1
|
Park JY, Bang S, Jeon TJ, Cho JH, Lee KJ. Risk of and factors influencing the progression from acute to recurrent acute to chronic pancreatitis. Pancreatology 2025:S1424-3903(25)00069-9. [PMID: 40280847 DOI: 10.1016/j.pan.2025.04.004] [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: 07/22/2024] [Revised: 04/08/2025] [Accepted: 04/11/2025] [Indexed: 04/29/2025]
Abstract
OBJECTIVES & AIMS Acute pancreatitis (AP) recurrence rates range from 11 to 36 % yet accurately predicting recurrent acute pancreatitis (RAP) and its progression to chronic pancreatitis (CP) after an initial episode remains challenging. Thus, this study explored the risk factors contributing to RAP and its progression to CP. METHODS This retrospective study included patients with AP from three tertiary medical centers between January 2010 and December 2017. The patients were followed up for up to 60 months. The primary endpoint was the incidence of RAP and CP; risk factors influencing these outcomes were also identified. RESULTS Overall, 501 patients were included, of which 164 (32.7 %) experienced RAP, and 71 (14.2 %) progressed to CP. The leading causes of AP were alcohol consumption (43.1 %), gallstones (41.5 %) and hypertriglyceridemia (4.4 %). Multivariate Cox regression analysis revealed that smoking (HR, 4.09; 95 % CI, 2.752-6.078, p < 0.001), and organ failure after 48 h of hospitalization (HR, 3.52; 95 % CI, 1.22-10.19, p < 0.02) were significant risk factors for RAP. Significant risk factors for progression to CP included age over 60 years (HR, 5.29; 95 % CI, 1.25-22.47, p = 0.024), smoking (HR, 2.50; 95 % CI, 1.04-6.01, p = 0.04), alcohol consumption (HR, 8.79; 95 % CI, 2.06-37.43, p = 0.003), computed tomography severity index (CTSI) (HR, 1.22; 95 % CI, 1.04-1.44, p = 0.015), and recurrence of AP (HR, 70.69; 95 % CI, 2.61-1914.86, p = 0.011). In alcohol-induced RAP patients, ≥3 recurrences (HR, 4.18; 95 % CI, 1.75-9.98, p = 0.001) was significant risk factor for progression to CP. CONCLUSIONS Alcohol consumption was the predominant cause of AP and RAP. The severity of the initial AP episode was the key determinant for RAP, and RAP was the most significant risk factor for the progression to CP. Therefore, smoking and alcohol cessation are important to prevent the development of recurrent AP and CP during long-term follow-up.
Collapse
Affiliation(s)
- Ji Young Park
- Division of Gastroenterology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, The Graduate School, Yonsei University College of Medicine, Republic of Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Tae Joo Jeon
- Division of Gastroenterology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea
| | - Jae Hee Cho
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Kyong Joo Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| |
Collapse
|
2
|
Wang Y, Wan X, Liu Z, Liu Z, Huang X. Radiomics-based prediction of recurrent acute pancreatitis in individuals with metabolic syndrome using T2WI magnetic resonance imaging data. Front Med (Lausanne) 2025; 12:1502315. [PMID: 40115788 PMCID: PMC11922943 DOI: 10.3389/fmed.2025.1502315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 02/24/2025] [Indexed: 03/23/2025] Open
Abstract
Objective This study sought to clarify the utility of T2-weighted imaging (T2WI)-based radiomics to predict the recurrence of acute pancreatitis (AP) in subjects with metabolic syndrome (MetS). Methods Data from 196 patients with both AP and MetS from our hospital were retrospectively analyzed. These patients were separated into two groups according to their clinical follow-up outcomes, including those with first-onset AP (n = 114) and those with recurrent AP (RAP) (n = 82). The 196 cases were randomly divided into a training set (n = 137) and a test set (n = 59) at a 7:3 ratio. The clinical characteristics of these patients were systematically compiled for further analysis. For each case, the pancreatic parenchyma was manually delineated slice by slice using 3D Slicer software, and the appropriate radiomics characteristics were retrieved. The K-best approach, the least absolute shrinkage and selection operator (LASSO) algorithm, and variance thresholding were all used in the feature selection process. The establishment of clinical, radiomics, and combined models for forecasting AP recurrence in patients with MetS was then done using a random forest classifier. Model performance was measured using the area under the receiver operating characteristic curve (AUC), and model comparison was done using the DeLong test. The clinical utility of these models was evaluated using decision curve analysis (DCA), and the optimal model was determined via a calibration curve. Results In the training set, the clinical, radiomics, and combined models yielded respective AUCs of 0.651, 0.825, and 0.883, with corresponding test sets of AUCs of 0.606, 0.776, and 0.878. Both the radiomics and combined models exhibited superior predictive effectiveness compared to the clinical model in both the training (p = 0.001, p < 0.001) and test sets (p = 0.04, p < 0.001). The combined model outperformed the radiomics model (training set: p = 0.025, test set: p = 0.019). The DCA demonstrated that the radiomics and combined models had greater clinical efficacy than the clinical model. The calibration curve for the combined model demonstrated good agreement between the predicted probability of AP recurrence and the observed outcomes. Conclusion These findings highlight the superior predictive power of a T2WI-based radiomics model for predicting AP recurrence in patients with MetS, potentially supporting early interventions that can mitigate or alleviate RAP.
Collapse
Affiliation(s)
- Yuan Wang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xiyao Wan
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ziyan Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ziyi Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xiaohua Huang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| |
Collapse
|
3
|
Wei W, Ma Y, Zeng J, Song Y, Han Y, Qian W, Yang X, Wu Z, Ma Z, Wang Z, Duan W. A Nomogram for Predicting the Transition From Recurrent Acute Pancreatitis to Chronic Pancreatitis. Pancreas 2025; 54:e201-e209. [PMID: 39999313 PMCID: PMC11882177 DOI: 10.1097/mpa.0000000000002420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 04/11/2024] [Indexed: 02/27/2025]
Abstract
OBJECTIVES Acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis are recognized as a continuum of pancreatic diseases. Recurrence increases the risk of progression to chronic pancreatitis. The aim of this study was to search for clinical features that may promote the progression of chronic pancreatitis in patients with recurrent acute pancreatitis. MATERIALS AND METHODS We retrospectively reviewed patients with recurrent acute pancreatitis from Medical Information Mart for Intensive Care-IV database. They were divided into a training cohort and a validation cohort. A nomogram was constructed based on clinical features during the second hospitalization. The discrimination and calibration of the nomogram were evaluated using the concordance index, area under the time-dependent receiver operating characteristic curve, and calibration plots. RESULTS A total of 432 recurrent acute pancreatitis patients were evaluated, of which 93 (21.53%) were diagnosed with chronic pancreatitis later. Age, biliary pancreatitis, admission interval, alcohol dependence, lipase, and platelet were selected. The concordance index was 0.717 (95% confidence interval: 0.691-0.743) for the training cohort and 0.718 (95% confidence interval: 0.662-0.774) for the validation cohort. The area under the time-dependent receiver operating characteristic curve was >0.7 over 1000 days. CONCLUSIONS A nomogram was developed and validated to evaluate the transition from recurrent acute pancreatitis to chronic pancreatitis.
