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Tang C, Zhou J, Song Y, Liu S. Etiologies of exocrine pancreatic insufficiency. Gastroenterol Rep (Oxf) 2025; 13:goaf019. [PMID: 40066317 PMCID: PMC11893156 DOI: 10.1093/gastro/goaf019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/30/2024] [Accepted: 11/12/2024] [Indexed: 04/11/2025] Open
Abstract
Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.
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Affiliation(s)
- Chengji Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
| | - Jia Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
- Central Laboratory of Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P. R. China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, P. R. China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People’s Hospital, Changsha, Hunan, P. R. China
- Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha, Hunan, P. R. China
- Hunan Key Laboratory for the Prevention and Treatment of Biliary Tract Diseases, Changsha, Hunan, P. R. China
- Research Center for Hepatobiliary and Pancreatic Diseases of Furong Laboratory, Changsha, Hunan, P. R. China
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Khatkov IE, Maev IV, Bordin DS, Kononenko IB, Kucheryavyy YA, Pokataev IA, Snegovoy AV, Tryakin AA, Feoktistova PS, Zhukova LG. Role of enzyme replacement therapy for exocrine and nutritional insufficiency in patients with malignancies: A review. JOURNAL OF MODERN ONCOLOGY 2024; 26:380-389. [DOI: 10.26442/18151434.2024.3.203007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Exocrine pancreatic insufficiency (EPI) is a condition in which the amount of secreted pancreatic enzymes is insufficient to maintain normal digestion. EPI is a frequent complication of pancreatic or other malignancies. The presence of EPI in a cancer patient may be suggested by symptoms of maldigestion, malabsorption, and alteration of nutritional markers; however, it is important to note that the EPI symptoms may be subtle. In the early stages, EPI may be latent and manifested by malnutrition. However, even in the later stages, the symptoms of EPI may be similar to those of cancer or be masked by the condition after chemoradiation therapy. Antitumor therapy itself may also cause EPI. Enzyme replacement therapy (ERT) is the standard of care for EPI, but it is rarely prescribed to cancer patients. However, supportive therapy plays an essential role in treating cancer patients because the quality of life and life expectancy of patients largely depend on the adequacy of the complex treatment. The review discusses the possible causes of EPI and its diagnosis and treatment in cancer patients. Special attention is paid to ERT regimens, including those for improving digestion and the drug's dosage form. It is shown that pancreatin in minimicrospheres is the drug of choice for ERT, since the minimum particle size facilitates the most physiological digestion process.
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Affiliation(s)
- Igor E. Khatkov
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
| | | | - Dmitry S. Bordin
- Loginov Moscow Clinical Scientific Center
- Russian University of Medicine
- Tver State Medical University
| | - Inessa B. Kononenko
- Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of National Medical Research Radiological Centre
| | | | - Ilya A. Pokataev
- Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department
| | - Anton V. Snegovoy
- Russian University of Medicine
- Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of National Medical Research Radiological Centre
| | | | - Polina S. Feoktistova
- Loginov Moscow Clinical Scientific Center
- Central State Medical Academy of the President of the Russian Federation
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Zhukova LG, Bordin DS, Dubtsova EA, Ilin MA, Kiriukova MA, Feoktistova PS, Egorov VI. How a significant increase in survival in pancreatic cancer is achieved. The role of nutritional status and supportive care: A review. JOURNAL OF MODERN ONCOLOGY 2024; 25. [DOI: 10.26442/18151434.2023.4.202541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.
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Lewis DM, Rieke JG, Almusaylim K, Kanchibhatla A, Blanchette JE, Lewis C. Exocrine Pancreatic Insufficiency Dosing Guidelines for Pancreatic Enzyme Replacement Therapy Vary Widely Across Disease Types. Dig Dis Sci 2024; 69:615-633. [PMID: 38117426 DOI: 10.1007/s10620-023-08184-w] [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: 06/26/2023] [Accepted: 11/06/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Pancreatic enzyme replacement therapy (PERT) is the standard treatment for exocrine pancreatic insufficiency (EPI). However, many individuals are inadequately treated, with gaps in clinical dosing, guidelines, and tools to aid individual titration. METHODS A systematic review identified research and guidelines on PERT dosing recommendations across conditions, systematically reviewing and synthesizing total PERT intake, meal/snack guidelines, and changes over time to provide an up-to-date look at the most common doses used in studies and guidelines. RESULTS This review of 257 articles found wide variability in PERT dosing guidelines within and across conditions. Many patients with EPI are underdosed, with guidelines differing globally and by disease type, and clinician prescribing may also play a role. The most common dosing guidelines focus on starting doses at 40,000-50,000 units of lipase/meal with increases of up to two to three times this amount before pursuing additive therapies. Guidelines and studies typically focus only on fat digestion, and comparison by total daily dose shows underdosing is common. Most PERT studies are on safety and efficacy rather than optimal titration. CONCLUSION The current guidelines for PERT in EPI demonstrate substantial variability in dosing recommendations, both within and across disease types. This variation highlights the need for further research to optimize PERT dosing and improve patient outcomes. Healthcare providers should consider individualizing PERT dosing based on nutritional status and response to therapy, ensuring regular follow-up with patients for dose titrations with consideration that most guidelines are framed as initial doses rather than upper limits.
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Affiliation(s)
| | - Jorden G Rieke
- Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, 44106, USA.
| | - Khaleal Almusaylim
- Diabetes and Metabolic Care Center, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA
- School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA
| | - Anuhya Kanchibhatla
- Department of Arts and Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA
| | - Julia E Blanchette
- Diabetes and Metabolic Care Center, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA
- School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA
| | - Claudia Lewis
- Diabetes and Metabolic Care Center, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA
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Hall LA, Powell-Brett S, Halle-Smith J, Ward L, Wiggins T, Markar SR, Roberts KJ. Pancreatic exocrine insufficiency after non-pancreatic upper gastrointestinal surgery: meta-analysis. Br J Surg 2024; 111:znad369. [PMID: 38064682 DOI: 10.1093/bjs/znad369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/12/2023] [Accepted: 10/14/2023] [Indexed: 01/07/2024]
Abstract
BACKGROUND Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection. METHODS A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy. RESULTS Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed. CONCLUSION PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy.
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Affiliation(s)
- Lewis A Hall
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, Birmingham, UK
- College of Medical and Dental Scientists, University of Birmingham, Birmingham, UK
| | - Sarah Powell-Brett
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, Birmingham, UK
| | - James Halle-Smith
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, Birmingham, UK
| | - Liz Ward
- Department Therapies and Dietetics, Churchill Hospital, Oxford University Hospitals Foundation NHS Trust, Oxford, UK
| | - Tom Wiggins
- Department of Bariatric Surgery and Upper Gastrointestinal Surgery, Birmingham Heartlands Hospital, University Hospitals Birmingham, Birmingham, UK
| | - Sheraz R Markar
- Nuffield Department of Surgery, University of Oxford, Oxford, UK
| | - Keith J Roberts
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, Birmingham, UK
- College of Medical and Dental Scientists, University of Birmingham, Birmingham, UK
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Garay MB, Carbajal-Maldonado ÁL, Rodriguez-Ortiz-DE-Rozas R, Guilabert L, DE-Madaria E. Post-surgical exocrine pancreatic insufficiency. Minerva Surg 2023; 78:671-683. [PMID: 38059441 DOI: 10.23736/s2724-5691.23.10125-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2023]
Abstract
Being an underdiagnosed and under or insufficiently treated condition, surgical pancreatic exocrine insufficiency (PSP) is the condition in which pancreatic enzymes are insufficient for digestion because of gastrointestinal (GI) surgery involving the upper GI tract, biliary ducts, or the pancreas, and and leading to potential malnutrition and deterioration in quality of life. Age, obesity, history of tobacco use, family history of diabetes, surgery due to a malignant tumor, presence of steatorrhea, jaundice, weight loss, and intraoperative findings of hard pancreatic texture have been associated with a higher risk of PSP. Pancreatoduodectomy (PD) has demonstrated an increased risk of developing PSP, with a prevalence between 19-100%. Distal pancreatectomy (DP) and central pancreatectomy (CenP) are associated with less risk of PSP, with a prevalence of 0-82% and 3.66-8.7%, respectively. In patients with chronic pancreatitis (CP), PSP was associated with 80% in Partington-Rochelle procedure, 86% in Frey procedure, 80% in duodenum preserving pancreatic head procedure, >60% in PD and 27.5-63% in DP. Fecal elastase-1 (FE-1) is a generally accepted tool for diagnosis. Treatment is recommended to start as soon as a diagnosis is achieved, or clinical suspicion is high. Pancreatic enzyme replacement therapy improves symptoms of malabsorption, facilitates weight gain, and ultimately improves patients' quality of life. Starting dosage is between 10,000-50,000 units in snacks and 50,000-75,000 units in main meals, administered throughout food intake, though further data specifically on PSP are needed. Follow-up in PSP is recommended on an on-demand basis, where malnutrition should be assessed.
