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Aronen A, Guilabert L, Hadi A, Kiudelis V, Panaitescu A, Wlodarczyk B, Laukkarinen J, Regner S, de-Madaria E. Idiopathic acute pancreatitis (IAP)-a review of the literature and algorithm proposed for the diagnostic work-up of IAP. Transl Gastroenterol Hepatol 2024; 9:71. [PMID: 39503029 PMCID: PMC11535791 DOI: 10.21037/tgh-23-125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 06/23/2024] [Indexed: 11/08/2024] Open
Abstract
Background and Objective This narrative review addresses idiopathic acute pancreatitis (IAP) and its epidemiology, diagnosis, clinical course and treatment during the last decade. As there is no previously validated protocol for finding the aetiology of acute pancreatitis (AP), the primary aim of this study is to find, describe and unify evidence about the diagnostic work-up of AP to diagnose the true IAP. By finding the aetiology with the highest possible yield it may be possible to reduce recurrent AP (RAP) episodes and related morbidity and thereby decrease health care costs and possibly improve patients' quality of life. Methods This narrative review includes articles retrieved from PubMed search with publications from 2013-2023. Cross references were used when found relevant. Key Content and Findings The rates of aetiologies of AP and the diagnostics performed behind these numbers vary widely between different studies, time periods and different geographical regions, as there is no unified algorithm in diagnostic work-up of IAP. In this study, we describe an up-to-date summary of epidemiology, diagnostic course and treatment of IAP, and propose an algorithm of IAP diagnostics in light of recent scientific studies and their outcomes and address possible treatments of IAP. Conclusions Although aetiology is key for AP management, there is still no validated protocol for aetiological diagnosis. IAP is relevant due to its recurrence rate and possible evolution to chronic pancreatitis. We still need more studies addressing this topic and evaluating new diagnostic protocols with advanced tests and treatment strategies in true IAP.
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Affiliation(s)
- Anu Aronen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Lucía Guilabert
- Gastroenterology Department, Dr. Balmis General University Hospital, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | - Amer Hadi
- Pancreatitis Centre East, Gastrounit, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Copenhagen, Denmark
| | - Vytautas Kiudelis
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Afrodita Panaitescu
- Gastroenterology and Interventional Endoscopy Department, Bucharest Clinical Emergency Hospital, Bucharest, Romania
| | - Barbara Wlodarczyk
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Sara Regner
- Surgery Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
- Department of Surgery and Gastroenterology, Skåne University Hospital, Malmö, Sweden
| | - Enrique de-Madaria
- Gastroenterology Department, Dr. Balmis General University Hospital, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
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2
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Tsomidis I, Voumvouraki A, Kouroumalis E. The Pathogenesis of Pancreatitis and the Role of Autophagy. GASTROENTEROLOGY INSIGHTS 2024; 15:303-341. [DOI: 10.3390/gastroent15020022] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.
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Affiliation(s)
- Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece
| | - Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
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3
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Hines OJ, Pandol SJ. Management of chronic pancreatitis. BMJ 2024; 384:e070920. [PMID: 38408777 DOI: 10.1136/bmj-2023-070920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Chronic pancreatitis results from repeated episodes of pancreatic inflammation and associated fibrosis leading to the loss of functional exocrine and endocrine pancreatic function. The disease is manifested by abdominal pain, deterioration in quality of life, food maldigestion and malabsorption, diabetes, and an increased risk for pancreatic adenocarcinoma. This review summarizes the latest evidence on the diagnosis and management of chronic pancreatitis and its manifestations. In particular, this review discusses advances in understanding of the role of genetic disorders in the mechanisms of the disease and surgical options for patients refractory to medical therapy. Furthermore, clinical trials are under way to develop medical therapeutics.
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Affiliation(s)
- O Joe Hines
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Stephen J Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Park SM. Sex/Gender Differences in Pancreatic and Biliary Diseases. SEX/GENDER-SPECIFIC MEDICINE IN CLINICAL AREAS 2024:219-230. [DOI: 10.1007/978-981-97-0130-8_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Lee JM, Han KD, Lee SH, Park JM, Park N, Jeon H, Kim HJ, Ryu JK, Kim YT. The association between smoking, changes in smoking behavior, and acute pancreatitis: A population-based cohort study in Korea. J Gastroenterol Hepatol 2023; 38:451-459. [PMID: 36367354 DOI: 10.1111/jgh.16061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 10/20/2022] [Accepted: 11/09/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND AND AIMS In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population. METHODS We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018. RESULTS The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in <10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54). CONCLUSIONS In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.
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Affiliation(s)
- Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, South Korea
| | - Kyung Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin Myung Park
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Namyoung Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Hankyu Jeon
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, South Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, South Korea
| | - Ji Kon Ryu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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Bhargava A. Unraveling corticotropin-releasing factor family-orchestrated signaling and function in both sexes. VITAMINS AND HORMONES 2023; 123:27-65. [PMID: 37717988 DOI: 10.1016/bs.vh.2023.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Stress responses to physical, psychological, environmental, or cellular stressors, has two arms: initiation and recovery. Corticotropin-releasing factor (CRF) is primarily responsible for regulating and/or initiating stress responses via, whereas urocortins (UCNs) are involved in the recovery response to stress via feedback inhibition. Stress is a loaded, polysemous word and is experienced in a myriad of ways. Some stressors are good for an individual, in fact essential, whereas other stressors are associated with bad outcomes. Perceived stress, like beauty, lies in the eye of the beholder, and hence the same stressor can result in individual-specific outcomes. In mammals, there are two main biological sexes with reproduction as primary function. Reproduction and nutrition can also be viewed as stressors; based on a body of work from my laboratory, we propose that the functions of all other organs have co-evolved to optimize and facilitate an individual's nutritional and reproductive functions. Hence, sex differences in physiologically relevant outcomes are innate and occur at all levels- molecular, endocrine, immune, and (patho)physiological. CRF and three UCNs are peptide hormones that mediate their physiological effects by binding to two known G protein-coupled receptors (GPCRs), CRF1 and CRF2. Expression and function of CRF family of hormones and their receptors is likely to be sexually dimorphic in all organs. In this chapter, based on the large body of work from others and my laboratory, an overview of the CRF family with special emphasis on sex-specific actions of peripherally expressed CRF2 receptor in health and disease is provided.
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Affiliation(s)
- Aditi Bhargava
- Center for Reproductive Sciences, Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, CA, United States.
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Zeng XP, Zeng JH, Wang R, Wang W. Pathogenesis, diagnosis, and treatment of malnutrition in patients with chronic pancreatitis. Shijie Huaren Xiaohua Zazhi 2023; 31:92-97. [DOI: 10.11569/wcjd.v31.i3.92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Chronic pancreatitis (CP) is a persistent and progressive pancreatic inflammatory disease. Malnutrition is a common clinical manifestation in CP patients, which is mainly caused by pancreatic exocrine insufficiency but may also be related to pancreatic endocrine insufficiency and changes of living habit. At present, there is still a lack of gold standard for the diagnosis of malnutrition in patients with CP. Clinicians should comprehensively evaluate such patients through anthropometric parameters, test parameters, imaging diagnosis, pancreatic exocrine function detection, etc., detect malnutrition early, and take timely intervention measures, including improving diet and living habits, enteral/parenteral nutrition, pancreatic enzyme replacement therapy, acid suppressant adjuvant therapy, regulating intestinal flora, and administration of Chinese medicine. And endoscopic and surgical treatment should be used when necessary.
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Affiliation(s)
- Xiang-Peng Zeng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fuzhou 350001, Fujian Province, China
| | - Jing-Hui Zeng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fuzhou 350001, Fujian Province, China
| | - Rong Wang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fuzhou 350001, Fujian Province, China
| | - Wen Wang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fuzhou 350001, Fujian Province, China
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Smoking as the most important risk factor for chronic pancreatitis in the general population. Eur J Epidemiol 2023; 38:95-107. [PMID: 36593333 DOI: 10.1007/s10654-022-00945-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 11/13/2022] [Indexed: 01/04/2023]
Abstract
We tested the hypothesis that six toxic risk factors from the TIGAR-O classification system are equally important for risk of chronic pancreatitis, at the level of the individual patient and in the general population. 108,438 women and men aged 20-100 years participating in the Copenhagen General Population Study from 2003 to 2015 were included. Associations of smoking, alcohol intake, waist/hip ratio, kidney function, plasma triglycerides, plasma Ca2+, and diseases within the causal pathway with risk of chronic pancreatitis, and corresponding population attributable risks were estimated. Information on chronic pancreatitis was from national Danish health registries. During median 9 years (range: 0-15) of follow-up, 313 individuals had a first diagnosis of chronic pancreatitis; the incidence of chronic pancreatitis per 10,000 person-years were 3.1 overall, 2.8 in women, and 3.5 in men. Of the six toxic risk factors and relative to individuals with low values, individuals in the top 5% had hazard ratios for chronic pancreatitis of 3.1(95% CI 2.1-4.5) for pack-years smoked, 2.5(1.5-4.0) for alcohol intake, and 1.6(1.1-2.6) for plasma triglycerides. Corresponding values versus those without the baseline disease were 12.6 (7.9-20.2) for acute pancreatitis, 1.9 (1.2-2.8) for gallstone disease, and 1.9 (1.3-2.7) for diabetes mellitus. The highest population attributable fractions were for women (1) ever smoking (31%), (2) gallstone disease (5%), and (3) diabetes mellitus (4%), and for men (1) ever smoking (38%), (2) acute pancreatitis (7%)/high alcohol intake (7%), and (3) high plasma triglycerides (5%). Smoking is the most important risk factor for chronic pancreatitis in the general population.
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9
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Nikkola A, Mäkelä KA, Herzig KH, Mutt SJ, Prasannan A, Seppänen H, Lehtimäki T, Kähönen M, Raitakari O, Seppälä I, Pakkanen P, Nordback I, Sand J, Laukkarinen J. Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis. Int J Mol Sci 2022; 23:ijms232415726. [PMID: 36555366 PMCID: PMC9778821 DOI: 10.3390/ijms232415726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/27/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022] Open
Abstract
Only 3-5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode (n = 60) and recurrent AAP (n = 43) and from heavy alcohol users without a history of AAP (n = 98) as well as from a control population (n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32-5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15-74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.
