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Nickerson JL, Cyr C, Arseneau RJ, Lee SN, Condon-Oldreive S, Zogopoulos G, Roberts K, Kim CA, Ng SSW, Haider M, Villalba E, Stephenson L, Tsang E, Johnston B, Gala-Lopez B, Cooper V, Hannon B, Gangloff A, Gill S, Servidio-Italiano F, Ramjeesingh R. Canadian National Pancreas Conference 2023: A Review of Multidisciplinary Engagement in Pancreatic Cancer Care. Curr Oncol 2024; 31:6191-6204. [PMID: 39451765 PMCID: PMC11506161 DOI: 10.3390/curroncol31100461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 10/02/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024] Open
Abstract
Pancreatic cancer is a complex malignancy associated with poor prognosis and high symptom burden. Optimal patient care relies on the integration of various sectors in the healthcare field as well as innovation through research. The Canadian National Pancreas Conference (NPC) was co-organized and hosted by Craig's Cause Pancreatic Cancer Society and The Royal College of Physicians and Surgeons in November 2023 in Montreal, Canada. The conference sought to bridge the gap between Canadian healthcare providers and researchers who share the common goal of improving the prognosis, quality of life, and survival for patients with pancreatic cancer. The accredited event featured discussion topics including diagnosis and screening, value-based and palliative care, pancreatic enzyme replacement therapy, cancer-reducing treatment, and an overview of the current management landscape. The present article reviews the NPC sessions and discusses the presented content with respect to the current literature.
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Affiliation(s)
- Jessica L. Nickerson
- Allumiqs Corporation, Halifax, NS B3H 0A8, Canada;
- Craig’s Cause Pancreatic Cancer Society, Halifax, NS B3K 5M3, Canada; (C.C.); (R.J.A.); (S.N.L.); (S.C.-O.)
| | - Chloe Cyr
- Craig’s Cause Pancreatic Cancer Society, Halifax, NS B3K 5M3, Canada; (C.C.); (R.J.A.); (S.N.L.); (S.C.-O.)
- Department of Kinesiology, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Beatrice Hunter Cancer Research Institute, Halifax, NS B3H 0A2, Canada
| | - Riley J. Arseneau
- Craig’s Cause Pancreatic Cancer Society, Halifax, NS B3K 5M3, Canada; (C.C.); (R.J.A.); (S.N.L.); (S.C.-O.)
- Beatrice Hunter Cancer Research Institute, Halifax, NS B3H 0A2, Canada
- Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - Stacey N. Lee
- Craig’s Cause Pancreatic Cancer Society, Halifax, NS B3K 5M3, Canada; (C.C.); (R.J.A.); (S.N.L.); (S.C.-O.)
- Beatrice Hunter Cancer Research Institute, Halifax, NS B3H 0A2, Canada
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Stefanie Condon-Oldreive
- Craig’s Cause Pancreatic Cancer Society, Halifax, NS B3K 5M3, Canada; (C.C.); (R.J.A.); (S.N.L.); (S.C.-O.)
| | | | - Keith Roberts
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK;
| | - Christina A. Kim
- Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada;
| | - Sylvia S. W. Ng
- Section of Medical Oncology and Hematology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada;
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
| | - Masoom Haider
- Joint Department of Medical Imaging, Sinai Health System, Toronto, ON M5G 1X6, Canada;
| | - Eva Villalba
- Quebec Cancer Coalition, Saint-Lambert, QC J4P 2J7, Canada;
| | | | - Erica Tsang
- Department of Medicine, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada;
| | - Brent Johnston
- Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Boris Gala-Lopez
- Department of Surgery, Dalhousie University, Halifax, NS B3H 2Y9, Canada;
| | - Valerie Cooper
- South East Local Health Integration Network, Belleville, ON K8N 5K3, Canada;
| | - Breffni Hannon
- Department of Supportive Care, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada;
| | - Anne Gangloff
- Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada;
| | | | | | - Ravi Ramjeesingh
- Division of Medical Oncology, Dalhousie University, Halifax, NS B3H 2Y9, Canada
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Chu P, Mioc J, O’Donovan P, Henry O. Clinical Efficacy and Safety of Treatments for Exocrine Pancreatic Insufficiency: A Systematic Literature Review. Digestion 2024; 106:45-61. [PMID: 39299226 PMCID: PMC11825132 DOI: 10.1159/000541326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 08/08/2024] [Indexed: 09/22/2024]
Abstract
INTRODUCTION Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI. METHODS A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. RESULTS We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. CONCLUSIONS This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes. INTRODUCTION Exocrine pancreatic insufficiency (EPI) is caused by multiple clinical conditions such as cystic fibrosis and chronic pancreatitis (CP). Standard management of EPI includes pancreatic enzyme replacement therapy (PERT) along with consultation with a dietitian. While PERTs have been on the market for several decades, newer publications on their clinical efficacy and safety raised the need for a comprehensive review of the literature. We aimed to identify the available evidence on the clinical efficacy and safety of treatments for EPI to understand the current treatment landscape and unmet need in patients with EPI. METHODS A systematic literature review (SLR) was conducted in Embase, Medline, and Evidence-Based Medicine databases from 2010 to 2022; conference proceedings from 2020 to 2022 were also searched. Articles were screened independently by two reviewers at abstract and full-text stage against predefined eligibility criteria. RESULTS We identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n = 12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. Ten studies reported coefficient of nitrogen absorption (CNA). Where reported, pancrelipase (including Creon®) increased CNA levels in EPI patients compared to placebo. Only one study compared PERT brands head-to-head: no significant differences were reported in the CNA-72 h values (Creon® 82.0% [SE: 1.2] vs. Zenpep® 80.9% [SE: 1.2]). Loss of body weight and low body mass index (BMI) are important features of EPI. Overall, treatment with PERT increased BMI and body weight, or limited their decline, with increases ranging from 0.1 to 6.1 kg. Based on the 18 studies that reported safety outcomes, PERT was considered safe and well tolerated. CONCLUSIONS This SLR confirmed that PERT is an effective and tolerable treatment option for patients with EPI. However, nutritional parameters and health-related quality of life data were sparsely reported, and future clinical trials should look to incorporate these data given their importance in clinical practice and patient outcomes.
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Affiliation(s)
- Paula Chu
- Organon International GmbH, Lucerne, Switzerland
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Hidaka Y, Tanoue S, Ayukawa T, Takumi K, Noguchi H, Higashi M, Idichi T, Kawasaki Y, Kurahara H, Mataki Y, Ohtsuka T, Koriyama C. Impact of pancreatic ductal occlusion on postoperative outcomes in pancreatic head cancer patients undergoing neoadjuvant therapy. J Gastroenterol 2024; 59:858-868. [PMID: 38900299 PMCID: PMC11338973 DOI: 10.1007/s00535-024-02125-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT). METHODS We analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD. RESULTS The occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct-parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08-4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10-3.72, p = 0.023), in multivariate analysis. CONCLUSIONS Pancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.