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Affiliation(s)
- Maria B Garay
- Department of Gastroenterology, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), General University Hospital of Alicante, Alicante, Spain
| | - Ángela L Carbajal-Maldonado
- Department of Gastroenterology, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), General University Hospital of Alicante, Alicante, Spain
| | - Rosario Rodriguez-Ortiz-DE-Rozas
- Department of Gastroenterology, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), General University Hospital of Alicante, Alicante, Spain
| | - Lucia Guilabert
- Department of Gastroenterology, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), General University Hospital of Alicante, Alicante, Spain
| | - Enrique DE-Madaria
- Department of Gastroenterology, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), General University Hospital of Alicante, Alicante, Spain -
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Lewis DM. A Systematic Review of Exocrine Pancreatic Insufficiency Prevalence and Treatment in Type 1 and Type 2 Diabetes. Diabetes Technol Ther 2023; 25:659-672. [PMID: 37440180 DOI: 10.1089/dia.2023.0157] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Type 1 diabetes and type 2 diabetes have high rates of associated exocrine pancreatic insufficiency (EPI). This review evaluated the current evidence on prevalence and treatment of EPI in type 1 and type 2 diabetes and compared general population prevalence rates of EPI and prevalence of other common gastrointestinal conditions such as celiac disease and gastroparesis based on within-diabetes rates of common gastrointestinal (GI) conditions. Prevalence of EPI in type 1 diabetes ranges from 14% to 77.5% (median 33%), while EPI in type 2 diabetes ranges from 16.8% to 49.2% (median 29%), and where type of diabetes is not specified in studies, ranges from 5.4% to 77%. In studies with control groups of the general population, prevalence of EPI overall in those without diabetes ranged from 4.4% to 18%, median 13%, which is comparable with other estimated general population prevalence rates of EPI (10%-20%). Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes (both type 1 and type 2) who present with gastrointestinal symptoms, such as steatorrhea or changes in stool, bloating, and/or abdominal pain, should be screened for EPI. Both diabetes specialists and gastroenterologists and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms.
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Lan X, Robin G, Kasnik J, Wong G, Abdel-Rahman O. Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:1331. [PMID: 36831673 PMCID: PMC9953920 DOI: 10.3390/cancers15041331] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 02/14/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients.
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Affiliation(s)
- Xiaoyang Lan
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Gabrielle Robin
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Jessica Kasnik
- Nutrition Services, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
| | - Grace Wong
- Pharmacy Department, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada
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Moore HN, Chirco AR, Plescia T, Ahmed S, Jachniewicz B, Rajasekar G, Ali MR, Lyo V. Exocrine pancreatic insufficiency after bariatric surgery: a bariatric surgery center of excellence experience. Surg Endosc 2023; 37:1466-1475. [PMID: 35768735 DOI: 10.1007/s00464-022-09388-3] [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: 03/24/2022] [Accepted: 06/06/2022] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Gastrointestinal symptoms such as diarrhea, bloating, abdominal pain, and nausea are common after bariatric surgery (BS) and can lead to significant morbidity. While many diagnoses can explain these symptoms, post-bariatric exocrine pancreatic insufficiency (EPI) is becoming increasingly recognized as contributor to gastrointestinal symptoms. The frequency and outcomes of EPI after BS are not well understood. We investigated the prevalence and outcomes of EPI over 18 years at a tertiary bariatric referral center. METHODS A retrospective review of patients who underwent primary or revisional BS from 2002 to 2020 was performed. Patients were included if they were suspected of having EPI or underwent fecal elastase testing (FE-1). EPI diagnosis was defined as positive FE-1 testing or improvement with empiric pancreatic enzyme replacement therapy (PERT). RESULTS EPI was suspected in 261 patients, and 190 were tested via FE-1 (89.5%) or empirically treated (10.5%). EPI was diagnosed in 79 (41.6%) patients and was associated with older age and lower BMI. Therapeutic PERT was given to 65 patients diagnosed with EPI, and 56 (86.2%) patients reported improved symptoms. Patients who underwent RYGB and BPD-DS were more likely to have EPI than those after SG (47.9% and 70.0% vs 17.4%, p < 0.01). EPI diagnosis was associated with a history chronic pancreatitis. While diarrhea and abdominal pain were the most common symptoms prompting FE-1 testing, no symptoms were significantly associated with EPI. EPI was also associated with abnormal fecal fat results and treatment with bile acid sequestrants, but not small intestinal bacterial overgrowth. CONCLUSION This study highlights that exocrine pancreatic insufficiency can account to for previously unexplained GI complaints after bariatric surgery. Therefore, bariatric surgery programs should consider this diagnosis in symptomatic patients, especially following RYGB and BPD-DS. Further work to define patient factors that should prompt evaluation, optimal treatment, and prevention is necessary.
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Affiliation(s)
- Hope N Moore
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | | | - Trevor Plescia
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | - Shushmita Ahmed
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | - Barbara Jachniewicz
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | - Ganesh Rajasekar
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | - Mohamed R Ali
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA
| | - Victoria Lyo
- Department of Surgery, University of California Davis Health, Sacramento, CA, USA. .,UC Davis Medical Center, 2335 Stockton Blvd., NAOB 6113, Sacramento, CA, 95817, USA.
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Incidence, Diagnosis and Management of Malabsorption Following Oesophagectomy: a Systematic Review. J Gastrointest Surg 2022; 26:1781-1790. [PMID: 35484473 DOI: 10.1007/s11605-022-05323-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/01/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Survival following oesophagectomy for cancer is improving, resulting in increased focus on quality of life and survivorship. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM). The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. METHODS A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until December 2021. RESULTS Of 464 identified studies, eight studies (n = 7 non-randomised longitudinal studies) were included where patients were identified with malnutrition following oesophagectomy. Studies included a combined sample of 328 (range 7-63) patients. Malabsorption syndromes including EPI, SIBO and BAM occurred in 15.9-100%, 37.8-100% and 3.33-100% over 21 days-60 months, 1-24 months and 1-24 months respectively. There was no consensus definition for EPI, SIBO or BAM, and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin or colesevelam showed improvement in symptoms and weight in all studies, where investigated. CONCLUSIONS Malabsorption syndromes following oesophagectomy are under-recognised, and thus under-reported. The resultant gastrointestinal symptoms may have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies; however, greater understanding of these conditions, their diagnosis and management is required to further understand which patients will benefit from treatment.