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Affiliation(s)
- Anssi Nikkola
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33520 Tampere, Finland; (A.N.); (J.S.)
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
| | - Kari Antero Mäkelä
- Research Unit of Biomedicine, Oulu University, 90220 Oulu, Finland; (K.A.M.); (K.-H.H.); (S.J.M.); (A.P.)
| | - Karl-Heinz Herzig
- Research Unit of Biomedicine, Oulu University, 90220 Oulu, Finland; (K.A.M.); (K.-H.H.); (S.J.M.); (A.P.)
- Medical Research Center Oulu, Oulu University, Oulu University Hospital, 90220 Oulu, Finland
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland
| | - Shivaprakash Jagalur Mutt
- Research Unit of Biomedicine, Oulu University, 90220 Oulu, Finland; (K.A.M.); (K.-H.H.); (S.J.M.); (A.P.)
| | - Aishwarya Prasannan
- Research Unit of Biomedicine, Oulu University, 90220 Oulu, Finland; (K.A.M.); (K.-H.H.); (S.J.M.); (A.P.)
| | - Hanna Seppänen
- Department of Surgery, Helsinki University Hospital, 00260 Helsinki, Finland;
| | - Terho Lehtimäki
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
- Fimlab Laboratories, Department of Clinical Chemistry, 33520 Tampere, Finland;
- Finnish Cardiovascular Research Center, 33520 Tampere, Finland
| | - Mika Kähönen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
- Finnish Cardiovascular Research Center, 33520 Tampere, Finland
- Department of Clinical Physiology, Tampere University Hospital, 33520 Tampere, Finland
| | - Olli Raitakari
- Centre for Population Health Research, University of Turku and Turku University Hospital, 20521 Turku, Finland;
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20014 Turku, Finland
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521 Turku, Finland
| | - Ilkka Seppälä
- Fimlab Laboratories, Department of Clinical Chemistry, 33520 Tampere, Finland;
| | - Pihla Pakkanen
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
- Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, 00260 Helsinki, Finland
| | - Isto Nordback
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
| | - Juhani Sand
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33520 Tampere, Finland; (A.N.); (J.S.)
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33520 Tampere, Finland; (A.N.); (J.S.)
- Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; (T.L.); (M.K.); (P.P.); (I.N.)
- Correspondence: ; Tel.:+358-3-311-64314
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Sagar AJ, Khan M, Tapuria N. Evidence-Based Approach to the Surgical Management of Acute Pancreatitis. Surg J (N Y) 2022; 8:e322-e335. [PMID: 36425407 PMCID: PMC9681540 DOI: 10.1055/s-0042-1758229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
Background
Acute pancreatitis is a significant challenge to health services. Remarkable progress has been made in the last decade in optimizing its management.
Methods
This review is a comprehensive assessment of 7 guidelines employed in current clinical practice with an appraisal of the underlying evidence, including 15 meta-analyses/systematic reviews, 16 randomized controlled trials, and 31 cohort studies.
Results
Key tenets of early management of acute pancreatitis include severity stratification based on the degree of organ failure and early goal-directed fluid resuscitation. Rigorous determination of etiology reduces the risk of recurrence. Early enteral nutrition and consideration of epidural analgesia have been pioneered in recent years with promising results. Indications for invasive intervention are becoming increasingly refined. The definitive indications for endoscopic retrograde cholangiopancreatography in acute pancreatitis are associated with cholangitis and common bile duct obstruction. The role of open surgical necrosectomy has diminished with the development of a minimally invasive step-up necrosectomy protocol. Increasing use of endoscopic ultrasound–guided intervention in the management of pancreatic necrosis has helped reduce pancreatic fistula rates and hospital stay.
Conclusion
The optimal approach to surgical management of complicated pancreatitis depends on patient physiology and disease anatomy, in addition to the available resources and expertise. This is best achieved with a multidisciplinary approach. This review provides a distillation of the recommendations of clinical guidelines and critical discussion of the evidence that informs them and presents an algorithmic approach to key areas of patient management.
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Affiliation(s)
- Alex James Sagar
- Nuffield Department of Surgical Sciences, Oxford University, Oxford, United Kingdom,Address for correspondence Alex James Sagar, MRCS Nuffield Department of Surgical Sciences, Oxford UniversityOxfordUnited Kingdom
| | - Majid Khan
- Acute Care Common Stem, Whipps Cross Hospital, London, United Kingdom
| | - Niteen Tapuria
- Department of General Surgery, Milton Keynes University Hospital, Milton Keynes, United Kingdom
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11
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Han E(F, Koea J, Hammill C, Srinivasa S. The importance of smoking cessation in pancreatitis. ANZ J Surg 2022; 92:2780-2781. [PMID: 36398341 PMCID: PMC9828374 DOI: 10.1111/ans.17843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/05/2022] [Accepted: 05/19/2022] [Indexed: 11/19/2022]
Affiliation(s)
- Eunjong (Franklin) Han
- Upper GI Unit, Department of Surgery, North Shore HospitalUniversity of AucklandAucklandNew Zealand
| | - Jonathan Koea
- Upper GI Unit, Department of Surgery, North Shore HospitalUniversity of AucklandAucklandNew Zealand
| | - Chet Hammill
- Section of HPB SurgeryWashington University/ Barnes Jewish HospitalSt LouisMissouriUSA
| | - Sanket Srinivasa
- Upper GI Unit, Department of Surgery, North Shore HospitalUniversity of AucklandAucklandNew Zealand
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12
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Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, Beyer G, Sutton R. Acute Pancreatitis: Diagnosis and Treatment. Drugs 2022; 82:1251-1276. [PMID: 36074322 PMCID: PMC9454414 DOI: 10.1007/s40265-022-01766-4] [Citation(s) in RCA: 200] [Impact Index Per Article: 66.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2022] [Indexed: 11/11/2022]
Abstract
Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal cross-sectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.
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Affiliation(s)
- Peter Szatmary
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, UK
| | - Wenhao Cai
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,West China Centre of Excellence for Pancreatitis and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Rajarshi Mukherjee
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.,Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool , UK
| | - Chris Halloran
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Georg Beyer
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. .,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. .,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
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Han SY, Conwell DL, Diaz PT, Ferketich A, Jeon CY, Yadav D, Hart PA. The deleterious effects of smoking on the development and progression of chronic pancreatitis. Pancreatology 2022; 22:683-687. [PMID: 35981948 PMCID: PMC9474634 DOI: 10.1016/j.pan.2022.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/05/2022] [Accepted: 08/07/2022] [Indexed: 12/11/2022]
Affiliation(s)
- Samuel Y Han
- Division of Gastroenterology, Hepatology, and Nutrition. the Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Darwin L Conwell
- Department of Internal Medicine. University of Kentucky College of Medicine, Lexington, KY, USA
| | - Philip T Diaz
- Division of Pulmonary, Critical Care, and Sleep Medicine. the Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Amy Ferketich
- Division of Epidemiology. the Ohio State University College of Public Health, Columbus, OH, USA
| | - Christie Y Jeon
- Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition. the Ohio State University Wexner Medical Center, Columbus, OH, USA.
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14
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Hao L, Liu Y, Dong ZQ, Yi JH, Wang D, Xin L, Guo HL, He L, Bi YW, Ji JT, Wang T, Du TT, Lin JH, Zhang D, Zeng XP, Zou WB, Chen H, Pan J, Liao Z, Xu GQ, Li ZS, Hu LH. Clinical characteristics of smoking-related chronic pancreatitis. Front Cell Infect Microbiol 2022; 12:939910. [PMID: 36061871 PMCID: PMC9433580 DOI: 10.3389/fcimb.2022.939910] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 07/25/2022] [Indexed: 11/17/2022] Open
Abstract
Objective The pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking. Design Patients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively. Results A total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea. Conclusion The clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.
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Affiliation(s)
- Lu Hao
- Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Yu Liu
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Zhi-Qi Dong
- Department of Gastroenterology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jin-Hui Yi
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Dan Wang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Lei Xin
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Hong-Lei Guo
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Lin He
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- Department of Gastroenterology and Endocrinology, 969th Hospital of People's Liberation Army (PLA), Hohhot, China
| | - Ya-Wei Bi
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- Department of Gastroenterology and Hepatology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Jun-Tao Ji
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- Shanghai Guangming Middle School, Shanghai, China
| | - Teng Wang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Ting-Ting Du
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Jin-Huan Lin
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Di Zhang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Xiang-Peng Zeng
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fuzhou, China
| | - Wen-Bin Zou
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Hui Chen
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Jun Pan
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhuan Liao
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Guo-Qiang Xu
- Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- *Correspondence: Guo-Qiang Xu, ; Zhao-Shen Li, ; Liang-Hao Hu,
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- *Correspondence: Guo-Qiang Xu, ; Zhao-Shen Li, ; Liang-Hao Hu,
| | - Liang-Hao Hu
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- *Correspondence: Guo-Qiang Xu, ; Zhao-Shen Li, ; Liang-Hao Hu,
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15
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Kassay N, Toldi V, Tőzsér J, Szabó A. Cigarette smoke toxin hydroquinone and misfolding pancreatic lipase variant cooperatively promote endoplasmic reticulum stress and cell death. PLoS One 2022; 17:e0269936. [PMID: 35704637 PMCID: PMC9200355 DOI: 10.1371/journal.pone.0269936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 05/31/2022] [Indexed: 01/07/2023] Open
Abstract
Mutation-induced protein misfolding of pancreatic secretory enzymes and consequent endoplasmic reticulum stress can cause chronic pancreatitis. A recent study revealed that cigarette smoke also increases the risk of the disease through endoplasmic reticulum stress. Here, we investigated the cumulative cellular effect of the G233E misfolding human pancreatic lipase variant and hydroquinone; a main toxic constituent of cigarette smoke, using mammalian cell lines. We found that hydroquinone reduces cell viability on a dose-dependent manner through programmed cell death, and diminishes lipase secretion without affecting its expression. Interestingly, hydroquinone decreased the viability more markedly in cells expressing the G233E lipase variant, than in cells producing wild-type lipase. The more substantial viability loss was due to increased endoplasmic reticulum stress, as demonstrated by elevated levels of X-box binding protein 1 mRNA splicing and immunoglobulin binding protein, NAD(P)H:quinone oxidoreductase 1 and C/EBP homologous protein expression. Unresolved endoplasmic reticulum stress, and especially up-regulation of the pro-apoptotic transcription factor C/EBP homologous protein were likely responsible for the increased cell death. Our observations demonstrated that the combination of hydroquinone and misfolding pancreatic lipase variant promote increased levels of endoplasmic reticulum stress and cell death, which may predispose to chronic pancreatitis.
