who share similar risk factors as patients with other high gastrointestinal disorders. As a result, there have been a number of studies examining the prevalence and risks of bone disease and fractures in patients with CP. This review aims to summarize the recent literature and current recommendations related to bone disease in CP.
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Affiliation(s)
- Awais Ahmed
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Aman Deep
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Darshan J Kothari
- Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, United States
| | - Sunil G Sheth
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
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45
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Barkin JA, Barkin JS. Chronic Pancreatitis and Bone Disease. J Clin Densitom 2020; 23:237-243. [PMID: 31558406 DOI: 10.1016/j.jocd.2019.08.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 08/18/2019] [Accepted: 08/19/2019] [Indexed: 12/22/2022]
Abstract
Patients with chronic pancreatitis (CP) may have a higher prevalence of osteoporosis than the general population thereby increasing the risk of bone fracture. The pathophysiology of bone disease in CP is multifactorial. Their risk factors for secondary osteoporosis include increasing age, low body mass index from sitophobia, maldigestion due to exocrine pancreatic insufficiency (EPI) with resulting low vitamin D, as well as smoking and alcohol abuse. An obvious association of bone disease with CP is from EPI with maldigestion of fat-soluble vitamins including vitamin-D, which has a significant role in the process of bone formation. Vitamin-D deficiency may be higher in CP patients vs controls, and it is especially so in CP patients with EPI. Screening for CP-associated osteopathy, including osteopenia and osteoporosis, should be initiated early in the course of CP, as the overall prevalence of bone disease is approximately two-thirds of CP patients. Our initial approach in the treatment of osteoporosis should include correction of maldigestion resulting from EPI with use of pancreatic enzyme replacement therapy (PERT). PERT, which is the treatment for EPI is associated with improvement in Dual energy X-ray absorptiometry (DXA) values and vitamin-D levels compared to those who are not treated. This should improve, in addition to body mass index, vitamin-D deficiency and calcium absorption as well as improve overall nutritional status. Osteopathy is common in CP patients, has significant associated morbidity, should be screened for regularly, and corrected with fat soluble vitamin supplementation and PERT to prevent clinical sequelae. In this article, we review the epidemiology, pathophysiology, and treatment of bone disease in patients with CP.
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Affiliation(s)
- Jodie A Barkin
- University of Miami, Leonard M. Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL USA.
| | - Jamie S Barkin
- University of Miami, Leonard M. Miller School of Medicine, Department of Medicine, Division of Gastroenterology, Miami, FL USA
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46
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Stigliano S, Archibugi L, Signoretti M, Zerboni G, Capurso G. The baseline nutritional status assessed by MUST score has a low accuracy in predicting the risk of hospitalization during follow-up in patients with chronic pancreatitis: A cohort study. Pancreatology 2020; 20:182-186. [PMID: 31926768 DOI: 10.1016/j.pan.2019.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 12/09/2019] [Accepted: 12/16/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hospitalization and death in patients with chronic pancreatitis (CP) are often due to extra-pancreatic events. Recent guidelines recommend the use of the MUST score to assess CP patients' nutritional status, but its association with clinical outcomes has been poorly investigated. The aims of this study are to evaluate the incidence of extra-pancreatic events in patients with CP during follow-up and their association with the nutritional status. METHODS Retrospective analysis of single-centre cohort of CP patients prospectively enrolled and followed-up. Exocrine pancreatic insufficiency (EPI) was assessed by fecal elastase, MUST score calculated at diagnosis. The occurrence of hospitalizations or death were recorded. Differences between subgroups were analysed by Fisher's and T-test and hospitalization-free survival with Kaplan-Meier curves and Cox regression analysis. RESULTS Of 111 enrolled patients (64% male; mean age 57); 52% had alcoholic aetiology, 53% EPI, 10% severe CP and 26% a MUST score≥2 at diagnosis. During a median follow-up of 37 months, 3.6% of patients died and 34.2% needed hospitalization, in 50% of cases for extrapancreatic events (2% cardiovascular events, 8% infections and 3% cancer). There was no significant association between EPI, BMI<20 kg/m2, MUST score≥2, alcoholic aetiology and extra pancreatic events or need of hospitalization. A baseline MUST score≥2 had an accuracy of only 64.8% in predicting subsequent hospitalization. CONCLUSIONS A sizeable portion of CP patients are at high risk of malnutrition and are hospitalized during the follow-up, often for extra-pancreatic events. The nutritional status evaluated with the MUST score lacks accuracy in predicting the risk of these events.