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11
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'You know where we are if you need us.' The role of primary care in supporting patients following pancreaticoduodenectomy for cancer: a qualitative study. BJGP Open 2022; 6:BJGPO.2021.0154. [PMID: 35045954 PMCID: PMC9447308 DOI: 10.3399/bjgpo.2021.0154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/22/2021] [Indexed: 11/13/2022] Open
Abstract
Background Ten per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. It is known that these patients have unmet psychological support needs, and GPs are key in enabling effective coordination of care for people living with life-shortening conditions. Aim To explore patients’ perspectives on the role of primary care in their management, and their sources of support. Design & setting Inductive qualitative study of patients who had undergone pancreaticoduodenectomy between 6 months and 6 years previously for pancreatic or distal biliary duct cancers. Participants were recruited by clinical nurse specialists (CNSs) from a single NHS trust in Northwest England. Method Semi-structured interviews, either face-to-face or via video link, were conducted with 20 participants. Interviews were audio-recorded, transcribed, and anonymised. Thematic analysis utilised principles of constant comparison. Results Participants described immense treatment burden and uncertainty around the role of the GP in their ongoing care. They recognised that GPs may have little experience of patients who have undergone pancreaticoduodenectomy, but felt that GPs can play a vital role in offering support. Participants wished for emotional support postoperatively, and valued support networks including family and friends. However, they found expressing their deepest fears difficult. Participants felt they would value greater recognition by primary care of both physical and psychological sequelae of major pancreatic surgery, and the impact on their families. Conclusion Patients may feel themselves to be a ‘burden’ to both healthcare professionals and their own support networks following pancreaticoduodenectomy. Primary care is in a key position to proactively offer psychological support.
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12
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Blonk L, Wierdsma NJ, Jansma EP, Kazemier G, van der Peet DL, Straatman J. Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature. Dis Esophagus 2021; 34:6131382. [PMID: 33558869 DOI: 10.1093/dote/doab003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 11/18/2020] [Accepted: 12/14/2020] [Indexed: 12/26/2022]
Abstract
Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 μg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 μg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.
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Affiliation(s)
- L Blonk
- Amsterdam UMC, Cancer Center Amsterdam, Department of Surgery, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.,Amsterdam UMC, Department of Nutrition and Dietetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - N J Wierdsma
- Amsterdam UMC, Department of Nutrition and Dietetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - E P Jansma
- Medical Library, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - G Kazemier
- Amsterdam UMC, Cancer Center Amsterdam, Department of Surgery, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - D L van der Peet
- Amsterdam UMC, Cancer Center Amsterdam, Department of Surgery, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - J Straatman
- Amsterdam UMC, Cancer Center Amsterdam, Department of Surgery, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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13
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Kunovský L, Dítě P, Jabandžiev P, Eid M, Poredská K, Vaculová J, Sochorová D, Janeček P, Tesaříková P, Blaho M, Trna J, Hlavsa J, Kala Z. Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis. J Clin Med 2021; 10:jcm10245779. [PMID: 34945075 PMCID: PMC8708123 DOI: 10.3390/jcm10245779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/30/2021] [Accepted: 12/02/2021] [Indexed: 12/12/2022] Open
Abstract
Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.
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Affiliation(s)
- Lumír Kunovský
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Petr Dítě
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic;
| | - Petr Jabandžiev
- Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, 61300 Brno, Czech Republic;
- Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic
| | - Michal Eid
- Department of Hematology, Oncology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic;
| | - Karolina Poredská
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
| | - Jitka Vaculová
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
| | - Dana Sochorová
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Pavel Janeček
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Pavla Tesaříková
- Department of Internal Medicine, Hospital Boskovice, 68001 Boskovice, Czech Republic;
| | - Martin Blaho
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic;
| | - Jan Trna
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Internal Medicine, Hospital Boskovice, 68001 Boskovice, Czech Republic;
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute Brno, 60200 Brno, Czech Republic
- Correspondence: (J.T.); (J.H.)
| | - Jan Hlavsa
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
- Correspondence: (J.T.); (J.H.)
| | - Zdeněk Kala
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
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Surmelioglu A, Ozkardesler E, Tilki M, Yekrek M. Exocrine pancreatic insufficiency in long-term follow-up after curative gastric resection with D2 lymphadenectomy: A cross-sectional study. Pancreatology 2021; 21:975-982. [PMID: 33839030 DOI: 10.1016/j.pan.2021.03.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 01/08/2021] [Accepted: 03/26/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Exocrine pancreatic insufficiency (EPI) can be a problem following gastrectomies. This study aimed to reveal the EPI prevalence and its possible causes in gastric cancer patients that underwent subtotal or total gastrectomy, with completed oncological treatments, and with long-term disease-free survival success. Additionally, we also sought to determine whether there were any relations between EPI and blood biomarkers, weight change, malnutrition parameters, and quality of life after gastrectomy. METHODS A total of 69 gastric cancer patients whose oncological treatments had already been completed, with a minimum follow-up period of 16 months, were included in the study. Fecal samples were taken from all patients for the Fecal Elastase-1 Test, and patients were stratified into three groups based on the results: low (<100 μg/g), moderate (100-200 μg/g), and normal (>200 μg/g). These results were compared with patients' clinical characteristics, blood nutrition biomarkers, Maastricht indexes (MI), Bristol stool scale, and Gastrointestinal Quality of Life Index (GIQLI) scores. RESULTS FE-1 levels were low in 33 (47.8%) of the patients, moderate in 11 (15.9%), and normal in 25 (36.2%). The rate of patients receiving chemoradiotherapy (CRT) in the low FE-1 group was higher than the normal FE-1 and moderate FE-1 groups (P < 0.001 and P = 0.012, respectively). The serum total protein and lipase levels were lower in the low FE-1 group than in the normal FE-1 group (P = 0.023 and P < 0.001, respectively). When compared to the normal FE-1 group, the MI score of the low FE-1 group was higher (P = 0.018). The low FE-1 group had lower GIQLI gastrointestinal symptom scores than the normal FE-1 group (P = 0.046). CONCLUSIONS During long-term follow-up, EPI can be seen in more than half of patients with gastric cancer after curative gastrectomy. Radiotherapy as an adjunct to adjuvant treatment in the postoperative period is considered a serious risk factor for EPI development. EPI contributes to malnutrition development after gastrectomy and negatively affects the patients' quality of life, especially in terms of gastrointestinal symptoms.
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Affiliation(s)
- Ali Surmelioglu
- Department of Gastrointestinal Surgery, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
| | - Ersan Ozkardesler
- Department of General Surgery, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Metin Tilki
- Department of General Surgery, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Murat Yekrek
- Department of Medical Biochemistry, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: a prospective, cross-sectional, and comparative study. Surg Obes Relat Dis 2021; 17:1766-1772. [PMID: 34332909 DOI: 10.1016/j.soard.2021.06.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 05/23/2021] [Accepted: 06/29/2021] [Indexed: 11/23/2022]
Abstract
BACKGROUND Gastrointestinal anatomical changes after restrictive and malabsorptive bariatric surgery lead to important disturbances in the process of digestion and absorption of nutrients and could lead to exocrine pancreatic insufficiency (EPI). OBJECTIVE The aim of the present study was to evaluate and to compare pancreatic function and the dynamic of digestion and absorption of nutrients after restrictive and malabsorptive bariatric surgical procedures. SETTING University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. METHODS A prospective, observational, cross-sectional, comparative study of patients after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with duodenal switch (BPD/DS) was carried out. Patients with obesity who did not undergo surgery were included as control group. Pancreatic function and the dynamic of digestion and absorption of nutrients were evaluated by the 13C-mixed triglyceride (13C-MTG) breath test. Six-hour 13C-cumulative recovery rate (13C-CRR), 13C exhalation peak, and 1-hour maximal 13C-CRR were calculated. RESULTS One-hundred five patients were included (mean age, 49.8 yr; 84 women). Six-hour 13C-CRR was significantly reduced after BPD/DS (P < .001) but not after SG and RYGB. EPI was present in 75% of patients after BPD/DS, 8.3% of patients after RYGB, and 4.3% of patients after SG. Compared with the control group who did not undergo surgery, digestion and absorption of nutrients tended to occur earlier after SG, whereas it was delayed after RYGB and mainly after BPD/DS (P < .001). CONCLUSION Bariatric surgery significantly alters the dynamic of the digestive process. EPI is very common after BPD/DS, frequent after RYGB, and less frequent after SG. This information is clinically relevant since EPI is a treatable condition associated with symptoms, nutritional deficiencies, and complications.