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Affiliation(s)
- Norbert Kassay
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Doctoral School of Molecular, Cell and Immune Biology, University of Debrecen, Debrecen, Hungary
| | - Vanda Toldi
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Doctoral School of Molecular, Cell and Immune Biology, University of Debrecen, Debrecen, Hungary
| | - József Tőzsér
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - András Szabó
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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16
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Li H, Wen W, Luo J. Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis. Biomedicines 2022; 10:biomedicines10010108. [PMID: 35052788 PMCID: PMC8773075 DOI: 10.3390/biomedicines10010108] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 02/04/2023] Open
Abstract
Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.
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Affiliation(s)
- Hui Li
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Wen Wen
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
| | - Jia Luo
- Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; (H.L.); (W.W.)
- Iowa City VA Health Care System, Iowa City, IA 52246, USA
- Correspondence: ; Tel.: +1-319-335-2256
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17
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Yelskyi IK, Vasylyev AA, Smirnov NL. USING NEURAL NETWORK MODELING TO PREDICT THE COURSE OF ACUTE PANCREATITIS. SURGICAL PRACTICE 2021. [DOI: 10.38181/2223-2427-2021-4-23-32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The database of studies of 82 patients with acute pancreatitis are presented. Using neural network analysis, the most indicative parameters for predicting acute pancreatitis were revealed: indexes of Kalf-Kalif intoxication modified by Kostyuchenko and Khomich, Reis, Garkavi, the ratio of leukocytes to ESR, leukocyte index, general intoxication index; sonographic parameters – the size of the head of the pancreas, the diameter of the splenic vein, the presence of free fluid in the abdominal cavity; biochemical parameters – blood amylase concentration, urine diastase. When conducting clustering in a multidimensional feature space, a Kohonen neural network was created. All analyzed objects were effectively divided into 3 clusters. The most severe and prognostically unfavorable is cluster 1, which included data from 30 patients, with the maximum mortality rate and maximum hospital stay.
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Affiliation(s)
- I. K. Yelskyi
- State educational institution of higher professional education «M. Gorky Donetsk national medical university»
| | - A. A. Vasylyev
- State educational institution of higher professional education «M. Gorky Donetsk national medical university»
| | - N. L. Smirnov
- State educational institution of higher professional education «M. Gorky Donetsk national medical university»
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18
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Grigor’eva IN, Efimova OV. Risk factors for pancreatitis and pancreatic cancer. TERAPEVT ARKH 2021; 93:875-882. [DOI: 10.26442/00403660.2021.08.200970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 08/31/2021] [Indexed: 12/16/2022]
Abstract
Aim. To identify and compare the frequency of alcohol consumption, tobacco smoking, levels of main macronutrients, vitamins and mineral elements consumption in patients with acute (AP) and chronic pancreatitis (CP) and pancreatic cancer (PC).
Materials and methods. At the observational clinical cross-sectional uncontrolled case-study 65 patients with AP or CP (group 1) and 45 patients with PC (group 2) were examined. A survey of patients was carried out: questionnaire on tobacco smoking, a frequency questionnaire on alcohol consumption, a questionnaire for assessing the frequency of food consumption.
Results. The frequency of smoking (33.8, 20.0%; p0.05), alcohol consumption 1 times/week during the last year (21.5, 15.6%; p0.05) did not differ significantly between the two groups. The highest consumption rates of total, vegetable, animal protein, total carbohydrates, refined sugar, animal fat, cholesterol, MUFA, dietary fiber, vitamins (-carotene, vitamin B1, B2, C, PP), mineral elements (iron, potassium, calcium, magnesium, sodium, phosphorus) and the daily energy content of the diet were determined in PC than in the AP and CP group. Among patients of group 1, deficient intake of fat-soluble vitamin A (93.3, 54.8%; p=0.009) and vitamin E (80.0, 48.4%; p=0.041) was more common in the subgroup of patients with excretory pancreatic insufficiency than without it, and the chance of having hypercholesterolemia was associated with a deficient intake of vitamin E [Ex(B)=3.3, 95% CI 1.59.3; p=0.027].
Conclusion. There were no differences in the frequency of smoking and alcohol consumption between patients with AP and CP and PC. The highest indices of the main macronutrients, daily energy content of the diet, micronutrients (except for vitamins A, E) were found in PC than in the group of patients with AP and CP. Among patients with AP and CP with excretory pancreatic insufficiency, a lower intake of fat-soluble vitamins was noted and associations of hypercholesterolemia with deficient intake of vitamin E were obtained.
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19
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Lin Y, Chen Y, Feng W, Zhang J, Hua R, Yin B, Yang X. STAT5 promotes chronic pancreatitis by enhancing GM-CSF-dependent neutrophil augmentation. J Leukoc Biol 2021; 110:293-300. [PMID: 34184320 DOI: 10.1002/jlb.3ma1020-647r] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 05/05/2021] [Accepted: 05/21/2021] [Indexed: 12/16/2022] Open
Abstract
Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas, characterized by fibrosis of the whole tissue. The regulatory mechanisms of the immune microenvironment in the pathogenesis of CP are still not clear. Immune cells, especially myeloid cells, play an important role in the pathogenesis of pancreatitis. Understanding the regulatory mechanisms of immune infiltration has a significant impact on CP intervention. Here, we demonstrated that transcription factor STAT5 was involved in and critical for the progression of CP. Inflammatory stress could significantly increase the expression and activation of STAT5 during CP. STAT5 deficiency or inhibition contributed to alleviating pancreatic inflammation and fibrosis in CP mice. The increased neutrophil infiltration, mediated by up-regulated GM-CSF, was responsible for the pancreatitis-promoting activity of STAT5. Our investigation highlighted the importance of STAT5 in regulating the immune microenvironment of CP. Targeting STAT5 may hold distinct promise for clinical treatment to alleviate CP.
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Affiliation(s)
- Yuli Lin
- Clinical Research Center, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yusheng Chen
- Department of Pancreatic Surgery, Department of Oncology, Shanghai Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wenxue Feng
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Junfeng Zhang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Rong Hua
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bo Yin
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Xuguang Yang
- Clinical Research Center, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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20
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Zhou L, Gao YW, Xu SX, Lu GT, Xiao WM. Meta-analysis of risk factors for recurrent acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2021; 29:517-525. [DOI: 10.11569/wcjd.v29.i10.517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND With the continuous improvement of living standards, the incidence of recurrent acute pancreatitis is also increasing year by year, and this disease has become a hot research topic in recent years. Understanding the etiology of recurrent acute pancreatitis has become an urgent problem to be solved in clinical practice.
AIM To explore the risk factors for recurrent acute pancreatitis (RAP) by means of systematic evaluation, and provide evidence for better prevention of RAP.
METHODS We searched CNKI, CBM, VIP, Wanfang, The Cochrane Library, PubMed, Embase, and Web of Science databases to collect case-control and cohort studies on the risk factors associated with RAP from January 1, 2000 to February 29, 2020. "Pancreatitis", "recurrence", "risk factors", and their free words were selected as keywords. The retrieved articles were evaluated and filtrated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed based on the articles scored above 6 by using Revman5.3 software.
RESULTS A total of 15 articles were included, with the cumulative number of cases and controls reaching 2258 and 8482, respectively. The results of meta-analysis showed that alcohol consumption [odds ratio [OR] = 1.83, 95%CI (1.30, 2.59), P = 0.0006], smoking [OR = 2.09, 95%CI (1.61, 2.73), P < 0.00001], biliary AP [OR = 1.82, 95%CI (1.28, 2.57), P = 0.0008], hypertriacylglyceremic AP [OR = 2.24, 95%CI (1.76, 2.85), P < 0.00001], alcoholic AP [OR = 2.68, 95%CI (2.03, 3.55), P < 0.00001], diabetes [OR = 1.57, 95%CI (1.48, 1.66), P < 0.00001], fatty liver [OR = 2.05, 95%CI (1.22, 3.47), P = 0.007], and CT score [OR = 3.52, 95%CI (2.28, 5.43), P < 0.00001] were statistically significant risk factors for RAP.
CONCLUSION Current evidence shows that the risk factors for RAP include disease factors (biliary, alcoholic, and hypertriacylglyceremic AP, fatty liver, and diabetes), behavioral factors (alcohol consumption and smoking), and related indicators (CT score). Due to the limited quantity and quality of included studies, more prospective high-quality clinical studies are needed to verify the above conclusion.