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Affiliation(s)
- Yoshifumi Hidaka
- Department of Epidemiology and Preventive Medicine, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Shiroh Tanoue
- Department of Epidemiology and Preventive Medicine, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
| | - Takuro Ayukawa
- Department of Radiology, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Koji Takumi
- Department of Radiology, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Hirotsugu Noguchi
- Department of Pathology, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Michiyo Higashi
- Department of Pathology, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Tetsuya Idichi
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yota Kawasaki
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Hiroshi Kurahara
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yuko Mataki
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Chihaya Koriyama
- Department of Epidemiology and Preventive Medicine, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Kjeseth T, Hagen RE, Edwin B, Lai X, Røsok BI, Tholfsen T, Sahakyan MA, Kleive D. Impact of pancreas transection site on incidence of pancreatic fistula after distal pancreatectomy: a propensity score matched study. HPB (Oxford) 2024; 26:1164-1171. [PMID: 38839509 DOI: 10.1016/j.hpb.2024.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 04/24/2024] [Accepted: 05/20/2024] [Indexed: 06/07/2024]
Abstract
BACKGROUND Distal pancreatectomy (DP) is performed for lesions in the body and tail of the pancreas. The morbidity profile is considerable, mainly due to clinically relevant postoperative pancreatic fistula (CR-POPF). This study aims to investigate potential differences in CR-POPF related to transection site. METHODS An observational cohort study from a prospectively maintained database was performed. Subtotal distal pancreatectomy (SDP) was defined as transection over the superior mesenteric vein, and DP was defined as transection lateral to this point. Propensity score matching (PSM) in 1:1 fashion was applied based on demographical and perioperative variables. RESULTS Six hundred and six patients were included in the analysis (1997-2020). Four hundred twenty (69.3%) underwent DP, while 186 (30.7%) underwent SDP. The rate of CR-POPF was 19.3% after DP and 20.4% after SDP (p = 0.74). SDP was associated with older age (63.1 vs 60.1 years, p = 0.016), higher occurrence of ductal adenocarcinoma (37.1 vs 17.6%, p = 0.001) and more frequent use of neoadjuvant chemotherapy (3.8 vs 0.7%, p = 0.012). After PSM, 155 patients were left in each group. The difference in CR-POPF between DP and SDP remained statistically non-significant (20.6 vs 18.7%, p = 0.67). CONCLUSION This study found no difference in CR-POPF related to transection site during distal pancreatectomy.
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Affiliation(s)
- Trond Kjeseth
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
| | - Rolf E Hagen
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Bjørn Edwin
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway; The Intervention Centre, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
| | - Xiaoran Lai
- Oslo Centre for Biostatistics and Epidemiology, University of Oslo, Oslo, Norway
| | - Bård I Røsok
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Tore Tholfsen
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Mushegh A Sahakyan
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway; The Intervention Centre, Oslo University Hospital, Oslo, Norway; Department of Surgery N1, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia
| | - Dyre Kleive
- Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Morris-Stiff G. Exocrine pancreatic insufficiency and fat malabsorption related to pancreatectomy and other gastrointestinal surgery: A narrative review. Nutr Clin Pract 2024; 39 Suppl 1:S35-S45. [PMID: 38429966 DOI: 10.1002/ncp.11123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/08/2024] [Accepted: 01/08/2024] [Indexed: 03/03/2024] Open
Abstract
Surgical resection is the mainstay of treatment for patients with tumors of the pancreas. There are a number of well-recognized complications that account for the significant morbidity associated with the operation, including exocrine pancreatic insufficiency (EPI). Patients with pancreatic cancer commonly have evidence of EPI prior to surgery, and this is exacerbated by an operation, the extent of the insult being dependent on the indication for surgery and the operation performed. There are accumulating data to demonstrate that treatment of EPI with pancreatic enzyme replacement (PERT) enhances clinical outcomes after surgery by reducing critical complications; this in turn may enhance oncological outcomes. Data would indicate that quality of life (QoL) is also improved after surgery when enzymes are prescribed. To date, many surgeons and clinicians have not appreciated the need for PERT or the benefits it may bring to their patients; therefore, education of clinicians remains a significant opportunity. In turn, patient education about consumption of the correct dose of enzymes at the appropriate time is key to an optimal outcome. In addition, because of the complex nature of the regulation of pancreatic exocrine function, there is evidence to support the presence of EPI following operations performed on other gastrointestinal (GI) organs, including the esophagus, stomach, and small intestine. The aim of this review is to document the existing published evidence in relation to EPI and its treatment with PERT following GI surgery.
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Barkin JA, Delk TB, Powell VJ. Symptoms, burden, and unmet needs of patients living with exocrine pancreatic insufficiency: a narrative review of the patient experience. BMC Gastroenterol 2024; 24:101. [PMID: 38481137 PMCID: PMC10938721 DOI: 10.1186/s12876-024-03188-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 02/26/2024] [Indexed: 03/17/2024] Open
Abstract
Exocrine pancreatic insufficiency (EPI) stems from a deficiency of functional pancreatic enzymes with consequent maldigestion and malnutrition. EPI shares clinical symptoms and manifestations with other disorders and is a considerable burden to individuals affected. In this narrative review, we analyzed the literature to identify relevant publications on living with EPI with the scope of individuating evidence gaps, including those related to symptoms, health-related quality of life (HRQoL), emotional functioning, disease burden, presence of comorbidities, and the use of pancreatic enzyme replacement therapy (PERT). Abdominal pain emerged as one of the most prominent symptoms. HRQoL was affected in EPI, but no articles examined emotional functioning. Comorbidities reported involved other pancreatic disorders, diabetes, gastrointestinal disorders, sarcopenia and osteopenia, cardiovascular disorders, bacterial overgrowth, and nutritional deficiencies. PERT was found to be effective in improving EPI symptoms and was well tolerated by most individuals. Our review revealed a dearth of literature evidence on patients' experience with EPI, such as emotional functioning and disease burden. We also revealed that studies on long-term effects of PERT are missing, as are studies that would help advance the understanding of the disease and its progression, risk/mitigating factors, and comorbidities. Future studies should address these identified gaps.
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Affiliation(s)
- Jodie A Barkin
- University of Miami Miller School of Medicine, 1120 NW 14th St., Clinical Research Building, Suite 1188 (D-49), 33136, Miami, FL, USA.
| | - Trudi B Delk
- Aimmune Therapeutics, a Nestlé Health Science Company, Brisbane, CA, USA
| | - Valerie J Powell
- CorEvitas, LLC, part of Thermo Fisher Scientific, Waltham, MA, USA
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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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Halle-Smith JM, Hall LA, Powell-Brett SF, Merali N, Frampton AE, Beggs AD, Moss P, Roberts KJ. Pancreatic Exocrine Insufficiency and the Gut Microbiome in Pancreatic Cancer: A Target for Future Diagnostic Tests and Therapies? Cancers (Basel) 2023; 15:5140. [PMID: 37958314 PMCID: PMC10649877 DOI: 10.3390/cancers15215140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 10/18/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is common amongst pancreatic cancer patients and is associated with poorer treatment outcomes. Pancreatic enzyme replacement therapy (PERT) is known to improve outcomes in pancreatic cancer, but the mechanisms are not fully understood. The aim of this narrative literature review is to summarise the current evidence linking PEI with microbiome dysbiosis, assess how microbiome composition may be impacted by PERT treatment, and look towards possible future diagnostic and therapeutic targets in this area. Early evidence in the literature reveals that there are complex mechanisms by which pancreatic secretions modulate the gut microbiome, so when these are disturbed, as in PEI, gut microbiome dysbiosis occurs. PERT has been shown to return the gut microbiome towards normal, so called rebiosis, in animal studies. Gut microbiome dysbiosis has multiple downstream effects in pancreatic cancer such as modulation of the immune response and the response to chemotherapeutic agents. It therefore represents a possible future target for future therapies. In conclusion, it is likely that the gut microbiome of pancreatic cancer patients with PEI exhibits dysbiosis and that this may potentially be reversible with PERT. However, further human studies are required to determine if this is indeed the case.
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Affiliation(s)
- James M. Halle-Smith
- Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK (K.J.R.)
- Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2GW, UK;
| | - Lewis A. Hall
- Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK (K.J.R.)
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
| | - Sarah F. Powell-Brett
- Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK (K.J.R.)
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
| | - Nabeel Merali
- Section of Oncology, Department of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, UK (A.E.F.); (P.M.)
- Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Guildford GU2 7WG, UK
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Adam E. Frampton
- Section of Oncology, Department of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, UK (A.E.F.); (P.M.)
- Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Guildford GU2 7WG, UK
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Andrew D. Beggs
- Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2GW, UK;
- Colorectal Surgery Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK
| | - Paul Moss
- Section of Oncology, Department of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, UK (A.E.F.); (P.M.)
| | - Keith J. Roberts
- Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK (K.J.R.)