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Pezzilli R. Diagnosis and Therapy of Exocrine Pancreatic Insufficiency after Gastric and Pancreatic Surgery. CLINICAL PANCREATOLOGY FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS 2021:651-661. [DOI: 10.1002/9781119570097.ch78] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sridhar RP, Yacob M, Chowdhury SD, Balasubramanian KA, Samarasam I. Exocrine Pancreatic Insufficiency Following Gastric Resectional Surgery-is Routine Pancreatic Enzyme Replacement Therapy Necessary? Indian J Surg Oncol 2021; 12:391-396. [PMID: 34295084 DOI: 10.1007/s13193-021-01315-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 03/21/2021] [Indexed: 10/21/2022] Open
Abstract
The data on exocrine pancreatic insufficiency (EPI) following gastric resectional surgery is variable, ranging from 26% to as high as 100%. This study aimed to document symptomatic EPI following gastric resectional surgery and to objectively document EPI, by fecal elastase (FE) testing. This was a cross-sectional study among patients undergoing gastric resection for adenocarcinoma of the stomach, at the Upper Gastrointestinal Surgical Unit at the Christian Medical College Hospital, Vellore, India. A detailed questionnaire was administered to the patients in the postoperative period, to evaluate clinical symptoms of EPI. Further, study participants were tested for FE pre- and postoperatively. Of the 60 patients in this study, the postoperative questionnaire administered to all patients during follow up. None showed symptoms suggestive of EPI. Pre- and post-operative FE testing were feasible in 27 of the 60 patients, which showed a 33% incidence of EPI. None of the patients had clinical symptoms of EPI, following gastric resectional surgery, on short-term follow-up. However, more than a third of the patients tested developed asymptomatic EPI after gastric resectional surgery, based on FE testing. This may be explained by the fact that in the early postoperative period, EPI following gastric resectional surgery perhaps has a mild, subclinical presentation. Therefore routine pancreatic supplementation after gastric resectional surgery may not be necessary. However, one needs to carefully look for worsening of symptoms of EPI on long-term follow-up, which may necessitate appropriate investigations followed by pancreatic enzyme replacement therapy.
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Affiliation(s)
- Rajeevan Philip Sridhar
- Department of General Surgery and Upper GI Surgery, Christian Medical College Hospital, Vellore, 632004 India
| | - Myla Yacob
- Department of General Surgery and Upper GI Surgery, Christian Medical College Hospital, Vellore, 632004 India
| | - Sudipta Dhar Chowdhury
- Department of Gastroenterology, Christian Medical College Hospital, Vellore, 632004 India
| | - Kunissery A Balasubramanian
- Division of Gastrointestinal Sciences, Wellcome Trust Research Laboratory, Christian Medical College Hospital, Vellore, 632004 India
| | - Inian Samarasam
- Department of General Surgery and Upper GI Surgery, Christian Medical College Hospital, Vellore, 632004 India
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Alterations in Small Intestine and Liver Morphology, Immunolocalization of Leptin, Ghrelin and Nesfatin-1 as Well as Immunoexpression of Tight Junction Proteins in Intestinal Mucosa after Gastrectomy in Rat Model. J Clin Med 2021; 10:jcm10020272. [PMID: 33450994 PMCID: PMC7828391 DOI: 10.3390/jcm10020272] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/01/2021] [Accepted: 01/11/2021] [Indexed: 02/07/2023] Open
Abstract
The stomach is responsible for the processing of nutrients as well as for the secretion of various hormones which are involved in many activities throughout the gastrointestinal tract. Experimental adult male Wistar rats (n = 6) underwent a modified gastrectomy, while control rats (n = 6) were sham-operated. After six weeks, changes in small intestine (including histomorphometrical parameters of the enteric nervous plexuses) and liver morphology, immunolocalization of leptin, ghrelin and nesfatin-1 as well as proteins forming adherens and tight junctions (E-cadherin, zonula occludens-1, occludin, marvelD3) in intestinal mucosa were evaluated. A number of effects on small intestine morphology, enteric nervous system ganglia, hormones and proteins expression were found, showing intestinal enteroplasticity and neuroplasticity associated with changes in gastrointestinal tract condition. The functional changes in intestinal mucosa and the enteric nervous system could be responsible for the altered intestinal barrier and hormonal responses following gastrectomy. The results suggest that more complicated regulatory mechanisms than that of compensatory mucosal hypertrophy alone are involved.
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Arutla M, Sarkar S, Unnisa M, Sarkar P, Raj MA, Mrudula MR, G D, Pasham S, Jakkampudi A, Prasanna A, Reddy DN, Talukdar R. Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice. Pancreatology 2021; 21:34-41. [PMID: 33303371 DOI: 10.1016/j.pan.2020.11.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 11/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND RCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status. OBJECTIVE In this study we evaluated factors responsible for persistence of malnutrition after PERT. METHODS In this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT. RESULTS 377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition. CONCLUSION Even though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.
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Affiliation(s)
- Madhulika Arutla
- Dept. of Clinical Nutrition, Asian Institute of Gastroenterology, Hyderabad, India
| | - Subhaleena Sarkar
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Misbah Unnisa
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Priyanka Sarkar
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Merlin Annie Raj
- Dept. of Clinical Nutrition, Asian Institute of Gastroenterology, Hyderabad, India
| | - M R Mrudula
- Dept. of Clinical Nutrition, Asian Institute of Gastroenterology, Hyderabad, India
| | - Deepika G
- Dept. of Biochemistry, Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Aparna Jakkampudi
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - Ambika Prasanna
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Dept. of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Rupjyoti Talukdar
- Wellcome DBT Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad, India; Dept. of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.
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The Effect of Bariatric Surgery on Exocrine Pancreatic Function. Obes Surg 2020; 31:580-587. [PMID: 32885359 DOI: 10.1007/s11695-020-04950-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/26/2020] [Accepted: 08/26/2020] [Indexed: 12/19/2022]
Abstract
INTRODUCTION After bariatric surgery (BS), patients might suffer from nutrient maldigestion, malabsorption, and vitamin deficiencies. In this study, our aim was to assess pancreatic functions after BS using fecal elastase-1 assay (FE-1). MATERIAL AND METHODS Sixty patients (21M) undergoing BS and 20 (6M) healthy controls were included into the study. Stool samples were collected 1 year after surgery. Ten patients from one anastomosis gastric bypass (OAGB) and single anastomosis duodenal switch (SADS) groups with the lowest value of FE-1 and GIQLI scores were given pancreatic enzyme replacement therapy (PERT). After PERT, FE-1, excess weight loss (EWL), BMI, GIQLI scores, and vitamin D levels were measured. RESULTS Vitamin D levels were detected as 19.04 (9-46.5) pg/ml, 15.1 (8.4-23.6) pg/ml, 17.8 (5-30) pg/ml, and 21.79 (11-40.3) pg/ml after sleeve gastrectomy (SG), OAGB, SADS, and control groups, respectively (p = 0.04). GIQLI scores in the first year were found to have increased in all patients (p = 0.02). FE-1 levels were found as 642.35 (566.3-711.4) μg/g, 378.52 (183.5-561.1) μg/g, 458.88 (252.5-593, 5) μg/g, and 518.2 (351.6-691) μg/g for the SG, OAGB, SADS, and control groups, respectively. There was a strong inverse correlation between EWL and FE-1 levels at the end of the first year (Spearman's rho = - 0.688, p = 0.003). After having performed PERT for patients with the lowest FE-1 levels, the levels increased to 683.39 (615.5-720) μg/g in the OAGB and 691.5 (643.1-720) μg/g in the SADS groups (p = 0.011). CONCLUSION FE-1 measurements demonstrated that many patients suffer from malabsorption after OAGB or SADS, whereas functions remain normal after SG. PERT corrects pancreatic functions without affecting weight loss and also contributes to the normal serum level of vitamin D.