Collapse
|
4
|
Rodriguez J, Coté GA. Clinical and Investigative Approach to Recurrent Acute Pancreatitis. Gastroenterol Clin North Am 2025; 54:113-127. [PMID: 39880522 DOI: 10.1016/j.gtc.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Recurrent acute pancreatitis (RAP) is a complex syndrome that presents variably, with many cases remaining idiopathic after thorough diagnostics. For evaluating structural etiologies, endoscopic ultrasound and MR cholangiopancreatography are preferred over endoscopic retrograde cholangiopancreatography (ERCP) given their more favorable risk profile and sensitivity. The diagnostic work-up remains paramount since treatment should focus on addressing underlying causes such as early cholecystectomy for gallstone pancreatitis. As more etiologic factors are uncovered, such as genetic susceptibility, causality becomes more nuanced. Earlier enthusiasm for endoscopic sphincterotomy as a treatment for idiopathic RAP has been tempered by less favorable studies in recent years.
Collapse
Affiliation(s)
- Jennifer Rodriguez
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR, USA
| | - Gregory A Coté
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR, USA.
| |
Collapse
|
5
|
Wang H, Ciccocioppo R, Terai S, Shoeibi S, Carnevale G, De Marchi G, Tsuchiya A, Ishii S, Tonouchi T, Furuyama K, Yang Y, Mito M, Abe H, Di Tinco R, Cardinale V. Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights. Cytotherapy 2025; 27:259-278. [PMID: 39755978 PMCID: PMC12068232 DOI: 10.1016/j.jcyt.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/08/2024] [Accepted: 11/10/2024] [Indexed: 01/07/2025]
Abstract
Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.
Collapse
Affiliation(s)
- Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA; Ralph H Johnson Veteran Medical Center, Charleston, South Carolina, USA.
| | - Rachele Ciccocioppo
- Department of Medicine, Gastroenterology Unit, Pancreas Institute, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Sara Shoeibi
- Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia De Marchi
- Department of Medicine, Gastroenterology Unit, Pancreas Institute, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Soichi Ishii
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takafumi Tonouchi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kaito Furuyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yuan Yang
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masaki Mito
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Rosanna Di Tinco
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Vincenzo Cardinale
- Department of Translational and Precision Medicine, University of Rome, Rome, Italy.
| |
Collapse
|
6
|
Yan X, Xie F, Zhao XD, Li L, Meng JX. Short-term efficacy of early percutaneous cholecystostomy for pancreatitis and factors associated with recurrence and mortality. World J Gastroenterol 2025; 31:101163. [PMID: 39958444 PMCID: PMC11752697 DOI: 10.3748/wjg.v31.i6.101163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/12/2024] [Accepted: 12/19/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND Percutaneous cholecystostomy (PC) can be used as a bridging therapy for moderately severe acute biliary pancreatitis (MSABP). Currently, there are only a limited number of reports of MSABP using PCs. AIM To assess the short-term outcomes of early PC in MSABP and factors associated with recurrence and death in MSABP. METHODS Patients who received conservative treatment or PC for acute biliary pancreatitis (ABP) in Liaoning Provincial People's Hospital from January 2017 to July 2022 were collected. A total of 54 patients with MSABP who received early-stage PC and 29 patients who received conservative treatment. The short-term efficacy of PC was evaluated. Depending on whether there is a recurrence, compare the characteristics of the pre-PC and explore the factors of recurrence. Pre-PC features were compared and predictors were discussed, depending on the outcome. RESULTS After 3 days of PC treatment, patients experienced a reduction in inflammatory markers compared to the conservative group. After PC, patients were divided into non-recurrence (n = 37) and recurrence (n = 10) groups, and the results showed that age was an independent correlation affecting ABP recurrence [odds ratio (OR) = 0.937, 95% confidence interval (CI): 0.878-0.999; P = 0.047 < 0.05]. Patient outcomes were divided into non-lethal (n = 47) and lethal (n = 7) groups, and Charlson Comorbidity Index (CCI) was a risk factor for mortality (OR = 2.397, 95%CI: 1.139-5.047; P = 0.021 < 0.05). CCI was highly accurate in predicting death in MSABP (area under the curve = 0.86 > 0.7). When the Youden index maximum was 0.565, the cut-off value was 5.5, the sensitivity was 71.4%, and the specificity was 85.1%. CONCLUSION PC is an important method in the early years (< 72 hours) of MSABP. Age is a protective factor against recurrence of ABP. High pre-PC CCI is significantly associated with mortality.
Collapse
Affiliation(s)
- Xin Yan
- Department of Nuclear Medicine, The People’s Hospital of Liaoning Province, Shenyang 110016, Liaoning Province, China
| | - Feng Xie
- Department of Interventional Medicine, Jin Qiu Hospital of Liaoning Province, Shenyang 110016, Liaoning Province, China
| | - Xiao-Dan Zhao
- Department of General Surgery, The People’s Hospital of Liaoning Province, Shenyang 110016, Liaoning Province, China
| | - Liang Li
- Department of General Surgery, The People’s Hospital of Liaoning Province, Shenyang 110016, Liaoning Province, China
| | - Jia-Xian Meng
- Department of Science and Education, The People’s Hospital of Liaoning Province, Shenyang 110016, Liaoning Province, China
| |
Collapse
|
7
|
Xu W, Lv Y, Zhu Y, Zhang Y, Gong W, Cui X. Complex pancreaticobiliary maljunction diagnosed by endoscopic ultrasound: A case report. Medicine (Baltimore) 2024; 103:e40841. [PMID: 39686500 PMCID: PMC11651483 DOI: 10.1097/md.0000000000040841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
RATIONALE This case report aims to enhance understanding of pancreatobiliary maljunction (PBM) and promote more proactive treatment. PATIENT CONCERNS The patient, a 24-year-old Chinese female, was admitted to the hospital on April 7, 2020, due to "recurrent abdominal pain for over 2 years, with a recent episode accompanied by nausea and vomiting for 1 day." She had a previous history of gallstones. DIAGNOSES The initial diagnosis upon admission was biliary acute pancreatitis. During the emergency endoscopic retrograde cholangiopancreatography (ERCP) procedure, anatomical abnormalities were discovered. Intraoperative endoscopic ultrasonography led to a diagnosis of complex PBM (JSPBM, type D) + choledochal cyst (Todani, Ic) + incomplete pancreatic divisum + early chronic pancreatitis. These diagnoses were confirmed by postoperative magnetic resonance cholangiopancreatography. INTERVENTIONS After multiple conservative treatments such as ERCP with accessory pancreatic duct stent placement, the patient underwent surgical treatment in April 2021, which included "laparoscopic left hemihepatectomy + choledochal cyst excision + cholecystectomy + hepatic portal cholangioplasty." OUTCOMES The patient has not experienced any abdominal pain since the surgery and is currently under regular follow-up. LESSONS Endoscopic ultrasound is effective for the diagnoses of complex PBM and incomplete pancreatic divisum. ERCP with pancreatic duct stent placement and surgical procedure is reliable for relieving the patient's symptoms.