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK
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Kanwat S, Singh H, Sharma AK, Sharma V, Gupta P, Gupta V, Yadav TD, Gupta R. Pancreatic Dysfunction and Reduction in Quality of Life Is Common After Pancreaticoduodenectomy. Dig Dis Sci 2023; 68:3167-3173. [PMID: 37160540 DOI: 10.1007/s10620-023-07966-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 05/02/2023] [Indexed: 05/11/2023]
Abstract
BACKGROUND Improvements in survival after pancreaticoduodenectomy has increased the number of patients potentially at risk of pancreatic insufficiency. AIMS We studied long-term (> 1 year) pancreatic functions (endocrine and exocrine) after pancreaticoduodenectomy and aimed to recognize the impact of various clinicopathological factors and postoperative complications on pancreatic functions. METHODS All patients who underwent pancreaticoduodenectomy at least 1 year prior were recruited from July 2020 to December 2021. Endocrine function was assessed using HbA1c, fasting blood sugar and postprandial blood sugar levels. Pancreatic exocrine function was assessed clinically with history of steatorrhea and objectively with quantitative estimation of fecal elastase-1 levels in stool samples. Volume of remnant pancreas, parenchymal thickness and duct diameter were assessed by computed tomography. Quality of life assessment was done using SF-36 questionnaire. RESULTS Of the 106 patients assessed, 64 patients met the inclusion criteria. Endocrine insufficiency was noted in 51.6%, and 34.3% had new onset diabetes mellitus. The incidence of pancreatic exocrine insufficiency was 87.5% and severe insufficiency was found in 62.5% of patients. Twenty-nine (45.3%) patients had both exocrine and endocrine insufficiency. Patients with CRPOPF had higher risk of severe exocrine insufficiency (5 vs. 2, OR 1.57(0.28-8.81) p = 0.6). The SF-36 scores were lower than general population especially in role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, general health perception and health change domains. CONCLUSION Post-pancreaticoduodenectomy patients have a high frequency of pancreatic insufficiency and should be screened for same. The post-operative pancreatic fistula increases the risk of pancreatic exocrine insufficiency.
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Affiliation(s)
- Shradha Kanwat
- Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Harjeet Singh
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER), F-block, Nehru Hospital, Sector 12, Chandigarh, India.
| | - Arun Kumar Sharma
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Gupta
- Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Vikas Gupta
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Thakur Deen Yadav
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Gupta
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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De Luca R, Gianotti L, Pedrazzoli P, Brunetti O, Rizzo A, Sandini M, Paiella S, Pecorelli N, Pugliese L, Pietrabissa A, Zerbi A, Salvia R, Boggi U, Casirati A, Falconi M, Caccialanza R. Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS® and neoadjuvant treatment. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:542-549. [PMID: 36577556 DOI: 10.1016/j.ejso.2022.12.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/21/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
Pancreatic cancer (PC) is an aggressive disease, with a growing incidence, and a poor prognosis. Neoadjuvant treatments in PC are highly recommended in borderline resectable and recently in upfront resectable PC. PC is characterized by exocrine insufficiency and nutritional imbalance, leading to malnutrition/sarcopenia. The concept of malnutrition in PC is multifaceted, as the cancer-related alterations create an interplay with adverse effects of anticancer treatments. All these critical factors have a negative impact on the postoperative and oncological outcomes. A series of actions and programs can be implemented to improve resectable and borderline resectable PC in terms of postoperative complications, oncological outcomes and patients' quality of life. A timely nutritional evaluation and the implementation of appropriate evidence-based nutritional interventions in onco-surgical patients should be considered of importance to improve preoperative physical fitness. Unfortunately, nutritional care and its optimization are often neglected in real-world clinical practice. Currently available studies and ERAS® guidelines mostly support the use of pre- or perioperative medical nutrition, including immunonutrition, in order to decrease the rate of postoperative infections and length of hospital stay. Further data also suggest that medical nutrition should be considered proactively in PC patients, to possibly prevent severe malnutrition and its consequences on disease and treatment outcomes. This narrative review summarizes the most recent data related to the role of prehabilitation, ERAS® program, medical nutrition, and the timing of intervention on clinical outcomes of upfront resectable and borderline PC, and their potential implementation within the timeframe of neoadjuvant treatments.
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Affiliation(s)
- Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca, HPB Unit, San Gerardo Hospital, Monza, Italy.
| | - Paolo Pedrazzoli
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo and Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Alessandro Rizzo
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Marta Sandini
- Surgical Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Salvatore Paiella
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Nicolò Pecorelli
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Luigi Pugliese
- Department of Surgery, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Andrea Pietrabissa
- Department of Surgery, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center - IRCCS and Humanitas University - Department of Biomedical Sciences Rozzano, Milan, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Ugo Boggi
- Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy
| | - Amanda Casirati
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Perioperative Drug Treatment in Pancreatic Surgery-A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12051750. [PMID: 36902534 PMCID: PMC10003556 DOI: 10.3390/jcm12051750] [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: 01/04/2023] [Revised: 02/17/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023] Open
Abstract
INTRODUCTION Pancreatic resections for malignant or benign diseases are associated with major morbidity and changes in physiology. To reduce perioperative complications and enhance recovery, many types of perioperative medical management have been introduced. The aim of this study was to provide an evidence-based overview on the best perioperative drug treatment. METHODS The electronic bibliographic databases Medline, Embase, CENTRAL, and Web of Science were systematically searched for randomized controlled trials (RCT) evaluating perioperative drug treatments in pancreatic surgery. The investigated drugs were somatostatin analogues, steroids, pancreatic enzyme replacement therapy (PERT), prokinetic therapy, antidiabetic drugs, and proton pump inhibitors (PPI). Targeted outcomes in each drug category were meta-analyzed. RESULTS A total of 49 RCT were included. The analysis of somatostatin analogues showed a significantly lower incidence of postoperative pancreatic fistula (POPF) in the somatostatin group compared to the control group (OR 0.58, 95% CI: 0.45 to 0.74). The comparison of glucocorticoids versus placebo showed significantly less POPF in the glucocorticoid group (OR 0.22, 95% CI: 0.07 to 0.77). There was no significant difference in DGE when erythromycin was compared to placebo (OR 0.33, 95% CI: 0.08 to 1.30). The other investigated drug regimens could only be analyzed qualitatively. CONCLUSION This systematic review provides a comprehensive overview on perioperative drug treatment in pancreatic surgery. Some often-prescribed perioperative drug treatments lack high quality evidence and further research is needed.
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12
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Shah P, Patel V, Ashkar M. De novo non-alcoholic fatty liver disease after pancreatectomy: A systematic review. World J Clin Cases 2022; 10:12946-12958. [PMID: 36569000 PMCID: PMC9782952 DOI: 10.12998/wjcc.v10.i35.12946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/10/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these patients as we continue to learn more about post-operative complications. Although pancreatic endocrine and exocrine insufficiencies are known complications of pancreatectomy, increased longevity of these patients has also led to a higher incidence of de novo fatty liver disease which differs from traditional fatty liver disease given the lack of metabolic syndrome. AIM To identify and summarize patterns and risk factors of post-pancreatectomy de novo fatty liver disease to guide future management. METHODS We performed a database search on PubMed selecting papers published between 2001 and 2022 in the English language. PubMed was last accessed 1 June 2022. RESULTS Various factors influence the development of de novo fatty liver including indication for surgery (benign vs malignant), type of pancreatectomy, amount of pancreas remnant, and peri-operative nutritional status. With an incidence rate up to 75%, de novo non-alcoholic fatty liver disease (NAFLD) can develop within 12 mo after pancreatectomy and various risk factors have been established including pancreatic resection line and remnant pancreas volume, peri-operative malnutrition and weight loss, pancreatic exocrine insufficiency (EPI), malignancy as the indication for surgery, and postmenopausal status. CONCLUSION Since majority of risk factors leads to EPI and malnutrition, peri-operative focus on nutrition and enzymes replacement is key in preventing and treating de novo NAFLD after pancreatectomy.