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Takahashi R, Nunobe S, Sai N, Makuuchi R, Ida S, Kumagai K, Ohashi M, Sano T. Pancreatic atrophy after gastrectomy for gastric cancer. Surg Today 2020; 51:432-438. [PMID: 32885349 DOI: 10.1007/s00595-020-02131-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/27/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate the phenomenon of pancreatic atrophy after gastrectomy for gastric cancer, using computed tomography (CT) volumetry. METHODS The subjects of this retrospective study were 77 patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for pStage I gastric cancer in 2014. The relative pancreatic volume ratio was assessed preoperatively, and then 1 and 5 years postoperatively and the results were compared between surgical procedures RESULTS: A total of 14 patients underwent TG with Roux-en-Y (RY) reconstruction, 24 underwent DG with Billroth-I (BI) reconstruction, and 39 underwent DG with RY reconstruction. We observed that the pancreatic volume continued to decrease over the 5 years after DG or TG. Furthermore, the incidence of pancreatic atrophy 5 years postoperatively was significantly greater after TG than after DG. In patients who underwent DG, a greater incidence of pancreatic atrophy was observed after RY reconstruction than after BI reconstruction, 5 years postoperatively. CONCLUSION The pancreatic volume continued to decrease after DG and TG for gastric cancer 5 years after treatment. TG was associated with a significantly greater incidence of pancreatic atrophy than DG 5 years postoperatively, as was RY reconstruction vs. BI reconstruction after DG.
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Affiliation(s)
- Ryo Takahashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.,Department of General Surgery, Hekinan Municipal Hospital, Aichi, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Naohito Sai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Rie Makuuchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
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Pathanki AM, Attard JA, Bradley E, Powell-Brett S, Dasari BVM, Isaac JR, Roberts KJ, Chatzizacharias NA. Pancreatic exocrine insufficiency after pancreaticoduodenectomy: Current evidence and management. World J Gastrointest Pathophysiol 2020; 11:20-31. [PMID: 32318312 PMCID: PMC7156847 DOI: 10.4291/wjgp.v11.i2.20] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 03/13/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreaticoduodenectomy (PD) is the commonest procedure performed for pancreatic cancer. Pancreatic exocrine insufficiency (PEI) may be caused or exacerbated by surgery and remains underdiagnosed and undertreated. The aim of this review was to ascertain the incidence of PEI, its consequences and management in the setting of PD for indications other than chronic pancreatitis. A literature search of databases (MEDLINE, EMBASE, Cochrane and Scopus) was carried out with the MeSH terms "pancreatic exocrine insufficiency" and "Pancreaticoduodenectomy". Studies that analysed PEI and its complications in the setting of PD for malignant and benign disease were included. Studies reporting PEI in the setting of PD for chronic pancreatitis, conference abstracts and reviews were excluded. The incidence of PEI approached 100% following PD in some series. The pre-operative incidence varied depending on the characteristics of the patient cohort and it was higher (46%-93%) in series where pancreatic cancer was the predominant indication for surgery. Variability was also recorded with regards to the method used for the diagnosis and evaluation of pancreatic function and malabsorption. Pancreatic enzyme replacement therapy is the mainstay of the management. PEI is common and remains undertreated after PD. Future studies are required for the identification of a well-tolerated, reliable and reproducible diagnostic test in this setting.
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Affiliation(s)
- Adithya M Pathanki
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Joseph A Attard
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Elizabeth Bradley
- Department of Nutrition and Dietetics, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Sarah Powell-Brett
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Bobby V M Dasari
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - John R Isaac
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Keith J Roberts
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of HPB and Liver Transplantation, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
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Pezzilli R, Caccialanza R, Capurso G, Brunetti O, Milella M, Falconi M. Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer. Cancers (Basel) 2020; 12:275. [PMID: 31979186 PMCID: PMC7073203 DOI: 10.3390/cancers12020275] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/14/2020] [Accepted: 01/20/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.
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Affiliation(s)
- Raffaele Pezzilli
- Gastroenterology Unit, San Carlo Hospital, Via P. Petrone, 85100 Potenza, Italy
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy;
| | - Gabriele Capurso
- Clinical Research, Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy;
| | - Oronzo Brunetti
- Medical Oncology Unit, National Cancer Institute “Giovanni Paolo II”, Viale O. Flacco 65, 70124 Bari, Italy;
| | - Michele Milella
- Residency Program in Medical Oncology, University of Verona, Via S. Francesco 22, 37129 Verona, Italy;
- AOUI Verona, Sede Policlinico Universitario G.B. Rossi Borgo Roma, P.le L.A. Scuro 10, 37134 Verona, Italy
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy;
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Domínguez-Muñoz JE. Pancreatic Insufficiency, Exocrine. ENCYCLOPEDIA OF GASTROENTEROLOGY 2020:79-87. [DOI: 10.1016/b978-0-12-801238-3.65869-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Chaudhary A, Domínguez-ñoz JE, Layer P, Lerch MM. Pancreatic Exocrine Insufficiency as a Complication of Gastrointestinal Surgery and the Impact of Pancreatic Enzyme Replacement Therapy. Dig Dis 2020; 38:53-68. [PMID: 31422398 PMCID: PMC6979421 DOI: 10.1159/000501675] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 06/01/2019] [Indexed: 02/02/2023]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) is characterized by inadequate production, insufficient secretion, and/or inactivation of pancreatic enzymes, resulting in maldigestion. The aim of this review was to analyze the prevalence and pathophysiology of PEI resulting from gastrointestinal (GI) surgery and to examine the use of pancreatic enzyme replacement therapy (PERT) for effectively managing PEI. SUMMARY A targeted PubMed search was conducted for studies examining the prevalence and pathophysiology of PEI in patients following GI surgery and for studies assessing the effects of PERT in these patients. PEI is a common complication following GI surgery that can lead to nutritional deficiencies, which may contribute to morbidity and mortality in patients. Timely treatment of PEI with PERT can prevent malnutrition, increase quality of life, and possibly reduce the associated mortality. Treatment of PEI should aim not only to alleviate symptoms but also to achieve significant improvements in nutritional parameters. Dose optimization of PERT is required for effective management of PEI, in addition to regular assessment of nutritional status, appropriate patient education, and reassessment if symptoms return. Key Messages: Difficulties in detecting PEI following GI surgery can result in undiagnosed and untreated maldigestion, leading to metabolic complications and increased morbidity. Both are preventable by early administration and monitoring for optimal doses of PERT.
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Affiliation(s)
- Adarsh Chaudhary
- aDepartment of Gastrointestinal Surgery, Gastrointestinal Oncology and Bariatric Surgery, Medanta, The Medicity, Gurgaon, India,*Adarsh Chaudhary, Department of Gastrointestinal Surgery, Gastrointestinal Oncology and Bariatric Surgery, Medanta, The Medicity, Sector 38, Gurgaon 122018 (India), E-Mail
| | - J. Enrique Domínguez-ñoz
- bDepartment of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Peter Layer
- cDepartment of Medicine, Israelitic Hospital, University of Hamburg, Hamburg, Germany
| | - Markus M. Lerch
- dDepartment of Medicine, University Medicine Greifswald, Greifswald, Germany
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Igata Y, Okubo S, Ohkura Y, Ueno M, Udagawa H. Anasarca, steatorrhea, and hypoalbuminemia 18 years after total gastrectomy: a case report. Surg Case Rep 2019; 5:155. [PMID: 31650279 PMCID: PMC6813405 DOI: 10.1186/s40792-019-0721-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 09/27/2019] [Indexed: 11/12/2022] Open
Abstract
Background Pancreatic exocrine insufficiency (PEI) is known to occur after total gastrectomy. We experienced a case of PEI occurring 18 years after surgery, leading to a potentially fatal condition of capillary leak syndrome (CLS). Case presentation The case is a 58-year-old man on a healthy diet who underwent total gastrectomy 18 years before. He was admitted for a 3-month history of anasarca, steatorrhea, and hypoalbuminemia. An episode of fever occurred during workup, followed by pulmonary edema and shock. The patient was transferred to the intensive care unit and was started on fluid management with albumin infusion. A multidisciplinary team meeting was held, and a clinical diagnosis of PEI resulted in CLS was made and we started administration of oral pancrelipase to show clinical improvement. The patient was discharged, and he remained asymptomatic for 13 months. Conclusion In a post-gastrectomy patient with malnutrition, PEI should be suspected regardless of the period since surgery. When recognized, immediate replenishment of albumin and pancreatic enzymes should be initiated to prevent clinical deterioration.