Collapse
Affiliation(s)
- Wen Xu
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| | - Yang Lv
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| | - Ying Zhu
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| | - Yingchun Zhang
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| | - Wei Gong
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| | - Xiaobing Cui
- Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shen Zhen, Guangdong, China
| |
Collapse
|
8
|
Rahib L, Salerno W, Abu-El-Haija M, Conwell DL, Freeman AJ, Hart PA, Pandol SJ, Perito ER, Yadav D, Palermo TM. Development of a core outcome set for recurrent acute and chronic pancreatitis: Results of a Delphi poll. Pancreatology 2024; 24:1237-1243. [PMID: 39609172 DOI: 10.1016/j.pan.2024.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 11/14/2024] [Accepted: 11/18/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND/OBJECTIVE Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) lack effective therapies. There is no consensus or guidance on which endpoints or outcome measures should be used in clinical trials. This study aimed to develop a core outcome set aligned with both patient and provider priorities for RAP and CP. Utilizing the Outcomes Measures in Rheumatology (OMERACT) framework, a multi-stakeholder approach was adopted to identify and prioritize outcome domains. METHODS A two-round Delphi poll was conducted among four stakeholder groups: adult patients, parents and pediatric patients, adult health care providers and pediatric health care providers. Steering committee consensus further refined the core outcome domains, categorizing them as mandatory, important but optional, or research agenda domains, with full consensus achieved. RESULTS Pain severity, ability to participate in social roles and activities, pancreatitis related hospitalization/ER visits and acute pancreatitis flare-ups were recommended as mandatory outcome domains for future clinical trials in RAP/CP. CONCLUSIONS Using the OMERACT framework, we developed a core outcome set for RAP and CP. Future research will focus on identifying validated measures for each domain, facilitating standardized assessments across clinical trials.
Collapse
Affiliation(s)
| | | | - Maisam Abu-El-Haija
- Division of Gastroenterology, Hepatology and Nutrition Cincinnati Children's Hospital Medical Center, Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | | | - A Jay Freeman
- Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, The Ohio State College of Medicine, Columbus, OH, USA
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Stephen J Pandol
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Emily R Perito
- Department of Pediatrics, University of California, San Francisco, CA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Tonya M Palermo
- Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA, USA.
| |
Collapse
|
9
|
Fusco S, Hanke GM, Büringer K, Minn L, Blumenstock G, Schempf U, Götz M, Malek NP, Wichmann D, Werner CR. Clinical course for pancreatic necrosis and pancreatic pseudocysts due to severe acute or chronic pancreatitis. Therap Adv Gastroenterol 2024; 17:17562848241301945. [PMID: 39582899 PMCID: PMC11585040 DOI: 10.1177/17562848241301945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 11/06/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy. OBJECTIVES This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis. DESIGN This is a retrospective observational single-centre study on 46 patients with severe pancreatitis. METHODS In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)). RESULTS Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study. CONCLUSION WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.
Collapse
Affiliation(s)
- Stefano Fusco
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Otfried-Müller-Str. 10, Tübingen 72076, Germany
| | - Greta M. Hanke
- Department of Nephrology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
| | - Karsten Büringer
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| | - Lisa Minn
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| | - Gunnar Blumenstock
- Department of Clinical Epidemiology, Eberhard-Karls-University, Tübingen, Germany
| | - Ulrike Schempf
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| | - Martin Götz
- Division of Gastroenterology, Klinikum Böblingen, Böblingen, Germany
| | - Nisar P. Malek
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| | - Dörte Wichmann
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| | - Christoph R. Werner
- Section of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology and Geriatrics, Department of Internal Medicine I, University Hospital of Tübingen, Tübingen, Germany
| |
Collapse
|
10
|
Gukovskaya AS, Lerch MM, Mayerle J, Sendler M, Ji B, Saluja AK, Gorelick FS, Gukovsky I. Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon? World J Gastroenterol 2024; 30:4417-4438. [PMID: 39534420 PMCID: PMC11551668 DOI: 10.3748/wjg.v30.i41.4417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/19/2024] [Accepted: 07/16/2024] [Indexed: 10/23/2024] Open
Abstract
Pancreatitis is a common, life-threatening inflammatory disease of the exocrine pancreas. Its pathogenesis remains obscure, and no specific or effective treatment is available. Gallstones and alcohol excess are major etiologies of pancreatitis; in a small portion of patients the disease is hereditary. Pancreatitis is believed to be initiated by injured acinar cells (the main exocrine pancreas cell type), leading to parenchymal necrosis and local and systemic inflammation. The primary function of these cells is to produce, store, and secrete a variety of enzymes that break down all categories of nutrients. Most digestive enzymes, including all proteases, are secreted by acinar cells as inactive proforms (zymogens) and in physiological conditions are only activated when reaching the intestine. The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens. It was proposed that pancreatitis results from proteolytic autodigestion of the gland, mediated by premature/inappropriate trypsinogen activation within acinar cells. The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis, and in human disease. On the basis of these observations, it has been considered the central pathogenic mechanism of pancreatitis - a concept with a century-old history. This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis, particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis; analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its' damaging effects; discusses the gaps in our knowledge, potential therapeutic approaches, and directions for future research. We conclude that trypsin is not the culprit in the disease pathogenesis but, at most, a mediator of some pancreatitis responses. Therefore, the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes, such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.