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Affiliation(s)
- Lu Zhou
- Yangzhou University Medical Academy, Yangzhou 225000, Jiangsu Province, China
| | - Yi-Wen Gao
- School of Nursing, Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Song-Xin Xu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Guo-Tao Lu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
| | - Wei-Ming Xiao
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
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21
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Huang C, Iovanna J, Santofimia-Castaño P. Targeting Fibrosis: The Bridge That Connects Pancreatitis and Pancreatic Cancer. Int J Mol Sci 2021; 22:4970. [PMID: 34067040 PMCID: PMC8124541 DOI: 10.3390/ijms22094970] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/04/2021] [Accepted: 05/05/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic fibrosis is caused by the excessive deposits of extracellular matrix (ECM) and collagen fibers during repeated necrosis to repair damaged pancreatic tissue. Pancreatic fibrosis is frequently present in chronic pancreatitis (CP) and pancreatic cancer (PC). Clinically, pancreatic fibrosis is a pathological feature of pancreatitis and pancreatic cancer. However, many new studies have found that pancreatic fibrosis is involved in the transformation from pancreatitis to pancreatic cancer. Thus, the role of fibrosis in the crosstalk between pancreatitis and pancreatic cancer is critical and still elusive; therefore, it deserves more attention. Here, we review the development of pancreatic fibrosis in inflammation and cancer, and we discuss the therapeutic strategies for alleviating pancreatic fibrosis. We further propose that cellular stress response might be a key driver that links fibrosis to cancer initiation and progression. Therefore, targeting stress proteins, such as nuclear protein 1 (NUPR1), could be an interesting strategy for pancreatic fibrosis and PC treatment.
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Affiliation(s)
| | | | - Patricia Santofimia-Castaño
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13288 Marseille, France; (C.H.); (J.I.)
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22
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Sex Differences in the Exocrine Pancreas and Associated Diseases. Cell Mol Gastroenterol Hepatol 2021; 12:427-441. [PMID: 33895424 PMCID: PMC8255941 DOI: 10.1016/j.jcmgh.2021.04.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
Differences in pancreatic anatomy, size, and function exist in men and women. The anatomical differences could contribute to the increase in complications associated with pancreatic surgery in women. Although diagnostic criteria for pancreatitis are the same in men and women, major sex differences in etiology are reported. Alcohol and tobacco predominate in men, whereas idiopathic and obstructive etiologies predominate in women. Circulating levels of estrogens, progesterone, and androgens contribute significantly to overall health outcomes; premenopausal women have lower prevalence of cardiovascular and pancreatic diseases suggesting protective effects of estrogens, whereas androgens promote growth of normal and cancerous cells. Sex chromosomes and gonadal and nongonadal hormones together determine an individual's sex, which is distinct from gender or gender identity. Human pancreatic disease etiology, outcomes, and sex-specific mechanisms are largely unknown. In rodents of both sexes, glucocorticoids and estrogens from the adrenal glands influence pancreatic secretion and acinar cell zymogen granule numbers. Lack of corticotropin-releasing factor receptor 2 function, a G protein-coupled receptor whose expression is regulated by both estrogens and glucocorticoids, causes sex-specific changes in pancreatic histopathology, zymogen granule numbers, and endoplasmic reticulum ultrastructure changes in acute pancreatitis model. Here, we review existing literature on sex differences in the normal exocrine pancreas and mechanisms that operate at homeostasis and diseased states in both sexes. Finally, we review pregnancy-related pancreatic diseases and discuss the effects of sex differences on proposed treatments in pancreatic disease.
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23
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Lin Y, Chen Y, Feng W, Hua R, Zhang J, Huo Y, Jiang H, Yin B, Yang X. Neddylation pathway alleviates chronic pancreatitis by reducing HIF1α-CCL5-dependent macrophage infiltration. Cell Death Dis 2021; 12:273. [PMID: 33723230 PMCID: PMC7960984 DOI: 10.1038/s41419-021-03549-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 02/19/2021] [Accepted: 02/22/2021] [Indexed: 12/14/2022]
Abstract
Chronic pancreatitis (CP) is characterized by a wide range of irreversible fibro-inflammatory diseases with largely ambiguous pathogenesis. Although neddylation pathway has been implicated in regulating immune responses, whether the dysregulation of neddylation is involved in the progression of CP and how neddylation regulates the inflammatory microenvironment of CP have not yet been reported. Here, we demonstrate that global inactivation of neddylation pathway by MLN4924 significantly exacerbates chronic pancreatitis. The increased M2 macrophage infiltration, mediated by the upregulated chemokine (C-C motif) ligand 5 (CCL5), is responsible for the enhanced pancreatitis-promoting activity of MLN4924. Both CCL5 blockade and macrophage depletion contribute to alleviating pancreatic fibrosis and inflammation in MLN4924-treated CP mice. Mechanistic investigation identifies that inactivation of Cullin-RING ligases (CRLs) stabilizes cellular levels of hypoxia-inducible factor 1α (HIF-1α), which increases CCL5 expression by promoting CCL5 transactivation. Clinically, UBE2M expression remarkably decreases in human CP tissues compared with normal specimens and the levels of CCL5 and M2 marker CD163 are negatively correlated with UBE2M intensity, suggesting that neddylation is involved in the pathogenesis of pancreatitis. Hence, our studies reveal a neddylation-associated immunopathogenesis of chronic pancreatitis and provide new ideas for the disease treatment.
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Affiliation(s)
- Yuli Lin
- Clinical Research Center, Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
| | - Yusheng Chen
- Department of Pancreatic Surgery, Department of Oncology, Pancreatic Cancer Institute, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenxue Feng
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Rong Hua
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Junfeng Zhang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yanmiao Huo
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Jiang
- Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - Bo Yin
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
| | - Xuguang Yang
- Clinical Research Center, Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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24
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Barreto SG, Habtezion A, Gukovskaya A, Lugea A, Jeon C, Yadav D, Hegyi P, Venglovecz V, Sutton R, Pandol SJ. Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis. Gut 2021; 70:194-203. [PMID: 32973069 PMCID: PMC7816970 DOI: 10.1136/gutjnl-2020-322163] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/01/2020] [Accepted: 08/19/2020] [Indexed: 12/11/2022]
Abstract
Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.
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Affiliation(s)
- Savio George Barreto
- Division of Surgery and Perioperative Medicine, Flinders Medical Center, Bedford Park, Adelaide, South Australia, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Aida Habtezion
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Anna Gukovskaya
- Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Medicine, West Los Angeles VA Healthcare Center, Los Angeles, California, USA
| | - Aurelia Lugea
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Christie Jeon
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Dhiraj Yadav
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Peter Hegyi
- First Department of Medicine, Faculty of Medicine, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine and First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Viktória Venglovecz
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
| | - Robert Sutton
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Stephen J Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Jeon CY, Feldman R, Pendergast FJ, AlKaade S, Brand RE, Guda N, Sandhu BS, Singh VK, Wilcox CM, Slivka A, Whitcomb DC, Yadav D. Divergent trends in lifetime drinking and smoking between Black and White Americans diagnosed with chronic pancreatitis. Pancreatology 2020; 20:1667-1672. [PMID: 33132046 PMCID: PMC7737506 DOI: 10.1016/j.pan.2020.10.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 09/08/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Black Americans are at increased risk of chronic pancreatitis (CP) compared to their White counterparts. We aimed to describe the race-specific smoking history and lifetime drinking in patients diagnosed with CP. METHODS We analyzed data on 334 Black and White CP participants of the North American Pancreatitis Study 2 Continuation and Validation Study and Ancillary Study. Lifetime drinking history and lifetime smoking history were collected through in-person interviews. Intensity, frequency, duration and current status of drinking and smoking were compared between Black and White CP participants, stratified by physician-defined alcohol etiology. In addition, drinking levels at each successive decades in life (20s, 30s, 40s) were compared by race and graphically portrayed as heat diagrams. RESULTS Among patients with alcoholic CP, current smoking levels were not different by race (67-70%), but a smaller proportion of Black patients reported having smoked 1 or more packs per day in the past (32%) as compared to White patients (58%, p < 0.0001). Black patients were more likely to report current consumption of alcohol (31%), as opposed to White patients (17%, p = 0.016). Black patients also reported more intense drinking at age 35 and 45 years as compared to White patients, while age at CP onset were similar between the two groups. CONCLUSION We found more intense drinking but less intense smoking history in Black CP patients as compared to White CP patients. Effective alcohol abstinence and smoking cessation program with sustained impact are needed in CP patients.
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Affiliation(s)
- Christie Y. Jeon
- Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA,Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA
| | - Robert Feldman
- Center for Research on Healthcare Data Center, University of Pittsburgh, Pittsburgh, PA
| | | | | | - Randall E. Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Nalini Guda
- Aurora St. Luke's Medical Center, Milwaukee, WI
| | | | - Vikesh K. Singh
- Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - C. Mel Wilcox
- Division of Gastroenterology and Hepatology, University of Alabama Birmingham, AL
| | - Adam Slivka
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - David C. Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Hegyi P, Párniczky A, Lerch MM, Sheel ARG, Rebours V, Forsmark CE, Del Chiaro M, Rosendahl J, de-Madaria E, Szücs Á, Takaori K, Yadav D, Gheorghe C, Rakonczay Z, Molero X, Inui K, Masamune A, Fernandez-Del Castillo C, Shimosegawa T, Neoptolemos JP, Whitcomb DC, Sahin-Tóth M. International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 2020; 20:579-585. [PMID: 32376198 DOI: 10.1016/j.pan.2020.03.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/10/2020] [Accepted: 03/22/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. METHODS An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers. CONCLUSIONS Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.