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Affiliation(s)
- Parth Shah
- Gastroenterology, Washington University in Saint Louis, Saint Louis, MO 63110, United States
| | - Vanisha Patel
- Internal Medicine, Washington University in Saint Louis, Saint Louis, MO 63110, United States
| | - Motaz Ashkar
- Gastroenterology, Washington University in Saint Louis, Saint Louis, MO 63110, United States
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13
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Rosenberg J, Reddy MN, Seelam P, Li O, Twal J, Pack J. A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States. Pancreas 2022; 51:1308-1314. [PMID: 37099771 PMCID: PMC10184798 DOI: 10.1097/mpa.0000000000002203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
OBJECTIVES This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D). METHODS Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline. RESULTS A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959). CONCLUSIONS Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.
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Affiliation(s)
- Jonathan Rosenberg
- From the Department of Gastroenterology, Illinois Gastroenterology Group, GI Alliance, Gurnee, IL
| | | | | | - Olivia Li
- RWE Analytics, Clarivate Analytics, Toronto, Canada
| | - Janine Twal
- Medical Science Liaison, Aimmune Therapeutics, a Nestlé Health Science company, Bridgewater Township, NJ
| | - Jennifer Pack
- Medical Science Liaison, Aimmune Therapeutics, a Nestlé Health Science company, Bridgewater Township, NJ
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14
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Thomas AS, Huang Y, Kwon W, Schrope BA, Sugahara K, Chabot JA, Wright JD, Kluger MD. Prevalence and Risk Factors for Pancreatic Insufficiency After Partial Pancreatectomy. J Gastrointest Surg 2022; 26:1425-1435. [PMID: 35318597 DOI: 10.1007/s11605-022-05302-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/11/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND This study aimed to determine the rate, timing, and predictors of diabetes and exocrine pancreatic insufficiency after pancreatectomy in order to inform preoperative patient counseling and risk management strategies. METHODS Using prescription claims as a surrogate for disease prevalence, IBM Watson Health MarketScan was queried for claims patterns pre- and post-pancreatectomy. Multivariable models explored associations between clinical characteristics and medication use within 2 years of surgery. RESULTS In total, 18.96% of 2,848 pancreaticoduodenectomy (PD) patients and 18.95% of 1,858 distal pancreatectomy (DP) patients had preoperative diabetic medication prescription claims. Fewer (6.6% and 3.88%, respectively) had pancreatic enzyme replacement therapy (PERT) claims. Diabetic medication claims increased to 28.69% after PD and 38.59% after DP [adjusted relative risk (aRR) = 1.36 (95% CI 1.27, 1.46)]. Other associated factors included age > 45, medical comorbidity, and obesity. The incidence of new diabetic medication claims among medication naïve patients was 13.78% for PD and 24.7% for DP (p < 0.001) with a median 4.7 and 4.9 months post-operatively. The prevalence of PERT claims was 55.97% after PD and 17.06% after DP [aRR = 0.32 (0.29, 0.36)]. The incidence of postoperative PERT claims 53.98% (PD) and 14.84% (DP) (p < 0.0001). The median time to new PERT claim was 3.0 (PD) and 3.2 (DP) months, respectively. Claims for both diabetic medications and PERT rose sharply after surgery and plateaued within 6 months. CONCLUSIONS This study defines prevalence, timing, and predictors for post-pancreatectomy insufficiency to inform preoperative counseling, risk modification strategies, and interventions related to quality of life.
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Affiliation(s)
- Alexander S Thomas
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA.
| | - Yongmei Huang
- Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY, USA
| | - Wooil Kwon
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA
- Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Beth A Schrope
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA
| | - Kazuki Sugahara
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA
| | - John A Chabot
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA
| | - Jason D Wright
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Michael D Kluger
- Department of Surgery, Division of GI/Endocrine Surgery, Columbia University Irving Medical Center, 177 Fort Washington Ave 7GS, New York, NY, 10032, USA
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15
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Roeyen G, Berrevoet F, Borbath I, Geboes K, Peeters M, Topal B, Van Cutsem E, Van Laethem JL. Expert opinion on management of pancreatic exocrine insufficiency in pancreatic cancer. ESMO Open 2022; 7:100386. [PMID: 35124465 PMCID: PMC8819032 DOI: 10.1016/j.esmoop.2022.100386] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/23/2021] [Accepted: 12/23/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is a common condition in patients with pancreatic cancer (PC). PEI can be due to the tumor, which, if located in the head, causes obstruction of the pancreatic duct with subsequent atrophy of the pancreatic parenchyma, or it can be the consequence of pancreatic surgical resection. The standard treatment of PEI is pancreatic enzyme replacement therapy (PERT). Clinical data to support the use of PERT in PC are however limited. There are very few randomized clinical trials that evaluated PERT in PC. Most data come from observational studies. Despite this limited clinical evidence, PERT treatment for PEI is an essential part of supportive therapy to ensure optimal nutritional status in PC patients who will receive surgery, neoadjuvant/adjuvant or palliative treatment. The objective of this review is to increase the awareness about PEI in PC patients and to provide expert recommendations on the use of PERT in resected, borderline resectable and unresectable patients, based on clinical experience and literature review.
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Affiliation(s)
- G Roeyen
- Department of Hepatobiliary Transplantation and Endocrine Surgery, Antwerp University Hospital and University of Antwerp, Edegem.
| | - F Berrevoet
- Department of General and Hepatobiliary Surgery, Ghent University Hospital, Ghent
| | - I Borbath
- Hepato-Gastroenterology Unit, Cliniques Universitaires Saint-Luc, Brussels
| | - K Geboes
- Department of Gastroenterology, Division of Digestive Oncology, Ghent University Hospital, Ghent
| | - M Peeters
- Department of Oncology, Antwerp University Hospital and University of Antwerp, Edegem
| | - B Topal
- Department of Visceral Surgery, University Hospitals KU Leuven, Leuven
| | - E Van Cutsem
- Department of Gastroenterology/Digestive Oncology, University Hospital Leuven, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven
| | - J-L Van Laethem
- Department of Digestive Oncology, University Hospital Erasmus Brussels, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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16
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Kumar TK, Tewari M, Shukla SK, Mishra SP. Pancreatic exocrine insufficiency occurs in most patients following pancreaticoduodenectomy. Indian J Cancer 2022; 58:511-517. [PMID: 34975096 DOI: 10.4103/ijc.ijc_764_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Pancreatic exocrine insufficiency (PEI) is a well-defined complication of malignant diseases and pancreatic resection; however, study results of PEI are less consistent. Assessment of PEI by estimation of fecal elastase (FE)-1 in stool by enzyme-linked immunosorbent essay (ELISA) is a relatively inexpensive, noninvasive, and simple test. This study assessed exocrine function of pancreas following pancreaticoduodenectomy (PD) by estimating FE-1. Methods This prospective hospital-based study involved 30 patients who had undergone PD for malignancy. All 30 patients had an uneventful postoperative period under the unit's enhanced recovery after surgery (ERAS) protocol with no Grade B, C postoperative pancreatic fistula/postpancreatectomy hemorrhage as per the International Study Group of Pancreatic Surgery (ISGPS) definitions. Stool samples were collected postoperatively 3 months after surgery from all patients irrespective of clinical symptoms. The analysis was based on a solid phase ELISA used for the quantitative determination of human elastase 1 in feces. Fecal elastase was considered normal if >200 μg/gm stool, moderately reduced if 100-200 μg/gm stool, and severely reduced if <100 μg/gm stool. Results Among 30 patients included, fecal elastase levels were moderately reduced in 10 (33.33%) and severely reduced in 20 (66.67%) patients (P <0.0001). Mean (± standard deviation) of fecal elastase was 87.12 ± 38.76 with median of 74.6 μg/gm stool. There was no significant difference in the fecal elastase levels between men and women (P = 0.057), age (P = 0.48), pancreatic duct diameter (P = 0.609), pancreatic texture (P = 0.286), and presence or absence of clinical symptoms (P = 0.181). Conclusions PD was frequently associated with PEI. Unfortunately PEI is an under recognized and under treated long-term sequel of PD. Fecal elastase 1 should be performed routinely in both symptomatic and asymptomatic patients. Pancreatic enzyme replacement therapy should be considered in every patient after PD.