Collapse
Affiliation(s)
- Anna S Gukovskaya
- Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90073, United States
- Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| | - Markus M Lerch
- Department of Medicine, Ludwig Maximilian University Hospital, Munich 81377, Germany
| | - Julia Mayerle
- Department of Medicine II, Ludwig Maximilian University of Munich, Munich 81377, Germany
| | - Matthias Sendler
- Department of Medicine A, University of Greifswald, Greifswald 17475, Germany
| | - Baoan Ji
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, United States
| | - Ashok K Saluja
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States
| | - Fred S Gorelick
- Departments of Cell Biology and Internal Medicine, Yale University School of Medicine and VA West Haven, New Haven, CT 06519, United States
| | - Ilya Gukovsky
- Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90073, United States
- Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| |
Collapse
|
11
|
Padula D, Mauro A, Maggioni P, Kurihara H, Di Sabatino A, Anderloni A. Practical approach to acute pancreatitis: from diagnosis to the management of complications. Intern Emerg Med 2024; 19:2091-2104. [PMID: 38850357 DOI: 10.1007/s11739-024-03666-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 05/28/2024] [Indexed: 06/10/2024]
Abstract
The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.
Collapse
Affiliation(s)
- Donatella Padula
- Emergency Department and Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, via F Sforza 35, Milan, Italy
| | - Aurelio Mauro
- Gastroenterology and Digestive Endoscopy Unit, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, Pavia, Italy.
| | - Paolo Maggioni
- Emergency Department and Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, via F Sforza 35, Milan, Italy
- Scuola di Specializzazione in Medicina di Emergenza-Urgenza, Università Degli Studi Di Milano, Milan, Italy
| | - Hayato Kurihara
- Emergency Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via F. Sforza 35, Milan, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Digestive Endoscopy Unit, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, Pavia, Italy
| |
Collapse
|
12
|
Choate R, Wasilchenko C, Thakur K, Hill R, Wright E, Conwell DL. Financial Toxicity in Patients With Chronic Pancreatitis. Pancreas 2024; 53:e774-e779. [PMID: 38904700 DOI: 10.1097/mpa.0000000000002384] [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: 06/22/2024]
Abstract
OBJECTIVES Patients with chronic illnesses are susceptible to the financial burden of disease-related treatment costs. Financial toxicity is well researched in cancer and several chronic diseases. This review explores the financial challenges faced by patients with chronic pancreatitis and the impact of financial hardship on their well-being. MATERIALS AND METHODS We performed a review of the published literature to summarize the body of existing research and to identify knowledge gaps related to the financial burden experienced by patients with chronic pancreatitis. RESULTS Research on financial burden, cost-coping behaviors, cost-related nonadherence to prescribed medications, and social vulnerabilities in people with chronic pancreatitis is sparse. No studies have assessed the suitability and validity of instruments measuring subjective financial toxicity in a patient population with chronic pancreatitis. CONCLUSIONS There is a critical need for further studies of financial toxicity in the patient population with chronic pancreatitis, considering that if the sources of financial burden can be identified, opportunities emerge to dampen or mitigate their impact on patients with chronic pancreatitis.
Collapse
Affiliation(s)
- Radmila Choate
- From the Department of Epidemiology and Environmental Health, University of Kentucky College of Public Health, Lexington, KY
| | - Carrigan Wasilchenko
- Department of Internal Medicine, University of Kentucky College of Medicine Department of Internal Medicine, University
| | - Kshitij Thakur
- Department of Internal Medicine, University of Kentucky College of Medicine Department of Internal Medicine, University
| | - Rachel Hill
- Division of Biomedical Informatics, University of Kentucky College of Medicine, Lexington, KY
| | - Elizabeth Wright
- Department of Internal Medicine, University of Kentucky College of Medicine Department of Internal Medicine, University
| | - Darwin L Conwell
- Department of Internal Medicine, University of Kentucky College of Medicine Department of Internal Medicine, University
| |
Collapse
|
13
|
Kim EJ, Lee SH, Jung MK, Jang DK, Jo JH, Lee JM, Choe JW, Han SY, Choi YH, Kim SH, Park JM, Paik KH. Current Diagnosis and Treatment of Acute Pancreatitis in Korea: A Nationwide Survey. Gut Liver 2024; 18:897-905. [PMID: 38712394 PMCID: PMC11391141 DOI: 10.5009/gnl230350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 01/20/2024] [Accepted: 01/22/2024] [Indexed: 05/08/2024] Open
Abstract
Background/Aims Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. Methods The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. Results In total, 676 patients were included, of whom 388 (57.4%) were male, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission. Conclusions This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. Results reveal disparities between clinical guidelines and their practical implementation for AP treatment.
Collapse
Affiliation(s)
- Eui Joo Kim
- Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Department of Medicine, Inha University Graduate School, Incheon, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Min Kyu Jung
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Dong Kee Jang
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Hyun Jo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Korea
| | - Jung Wan Choe
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Sung Yong Han
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital and Pusan National University School of Medicine Busan, Korea
| | - Young Hoon Choi
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seong-Hun Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Jin Myung Park
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Kyu-Hyun Paik
- Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| |
Collapse
|
14
|
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.
Collapse
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
| |
Collapse
|
15
|
Cook ME, Bruun NH, Davidsen L, Vestergaard P, Drewes AM, Olesen SS. Metabolic Sequelae and All-Cause Mortality in Chronic Pancreatitis With and Without Prior Acute Pancreatitis: A Nationwide Population-Based Cohort Study. Am J Gastroenterol 2024; 119:1921-1929. [PMID: 38587288 DOI: 10.14309/ajg.0000000000002799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 04/03/2024] [Indexed: 04/09/2024]
Abstract
INTRODUCTION The purpose of this study was to investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP). METHODS We used nationwide health registries to identify all Danish residents (18 years and older) with incident CP from 2000 to 2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus [PPDM], exocrine pancreatic dysfunction, and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP before CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models. RESULTS A total of 9,655 patients with CP were included. Among patients with CP, 3,913 (40.5%) had a prior AP diagnosis. Compared with patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79, 95% CI 0.74-0.84), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53, 95% CI 1.38-1.69), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for exocrine pancreatic dysfunction (HR 0.97, 95% CI 0.87-1.07) and osteoporosis (HR 0.87, 95% CI 0.74-1.02). DISCUSSION This nationwide study revealed that most of the patients with CP have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality.
Collapse
Affiliation(s)
- Mathias Ellgaard Cook
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Niels Henrik Bruun
- Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark
| | - Line Davidsen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Peter Vestergaard
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Centre North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Schou Olesen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| |
Collapse
|
16
|
Hamo-Giladi DB, Fokra A, Sabo E, Kabala A, Minkov I, Hamoud S, Hadad S, Abassi Z, Khamaysi I. Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches. J Cell Mol Med 2024; 28:e18512. [PMID: 39248454 PMCID: PMC11382361 DOI: 10.1111/jcmm.18512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 06/07/2024] [Accepted: 06/18/2024] [Indexed: 09/10/2024] Open
Abstract
Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.