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Affiliation(s)
- Péter Hegyi
- Institute for Translational Medicine & Department of Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary; MTA-SZTE Momentum Translational Gastroenterology Research Group, Faculty of Medicine, University of Szeged, Szeged, Hungary; First Department of Medicine, Faculty of Medicine, University of Szeged, Szeged, Hungary.
| | - Andrea Párniczky
- Institute for Translational Medicine & Department of Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Institute of Pediatrics, Budapest, Hungary
| | - Markus M Lerch
- Department of Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Andrea R G Sheel
- Department of Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, United Kingdom
| | - Vinciane Rebours
- Pancreatology Unit, Beaujon Hospital, APHP, Paris, Université de Paris, Paris-Diderot, France
| | - Chris E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery - University of Colorado Anschutz Medical Campus, Denver, USA
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - Ákos Szücs
- First Department of Surgery, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Kyoichi Takaori
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Cristian Gheorghe
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Zoltán Rakonczay
- Department of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Xavier Molero
- Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron - Institut de Recerca, Autonomous University of Barcelona, CIBEREHD, Barcelona, Spain
| | - Kazuo Inui
- Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Nagoya, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Tooru Shimosegawa
- Department of Gastroenterology, South Miyagi Medical Center, Ohgawara, Miyagi, Japan
| | - John P Neoptolemos
- Department of General Surgery, University of Heidelberg, Heidelberg, Germany
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Miklós Sahin-Tóth
- Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
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Samgina T, Nazarenko P, Polonikov A, Lazarenko V. The role of some xenobiotic biotransformation genes snp in the development of acute pancreatitis. BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY 2020:34-39. [DOI: 10.24075/brsmu.2020.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Genetically determined features of the xenobiotic biotransformation system play an important role in the development of acute pancreatitis (AP) and its complications. The aim of this study was to assess the contribution of 3 SNPs (CYP1A1 -462 T>C rs1048943, CYP2E1 -1293 G>C rs3813867 and ABCB1 -3435 G>A rs1045642) to the development of AP and its complications. DNA samples were collected from 547 unrelated patients with AP (154 women and 393 men; mean age 48.9 ± 13.1 years) undergoing therapy at surgery departments of Kursk and 573 unrelated individuals without gastrointestinal diseases (161 women and 412 men; mean age 47.8 ± 12.1 years). The polymorphisms were genotyped by PCR using TaqMan probes for allele discrimination. Infected pancreatic necrosis (IPN) was observed in 97 patients; 101 patients developed a pseudocyst (PC); 111 patients had a peripancreatic necrosis (PN). AP was the most common in the carriers of the А allele in ABCB1 G>A (rs1045642) (p = 0.0008). The carriers of the G/G genotype rarely developed both AP (p = 5·10–4) and its complications: IPN (p = 0.03R), PN (p = 0.036R), PC (p = 0.04R). The carriers of the G/C–C/C CYP2E1 G>C (rs3813867) genotypes who had no long-term history of alcohol abuse rarely developed AP (p = 0.03). The carriers of the G/C CYP2E1 (rs3813867) genotype tended to develop pseudocysts (p = 0.05OD). AP was more frequently complicated by IPN (p = 0.009R), PN (p = 0.003R) and PC (p = 0.003D) in the carriers of the C/C CYP1A1 T>C (rs1048943) genotype. A milder course of AP was typical for the carriers of the G/G ABCB1 G>A (rs1045642) genotype; a more severe course was characteristic of the carriers of the C/C CYP1A1 T>C (rs1048943) genotype.
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Xu Y, Cai X, Shi Y, Yin M, Lan G, Zhang X, Ji R, Chang Liu. Normative Pancreatic Stiffness Levels and Related Influences Established by Magnetic Resonance Elastography in Volunteers. J Magn Reson Imaging 2020; 52:448-458. [PMID: 31943515 DOI: 10.1002/jmri.27052] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 12/24/2019] [Accepted: 12/27/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Large-scale normative studies of pancreatic stiffness and potential influences have yet to be pursued via magnetic resonance elastography (MRE). PURPOSE To determine normative MRE-based pancreatic stiffness values and to examine related influential factors. STUDY TYPE Prospective. SUBJECTS In all, 361 volunteers (men, 199; women, 162) with a median age of 54.0 years and a median body mass index (BMI) of 22.86 kg/m2 were prospectively recruited. Those with no histories of smoking, alcohol abuse, and diabetes mellitus (DM) were grouped as healthy volunteers, designating all others as positive controls. FIELD STRENGTH/SEQUENCE Each volunteer underwent 3.0T pancreatic MRI at a frequency of 40 Hz. ASSESSMENT Pancreatic stiffness values, pancreatic width and volume, waist circumference, and wave distance were measured in all subjects. STATISTICAL TESTS Multiple linear regression analyses were performed to determine variables that influence MRE-determined stiffness. RESULTS The mean pancreatic stiffness in all volunteers was 1.20 ± 0.16 kPa. Stiffness levels in positive control volunteers proved significantly greater than levels in healthy volunteers (1.29 ± 0.17 kPa vs. 1.14 ± 0.13 kPa; P < 0.001). In multiple linear regression analysis, sex (P = 0.004), BMI (P < 0.001), pancreatic width (P = 0.005), smoking (P < 0.001), alcohol abuse (P < 0.001), and DM (P = 0.001) emerged as significant independent factors impacting pancreatic stiffness. Smoking, alcohol abuse, DM, and wide pancreas were associated with greater pancreatic stiffness (coefficients = 0.202, 0.183, 0.149, and 0.160, respectively), while reduced pancreatic stiffness corresponded with female sex and larger BMI (coefficient = -0.155 and -0.192, respectively). DATA CONCLUSION MRE-based pancreatic stiffness values are impacted by sex, BMI, pancreatic width, smoking, alcohol abuse, and DM. Reference values are essential for future clinical studies. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:448-458.
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Affiliation(s)
- Youli Xu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoli Cai
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu Shi
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Meng Yin
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Gongyu Lan
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xianyi Zhang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ruoyun Ji
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chang Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
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Relationship of pancreas volume to tobacco smoking and alcohol consumption following pancreatitis. Pancreatology 2020; 20:60-67. [PMID: 31708473 DOI: 10.1016/j.pan.2019.10.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/02/2019] [Accepted: 10/30/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Tobacco smoking and alcohol consumption are established risk factors for diseases of the pancreas. With the recent advances in imaging modalities (such as magnetic resonance (MR) imaging), opportunities have arisen to study pancreas size, in both health and disease. Studies investigating the relationship between tobacco smoking, alcohol consumption, and total pancreas volume (TPV) - a holistic measure of pancreatic exocrine reserve - are lacking. The aim of the present study was to investigate the associations between MR-derived TPV and tobacco smoking/alcohol consumption. METHODS This cross-sectional study recruited individuals with a history of pancreatitis and healthy controls. A validated questionnaire was used to ascertain current and lifetime tobacco smoking and alcohol consumption. TPV was quantified using MR images by two independent raters. Generalized additive models and linear regression analyses were conducted and adjusted for demographic, metabolic, and pancreatitis-related factors. RESULTS A total of 107 individuals following pancreatitis and 38 healthy controls were included. There was no statistically significant difference in TPV between any of the tobacco smoking/alcohol consumption categories of individuals following pancreatitis and healthy controls, in both unadjusted and adjusted analyses. In individuals following pancreatitis, multivariate linear regression found no association between TPV and 7 smoking- and alcohol-related variables. Sensitivity analyses constrained to individuals who did not abstain from either smoking or drinking following their first attack of pancreatitis did not yield statistical significance with TPV. In post-hoc analysis, age was significantly inversely associated with TPV in the most adjusted model (p = 0.016). CONCLUSIONS This is the first study to investigate the association between tobacco smoking, alcohol consumption, and MR-derived TPV following pancreatitis. It appears that age, but not tobacco smoking or alcohol consumption, is associated with a significantly reduced TPV.
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Abstract
The risks, measurements of severity, and management of severe acute pancreatitis and its complications have evolved rapidly over the past decade. Evidence suggests that initial goal directed therapy, nutritional support, and vigilance for pancreatic complications are best practice. Patients can develop pancreatic fluid collections including acute pancreatic fluid collections, pancreatic pseudocysts, acute necrotic collections, and walled-off necrosis. Several randomized controlled trials and cohort studies have recently highlighted the advantage of managing these conditions with a progressive approach, with initial draining for infection followed by less invasive techniques. Surgery is no longer an early intervention and may not be needed. Instead, interventional radiologic and endoscopic methods seem to be safer with at least as good survival outcomes. Newly developed evidence based quality indicators are available to assess and improve performance. Development and clinical testing of drugs to target the mechanisms of disease are necessary for further advancements.
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Affiliation(s)
- O Joe Hines
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-6904, USA
| | - Stephen J Pandol
- Department of Medicine, Cedar-Sinai Medical Center, Los Angeles, CA 90048, USA
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Aune D, Mahamat-Saleh Y, Norat T, Riboli E. Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies. Pancreatology 2019; 19:1009-1022. [PMID: 31668562 DOI: 10.1016/j.pan.2019.09.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 07/17/2019] [Accepted: 09/11/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Tobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association. METHODS PubMed and Embase databases were searched for relevant studies up to April 13th, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model. RESULTS Ten prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29-1.72, I2 = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15-1.34, I2 = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25-1.54, I2 = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18-1.42, I2 = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08-1.17, I2 = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined. CONCLUSIONS These results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.
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Affiliation(s)
- Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Nutrition, Bjørknes University College, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
| | - Yahya Mahamat-Saleh
- CESP, Fac. de Médecine - Univ. Paris-Sud, Fac. de Médecine - UVSQ, INSERM (French National Institute for Health and Medical Research), Université Paris-Saclay, 94805, Villejuif, France; Gustave Roussy, F-94805, Villejuif, France
| | - Teresa Norat
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
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Diabetes and Younger Age Are Vital and Independent Risk Factors for Acute Pancreatitis in Patients with Severe Hypertriglyceridemia. BIOMED RESEARCH INTERNATIONAL 2019; 2019:2620750. [PMID: 31737657 PMCID: PMC6817920 DOI: 10.1155/2019/2620750] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 08/24/2019] [Indexed: 02/04/2023]
Abstract
Background. The incidence of hypertriglyceridemia-induced acute pancreatitis (HIAP) is increasing worldwide, and now it is the third leading cause of acute pancreatitis in the United States. But, there are only 5% of patients with severe hypertriglyceridemia (>1000 mg/dl) which might generate acute pancreatitis. In order to explore which part of the patients is easy to develop into pancreatitis, a case-control study was performed by us to consider which patient population tend to develop acute pancreatitis in patients with severe hypertriglyceridemia. To perform a retrospective case-control study, we identified severe hypertriglyceridemia patients without AP (HNAP) and with HIAP with a fasting triglyceride level of >1000 mg/dl from The First Affiliated Hospital of Nanjing Medical University during January 1, 2014, to December 31, 2016. Baseline patient characteristics, comorbidities, and risk factors were recorded and evaluated by the univariate and multivariate logistic regression analysis for HIAP and HNAP patients. A total of 124 patients with severe hypertriglyceridemia were included in this study; of which, 62 patients were in the HIAP group and 62 were in the HNAP group. Univariate logistic regression analysis showed that there was no gender difference in both groups; however, there were more younger patients in the HIAP group than in the HNAP group (P value < 0.001), and the HIAP group had low level of high-density lipoprotein compared to the HNAP group (P<0.05). Meanwhile, the presence of pancreatitis was associated with higher level of glycemia and a history of diabetes (P<0.05). Multivariate logistic regression analysis indicated that a history of diabetes and younger age were independent risk factors for acute pancreatitis in patients with severe hypertriglyceridemia. Uncontrolled diabetes and younger age are potential risk factors in patients with severe hypertriglyceridemia to develop acute pancreatitis.