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Affiliation(s)
- Serena Stigliano
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Italy; Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Italy
| | - Livia Archibugi
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Italy; Pancreato-biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Marianna Signoretti
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Italy; Department of Gastroenterology, Morgagni-Pierantoni Hospital, Forli, Italy
| | - Giulia Zerboni
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University of Rome, Italy; Pancreato-biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.
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47
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Lam KW, Leeds J. How to manage: patient with a low faecal elastase. Frontline Gastroenterol 2019; 12:67-73. [PMID: 33489070 PMCID: PMC7802491 DOI: 10.1136/flgastro-2018-101171] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Kwan Wai Lam
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
| | - John Leeds
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
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48
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Pancreatic Function in Chronic Pancreatitis: A Cohort Study Comparing 3 Methods of Detecting Fat Malabsorption and the Impact of Short-term Pancreatic Enzyme Replacement Therapy. Pancreas 2019; 48:1068-1078. [PMID: 31404029 PMCID: PMC7243202 DOI: 10.1097/mpa.0000000000001381] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL). METHODS Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed. RESULTS The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased. CONCLUSIONS The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.
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49
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Greer JB, Greer P, Sandhu BS, Alkaade S, Wilcox CM, Anderson MA, Sherman S, Gardner TB, Lewis MD, Guda NM, Muniraj T, Conwell D, Cote GA, Forsmark CE, Banks PA, Tang G, Stello K, Gelrud A, Brand RE, Slivka A, Whitcomb DC, Yadav D. Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients. Nutr Clin Pract 2019; 34:387-399. [PMID: 30101991 PMCID: PMC6642676 DOI: 10.1002/ncp.10186] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. METHODS We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-α; and C-reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement. RESULTS After correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 μg/dL) and vitamin E (α-tocopherol [8.7 vs 10.3 mg/L] and γ-tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both α-tocopherol and γ-tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP. CONCLUSIONS CP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.
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Affiliation(s)
- Julia B. Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Phil Greer
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Samer Alkaade
- Department of Medicine, Saint Louis University, St. Louis, Missouri
| | - C. Mel Wilcox
- Department of Medicine, University of Alabama Birmingham, Birmingham, Alabama
| | | | - Stuart Sherman
- Department of Medicine, Indiana University, Indianapolis, Indiana
| | - Timothy B. Gardner
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
| | | | - Nalini M. Guda
- GI Associates LLC, Aurora Health Care, St. Luke’s Medical Center, Milwaukee, Wisconsin
| | | | - Darwin Conwell
- Department of Medicine, The Ohio State University, Columbus, Ohio
| | - Gregory A. Cote
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
| | | | - Peter A. Banks
- Department of Medicine, Brigham and Women’s Hospital, Boston Massachusetts
| | - Gong Tang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Kim Stello
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andres Gelrud
- GastroHealth and Miami Cancer Institute, Baptist Hospital, Miami, Florida
| | - Randall E. Brand
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - David C. Whitcomb
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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50
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Robinson SM, Rasch S, Beer S, Valantiene I, Mickevicius A, Schlaipfer E, Mann J, Maisonneuve P, Charnley RM, Rosendahl J. Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis. Sci Rep 2019; 9:7318. [PMID: 31086257 PMCID: PMC6513859 DOI: 10.1038/s41598-019-43846-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 05/01/2019] [Indexed: 02/07/2023] Open
Abstract
Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1β, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.
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Affiliation(s)
- Stuart M Robinson
- HPB Unit, Department of Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Sebastian Rasch
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany.
| | - Sebastian Beer
- Department for Internal Medicine, Neurology and Dermatology, Division of Gastroenterology, University of Leipzig, Leipzig, Germany
| | - Irena Valantiene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Artautas Mickevicius
- Centre of Hepatology, Gastroenterology and Dietetics, Vilnius University Hospital Santaros Klinikos & Vilnius University Faculty of Medicine, Vilnius, Lithuania
| | - Elisabeth Schlaipfer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany
| | - Jelena Mann
- HPB Unit, Department of Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Richard M Charnley
- HPB Unit, Department of Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Saale, Germany
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