Collapse
Affiliation(s)
- Dalit B Hamo-Giladi
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Ahmad Fokra
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Edmond Sabo
- Department of Pathology, Carmel Hospital, Haifa, Israel
| | - Aviva Kabala
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
| | - Irena Minkov
- Department of Pathology, Rambam Health Care Center, Haifa, Israel
| | - Shadi Hamoud
- Department of Internal Medicine E, Rambam Health Care Center, Haifa, Israel
| | - Salim Hadad
- Department of Pharmacy, Rambam Health Care Center, Haifa, Israel
| | - Zaid Abassi
- Department of Physiology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Department of Laboratory Medicine, Rambam Health Care Center, Haifa, Israel
| | - Iyad Khamaysi
- Department of Gastroenterology, Rambam Health Care Center, Haifa, Israel
| |
Collapse
|
17
|
Tomaszewska E, Wojtysiak D, Grzegorzewska A, Świątkiewicz M, Donaldson J, Arciszewski MB, Dresler S, Puzio I, Szymańczyk S, Dobrowolski P, Bonior J, Mielnik-Błaszczak M, Kuc D, Muszyński S. Understanding Secondary Sarcopenia Development in Young Adults Using Pig Model with Chronic Pancreatitis. Int J Mol Sci 2024; 25:8735. [PMID: 39201422 PMCID: PMC11354544 DOI: 10.3390/ijms25168735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
Chronic pancreatitis (CP) in young individuals may lead to disease-related secondary sarcopenia (SSARC), characterized by muscle loss and systemic inflammation. In this study, CP was induced in young pigs, and serum levels of key hormones, muscle fiber diameters in various muscles, and the mRNA expression of genes related to oxidative stress and programmed cell death were assessed. A decrease in muscle fiber diameters was observed in SSARC pigs, particularly in the longissimus and diaphragm muscles. Hormonal analysis revealed alterations in dehydroepiandrosterone, testosterone, oxytocin, myostatin, and cortisol levels, indicating a distinct hormonal response in SSARC pigs compared to controls. Oxytocin levels in SSARC pigs were significantly lower and myostatin levels higher. Additionally, changes in the expression of catalase (CAT), caspase 8 (CASP8), B-cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX) mRNA suggested a downregulation of oxidative stress response and apoptosis regulation. A reduced BAX/BCL2 ratio in SSARC pigs implied potential caspase-independent cell death pathways. The findings highlight the complex interplay between hormonal changes and muscle degradation in SSARC, underscoring the need for further research into the apoptotic and inflammatory pathways involved in muscle changes due to chronic organ inflammation in young individuals.
Collapse
Affiliation(s)
- Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland; (I.P.); (S.S.)
| | - Dorota Wojtysiak
- Department of Animal Genetics, Breeding and Ethology, Faculty of Animal Sciences, University of Agriculture in Kraków, 30-059 Kraków, Poland;
| | - Agnieszka Grzegorzewska
- Department of Animal Physiology and Endocrinology, University of Agriculture in Kraków, 30-059 Kraków, Poland;
| | - Małgorzata Świątkiewicz
- Department of Animal Nutrition and Feed Science, National Research Institute of Animal Production, 32-083 Balice, Poland;
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa;
| | - Marcin B. Arciszewski
- Department of Animal Anatomy and Histology, University of Life Sciences in Lublin, 20-950 Lublin, Poland;
| | - Sławomir Dresler
- Department of Analytical Chemistry, Medical University of Lublin, 20-093 Lublin, Poland;
- Department of Plant Physiology and Biophysics, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Iwona Puzio
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland; (I.P.); (S.S.)
| | - Sylwia Szymańczyk
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland; (I.P.); (S.S.)
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, 20-033 Lublin, Poland;
| | - Joanna Bonior
- Department of Medical Physiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-501 Kraków, Poland;
| | - Maria Mielnik-Błaszczak
- Chair and Department of Developmental Dentistry, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.-B.); (D.K.)
| | - Damian Kuc
- Chair and Department of Developmental Dentistry, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.-B.); (D.K.)
| | - Siemowit Muszyński
- Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, 20-950 Lublin, Poland;
| |
Collapse
|
18
|
Baldaque P, Coutinho G, de Lima Moreira JP, Luiz RR, Fogaça HS, de Souza LMP, de Souza HSP. Chronic Pancreatitis in a Large Developing Country: Temporal Trends of Over 64,000 Hospitalizations from 2009 to 2019. Dig Dis Sci 2024; 69:2817-2827. [PMID: 38816599 DOI: 10.1007/s10620-024-08488-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/08/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND/OBJECTIVES Chronic pancreatitis (CP) is a progressive inflammatory disorder associated with marked morbidity and mortality and frequently requires hospitalization. This study aimed to investigate the time trends and geographical distribution of hospital admissions, the lethality rate of CP across Brazil, and the potential relationship with social indicators and associated risk factors. METHODS Data were retrospectively obtained from the Brazilian Public Health System Registry between January 2009 and December 2019. The prevalence and lethality rates of CP per 100,000 inhabitants in each municipality were estimated from hospitalizations to in-hospital deaths and classified by age, sex, and demographic features. RESULTS During the study period, 64,609 admissions were retrieved, and most of the patients were males (63.54%). Hospitalization decreased by nearly half (-54.68%) in both sexes. CP rates in males were higher in all age groups. The greatest reduction in admissions (- 64%) was also noted in patients ≥ 70y. CP In-hospital lethality remained stable (5-6%) and similar for males and females. Patients ≥ 70y showed the highest lethality. The greatest increase in CP lethality rates (+ 10%) was observed in municipalities integrated into metropolises, which was mainly driven by small-sized municipalities (+ 124%). CONCLUSIONS CP hospitalizations decrease in both urban and rural areas, particularly in the North, Northeast, and Central-West regions, and in those above 70 years of age, but are not correlated with lethality rates in the South. This suggests ongoing changes in the environmental and socioeconomic factors in Brazil.
Collapse
Affiliation(s)
- Pedro Baldaque
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil
| | - Gabriela Coutinho
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil
| | | | - Ronir Raggio Luiz
- Institute of Public Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-598, Brazil
| | - Homero Soares Fogaça
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil
| | - Lucila Marieta Perrotta de Souza
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil
| | - Heitor Siffert Pereira de Souza
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Rio de Janeiro, 21941-913, Brazil.