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Affiliation(s)
- Thogari K Kumar
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Mallika Tewari
- Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - S K Shukla
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - S P Mishra
- Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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Bharati SJ, Hoda W, Ratre BK. Critical Care of Hepatopancreatobiliary Surgery Patient. ONCO-CRITICAL CARE 2022:475-490. [DOI: 10.1007/978-981-16-9929-0_38] [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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18
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Cho A, Kim H, Sohn HJ, Lee M, Kang YH, Kim HS, Han Y, Kang JS, Kwon W, Jang JY. Risk factors deteriorating severe exocrine pancreatic insufficiency measured by stool elastase after pancreatoduodenectomy and the risk factors for weight loss. Ann Surg Treat Res 2022; 102:20-28. [PMID: 35071116 PMCID: PMC8753381 DOI: 10.4174/astr.2022.102.1.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/07/2021] [Accepted: 11/11/2021] [Indexed: 11/30/2022] Open
Abstract
Purpose The measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level. Methods Among patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to <100 µg/g postoperatively. Patients whose weight 12 months postoperatively was greater than that 3 months postoperatively were classified into the weight-recovery group. Results Of the 202 included patients, the deteriorated group had a higher incidence of preoperative SE level above 200 µg/g, benign pathology, and the presence of a clinically relevant postoperative pancreatic fistula than the maintained group. Patients who did not undergo weight recovery had a higher rate of history of adjuvant radiotherapy compared to the no-recovery group. Conclusion The evaluation of EPI by measuring SE alone is not sufficient because it does not reflect the nutritional status of patients, and a comprehensive approach that considers other parameters is required for EPI management.
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Affiliation(s)
- Ara Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Ju Sohn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Mirang Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Hyung Kang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeong Seok Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Petzel MQB, Ebrus CS. Nutrition in Pancreatic Cancer. PANCREATIC CANCER: A MULTIDISCIPLINARY APPROACH 2022:317-341. [DOI: 10.1007/978-3-031-05724-3_26] [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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20
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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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21
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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22
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Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study. Pancreatology 2021; 21:S1424-3903(21)00469-5. [PMID: 34053863 DOI: 10.1016/j.pan.2021.05.299] [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: 03/17/2021] [Revised: 05/14/2021] [Accepted: 05/18/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. DESIGN RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. RESULTS Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5-7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). CONCLUSION Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required.
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Achieving 'Marginal Gains' to Optimise Outcomes in Resectable Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13071669. [PMID: 33916294 PMCID: PMC8037133 DOI: 10.3390/cancers13071669] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/19/2021] [Accepted: 03/24/2021] [Indexed: 12/21/2022] Open
Abstract
Simple Summary Improving outcomes in pancreatic cancer is achievable through the accumulation of marginal gains. There exists evidence of variation and undertreatment in many areas of the care pathway. By fully realising the existing opportunities, there is the potential for immediate improvements in outcomes and quality of life. Abstract Improving outcomes among patients with resectable pancreatic cancer is one of the greatest challenges of modern medicine. Major improvements in survival will result from the development of novel therapies. However, optimising existing pathways, so that patients realise benefits of already proven treatments, presents a clear opportunity to improve outcomes in the short term. This narrative review will focus on treatments and interventions where there is a clear evidence base to improve outcomes in pancreatic cancer, and where there is also evidence of variation and under-treatment. Avoidance of preoperative biliary drainage, treatment of pancreatic exocrine insufficiency, prehabiliation and enhanced recovery after surgery, reducing perioperative complications, optimising opportunities for elderly patients to receive therapy, optimising adjuvant chemotherapy and regular surveillance after surgery are some of the strategies discussed. Each treatment or pathway change represents an opportunity for marginal gain. Accumulation of marginal gains can result in considerable benefit to patients. Given that these interventions already have evidence base, they can be realised quickly and economically.
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Narayanan S, Bhutiani N, Adamson DT, Jones CM. Pancreatectomy, Islet Cell Transplantation, and Nutrition Considerations. Nutr Clin Pract 2020; 36:385-397. [PMID: 33002260 DOI: 10.1002/ncp.10578] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Pancreatic islet transplantation is a reliable approach for treating insulin-deficient diabetes. This established β-cell replacement approach has shown considerable improvements in the last 2 decades. It has helped achieve metabolic homeostasis and safe outcomes for a subset of patients with type 1 diabetes and severe pancreatitis. Nutrition support, until recently, was considered as a secondary factor, merely identified as a means of providing all the necessary nutrients for such patients. However, new literature suggests that several factors, such as the route, timing, quantity, and composition of all the nutrients administered, have key disease-altering properties and are vital during the perioperative management of such patients. This review will highlight the benefits of performing the clinical islet transplantation on a subgroup of patients with type 1 diabetes and pancreatitis and summarize new data that identify the pivotal role of nutrition support as a critical intervention in their management.
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Affiliation(s)
- Siddharth Narayanan
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Neal Bhutiani
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Dylan T Adamson
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Christopher M Jones
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
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25
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Pusceddu S, Rossi RE, Torchio M, Prinzi N, Niger M, Coppa J, Giacomelli L, Sacco R, Facciorusso A, Corti F, Raimondi A, Prisciandaro M, Colombo E, Beninato T, Del Vecchio M, Milione M, Di Bartolomeo M, de Braud F. Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors. J Clin Med 2020; 9:2468. [PMID: 32752158 PMCID: PMC7464810 DOI: 10.3390/jcm9082468] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/22/2020] [Accepted: 07/26/2020] [Indexed: 02/07/2023] Open
Abstract
Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.
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Affiliation(s)
- Sara Pusceddu
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Roberta Elisa Rossi
- Gastro-intestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (R.E.R.); (J.C.)
- Department of Pathophysiology and Organ Transplant, Università degli Studi di Milano, 20122 Milan, Italy
| | - Martina Torchio
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Natalie Prinzi
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Monica Niger
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Jorgelina Coppa
- Gastro-intestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (R.E.R.); (J.C.)
| | - Luca Giacomelli
- Polistudium SRL, 20135 Milan, Italy;
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, 16126 Genoa, Italy
| | - Rodolfo Sacco
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, 71122 Foggia, Italy; (R.S.); (A.F.)
| | - Antonio Facciorusso
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, 71122 Foggia, Italy; (R.S.); (A.F.)
| | - Francesca Corti
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Alessandra Raimondi
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Michele Prisciandaro
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Elena Colombo
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Teresa Beninato
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Marta Del Vecchio
- Unit of Pharmacy, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Massimo Milione
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS–Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Maria Di Bartolomeo
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
| | - Filippo de Braud
- Department of Medical Oncology, Gastro-entero-pancreatic and Neuroendocrine Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (M.T.); (N.P.); (M.N.); (F.C.); (A.R.); (M.P.); (E.C.); (T.B.); (M.D.B.); (F.d.B.)