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Affiliation(s)
- Yu Igata
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
| | - So Okubo
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yu Ohkura
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masaki Ueno
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Harushi Udagawa
- Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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Shobassy M, Husainat N, Tabash A, Patel K, El-Serag HB, Othman MO. Endoscopic Ultrasound Findings in Patients Diagnosed with Exocrine Pancreatic Insufficiency by Low Fecal Elastase-1. Gastroenterol Res Pract 2019; 2019:5290642. [PMID: 31485218 PMCID: PMC6710758 DOI: 10.1155/2019/5290642] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 05/09/2019] [Accepted: 07/02/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIMS Fecal elastase-1 (FE-1) as a screening test for exocrine pancreatic insufficiency (EPI) is gaining popularity in clinical practice. The role of imaging in patients with FE-1-related suspicion of EPI remains unclear. The aim of this study was to characterize endoscopic ultrasound (EUS) findings for patients with low FE-1. METHODS A retrospective cross-sectional study was performed in 40 patients who had low FE-1 and underwent EUS to evaluate the pancreas. We obtained data on demographic and lifestyle factors, EUS findings, and histopathology results. We compared these variables between patients with FE-1 < 100 mcg/g vs. 100-200 mcg/g. RESULTS Most patients (82.5%) established one or more new diagnoses from EUS. Diagnoses included: definitive chronic pancreatitis (n = 29, 72.5%), fatty pancreas (n = 9, 22.5%), and pancreatic solid mass or cyst (n = 9, 22.5%). Half (n = 4) of the solid or cystic lesions were neoplastic. All patients with a solid pancreatic mass also had concurrent chronic pancreatitis. There were no significant differences in EUS findings or demographic or lifestyle factors between groups with FE-1 < 100 mcg/g vs. 100-200 mcg/g. CONCLUSION Chronic pancreatitis is the most common EUS finding in patients with low FE-1 levels. EUS appears helpful in determining the cause of EPI in most patients with low FE-1 and may detect unsuspected pancreatic neoplasia.
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Affiliation(s)
- Mazen Shobassy
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Nedaa Husainat
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Abdalaziz Tabash
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Kalpesh Patel
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
- Section of Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Mohamed O. Othman
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
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Thogari K, Tewari M, Shukla SK, Mishra SP, Shukla HS. Assessment of Exocrine Function of Pancreas Following Pancreaticoduodenectomy. Indian J Surg Oncol 2019; 10:258-267. [PMID: 31168245 PMCID: PMC6527627 DOI: 10.1007/s13193-019-00901-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 01/07/2019] [Accepted: 03/03/2019] [Indexed: 12/31/2022] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is a common long-term complication after pancreaticoduodenectomy (PD) and is observed in 23-80% of patients. As the postoperative mortality after PD has substantially decreased, it warrants more attention on the diagnosis and treatment of functional long-term consequences after PD. These include PEI and endocrine insufficiency that can result in significant nutritional impairment and often adversely impacts quality of life (QOL) of the patient. A PubMed search was performed for articles using key words "pancreatic exocrine insufficiency"; "pancreaticoduodenectomy"; "quality of life after pancreaticoduodenectomy"; "stool elastase"; "direct, indirect tests for pancreatic exocrine insufficiency"; "pancreatic enzyme replacement therapy." Relevant studies were shortlisted and analyzed. This review summarizes relevant studies addressing PEI following PD. We also discuss functional changes after PD, risk factors and predictive factors for postoperative PEI, clinical symptoms, direct and indirect tests for estimation of PEI, pancreatic enzyme replacement therapy (PERT), and QOL after pancreatic resection for malignancy. It was found that significant PEI occurs in most patients following PD. Fecal elastase 1 is an easy indirect test and should be performed routinely in both symptomatic and asymptomatic patients after PD. PERT should be considered in every patient after PD with the aim to improve the QOL and perhaps even their long time survival.
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Affiliation(s)
- Kiran Thogari
- Division of Hepatopancreatobiliary and GastroIntestinal Oncology, Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India
| | - Mallika Tewari
- Division of Hepatopancreatobiliary and GastroIntestinal Oncology, Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India
| | - S. K. Shukla
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India
| | - S. P. Mishra
- Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India
| | - H. S. Shukla
- Division of Hepatopancreatobiliary and GastroIntestinal Oncology, Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India
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Layer P, Kashirskaya N, Gubergrits N. Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency. World J Gastroenterol 2019; 25:2430-2441. [PMID: 31171887 PMCID: PMC6543241 DOI: 10.3748/wjg.v25.i20.2430] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 04/02/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.
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Affiliation(s)
- Peter Layer
- Department of Internal Medicine, Israelitic Hospital, Hamburg 22297, Germany
| | - Nataliya Kashirskaya
- Department of Genetic Epidemiology (Cystic Fibrosis group), Federal State Budgetary Institution “Research Centre for Medical Genetics”, Moscow 115522, Russia
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman 83001, Ukraine
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Khatkov IE, Maev IV, Abdulkhakov SR, Alekseenko SA, Alikhanov RB, Bakulin IG, Bakulina NV, Baranovskiy AY, Beloborodova EV, Belousova EA, Voskanyan SE, Vinokurova LV, Grinevich VB, Darvin VV, Dubtsova EA, Dyuzheva TG, Egorov VI, Efanov MG, Izrailov RE, Korobka VL, Kotiv BN, Kokhanenko NY, Kucheryavyy YA, Livzan MA, Lyadov VK, Nikolskaya KA, Osipenko MF, Pasechnikov VD, Plotnikova EY, Sablin OA, Simanenkov VI, Tsvirkun VV, Tsukanov VV, Shabunin AV, Bordin DS. Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment. TERAPEVT ARKH 2018; 90:13-26. [PMID: 30701935 DOI: 10.26442/terarkh201890813-26] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo- and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons.
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Affiliation(s)
- I E Khatkov
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - I V Maev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - S R Abdulkhakov
- Kazan State Medical University, Ministry of Health of Russia, Kazan, Russia
| | - S A Alekseenko
- The Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk, Russia
| | - R B Alikhanov
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - I G Bakulin
- I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint-Petersburg, Russia
| | - N V Bakulina
- I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint-Petersburg, Russia
| | | | - E V Beloborodova
- Siberian State Medical University, Ministry of Health of Russia, Tomsk, Russia
| | - E A Belousova
- M.F. Vladimirskiy Moscow Regional Research and Clinical Institute, Moscow, Russia
| | - S E Voskanyan
- A.I. Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russia
| | - L V Vinokurova
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - V B Grinevich
- S.M. Kirov Military Medical Academy, Ministry of Defence of Russia, Saint-Petersburg, Russia
| | - V V Darvin
- Medical Institute of Surgut State University, Surgut, Russia
| | - E A Dubtsova
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - T G Dyuzheva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia
| | - V I Egorov
- City Clinical Hospital named after the Bakhrushin Brothers, Moscow, Russia
| | - M G Efanov
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - R E Izrailov
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - V L Korobka
- Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don, Russia
| | - B N Kotiv
- S.M. Kirov Military Medical Academy, Ministry of Defence of Russia, Saint-Petersburg, Russia
| | - N Yu Kokhanenko
- Saint-Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint-Petersburg, Russia
| | - Yu A Kucheryavyy
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - M A Livzan
- Omsk State Medical University, Ministry of Health of Russia, Omsk, Russia
| | - V K Lyadov
- Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia, Moscow, Russia
| | - K A Nikolskaya
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - M F Osipenko
- Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk, Russia
| | - V D Pasechnikov
- Stavropol State Medical University, Ministry of Health of Russia, Stavropol, Russia
| | - E Yu Plotnikova
- Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo, Russia
| | - O A Sablin
- A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine, Russian Ministry for Emergency Situations, Saint-Petersburg, Russia
| | - V I Simanenkov
- I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint-Petersburg, Russia
| | - V V Tsvirkun
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - V V Tsukanov
- Krasnoyarsk Scientific Center of Siberian Branch in Russian Academy of Sciences, Krasnoyarsk, Russia
| | - A V Shabunin
- S.P. Botkin City Hospital, Moscow Healthcare Department, Moscow, Russia
| | - D S Bordin
- A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
- Tver State Medical University, Ministry of Health of Russia, Tver, Russia
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Domínguez-Muñoz JE, Nieto-Garcia L, López-Díaz J, Lariño-Noia J, Abdulkader I, Iglesias-Garcia J. Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis. BMC Cancer 2018; 18:534. [PMID: 29728096 PMCID: PMC5935964 DOI: 10.1186/s12885-018-4439-x] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 04/26/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer. METHODS A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan-Meier and Cox regression; groups were compared using the log-rank test. RESULTS Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28-100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19-9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0-211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4-114.6 days) (HR 2.117, 95% CI 1.493-3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55-4.11; P < 0.001). CONCLUSIONS In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.