- D'Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, 22281-100, Brazil.
| |
Collapse
|
19
|
Wang T, Xiong K, He Y, Feng B, Guo L, Gu J, Zhang M, Wang H, Wu X. Chronic pancreatitis-associated metabolic bone diseases: epidemiology, mechanisms, and clinical advances. Am J Physiol Endocrinol Metab 2024; 326:E856-E868. [PMID: 38656128 DOI: 10.1152/ajpendo.00113.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/11/2024] [Accepted: 04/17/2024] [Indexed: 04/26/2024]
Abstract
Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.
Collapse
Affiliation(s)
- Tianlin Wang
- Department of Emergency, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ke Xiong
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanli He
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Binbin Feng
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - LinBin Guo
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jingliang Gu
- Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mengrui Zhang
- Quantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, California, United States
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
| | - Hong Wang
- Department of General Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaohao Wu
- Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
| |
Collapse
|
20
|
Zhou Y, Huang X, Jin Y, Qiu M, Ambe PC, Basharat Z, Hong W. The role of mitochondrial damage-associated molecular patterns in acute pancreatitis. Biomed Pharmacother 2024; 175:116690. [PMID: 38718519 DOI: 10.1016/j.biopha.2024.116690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/27/2024] [Accepted: 04/29/2024] [Indexed: 06/03/2024] Open
Abstract
Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.
Collapse
Affiliation(s)
- Yan Zhou
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Xiaoyi Huang
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Yinglu Jin
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China; School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Minhao Qiu
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Peter C Ambe
- Department of General Surgery, Visceral Surgery and Coloproctology, Vinzenz-Pallotti-Hospital Bensberg, Vinzenz-Pallotti-Str. 20-24, Bensberg 51429, Germany
| | | | - Wandong Hong
- Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
| |
Collapse
|
21
|
Vlodavsky I, Hilwi M, Kayal Y, Soboh S, Ilan N. Impact of heparanase-2 (Hpa2) on cancer and inflammation: Advances and paradigms. FASEB J 2024; 38:e23670. [PMID: 38747803 DOI: 10.1096/fj.202400286r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/09/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024]
Abstract
HPSE2, the gene-encoding heparanase 2 (Hpa2), is mutated in urofacial syndrome (UFS), a rare autosomal recessive congenital disease attributed to peripheral neuropathy. Hpa2 lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase (Hpa1), yet it exhibits a high affinity toward HS, thereby inhibiting Hpa1 enzymatic activity. Hpa2 regulates selected genes that promote normal differentiation, tissue homeostasis, and endoplasmic reticulum (ER) stress, resulting in antitumor, antiangiogenic, and anti-inflammatory effects. Importantly, stress conditions induce the expression of Hpa2, thus establishing a feedback loop, where Hpa2 enhances ER stress which, in turn, induces Hpa2 expression. In most cases, cancer patients who retain high levels of Hpa2 survive longer than patients bearing Hpa2-low tumors. Experimentally, overexpression of Hpa2 attenuates the growth of tumor xenografts, whereas Hpa2 gene silencing results in aggressive tumors. Studies applying conditional Hpa2 knockout (cHpa2-KO) mice revealed an essential involvement of Hpa2 contributed by the host in protecting against cancer and inflammation. This was best reflected by the distorted morphology of the Hpa2-null pancreas, including massive infiltration of immune cells, acinar to adipocyte trans-differentiation, and acinar to ductal metaplasia. Moreover, orthotopic inoculation of pancreatic ductal adenocarcinoma (PDAC) cells into the pancreas of Hpa2-null vs. wild-type mice yielded tumors that were by far more aggressive. Likewise, intravenous inoculation of cancer cells into cHpa2-KO mice resulted in a dramatically increased lung colonization reflecting the involvement of Hpa2 in restricting the formation of a premetastatic niche. Elucidating Hpa2 structure-activity-relationships is expected to support the development of Hpa2-based therapies against cancer and inflammation.
Collapse
Affiliation(s)
- Israel Vlodavsky
- Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Maram Hilwi
- Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Yasmin Kayal
- Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Soaad Soboh
- Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Neta Ilan
- Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| |
Collapse
|
22
|
Hagn-Meincke R, Yadav D, Andersen DK, Vege SS, Fogel EL, Serrano J, Bellin MD, Topazian MD, Conwell DL, Li L, Van Den Eeden SK, Drewes AM, Pandol SJ, Forsmark CE, Fisher WE, Hart PA, Olesen SS, Park WG. Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study. Pancreatology 2024; 24:384-393. [PMID: 38461145 PMCID: PMC11023786 DOI: 10.1016/j.pan.2024.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 02/05/2024] [Accepted: 02/21/2024] [Indexed: 03/11/2024]
Abstract
OBJECTIVE To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP). METHODS We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups. RESULTS In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10. CONCLUSION CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.
Collapse
Affiliation(s)
- Rasmus Hagn-Meincke
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark; Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - Dana K Andersen
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Santhi Swaroop Vege
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Evan L Fogel
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jose Serrano
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Melena D Bellin
- Division of Pediatric Endocrinology, University of Minnesota, Minnesota, MN, USA
| | - Mark D Topazian
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Darwin L Conwell
- Department of Medicine, University of Kentucky, Lexington, KY, USA
| | - Liang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | | | - Asbjørn M Drewes
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Stephen J Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Chris E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition. University of Florida, Gainesville, FL, USA
| | - William E Fisher
- Division of General Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Søren S Olesen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Walter G Park
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
| |
Collapse
|
23
|
Vahapoğlu A, Çalik M. A comparison of scoring systems and biomarkers to predict the severity of acute pancreatitis in patients referring to the emergency clinic. Medicine (Baltimore) 2024; 103:e37964. [PMID: 38669403 PMCID: PMC11049751 DOI: 10.1097/md.0000000000037964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 03/29/2024] [Indexed: 04/28/2024] Open
Abstract
To investigate scoring systems and biomarkers for determining the severity and prognosis of acute pancreatitis (AP). Between January and July 2023, 100 patients with AP diagnosed and treated in the emergency department were included. AP was divided into 2 groups according to severity: mild AP and moderately severe AP (MSAP-SAP), according to the revised Atlanta Classification in 2012. Demographic characteristics, severity, intensive care unit (ICU) admission, white blood cell count (WBC), hematocrit, red cell distribution width from whole blood taken at admission and 48 hours later, C-reactive protein (CRP) and biochemistry values, Bedside Index for Severity in Acute Pancreatitis (BISAP), Pancreatitis Activity Scoring System (PASS), and harmless AP score scores were recorded retrospectively. Our variables, which were found to be significant in multiple logistic regression results, were found to increase MSAP-SAP expectation by 4.36-, 7.85-, 6.63 and 5.80 times in the presence of CRP > 47.10, WBC > 13.10, PASS > 0, and necrotizing computed tomography findings, respectively. It was detected that the risk factor which was found significant as a single variable affecting the ICU admission increased the risk of ICU requirement by 28.88 when PASS > 0, by 3.96 when BISAP > 1, and it increased the Atlanta score by 9.93-fold. We found that WBC and CRP values at the time of hospital admission and WBC, CRP, and red cell distribution width values after 48 had the highest accuracy in determining AP disease severity. BISAP, which was found to be significant in determining MSAP-SAP expectations, lost its significance in multiple logistic regression results, and PASS was found to be effective. The PASS is an important score in the clinical evaluation of patients with AP and in determining the need for ICU hospitalization.