- Oncology and Hematology-Oncology Department, University of Milan, 20122 Milan, Italy
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Pezzilli R, Capurso G, Falconi M, Frulloni L, Macarri G, Costamagna G, Di Leo A, Salacone P, Carroccio A, Zerbi A. The Applicability of a Checklist for the Diagnosis and Treatment of Exocrine Pancreatic Insufficiency: Results of the Italian Exocrine Pancreatic Insufficiency Registry. Pancreas 2020; 49:793-798. [PMID: 32541636 DOI: 10.1097/mpa.0000000000001575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To evaluate a rapid checklist capable of identifying exocrine pancreatic insufficiency in outpatients. METHODS Prospective observational study of a multicenter cohort. RESULTS One hundred and two patients were enrolled; 61.8% of the patients had medically-treated benign or malignant pancreatic disease, and 38.2% had a pancreatic resection. Visual examination of the feces was evaluated in 84 patients and it was related to steatorrhea in 51 patients (50.0%). Receiver operating characteristic curves were evaluated for each symptom or clinical sign and four of them (ie, increase in daily bowel movements, number of bowel movements, fatty stools, >10% weight loss) had a satisfactory area under the curve. At multivariate analysis, fatty stools and >10% weight loss entered into this analysis having an area under the curve of 0.916 (95% confidence interval, 0.851-0.981). At 1 month and at one year of follow-up, the pancreatic enzyme replacement therapy administered showed that pancreatic extracts were able to significantly improve the increase in daily bowel movements, the number of bowel movements, fatty and bulky stools and >10% weight loss. CONCLUSION Both fatty stools and >10% weight loss were able to clinically evaluate steatorrhea, and their improvement was sufficient to evaluate substitution therapy.
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Affiliation(s)
- Raffaele Pezzilli
- From the Department of Gastroenterology, Polyclinic of Sant'Orsola, Bologna
| | | | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan
| | - Luca Frulloni
- Department of Gastroenterology, Borgoroma Hospital, Verona
| | | | - Guido Costamagna
- Department of Surgical Digestive Endoscopy, Gemelli Hospital, Rome
| | - Alfredo Di Leo
- Department of Gastroenterology, University Hospital, Bari
| | - Paola Salacone
- Department of Gastroenterology, Mauriziano Hospital, Turin
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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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Kim H, Yoon YS, Han Y, Kwon W, Kim SW, Han HS, Yoon DS, Park JS, Park SJ, Han SS, Lee SE, Choi SH, Han IW, Kim E, Jang JY. Effects of Pancreatic Enzyme Replacement Therapy on Body Weight and Nutritional Assessments After Pancreatoduodenectomy in a Randomized Trial. Clin Gastroenterol Hepatol 2020; 18:926-934.e4. [PMID: 31520730 DOI: 10.1016/j.cgh.2019.08.061] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 08/18/2019] [Accepted: 08/30/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We studied the effects of pancreatic enzyme replacement therapy (PERT) on body weight, nutritional status, and quality of life (QoL) in patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. METHODS We performed a randomized, double-blind trial of 304 patients who underwent pancreatoduodenectomy at 7 tertiary referral hospitals in South Korea. Patients with fecal levels of elastase of 200 μg/g or less, before and after surgery, were assigned randomly to groups that received PERT (a single capsule of 40,000 IU pancreatin, Norzyme (40,000 IU, Pankreatan; Nordmark Arzneimittel GmbH & Co, Uetersen, Germany), 3 times each day during meals for 3 months; n = 151) or placebo (n = 153). Protocol completion was defined as taking more than two thirds of the total dose without taking other digestive enzymes; the protocol was completed by 71 patients in the PERT group and 93 patients in the placebo group. Patients underwent a physical examination, oral glucose tolerance tests, and blood tests at baseline and at month 3 of the study period. The primary end point was change in body weight. Secondary end points were changes in bowel habits, nutritional parameters, and QoL. RESULTS In the per-protocol analysis, 3 months after the study began, patients in the PERT group gained a mean of 1.09 kg in weight and patients in the placebo group lost a mean of 2.28 kg (difference between groups, 3.37 kg; P < .001). However, no difference in body weight was observed between groups in the intent-to-treat analysis. Three months after the study began, the mean serum levels of prealbumin increased by 10.9 mg/dL in the PERT group and increased by 7.8 mg/dL in the placebo group (P = .002). Poor compliance to PERT was a significant risk factor for weight loss (P < .001). There was no significant difference in QoL scores between groups. CONCLUSIONS In the intent-to-treat analysis of data from a randomized trial, we found no significant effect of PERT on mean body weights of patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. However, with active education and monitoring, PERT could increase body weight and nutritional parameters. ClinicalTrials.gov no: NCT02127021.
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Affiliation(s)
- Hongbeom Kim
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul, Korea
| | - Youngmin Han
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sun-Whe Kim
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Center for Liver and Pancreatobilary Cancer, National Cancer Center, Goyang, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul, Korea
| | - Dong-Sup Yoon
- Department of Surgery, Gangnam Severance Hospital, Seoul, Korea
| | - Joon Seong Park
- Department of Surgery, Gangnam Severance Hospital, Seoul, Korea
| | - Sang-Jae Park
- Center for Liver and Pancreatobilary Cancer, National Cancer Center, Goyang, Korea
| | - Sung-Sik Han
- Center for Liver and Pancreatobilary Cancer, National Cancer Center, Goyang, Korea
| | - Seung Eun Lee
- Department of Surgery, Chung-Ang University Hospital, Seoul, Korea
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Seoul, Korea
| | - In Woong Han
- Department of Surgery, Dongguk University Ilsan Hospital, Goyang, Korea; Department of Surgery, Samsung Medical Center, Seoul, Korea
| | - Eunjung Kim
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Nursing, Graduate School, Kyung Hee University, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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Pancreatic Enzyme Replacement Therapy in Post-Whipple Patients: Optimizing the Dose and Maximizing Compliance. Clin Gastroenterol Hepatol 2020; 18:789-791. [PMID: 31629884 DOI: 10.1016/j.cgh.2019.10.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/08/2019] [Accepted: 10/10/2019] [Indexed: 02/07/2023]
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30
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Powell-Brett S, de Liguori Carino N, Roberts K. Understanding pancreatic exocrine insufficiency and replacement therapy in pancreatic cancer. Eur J Surg Oncol 2020; 47:539-544. [PMID: 32178962 DOI: 10.1016/j.ejso.2020.03.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 03/06/2020] [Indexed: 02/08/2023] Open
Abstract
Pancreatic exocrine insufficiency (PEI) is highly prevalent in patients with pancreatic cancer, and has substantial implications for quality of life and survival. Post resection, PEI is associated with increased post-operative complications, longer hospital stays and higher costs. Treatment with pancreatic enzyme replacement therapy (PERT) improves quality of life and confers significant survival advantages. Despite this many patients with pancreatic cancer do not currently receive PERT. The nutritional consequences of PEI are extensive and even more relevant in the elderly owing to age related gastrointestinal tract and pancreatic changes that predispose to malnutrition.
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Affiliation(s)
- S Powell-Brett
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospital Birmingham, Birmingham, UK.