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Habtezion A, Gukovskaya AS, Pandol SJ. Acute Pancreatitis: A Multifaceted Set of Organelle and Cellular Interactions. Gastroenterology 2019; 156:1941-1950. [PMID: 30660726 PMCID: PMC6613790 DOI: 10.1053/j.gastro.2018.11.082] [Citation(s) in RCA: 177] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 10/29/2018] [Accepted: 11/15/2018] [Indexed: 12/15/2022]
Abstract
Acute pancreatitis is an inflammatory disorder of the exocrine pancreas associated with tissue injury and necrosis. The disease can be mild, involving only the pancreas, and resolve spontaneously within days or severe, with systemic inflammatory response syndrome-associated extrapancreatic organ failure and even death. Importantly, there are no therapeutic agents currently in use that can alter the course of the disease. This article emphasizes emerging findings that stressors (environmental and genetic) that cause acute pancreatitis initially cause injury to organelles of the acinar cell (endoplasmic reticulum, mitochondria, and endolysosomal-autophagy system), and that disorders in the functions of the organelles lead to inappropriate intracellular activation of trypsinogen and inflammatory pathways. We also review emerging work on the role of damage-associated molecular patterns in mediating the local and systemic inflammatory response in addition to known cytokines and chemokine pathways. In the review, we provide considerations for correction of organelle functions in acute pancreatitis to create a discussion for clinical trial treatment and design options.
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Affiliation(s)
- Aida Habtezion
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Anna S. Gukovskaya
- Division of Gastroenterology, Department of Medicine, Department of Veterans Affairs and David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California
| | - Stephen J. Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Cedars Sinai Medical Center, Los Angeles, California
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Li J, Chen J, Tang W. The consensus of integrative diagnosis and treatment of acute pancreatitis-2017. J Evid Based Med 2019; 12:76-88. [PMID: 30806495 DOI: 10.1111/jebm.12342] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Indexed: 01/11/2023]
Abstract
Acute pancreatitis (AP) is one of the most common acute abdominal diseases. The digestive disease committee, Chinese Association of Integrative Medicine, released Integrated traditional Chinese and Western medicine for diagnosis and treatment of acute pancreatitis in 2010.1 Since then, further studies and great progress have been made by domestic and foreign counterparts from the perspective of both Chinese and Western medicine in AP, including the classification, fluid resuscitation, organ function maintenance, surgery intervention, enteral nutrition (EN), and syndrome differentiation and treatment. It is necessary to update the consensus on diagnosis and treatment of integrated Chinese and Western medicine to meet clinical needs. Therefore, the 2012 Revision of the Atlanta Classification Standard (RAC) by the International AP Consensus,2 the 2013 the Management of Acute Pancreatitis by the American College of Gastroenterology,3, 4 the 2014 Guidelines for diagnosis and treatment of the acute pancreatitis guide (2014) by the Chinese medical association branch,5 the 2014 Guidelines on Integrative Medicine for Severe Acute Pancreatitis by the General Surgery Committee of the Chinese Society of Integrated Traditional Chinese and Western Medicine,6 and Traditional Chinese Medicine Consensus on the Diagnosis and Treatment for Acute Pancreatitis by the Spleen and Stomach committee of China Association of Traditional Chinese Medicine7, 8 were taken into account for the revision of the consensus published in 2010. The digestive specialists in Chinese and Western medicine had a discussion on traditional Chinese medicine (TCM) types, syndrome differentiation, the main points of integrative medicine, and so on. According to the Delphi method, Consensus of Integrative Diagnosis and Treatment of Acute Pancreatitis (the 2017 revision) has been passed after three rounds votes. (The voting options are as follows: (a) totally agree; (b) agree, but with some reservations; (c) agree, but with larger reservations; (d) disagree, but reserved; and (e) absolutely disagree. If more than two out of three choose (a), or over 85% choose (a) + (b), the consensus will be passed.) The final validation was carried out by the core expert group in Taizhou, Jiangsu on June 9, 2017. The full text is as follows.
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Affiliation(s)
- Junxiang Li
- Digestive Disease Committee, Chinese Association of Integrative Medicine
| | - Jing Chen
- Digestive Disease Committee, Chinese Association of Integrative Medicine
| | - Wenfu Tang
- Digestive Disease Committee, Chinese Association of Integrative Medicine
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Abstract
OBJECTIVE To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis. METHODS All patients with first-time acute pancreatitis from 2006-2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted. RESULTS 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51-3.46), male gender (HR 1.48, 95%CI 1.08-2.04), and smoking (HR 1.62, 95%CI 1.15-2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94-19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71-30.9), local complications (HR 4.77, 95%CI 1.93-11.79), and organ-failure (HR 2.86, 95%CI 1.10-7.42). CONCLUSIONS Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.
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Abstract
PURPOSE OF REVIEW Alcohol and smoking play an important role in pancreatitis. The present review will address the myths and evidences about alcohol and smoking with pancreatitis to help improve the approach of healthcare professionals when managing of these patients. RECENT FINDINGS There is a growing recognition that chronic pancreatitis is a multifactorial disease. Eliciting an accurate history of alcohol consumption and smoking from patients, and if necessary, family members, can help determine their contribution to the patient's disease. In the absence of a convincing history, physicians should be open to consideration of other etiologies. The amount and duration of alcohol consumption is the most important determinant in increasing pancreatitis risk. Alcohol sensitizes the pancreas to other insults or injury and promotes disease progression. Smoking is an independent risk factor or chronic pancreatitis and has synergistic pathogenic effects with alcohol. The natural history of chronic pancreatitis is highly variable. A patient with alcoholic pancreatitis can have symptoms, recurrences or exacerbations from disease-related complications or nonpancreatic causes. Novel strategies are needed to enable patients quit smoking. SUMMARY Obtaining accurate history, appropriate evaluation and management can help to achieve meaningful improvement in symptoms in patients with chronic pancreatitis. Abstinence from alcohol and smoking cessation, when applicable, should be recommended in all patients to prevent disease recurrences and progression.
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Naudin S, Li K, Jaouen T, Assi N, Kyrø C, Tjønneland A, Overvad K, Boutron-Ruault MC, Rebours V, Védié AL, Boeing H, Kaaks R, Katzke V, Bamia C, Naska A, Trichopoulou A, Berrino F, Tagliabue G, Palli D, Panico S, Tumino R, Sacerdote C, Peeters PH, Bueno-de-Mesquita B, Weiderpass E, Gram IT, Skeie G, Chirlaque MD, Rodríguez-Barranco M, Barricarte A, Quirós J, Dorronsoro M, Johansson I, Sund M, Sternby H, Bradbury KE, Wareham N, Riboli E, Gunter M, Brennan P, Duell EJ, Ferrari P. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study. Int J Cancer 2018; 143:801-812. [PMID: 29524225 PMCID: PMC6481554 DOI: 10.1002/ijc.31367] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 01/18/2018] [Accepted: 02/02/2018] [Indexed: 02/06/2023]
Abstract
Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.