Collapse
Affiliation(s)
- Ayşe Vahapoğlu
- Department of Anesthesiology and Reanimation, University of Health Sciences Turkey, Gaziosmanpaşa Training Research Hospital, İstanbul, Turkey
| | - Mustafa Çalik
- Department of Emergency Medicine, University of Health Sciences Turkey, Gaziosmanpaşa Training Research Hospital, İstanbul, Turkey
| |
Collapse
|
24
|
de Rijk F, Sissingh NJ, Boel TT, Timmerhuis HC, de Jong M, Pauw HS, van Veldhuisen CL, Hallensleben ND, Anten M, Brink MA, Curvers WL, van Duijvendijk P, Hazen WL, Kuiken SD, Poen AC, Quispel R, Römkens T, Spanier B, Tan A, Vleggaar FP, Voorburg A, Witteman B, Ali UA, Issa Y, Bouwense S, Voermans RP, van Wanrooij R, Stommel M, van Hooft JE, de Jonge PJ, van Goor H, Boermeester MA, Besselink MG, Bruno MJ, Verdonk RC, van Santvoort HC. Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort. J Gastroenterol Hepatol 2024; 39:674-684. [PMID: 38191176 DOI: 10.1111/jgh.16453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/30/2023] [Accepted: 12/11/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND AND AIM More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.
Collapse
Affiliation(s)
- Fem de Rijk
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - N J Sissingh
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - T T Boel
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - H C Timmerhuis
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - Mjp de Jong
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands
| | - H S Pauw
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - C L van Veldhuisen
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - N D Hallensleben
- Department of Research and Development, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Mpgf Anten
- Department of Gastroenterology and Hepatology, Sint Franciscus Hospital, Rotterdam, The Netherlands
| | - M A Brink
- Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, The Netherlands
| | - W L Curvers
- Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands
| | | | - W L Hazen
- Department of Gastroenterology and Hepatology, Elisabeth TweeSteden Hospital, Tilburg, The Netherlands
| | - S D Kuiken
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - A C Poen
- Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands
| | - R Quispel
- Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Teh Römkens
- Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - Bwm Spanier
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands
| | - Acitl Tan
- Department of Gastroenterology and Hepatology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - F P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands
| | - Amcj Voorburg
- Department of Gastroenterology and Hepatology, Diakonessenhuis, Utrecht, The Netherlands
| | - Bjm Witteman
- Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, The Netherlands
| | - U Ahmed Ali
- Department of Surgery, Division of Colorectal Surgery, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York, USA
| | - Y Issa
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Saw Bouwense
- Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
- Department of Nutrition and Movement Sciences, School of Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - R P Voermans
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Rlj van Wanrooij
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Mwj Stommel
- Department of Surgery, Radboudumc, Nijmegen, The Netherlands
| | - J E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - P J de Jonge
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - H van Goor
- Department of Surgery, Radboudumc, Nijmegen, The Netherlands
| | - M A Boermeester
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - M G Besselink
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - M J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - R C Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - H C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
25
|
Lan WP, Guo W, Zhou X, Li Z. Research trends on traditional Chinese medicine and acute pancreatitis: A bibliometric analysis from 2007 to mid-2023. Heliyon 2024; 10:e25659. [PMID: 38455538 PMCID: PMC10918020 DOI: 10.1016/j.heliyon.2024.e25659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 01/23/2024] [Accepted: 01/31/2024] [Indexed: 03/09/2024] Open
Abstract
Traditional Chinese Medicine (TCM) is a unique medical system of historic significance, holding substantial influence within China and beyond. In recent years, the efficacy of TCM in treating acute pancreatitis has been substantiated. Despite over two decades of development in this domain, a bibliometric analysis illustrating TCM's role in acute pancreatitis remains scarce. OBJECTIVE This study aims to conduct a comprehensive analysis of findings in the field of acute pancreatitis and TCM using machine learning and text-analyzing methodologies. The intent is to provide scientific and intuitive support to researchers and clinicians. METHODS We searched the Web of Science Core Collection database for publications and related literature from 2007 to mid-2023. Tools such as Excel, Citespace V, and Vosviewer were utilized for bibliometric analysis. That included assessing published and cited counts, co-authorship mapping, co-citation analysis, burst detection, and keyword analysis. RESULTS The study revealed a fluctuating growth trend in the number of publications and citations since 2007. As many as 147 institutions from 13 countries, with a total of 756 authors, have published 202 papers in 76 academic journals. Sichuan University in China and Tang Wenfu have been recognized as the most influential national institution and author. The most frequently published journal is "Pancreas", while the most cited is the "World Journal of Gastroenterology". Commonly used single herbs in this field include Baicalin, Emodin, Rhubarb, and Salvia miltiorrhizae. Frequently used herbal formulations include Da chengqi decoction, Chaiqin chengqi decoction, and Qing yi decoction. Current research hotspots primarily surround concepts like hmgb1, nf-kappab, nfr2, oxidative stress, exosomes, nlrp3, pyroptosis, etc. Potential future research themes could relate to pharmacology, reducing hmgb1, inflammatory response, cell activation, Qing Yi-decoction, etc. This review holds significant guiding importance for clinical and scientific research into TCM treatment for acute pancreatitis in the future.