| | - N de Liguori Carino
- Department of Hepatobiliary and Pancreatic Surgery, Manchester Royal Infirmary, Manchester University Hospitals Foundation Trust, UK
| | - K Roberts
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University Hospital Birmingham, Birmingham, UK
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31
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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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Sankararaman S, Schindler T, Sferra TJ. Management of Exocrine Pancreatic Insufficiency in Children. Nutr Clin Pract 2019; 34 Suppl 1:S27-S42. [DOI: 10.1002/ncp.10388] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology; Department of Pediatrics; UH Rainbow Babies & Children's Hospital; Case Western Reserve University School of Medicine; Cleveland Ohio USA
| | - Teresa Schindler
- Division of Pediatric Pulmonology; Department of Pediatrics; UH Rainbow Babies & Children's Hospital; Cleveland Ohio USA
| | - Thomas J. Sferra
- Division of Pediatric Gastroenterology; Department of Pediatrics; UH Rainbow Babies & Children's Hospital; Case Western Reserve University School of Medicine; Cleveland Ohio USA
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Kusakabe J, Anderson B, Liu J, Williams GA, Chapman WC, Doyle MMB, Khan AS, Sanford DE, Hammill CW, Strasberg SM, Hawkins WG, Fields RC. Long-Term Endocrine and Exocrine Insufficiency After Pancreatectomy. J Gastrointest Surg 2019; 23:1604-1613. [PMID: 30671791 PMCID: PMC6646099 DOI: 10.1007/s11605-018-04084-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/13/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE To identify peri-operative risk factors and time to onset of pancreatic endocrine/exocrine insufficiency. METHODS We retrospectively analyzed a single institutional series of patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between 2000 and 2015. Endocrine/exocrine insufficiencies were defined as need for new pharmacologic intervention. Cox proportional modeling was used to identify peri-operative variables to determine their impact on post-operative pancreatic insufficiency. RESULTS A total of 1717 patient records were analyzed (75.47% PD, 24.53% DP) at median follow-up 17.88 months. Average age was 62.62 years, 51.78% were male, and surgery was for malignancy in 74.35% of patients. Post-operative endocrine insufficiency was present in 20.15% (n = 346). Male gender (p = 0.015), increased body mass index (BMI) (p < 0.001), tobacco use (p = 0.011), family history of diabetes (DM) (p < 0.001), personal history of DM (p ≤ 0.001), and DP (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 20.80 ± 33.60 (IQR: 0.49-28.37) months. Post-operative exocrine insufficiency was present in 36.23% (n = 622). Race (p = 0.014), lower BMI (p < 0.001), family history of DM (p = 0.007), steatorrhea (p < 0.001), elevated pre-operative bilirubin (p = 0.019), and PD (p ≤ 0.001) were correlated with increased risk. Mean time to onset was 14.20 ± 26.90 (IQR: 0.89-12.69) months. CONCLUSIONS In this large series of pancreatectomy patients, 20.15% and 36.23% of patients developed post-operative endocrine and exocrine insufficiency at a mean time to onset of 20.80 and 14.20 months, respectively. Patients should be educated regarding post-resection insufficiencies and providers should have heightened awareness long-term.
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Affiliation(s)
- Jiro Kusakabe
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Blaire Anderson
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Jingxia Liu
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Gregory A Williams
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - William C Chapman
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Majella MB Doyle
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Adeel S Khan
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Dominic E Sanford
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Chet W Hammill
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Steven M Strasberg
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - William G Hawkins
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
| | - Ryan C Fields
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO
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Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis. Pancreatology 2019; 19:595-601. [PMID: 31005377 DOI: 10.1016/j.pan.2019.04.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 04/10/2019] [Accepted: 04/14/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ± 4.1 vs 18.2 ± 3.6 g/day; FE-1 121.4 ± 6.7 vs 170.2 ± 25.5 μg/g, vitamin D 18.1 ± 1.8 vs. 23.2 ± 3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ± 3.1 vs. 36 ± 4.1 cm3) and a more dilated pancreatic duct (4.6 ± 0.92 vs. 2.4 ± 0.18 mm) in patients with PG compared to those with PJ. CONCLUSION Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.
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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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Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol 2019; 12:129-139. [PMID: 30962702 PMCID: PMC6432881 DOI: 10.2147/ceg.s168266] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Exocrine pancreatic insufficiency (EPI) is a condition caused by reduced or inappropriate secretion or activity of pancreatic juice and its digestive enzymes, pancreatic lipase in particular. EPI can result in clinical manifestation and biochemical alterations causing reduced quality of life and life-threating complications. EPI is common in pancreatic disorders, where it should be suspected and actively investigated, and in many extrapancreatic conditions. There are various tests available to diagnose EPI, with indirect, noninvasive ones, such as concentration of fecal elastase being more commonly employed. Administration of pancreatic enzymes replacement therapy remains the mainstay of EPI treatment. The present review article will discuss current evidence regarding the prevalence of EPI, the available tests to diagnose it and its treatment.
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Affiliation(s)
- Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy,
| | - Mariaemilia Traini
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy,
| | - Matteo Piciucchi
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Marianna Signoretti
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy,
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Landers A, Brown H, Strother M. The effectiveness of pancreatic enzyme replacement therapy for malabsorption in advanced pancreatic cancer, a pilot study. Palliat Care 2019; 12:1178224218825270. [PMID: 30799929 PMCID: PMC6378466 DOI: 10.1177/1178224218825270] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 11/29/2018] [Indexed: 12/14/2022] Open
Abstract
Advanced adenocarcinoma of the pancreas has a globally poor prognosis. One of the characteristic features of pancreatic cancer (PC) is pancreatic exocrine insufficiency (PEI). This leads to a malabsorption syndrome and subsequent digestive symptoms. Given the high prevalence of PEI and malabsorption in PC, empiric use of pancreatic enzyme replacement therapy (PERT) is recommended. The aim of this pilot study was to determine the potential efficacy of PERT in improving symptoms and quality of life in those with metastatic PC. The study recruited patients with advanced PC referred to a specialist palliative care service. Following an initial assessment, patients were commenced on pancrealipase 25,000IU (Creon) and reassessed after 1 week and 3 weeks post-initiation of supplementation. These assessments included demographics, malabsorption symptom checklist, and completion of two validated quality-of-life questionnaires, the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26. PERT was associated with statistically significant improvement of symptoms in both the general (QLQ-C30) and pancreatic cancer specific tool (PAN26). Within 1 week of PERT initiation, there was a reduction in diarrhoea scores (26 vs. 8, p<0.005), pancreatic and hepatic pain (47 vs. 33 and 24 vs. 11, respectively, p<0.05). After 3 weeks, there were significant improvements in pancreatic pain and bloating/gas symptoms (47 vs. 26 and 46 vs. 26, respectively, p< 0.005). PERT appears to have the potential to improve symptoms of malabsorption in patients with metastatic PC.
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Affiliation(s)
- Amanda Landers
- Department of Medicine, University of Otago, Christchurch New Zealand
| | - Helen Brown
- Nurse Maude Hospice Palliative Care Service, Nurse Maude Association, Christchurch, New Zealand
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Roberts KJ, Bannister CA, Schrem H. Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study. Pancreatology 2019; 19:114-121. [PMID: 30385188 DOI: 10.1016/j.pan.2018.10.010] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 10/22/2018] [Accepted: 10/23/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) and malnutrition are prevalent among patients with pancreatic adenocarcinoma. Pancreatic enzyme replacement therapy (PERT) can correct PEI but its use among patients with pancreatic cancer is unclear as are effects upon survival. This population-based study sought to address these issues METHODS: Subjects with pancreatic adenocarcinoma were identified from the UK Clinical Practice Research Datalink (CPRD). Propensity score matching generated matched pairs of subjects who did and did not receive PERT. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables RESULTS: PERT use among the whole cohort (987/4554) was 21.7%. Some 1614 subjects generated 807 matched pairs. This resulted in a total, censored follow-up period of 1643 years. There were 1403 deaths in total, representing unadjusted mortality rates of 748 and 994 deaths per 1000 person-years for PERT-treated cases and their matched non-PERT-treated controls, respectively. With reference to the observed survival in pancreatic adenocarcinoma patients, adjusted median survival time was 262% greater in PERT-treated cases (survival time ratio (STR) = 2.62, 95% CI 2.27-3.02) when compared with matched, non-PERT-treated controls. Survival remained significantly greater among subjects receiving PERT regardless of the studied subgroup with respect to use of surgery or chemotherapy CONCLUSIONS: This population based study observes that the majority of patients with pancreatic adenocarcinoma do not receive PERT. PERT is associated with increased survival among patients with pancreatic adenocarcinoma suggesting a lack of clinical awareness and potential benefit of addressing malnutrition among these patients.