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Affiliation(s)
- Sabine Naudin
- Nutritional Methodology and Biostatistics group, International Agency for Research on Cancer, Lyon, France
| | - Kuanrong Li
- Nutritional Methodology and Biostatistics group, International Agency for Research on Cancer, Lyon, France
| | - Tristan Jaouen
- Nutritional Methodology and Biostatistics group, International Agency for Research on Cancer, Lyon, France
| | - Nada Assi
- Nutritional Methodology and Biostatistics group, International Agency for Research on Cancer, Lyon, France
| | - Cecilie Kyrø
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | | | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Marie-Christine Boutron-Ruault
- CESP, INSERM U1018, University of Paris-Sud, UVSQ, University of Paris-Saclay, Villejuif, France
- Institut Gustave Roussy, Villejuif, France
| | - Vinciane Rebours
- Pancreatology Unit, Beaujon Hospital, Clichy, France, INSERM U1149, University Paris 7, Paris, France
| | - Anne-Laure Védié
- Pancreatology Unit, Beaujon Hospital, Clichy, France, INSERM U1149, University Paris 7, Paris, France
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Postdam, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christina Bamia
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Androniki Naska
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Franco Berrino
- Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanna Tagliabue
- Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
| | - Salvatore Panico
- Department of Clinical and Experimental Medecine, University Federico II, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Civic M.P.Arezzo Hospital, Ragusa, Italy, Ragusa, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University, Hospital and Center for Cancer Prevention (CPO), Turin, Italy
| | - Petra H. Peeters
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Bas Bueno-de-Mesquita
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland
| | - Inger Torhild Gram
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Maria-Dolores Chirlaque
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - Miguel Rodríguez-Barranco
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain
| | - Aurelio Barricarte
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Navarra Public Health Institute, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | | | - Miren Dorronsoro
- Subdirección de Salud Pública de Gipuzkoa, Gobierno Vasco, San Sebastian, Spain
| | | | - Malin Sund
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Hanna Sternby
- Department of Surgery, Institution of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Kathryn E Bradbury
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Nick Wareham
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Elio Riboli
- School of Public Health, Imperial College London, United Kingdom
| | - Marc Gunter
- Nutrition and Epidemiology group, International Agency for Research on Cancer, Lyon, France
| | - Paul Brennan
- Genetic Epidemiology group, International Agency for Research on Cancer, Lyon, France
| | - Eric J Duell
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain
| | - Pietro Ferrari
- Nutritional Methodology and Biostatistics group, International Agency for Research on Cancer, Lyon, France
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Epidemiology and Etiology of Acute Pancreatitis in Urban and Suburban Areas in Shanghai: A Retrospective Study. Gastroenterol Res Pract 2018; 2018:1420590. [PMID: 30158961 PMCID: PMC6109519 DOI: 10.1155/2018/1420590] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 05/14/2018] [Accepted: 05/24/2018] [Indexed: 01/30/2023] Open
Abstract
Aim To investigate the epidemiology, etiology, and severity of acute pancreatitis (AP) in urban and suburban areas of Shanghai in 2011 and 2016. Methods A retrospective study of patients admitted to Shanghai General Hospital (urban and suburban campuses) with AP in 2011 and 2016 was undertaken. Patients were divided into acute biliary pancreatitis (ABP), hypertriglyceridemic pancreatitis (HTGP), alcoholic pancreatitis, and pancreatitis of other causes according to etiology. Severity of AP was divided into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP). Results AP patients in the suburban area increased more rapidly than those in the urban area. The mean onset age of AP in the urban area in 2016 was older than that in the suburban area (p < 0.05). The suburban patients in 2016 have significantly younger mean onset age than those in 2011 (p < 0.05). HTGP incidence in suburban patients increased from 2011 to 2016, which changed little in the urban area. Urban females were more likely to develop HTGP than suburban ones in 2011, which reversed in 2016. As to the male patients, the incidence of HTGP increased in both urban and suburban areas. Nonelderly (<60 years old) patients had higher HTGP incidence than elderly ones in both 2011 and 2016. The descending trend of SAP in the suburban area was more obvious than that in the urban area. The length of hospitalization decreased from 2011 to 2016, especially in SAP patients. Conclusions AP patients increased more rapidly in the suburban area of Shanghai with younger onset age. The incidence of HTGP increased significantly in the suburban area, reminding of the prevention and screening of HTG.
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Abstract
OBJECTIVE This study aimed to develop a diagnostic model that predicts acute pancreatitis (AP) risk before imaging. METHODS Emergency department patients with serum lipase elevated to 3 times the upper limit of normal or greater were identified retrospectively (September 1, 2013-August 31, 2015). An AP diagnosis was established by expert review of full hospitalization records. Candidate predictors included demographic and clinical characteristics at presentation. Using a derivation set, a multivariable logistic regression model and corresponding point-based scoring system was developed to predict AP. Discrimination accuracy and calibration were assessed in a separate validation set. RESULTS In 319 eligible patients, 182 (57%) had AP. The final model (area under curve, 0.92) included 8 predictors: number of prior AP episodes; history of cholelithiasis; no abdominal surgery (prior 2 months); time elapsed from symptom onset; pain localized to epigastrium, of progressively worsening severity, and severity level at presentation; and extent of lipase elevation. At a diagnostic risk threshold of 8 points or higher (≥99%), the model identified AP with a sensitivity of 45%, and a specificity and a positive predictive value of 100%. CONCLUSIONS In emergency department patients with lipase elevated to 3 times the upper limit of normal or greater, this model helps identify AP risk before imaging. Prospective validation studies are needed to confirm diagnostic accuracy.
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Abstract
Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.
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Juliusson SJ, Nielsen JK, Runarsdottir V, Hansdottir I, Sigurdardottir R, Björnsson ES. Lifetime alcohol intake and pattern of alcohol consumption in patients with alcohol-induced pancreatitis in comparison with patients with alcohol use disorder. Scand J Gastroenterol 2018; 53:748-754. [PMID: 29595342 DOI: 10.1080/00365521.2018.1455893] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To examine lifetime drinking patterns in men and women with alcohol-induced pancreatitis (AIP) in comparison with patients with alcoholic use disorder (AUD) without pancreatic disease. METHODS Alcohol consumption patterns were assessed using a validated questionnaire, the Lifetime Drinking History (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for gender and age (+/- 5 years) with patients with AUD in addiction treatment. RESULTS A total of 45 patients with AIP (35 males, 10 females) and 45 AUD patients were included. Alcohol consumption patterns were not significantly different between males and females with AIP and those with history of acute AIP and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD patients were similar in terms of onset age and duration of alcohol consumption, lifetime alcohol intake and drinks per drinking day. A higher proportion of binge drinking was found among patients with AUD than those with AIP (median 1.00 vs. 0.94, p = .01). Males with AUD had lower onset age (15 vs. 16 years, p = .03), higher total amount of spirits (35520 vs. 10450 drinks, p = .04) and higher proportion of binge drinking (1.00 vs. 0.97, p = .01) than males with AIP, whereas females with AIP and AUD had similar drinking patterns. CONCLUSIONS Alcohol drinking patterns and lifetime drinking history was similar in patients with AIP and patients with AUD. Males with AIP had lower total amount of spirits and lower proportion of binge drinking than those with AUD, suggesting the idiosyncratic etiology of AIP.
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Affiliation(s)
| | | | - Valgerdur Runarsdottir
- c SAA - National Center of Addiction Medicine, University of Iceland , Reykjavik , Iceland
| | - Ingunn Hansdottir
- c SAA - National Center of Addiction Medicine, University of Iceland , Reykjavik , Iceland.,d Faculty of Psychology , University of Iceland , Reykjavik , Iceland
| | | | - Einar S Björnsson
- a Department of Internal Medicine , University of Iceland , Reykjavik , Iceland.,e Faculty of Medicine , University of Iceland , Reykjavik , Iceland
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Quality of life comparison between smokers and non-smokers with chronic pancreatitis. Pancreatology 2018; 18:269-274. [PMID: 29500114 PMCID: PMC5879011 DOI: 10.1016/j.pan.2018.02.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 02/19/2018] [Accepted: 02/22/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the impact of smoking on quality of life in patients with chronic pancreatitis. METHODS This is a cross-sectional study of chronic pancreatitis patients followed at a single institution comparing smokers with non-smokers. The primary outcome was quality of life and secondary outcomes included demographics, drug and alcohol use, anxiety and depression, pain level, nutritional status, and metabolic factors. RESULTS 48 smokers and 45 non-smokers participated in this study. Smokers had a worse overall quality of life and higher rates of opioid addiction and depression than non-smokers. Smokers also had less racial diversity, lower education levels, and higher amounts of narcotic use than non-smokers. Furthermore, smokers had a lower BMI and a higher proportional use of pancreatic enzyme replacement therapy. Smoking was found to be independently associated with worse quality of life on multivariable regression. CONCLUSIONS The worse overall quality of life and higher rates of depression and anxiety create cause for concern in chronic pancreatitis patients who smoke. Smoking cessation should be an important target in chronic pancreatitis patients. Multicenter, multiethnic studies are needed to further elucidate this relationship.
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Xuan X, Tian Z, Zhang M, Zhou J, Gao W, Zhang Y, Zhang Y, Lei B, Ni B, Wu Y, Fan W. Diverse effects of interleukin-22 on pancreatic diseases. Pancreatology 2018; 18:231-237. [PMID: 29502986 DOI: 10.1016/j.pan.2018.02.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 02/20/2018] [Accepted: 02/23/2018] [Indexed: 12/11/2022]
Abstract
Interleukin-22 (IL-22) is involved in the development of lymphocytes and serves as a rapid and early source of the effector cytokines that are released in response to pathogen-induced changes in the microenvironment. Recent research has implicated IL-22 as a potential contributing factor to the spectrum of inflammation-related pancreatic diseases, particularly pancreatitis, fibrosis, carcinoma and diabetes. In this review, we summarize the current knowledge on the roles of IL-22 in the various pancreatic pathogenesis, providing insights into the underlying cellular and signaling mechanisms that will help guide future research into promising interventional targets with therapeutic potential.
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Affiliation(s)
- Xiuyun Xuan
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China; Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 030200, China
| | - Zhiqiang Tian
- Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, China
| | - Mengjie Zhang
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China
| | - Jian Zhou
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China
| | - Weiwu Gao
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China
| | - Yi Zhang
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China
| | - Yue Zhang
- Department of Dermatology, 105th Hospital of PLA, Bengbu Medical College, Hefei, 230001, China
| | - Bo Lei
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 030200, China
| | - Bing Ni
- Department of Pathophysiology, Third Military Medical University, Chongqing, 400038, China
| | - Yuzhang Wu
- Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, China.
| | - Weiping Fan
- Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 030200, China.
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Ethanol Induced Disordering of Pancreatic Acinar Cell Endoplasmic Reticulum: An ER Stress/Defective Unfolded Protein Response Model. Cell Mol Gastroenterol Hepatol 2018; 5:479-497. [PMID: 29930975 PMCID: PMC6009017 DOI: 10.1016/j.jcmgh.2018.01.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Accepted: 01/02/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Heavy alcohol drinking is associated with pancreatitis, whereas moderate intake lowers the risk. Mice fed ethanol long term show no pancreas damage unless adaptive/protective responses mediating proteostasis are disrupted. Pancreatic acini synthesize digestive enzymes (largely serine hydrolases) in the endoplasmic reticulum (ER), where perturbations (eg, alcohol consumption) activate adaptive unfolded protein responses orchestrated by spliced X-box binding protein 1 (XBP1). Here, we examined ethanol-induced early structural changes in pancreatic ER proteins. METHODS Wild-type and Xbp1+/- mice were fed control and ethanol diets, then tissues were homogenized and fractionated. ER proteins were labeled with a cysteine-reactive probe, isotope-coded affinity tag to obtain a novel pancreatic redox ER proteome. Specific labeling of active serine hydrolases in ER with fluorophosphonate desthiobiotin also was characterized proteomically. Protein structural perturbation by redox changes was evaluated further in molecular dynamic simulations. RESULTS Ethanol feeding and Xbp1 genetic inhibition altered ER redox balance and destabilized key proteins. Proteomic data and molecular dynamic simulations of Carboxyl ester lipase (Cel), a unique serine hydrolase active within ER, showed an uncoupled disulfide bond involving Cel Cys266, Cel dimerization, ER retention, and complex formation in ethanol-fed, XBP1-deficient mice. CONCLUSIONS Results documented in ethanol-fed mice lacking sufficient spliced XBP1 illustrate consequences of ER stress extended by preventing unfolded protein response from fully restoring pancreatic acinar cell proteostasis during ethanol-induced redox challenge. In this model, orderly protein folding and transport to the secretory pathway were disrupted, and abundant molecules including Cel with perturbed structures were retained in ER, promoting ER stress-related pancreas pathology.