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Affiliation(s)
- Juan Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Laura Nieto-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Javier López-Díaz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Jose Lariño-Noia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Ihab Abdulkader
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Department of Pathology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
- Health Research Institute (IDIS), University Hospital of Santiago de Compostela, C/ Choupana s/n, 15706 Santiago de Compostela, Spain
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Antonini F, Crippa S, Falconi M, Macarri G, Pezzilli R. Pancreatic enzyme replacement therapy after gastric resection: An update. Dig Liver Dis 2018; 50:1-5. [PMID: 29170072 DOI: 10.1016/j.dld.2017.10.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2017] [Revised: 10/07/2017] [Accepted: 10/24/2017] [Indexed: 02/07/2023]
Abstract
Exocrine pancreatic insufficiency (EPI) is one of the possible mechanisms of fat maldigestion following gastric surgery, together with reduced food intake, loss of gastric reservoir, small bowel bacterial overgrowth and rapid small bowel transit. Oral pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment for EPI. The efficacy and safety of pancreatic enzyme substitution in patients following gastric resection remains unclear. This review article summarizes relevant studies addressing PERT after gastric resection.
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Affiliation(s)
- Filippo Antonini
- Department of Gastroenterology, A. Murri Hospital, Polytechnic University of Marche, Fermo, Italy.
| | - Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Giampiero Macarri
- Department of Gastroenterology, A. Murri Hospital, Polytechnic University of Marche, Fermo, Italy
| | - Raffaele Pezzilli
- Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy
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Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23:7059-7076. [PMID: 29093615 PMCID: PMC5656454 DOI: 10.3748/wjg.v23.i39.7059] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 05/27/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.
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Affiliation(s)
- Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Mark E Haupt
- Medical Affairs, AbbVie Inc., North Chicago, IL 60064, United States
| | - David E Geller
- Cystic Fibrosis Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
| | - Jerry A Hall
- CREON® Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
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Domínguez-Muñoz JE, D Hardt P, Lerch MM, Löhr MJ. Potential for Screening for Pancreatic Exocrine Insufficiency Using the Fecal Elastase-1 Test. Dig Dis Sci 2017; 62:1119-1130. [PMID: 28315028 DOI: 10.1007/s10620-017-4524-z] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 02/28/2017] [Indexed: 01/14/2023]
Abstract
The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.
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Affiliation(s)
- J Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain.
| | - Philip D Hardt
- Medical Department V, University Hospital, Giessen, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Matthias J Löhr
- Department of Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Sabater L, Ausania F, Bakker OJ, Boadas J, Domínguez-Muñoz JE, Falconi M, Fernández-Cruz L, Frulloni L, González-Sánchez V, Lariño-Noia J, Lindkvist B, Lluís F, Morera-Ocón F, Martín-Pérez E, Marra-López C, Moya-Herraiz Á, Neoptolemos JP, Pascual I, Pérez-Aisa Á, Pezzilli R, Ramia JM, Sánchez B, Molero X, Ruiz-Montesinos I, Vaquero EC, de-Madaria E. Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery. Ann Surg 2016; 264:949-958. [PMID: 27045859 DOI: 10.1097/sla.0000000000001732] [Citation(s) in RCA: 86] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. BACKGROUND EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. METHODS Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. RESULTS These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. CONCLUSIONS EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.
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Affiliation(s)
- Luis Sabater
- *Department of Surgery, Hospital Clinico, University of Valencia, Valencia, Spain †Department of Surgery, Complejo Hospitalario Universitario de Vigo, Vigo, Spain ‡Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands §Department of Gastroenterology, Consorci Sanitari de Terrassa, Terrassa, Spain ¶Department of Gastroenterology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain ||Department of Surgery, Università Vita e Salute, Ospedale San Raffaele IRCCS, Milano, Italy **Department of Surgery, Institut de Malalties Digestives I Metabòliques, Hospital Clínic, IDIBAPS, Barcelona, Spain ††Department of Medicine, Pancreas Center, University of Verona, Verona, Italy ‡‡Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. §§Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ¶¶Department of Surgery, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. ||||Department of Surgery, Hospital Universitario de La Princesa, Madrid, Spain ***Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona, Spain †††Unidad de Cirugía Hepato-bilio-pancreática y Trasplante, Hospital Universitari i Politecnic. La Fe, Valencia, Spain ‡‡‡NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK §§§Department of Gastroenterology, Hospital Clinico, University of Valencia, Valencia, Spain ¶¶¶Unit of Digestive Disease, Agencia Sanitaria Costa del Sol, Marbella, Málaga ||||||Department Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy ****Department of Surgery, Hospital Universitario de Guadalajara, Guadalajara, Spain ††††Department of HPB Surgery and Liver Transplantation, Hospital Carlos Haya, Malaga, Spain ‡‡‡‡Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain §§§§Department of Digestive Surgery- Division of HBP Surgery, Hospital Universitario Donostia, San Sebastián, Spain ¶¶¶¶Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, IDIBAPS, CiberEHD, Barcelona, Spain ||||||||Department of Gastroenterology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain
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Phillips ME. Pancreatic exocrine insufficiency following pancreatic resection. Pancreatology 2015; 15:449-455. [PMID: 26145836 DOI: 10.1016/j.pan.2015.06.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 05/06/2015] [Accepted: 06/10/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Untreated pancreatic exocrine dysfunction is associated with poor quality of life and reduced survival, but is difficult to diagnose following pancreatic resection. Many factors including the extent of the surgery, the health of the residual pancreas and the type of reconstruction must be considered. Patients remain undertreated, and consequently there is much debate to whether or not pancreatic enzyme replacement therapy should be routinely prescribed following pancreatic resection. METHODS A review of the literature was undertaken to establish the incidence of PEI and factors identifying treatment. RESULTS Forty two to forty five percent of patients undergoing pancreatico-duodenectomy (PD) experience pancreatic exocrine insufficiency pre-operatively, whilst the post-operative incidence is 56-98% in PD, and 12-80% following distal and central pancreatectomy. CONCLUSIONS Routine use of pancreatic enzyme replacement should be considered at a starting dose of 50 to 75,000 units lipase with meals and 25,000 to 50,000 units with snacks in this patient group. Patients who have had a central or distal pancreatectomy should be individually assessed for pancreatic exocrine insufficiency in the post operative period, with those undergoing extensive resection most likely to experience insufficiency. Patients who fail to respond to pancreatic enzyme replacement therapy should be referred to a specialist dietitian, be advised on dose adjustment, and undergo investigation to exclude other gastro-intestinal pathology, including small bowel bacterial overgrowth and bile acid malabsorption.
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Affiliation(s)
- Mary E Phillips
- Royal Surrey County Hospital, Regional HPB Unit, Egerton Road, Guildford GU2 7XX, United Kingdom.