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Affiliation(s)
- K J Roberts
- Honorary Reader and Consultant Surgeon, Institute of Immunology and Immunotherapy, University of Birmingham, UK.
| | | | - H Schrem
- Consultant Surgeon, Dept Visceral, General and Transplant Surgery, Hannover Medical School, Germany
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Shandro BM, Nagarajah R, Poullis A. Challenges in the management of pancreatic exocrine insufficiency. World J Gastrointest Pharmacol Ther 2018; 9:39-46. [PMID: 30397535 PMCID: PMC6212541 DOI: 10.4292/wjgpt.v9.i5.39] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/06/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic exocrine insufficiency (PEI) occurs when the insufficient secretion or function of pancreatic enzymes leads to maldigestion, most commonly as a result of chronic pancreatitis and pancreatic cancer. The condition is associated with significant morbidity and reductions in quality of life, even in milder forms. The challenges in approaching this condition include the non-specific presentation of mild to moderate PEI, and the lack of a convenient, accurate diagnostic test in this cohort. Classical symptoms appear late in the disease, and the diagnosis should be considered before steatorrhoea develops. Direct pancreatic function tests are the reference standard for diagnosis, but are invasive and not widely available. The faecal elastase-1 (FE-1) stool test is widely available and has been shown to be as effective as the 13C-mixed triglyceride breath test in more advanced disease. We recommend a pragmatic diagnostic approach that combines clinical history, assessment of nutritional status and measurement of FE-1. The critical first step is to consider the diagnosis. Once the diagnosis is confirmed, pancreatic enzyme replacement therapy should be initiated. The variety of enzyme preparations and recommended dosing regimens can present a challenge when selecting an adequate initial dose. Non-response should be actively sought and addressed in a systematic manner. This article discusses these challenges, and presents a practical approach to the diagnosis and management of PEI.
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Affiliation(s)
- Benjamin Myles Shandro
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
| | - Rani Nagarajah
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
| | - Andrew Poullis
- Department of Gastroenterology, St George’s University Hospitals NHS Foundation Trust, Tooting, London SW17 0QT, United Kingdom
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Abstract
PURPOSE OF REVIEW Pancreatic exocrine insufficiency (PEI), defined as a secretion of pancreatic enzymes and bicarbonate insufficient to maintain a normal digestion, is a frequent but frequently underdiagnosed and undertreated condition. PEI may be secondary to different pancreatic diseases and extrapancreatic conditions. Recent data support the high clinical relevance of PEI and its treatment. RECENT FINDINGS Together with symptoms of maldigestion, PEI is associated with nutritional deficiencies leading to osteoporosis, low-trauma fractures, sarcopenia and increased mortality. No single widely available test allows to diagnose PEI accurately. Diagnosis of PEI requires the evaluation of symptoms, nutritional markers and a noninvasive pancreatic function test in the appropriate clinical context. Pancreatic enzyme replacement therapy (PERT) improves digestion, symptoms, nutritional status and quality of life of patients with PEI. In addition, PERT is associated with a longer survival in patients with unresectable pancreatic cancer and after surgery for pancreatic cancer or chronic pancreatitis. SUMMARY Awareness of PEI in different clinical conditions is required. Nutritional advice and appropriate PERT are mandatory to reduce the morbidity and mortality associated with PEI. Further studies on the clinical impact of PEI and its treatment are needed, especially in diseases other than chronic pancreatitis and cystic fibrosis.
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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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Yang L, Yan S, Zhang Y, Hu X, Guo Q, Yuan Y, Zhang J. Novel enzyme formulations for improved pharmacokinetic properties and anti-inflammatory efficacies. Int J Pharm 2018; 537:268-277. [DOI: 10.1016/j.ijpharm.2017.12.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 12/10/2017] [Accepted: 12/12/2017] [Indexed: 02/06/2023]
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Durie P, Baillargeon JD, Bouchard S, Donnellan F, Zepeda-Gomez S, Teshima C. Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel. Curr Med Res Opin 2018; 34:25-33. [PMID: 28985688 DOI: 10.1080/03007995.2017.1389704] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release. PURPOSE To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI. METHODS For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co-chairs (P.D. and C.T.) were vetted and approved based on the authors? FINDINGS The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist. CONCLUSIONS In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co-managing patients with confirmed PEI.
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Affiliation(s)
- P Durie
- a Hospital for Sick Children and University of Toronto , Toronto , ON , Canada
| | - J-D Baillargeon
- b Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke , Sherbrooke , QC , Canada
| | - S Bouchard
- c Centre Hospitalier de l'Université de Montréal , Montréal , QC , Canada
| | - F Donnellan
- d Vancouver General Hospital , Vancouver , BC , Canada
| | | | - C Teshima
- f St. Michael's Hospital and University of Toronto , Toronto , ON , Canada
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Gan C, Chen YH, Liu L, Gao JH, Tong H, Tang CW, Liu R. Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis. Oncotarget 2017; 8:94920-94931. [PMID: 29212278 PMCID: PMC5706924 DOI: 10.18632/oncotarget.21659] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/21/2017] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pancreatic enzyme replacement therapy (PERT) is widely applied to patients with exocrine pancreatic insufficiency (EPI), but its effect and safety has not been quantified. Therefore we performed a meta-analysis to determine the efficacy and tolerance of PERT on patients with EPI. MATERIALS AND METHODS PubMed, Medline, Cochrane library database, Evidence-based medicine/clinical trials published before December 2016 were searched by two independent reviewers to identify prospective randomized controlled trials (RCTs). RESULTS Seven RCTs, randomizing a total of 282 patients, were filtrated and assessed qualitatively (Jadad score). PERT increased CFA (WMD: 26.56, 20.35 to 32.76, I2= 79.6%, P < 0.001) compared with baseline, and CFA (WMD: 17.97, 12.61 to 23.34, I2 = 76.7%, P < 0.001) vs. placebo. Meanwhile, CNA, SFE, SNE and SW were significantly improved in PERT compared with baseline and placebo, with no statistical differences in adverse events. Subgroup analysis indicated that standard forms of PERT displayed more effectiveness with significantly decreased heterogeneity, and large sample size also reduced the heterogeneity to some degree. CONCLUSIONS PERT is demonstrated to be effective and tolerable in patients with EPI, especially using standard administration of PERT. Larger and higher quality studies on EPI are demanded to long-term effect of standard PERT treatment.
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Affiliation(s)
- Can Gan
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yan-Hua Chen
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Ling Liu
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Jin-Hang Gao
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Huan Tong
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Cheng-Wei Tang
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Liu
- Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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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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Sperti C, Moletta L. Staging chronic pancreatitis with exocrine function tests: Are we better? World J Gastroenterol 2017; 23:6927-6930. [PMID: 29097865 PMCID: PMC5658310 DOI: 10.3748/wjg.v23.i38.6927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/07/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023] Open
Abstract
Chronic pancreatitis (CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1 (EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.
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Affiliation(s)
- Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
| | - Lucia Moletta
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, 35128 Padua, Italy
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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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Vujasinovic M, Valente R, Del Chiaro M, Permert J, Löhr JM. Pancreatic Exocrine Insufficiency in Pancreatic Cancer. Nutrients 2017; 9:183. [PMID: 28241470 PMCID: PMC5372846 DOI: 10.3390/nu9030183] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/27/2017] [Accepted: 02/17/2017] [Indexed: 12/12/2022] Open
Abstract
Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.
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Affiliation(s)
- Miroslav Vujasinovic
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm SE-141 86, Sweden.
| | - Roberto Valente
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm SE-141 86, Sweden.
| | - Marco Del Chiaro
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm SE-141 86, Sweden.
| | - Johan Permert
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm SE-141 86, Sweden.
| | - J-Matthias Löhr
- Center for Digestive Diseases, Karolinska University Hospital, Stockholm SE-141 86, Sweden.
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Limitations of Postoperative Assessment for Pancreatic Exocrine Insufficiency in Pancreatic Malignancy. Pancreas 2017; 46:e12. [PMID: 28085754 DOI: 10.1097/mpa.0000000000000702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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