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Key Words
- %-ox, percentage oxidized
- ATPase, adenosine triphosphatase
- Alcohol Pancreatitis
- Carboxyl Ester Lipase
- Cel, carboxyl ester lipase
- DTT, dithiothreitol
- Disulfide Bond
- ER, endoplasmic reticulum
- ERAD, endoplasmic reticulum–associated degradation
- FAEE, fatty acid ethyl esters
- FP, fluorophosphonate
- ICAT, isotope-coded affinity tags
- LC-MS/MS, liquid chromatography-tandem mass spectrometry
- MW, molecular weight
- RER, rough ER
- UPR, unfolded protein response
- Unfolded Protein Response
- WT, wild type
- sXBP1, spliced X box-binding protein 1
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Xiang JX, Hu LS, Liu P, Tian BY, Su Q, Ji YC, Zhang XF, Liu XM, Wu Z, Lv Y. Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis. World J Gastroenterol 2017; 23:8387-8394. [PMID: 29307998 PMCID: PMC5743509 DOI: 10.3748/wjg.v23.i47.8387] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 11/11/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis (HLAP).
METHODS A total of 863 patients were admitted to our hospital for acute pancreatitis (AP) from January 2013 to March 2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During follow-up, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test.
RESULTS No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP (50.0% and 77.8%, respectively) than non-smokers (9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23 (26.1%) patients. Multivariate analysis identified current smoking (HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers (23 mo vs 42 mo), but no significant difference was documented between ex-smokers (34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers.
CONCLUSION Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.
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Affiliation(s)
- Jun-Xi Xiang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
| | - Liang-Shuo Hu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
| | - Peng Liu
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
| | - Bo-Yan Tian
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Qing Su
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi-Chun Ji
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Xu-Feng Zhang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
| | - Xue-Min Liu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
- Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi’an 710061, Shaanxi Province, China
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Lugea A, Gerloff A, Su HY, Xu Z, Go A, Hu C, French SW, Wilson JS, Apte MV, Waldron RT, Pandol SJ. The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells. Gastroenterology 2017; 153:1674-1686. [PMID: 28847752 PMCID: PMC5705421 DOI: 10.1053/j.gastro.2017.08.036] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 08/11/2017] [Accepted: 08/21/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS Smoking, an independent risk factor for pancreatitis, accelerates the development of alcoholic pancreatitis. Alcohol feeding of mice induces up-regulation of spliced X-box binding protein 1 (XBP1s), which regulates the endoplasmic reticulum (ER) unfolded protein response and promotes cell survival upon ER stress. We examined whether smoking affects the adaptive mechanisms induced by alcohol and accelerates disorders of the ER in pancreatic acinar cells. METHODS We studied the combined effects of ethanol (EtOH) and cigarette smoke extract (CSE) on ER stress and cell death responses in mouse and human primary acini and the acinar cell line AR42J. Cells were incubated with EtOH (50 mmol/L), CSE (20-40 μg/mL), or both (CSE+EtOH), and analyzed by immunoblotting, quantitative reverse-transcription polymerase chain reaction, and cell death assays. Some cells were incubated with MKC-3946, an inhibitor of endoplasmic reticulum to nucleus signaling 1 (ERN1, also called IRE1) that blocks XBP1s formation. Male Sprague-Dawley rats were fed isocaloric amounts of an EtOH-containing (Lieber-DeCarli) or control diet for 11 weeks and exposed to cigarette smoke or room air in an exposure chamber for 2 hours each day. During the last 3 weeks, a subset of rats received intravenous injections of lipopolysaccharide (LPS, 3 mg/kg per week) to induce pancreatitis or saline (control). Pancreatic tissues were collected and analyzed by histology and immunostaining techniques. RESULTS In AR42J and primary acini, CSE+EtOH induced cell death (necrosis and apoptosis), but neither agent alone had this effect. Cell death was associated with a significant decrease in expression of XBP1s. CSE+EtOH, but neither agent alone, slightly decreased adenosine triphosphate levels in AR42J cells, but induced oxidative stress and sustained activation (phosphorylation) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, also called PERK) and increased protein levels of DNA damage inducible transcript 3 (DDIT3, also called CHOP). CHOP regulates transcription to promote apoptosis. Incubation of AR42J or primary mouse or human acinar cells with MKC-3946 reduced expression of XBP1s, increased levels of CHOP, and induced cell death. In rats fed an EtOH diet, exposure to cigarette smoke increased ER stress in acinar cells and sensitized the pancreas to LPS-induced pathology. CONCLUSIONS Cigarette smoke promotes cell death and features of pancreatitis in EtOH-sensitized acinar cells by suppressing the adaptive unfolded protein response signaling pathway. It also activates ER stress pathways that promote acinar cell death.
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Affiliation(s)
- Aurelia Lugea
- Cedars-Sinai Medical Center, Los Angeles, California; VA Greater Los Angeles Healthcare System/University of California, Los Angeles, California.
| | - Andreas Gerloff
- VA Greater Los Angeles Healthcare System/University of California, Los Angeles, CA
| | | | - Zhihong Xu
- University of New South Wales, Liverpool, Australia and Ingham Institute for Applied Medical Research, Liverpool, Australia
| | - Ariel Go
- Cedars-Sinai Medical Center, Los Angeles, CA
| | - Cheng Hu
- Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Jeremy S. Wilson
- University of New South Wales, Liverpool, Australia and Ingham Institute for Applied Medical Research, Liverpool, Australia
| | - Minoti V. Apte
- University of New South Wales, Liverpool, Australia and Ingham Institute for Applied Medical Research, Liverpool, Australia
| | - Richard T. Waldron
- Cedars-Sinai Medical Center, Los Angeles, CA,VA Greater Los Angeles Healthcare System/University of California, Los Angeles, CA
| | - Stephen J. Pandol
- Cedars-Sinai Medical Center, Los Angeles, CA,VA Greater Los Angeles Healthcare System/University of California, Los Angeles, CA
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Canha MI, Oliveiros B, Franco C, Figueiredo P. The lifestyle influence on alcoholic pancreatitis versus alcoholic liver disease: a case-control study. Scand J Gastroenterol 2017; 52:1278-1285. [PMID: 28830264 DOI: 10.1080/00365521.2017.1365167] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the association of lifestyle with the development of alcoholic liver disease (ALD) or alcoholic pancreatitis (AlcP). METHODS A case-control study was conducted on 80 patients attending a tertiary university hospital, subdivided into three groups: ALD (n = 34), AlcP (n = 21) and a control (CT) group (n = 25) of alcohol abusers without clinical evidence of hepatic or pancreatic disease. Participants were interviewed regarding alcohol consumption, tobacco use and diet. A physical examination was concomitantly performed and we had access to their complementary investigation. RESULTS We included 10 females and 70 males (mean age 57 ± 10 years). The pure amount of alcohol consumed by the ALD group was significantly higher than the AlcP group, regarding both daily (grams/day) and lifetime (kilograms) consumptions (p = .018 and p = .009, respectively); no statistically significant differences were seen with the CT group. We found no differences regarding the beverage type or drinking outside meals. Smoking was very common in every study group, with higher consumptions and a significantly higher prevalence of ever smokers in the AlcP group, in comparison with ALD and CT patients (p = .033 and p = .036, respectively). There were significant differences in the patients' eating habits before the onset of disease between groups (p < .001), with ALD subjects reporting a less abundant diet and AlcP a more abundant diet in the past; most of the controls had unchanged habits. CONCLUSION We found differences in lifestyle between ALD and AlcP, not considered sufficient to explain the subjects' susceptibility to one disease or the other.
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Affiliation(s)
- Maria Inês Canha
- a Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Bárbara Oliveiros
- b Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine , University of Coimbra (LBIM, FMUC) , Coimbra , Portugal.,c Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine , University of Coimbra (IBILI FMUC) , Coimbra , Portugal
| | - Célia Franco
- d Dual Disorders Unit, Psychiatric Service , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
| | - Pedro Figueiredo
- a Faculty of Medicine , University of Coimbra , Coimbra , Portugal.,e Department of Gastroenterology , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
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Abstract
PURPOSE OF REVIEW This report reviews recent aspects of pancreatitis immunology and environmental factors that link to development and progression of disease. RECENT FINDINGS Limited human and animal model studies have recently attempted to understand immune mechanisms that lead to the pathogenesis of acute and chronic pancreatitis. Based on these studies innate immune responses emerge as critical elements in disease pathogenesis and severity of inflammation. The immune basis for environmental factors such as smoking, which are highly associated with disease progression highlight novel cross talk mechanisms between immune and nonimmune pancreatic cells such as the pancreatic stellate cells. SUMMARY Better understanding of immune responses and signaling pathways are emerging as important contributors in pancreatitis development and progression. Such mechanisms are likely to offer future targetable therapies that can either halt or reverse disease progression.
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Abstract
PURPOSE OF REVIEW Summarize key clinical advances in chronic pancreatitis reported in 2016. RECENT FINDINGS Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. SUMMARY Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.
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