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Pezzilli R, Andriulli A, Bassi C, Balzano G, Cantore M, Fave GD, Falconi M, Group LFTEPIC(EPI. Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas. World J Gastroenterol 2013; 19:7930-7946. [PMID: 24307787 PMCID: PMC3848141 DOI: 10.3748/wjg.v19.i44.7930] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 08/18/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013.
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Lindkvist B. Diagnosis and treatment of pancreatic exocrine insufficiency. World J Gastroenterol 2013; 19:7258-7266. [PMID: 24259956 PMCID: PMC3831207 DOI: 10.3748/wjg.v19.i42.7258] [Citation(s) in RCA: 142] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 08/22/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis. Normal digestion requires adequate stimulation of pancreatic secretion, sufficient production of digestive enzymes by pancreatic acinar cells, a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food. Failure in any of these steps may result in pancreatic exocrine insufficiency, which leads to steatorrhea, weight loss and malnutrition-related complications, such as osteoporosis. Methods evaluating digestion, such as fecal fat quantification and the 13C-mixed triglycerides test, are the most accurate tests for pancreatic exocrine insufficiency, but the probability of the diagnosis can also be estimated based on symptoms, signs of malnutrition in blood tests, fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging. Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption, dietary consultation, enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment. Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicrospheres during meals. The dose should be in proportion to the fat content of the meal, usually 40-50000 lipase units per main meal, and half the dose is required for a snack. In cases that do not respond to initial treatment, the doses can be doubled, and proton inhibitors can be added to the treatment. This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency.
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Seiler CM, Izbicki J, Varga-Szabó L, Czakó L, Fiók J, Sperti C, Lerch MM, Pezzilli R, Vasileva G, Pap A, Varga M, Friess H. Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension. Aliment Pharmacol Ther 2013; 37:691-702. [PMID: 23383603 PMCID: PMC3601428 DOI: 10.1111/apt.12236] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 12/03/2012] [Accepted: 01/17/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. AIM To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection. METHODS A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova). RESULTS All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE. CONCLUSIONS This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).
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Affiliation(s)
- C M Seiler
- Department of General, Visceral and Vascular Surgery, Josephs-Hospital Warendorf, Warendorf, Germany.
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Sikkens ECM, Cahen DL, Koch AD, Braat H, Poley JW, Kuipers EJ, Bruno MJ. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis. Pancreatology 2013; 13:238-42. [PMID: 23719594 DOI: 10.1016/j.pan.2013.02.008] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 02/11/2013] [Accepted: 02/14/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES In chronic pancreatitis, malabsorption of fat is common due to loss of exocrine function. Consequently, these patients are at risk to acquire deficiencies of the fat-soluble vitamins, which may result in a decreased bone mineral density (BMD) and the development of osteopenia and osteoporosis. METHODS We prospectively enrolled all patients diagnosed with chronic pancreatitis, who visited our outpatient clinic between March and November 2011. Data were collected regarding demographic characteristics, symptoms, and pancreatic function. Serum concentrations of vitamins A, E, K, and D were determined, and BMD was assessed by means of bone densitometry. Results were analyzed according to pancreatic function status and enzyme use, and compared to reference data, when available. RESULTS Forty patients were included (43% female; mean age of 52). Alcohol abuse was the major cause of pancreatitis (50%). Twenty-eight patients were exocrine insufficient (70%), of whom 19 used pancreatic enzymes. Vitamin A, D, E, and K deficiencies were present in 3, 53, 10, and 63% of patients, respectively. Osteopenia and osteoporosis were observed in 45% and 10% of patients. A decreased BMD was more frequently observed than expected, based on reference data, even in exocrine sufficient patients. CONCLUSIONS Deficiencies of fat-soluble vitamins and a decreased BMD are frequently present in chronic pancreatitis, even in exocrine sufficient patients. Consequently, all patients with chronic pancreatitis should be routinely screened for fat-soluble vitamin deficiencies and a decreased BMD.
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Affiliation(s)
- Edmée C M Sikkens
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
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Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. CORE EVIDENCE 2012; 7:77-91. [PMID: 22936895 PMCID: PMC3426252 DOI: 10.2147/ce.s26705] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.
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Affiliation(s)
- Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Haruki Oshida
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Toshitaka Muneyuki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
| | - Masafumi Kakei
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
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Sikkens ECM, Cahen DL, van Eijck C, Kuipers EJ, Bruno MJ. The daily practice of pancreatic enzyme replacement therapy after pancreatic surgery: a northern European survey: enzyme replacement after surgery. J Gastrointest Surg 2012; 16:1487-92. [PMID: 22711213 PMCID: PMC3399077 DOI: 10.1007/s11605-012-1927-1] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 05/30/2012] [Indexed: 02/06/2023]
Abstract
INTRODUCTION After pancreatic surgery, up to 80 % of patients will develop exocrine insufficiency. For enzyme supplementation to be effective, prescribing an adequate dose of pancreatic enzymes is mandatory but challenging because the required dose varies. Data on the practice of enzyme replacement therapy after surgery are lacking, and therefore, we conducted this analysis. METHODS An anonymous survey was distributed to members of the Dutch and German patient associations for pancreatic disorders. The target population consisted of patients with chronic pancreatitis or pancreatic cancer who had undergone pancreatic surgery and were using enzymes to treat exocrine insufficiency. Results were compared to a similar group of non-operated patients. RESULTS Ninety-one cases were analyzed (84 % underwent a resection procedure). The median daily enzyme dose was 6, and 25 % took three or less capsules. Despite treatment, 68 % of patients reported steatorrhea-related symptoms, 48 % adhered to a non-indicated dietary fat restriction, and only 33 % had visited a dietician. The outcome was equally poor for the 91 non-operated patients. CONCLUSION Most patients suffering from exocrine insufficiency after pancreatic surgery are undertreated. To improve efficacy, physicians should be more focused on treating exocrine insufficiency and educate patients to adjust the dose according to symptoms and their diet.
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Affiliation(s)
- Edmée C. M. Sikkens
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, PO Box 2040, 3015 CE Rotterdam, The Netherlands
| | - Djuna L. Cahen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, PO Box 2040, 3015 CE Rotterdam, The Netherlands
| | - Casper van Eijck
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Ernst J. Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, PO Box 2040, 3015 CE Rotterdam, The Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, PO Box 2040, 3015 CE Rotterdam, The Netherlands
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Ockenga J. Importance of nutritional management in diseases with exocrine pancreatic insufficiency. HPB (Oxford) 2009; 11 Suppl 3:11-5. [PMID: 20495627 PMCID: PMC2798168 DOI: 10.1111/j.1477-2574.2009.00134.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2009] [Accepted: 09/21/2009] [Indexed: 12/12/2022]
Abstract
Exocrine pancreatic insufficiency (EPI) resulting from conditions such as chronic pancreatitis (CP), acute pancreatitis (AP) and upper gastrointestinal (GI) surgery increases risk for malnutrition and metabolic problems. Poor nutrition is associated with more complications and higher mortality. Therefore, effective nutritional management should be a high priority in these patients. In CP, poor nutrition has been shown to significantly affect quality of life and functional status. Clinical study data show that dietary counselling combined with pancreatic enzyme replacement therapy is effective in improving nutritional status and is therefore recommended in these patients. In AP, early enteral nutrition reduces complications and mortality. However, EPI persists in many cases after the resolution of AP; these patients remain at increased risk for malnutrition and require further nutritional support. In patients undergoing surgery, preoperative weight loss is a risk factor for postoperative morbidity and mortality; outcomes can be improved considerably by preoperative screening to identify high-risk patients and by providing appropriate perioperative nutritional support. Pre- and perioperative enteral nutrition are cost-effective interventions that can improve outcomes in patients undergoing GI surgery. In all of these patient populations, nutritional management, including risk assessment and individualized nutritional support, is a key component of an effective multimodal therapeutic approach.
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Affiliation(s)
- Johann Ockenga
- Department of Gastroenterology, Hepatology, Endocrinology and Nutrition, Klinikum Bremen Mitte Bremen, Germany
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