Collapse
Affiliation(s)
- Wang-peng Lan
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, Affiliated Traditional Medicine Hospital of Southwest Medical University, Lu zhou, 646000, China
- Department of Spleen and Stomach Diseases, the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, Sichuan, 646000, China
| | - Wen Guo
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, Affiliated Traditional Medicine Hospital of Southwest Medical University, Lu zhou, 646000, China
- Department of Spleen and Stomach Diseases, the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, Sichuan, 646000, China
| | - Xin Zhou
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, Affiliated Traditional Medicine Hospital of Southwest Medical University, Lu zhou, 646000, China
- Department of Spleen and Stomach Diseases, the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, Sichuan, 646000, China
| | - Zhi Li
- The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, Affiliated Traditional Medicine Hospital of Southwest Medical University, Lu zhou, 646000, China
- Department of Spleen and Stomach Diseases, the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, Sichuan, 646000, China
| |
Collapse
|
26
|
Jamal S, Shaw M, Quasim T, Puxty K, McGovern C. Long term opioid use after burn injury: a retrospective cohort study. Br J Anaesth 2024; 132:599-606. [PMID: 38216388 PMCID: PMC10870133 DOI: 10.1016/j.bja.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 11/30/2023] [Accepted: 12/04/2023] [Indexed: 01/14/2024] Open
Abstract
BACKGROUND Patients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge. METHODS This retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use. RESULTS A total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge. CONCLUSIONS Opioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.
Collapse
Affiliation(s)
- Sherzah Jamal
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
| | - Martin Shaw
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Tara Quasim
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Kathryn Puxty
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | | |
Collapse
|
27
|
Edmiston T, Vishnupriya K, Chanmugam A. Recurrent acute pancreatitis: a harbinger for irreversible chronic pancreatitis. Hosp Pract (1995) 2024; 52:5-12. [PMID: 38686624 DOI: 10.1080/21548331.2024.2348990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/25/2024] [Indexed: 05/02/2024]
Abstract
Recurrent acute pancreatitis is beginning to be recognized as an intermediary stage in the continuous spectrum between acute and chronic pancreatitis. It is crucial to identify this disease stage and intervene with diagnostic and therapeutic modalities to prevent the painful and irreversible condition of chronic pancreatitis. We review the recent advances in diagnosing and managing this important 'call for action' condition.
Collapse
Affiliation(s)
- Thomas Edmiston
- School of Clinical Medicine, Cambridge University, Cambridge, UK
| | | | | |
Collapse
|
28
|
Ashfaq A, Kolanu ND, Mohammed M, Oliveira Souza Lima SR, Rehman A, Shehryar A, Fathallah NA, Abdallah S, Abougendy IS, Raza A. Surgical Interventions in Chronic Pancreatitis: A Systematic Review of Their Impact on Quality of Life. Cureus 2024; 16:e53989. [PMID: 38476813 PMCID: PMC10928306 DOI: 10.7759/cureus.53989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2024] [Indexed: 03/14/2024] Open
Abstract
This systematic review evaluates the efficacy of surgical interventions in improving the quality of life for patients with chronic pancreatitis (CP). A thorough literature search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identified 11 studies that focused on patient-reported outcomes after surgical treatments, including pancreatic resections, drainage procedures, and duodenum-preserving head resections. The findings indicate that organ-preserving procedures, notably the Frey and Beger operations, significantly enhance pain control and overall quality of life while reducing analgesic dependency. This review provides crucial insights into the long-term efficacy and comparative benefits of different surgical approaches, highlighting the need for personalized surgical strategies in CP management. It emphasizes the necessity for standardized outcome measures and further comparative research to refine CP treatment protocols.
Collapse
Affiliation(s)
- Abdullah Ashfaq
- Surgery, Gujranwala Medical Teaching Hospital, Gujranwala, PAK
| | | | - Mathani Mohammed
- General Surgery, Sudan Medical Specialization Board Hospital, Khartoum, SDN
| | | | | | | | - Nader A Fathallah
- Accident and Emergency, Nasr City Hospital for Health Insurance, Cairo, EGY
| | | | | | - Ali Raza
- Internal Medicine, Nishtar Medical University, Multan, PAK
| |
Collapse
|
29
|
Takaki T, Chujo D, Kurokawa T, Kawabe A, Takahashi N, Ito K, Maruyama K, Inagaki F, Shinohara K, Ajima K, Yamashita Y, Kajio H, Yanase M, Hinohara C, Tokuhara M, Uemura Y, Edamoto Y, Takemura N, Kokudo N, Matsumoto S, Shimoda M. Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan. Islets 2023; 15:2202092. [PMID: 37087752 PMCID: PMC10124982 DOI: 10.1080/19382014.2023.2202092] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 04/04/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. METHODS We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28). RESULTS Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. CONCLUSION The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.
Collapse
Affiliation(s)
- Tadashi Takaki
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
- Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Tokyo, Japan
- Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA), Fujisawa, Kanagawa, Japan
| | - Daisuke Chujo
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global health and Medicine, Tokyo, Japan
- Center for Clinical Research, Toyama University Hospital, Toyama, Japan
| | | | - Akitsu Kawabe
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| | - Nobuyuki Takahashi
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global health and Medicine, Tokyo, Japan
| | - Kyoji Ito
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Koji Maruyama
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global health and Medicine, Tokyo, Japan
| | - Fuyuki Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Koya Shinohara
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| | - Kumiko Ajima
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yzumi Yamashita
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroshi Kajio
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global health and Medicine, Tokyo, Japan
| | - Mikio Yanase
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Chihaya Hinohara
- Palliative care, National Center for Global Health and Medicine, Tokyo, Japan
| | - Makoto Tokuhara
- Palliative care, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yukari Uemura
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | | | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shinichi Matsumoto
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masayuki Shimoda
- Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, Tokyo, Japan
| |
Collapse
|
30
|
Cook ME, Bruun NH, Davidsen L, Drewes AM, Olesen SS. Multistate Model of the Natural History of Inflammatory Pancreatic Diseases: A Nationwide Population-based Cohort Study. Gastroenterology 2023; 165:1547-1557.e4. [PMID: 37659669 DOI: 10.1053/j.gastro.2023.08.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 08/18/2023] [Accepted: 08/26/2023] [Indexed: 09/04/2023]
Abstract
BACKGROUND & AIMS Understanding the nature of inflammatory pancreatic diseases is essential for planning health care system requirements and interventions. The aim of this study was to quantify the trajectories of inflammatory pancreatic diseases and their association with pancreatic cancer in a population-based setting. METHODS National health registries were used to identify all Danish residents (18 years or older) in the period from 2000 through 2018 with incident cases of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. We used a multistate model to examine transitions from a healthy state to intermediate states of acute pancreatic inflammation (AP and RAP) to chronic states (CP and pancreatic cancer) and, ultimately, death. Results were reported as transition incidence rates per 1000 person-years with 95% CIs. RESULTS There were 4,663,864 individuals included (mean age, 46 years; 51% were women). During a mean follow-up of 16.8 years, 31,396 individuals were diagnosed with incident AP, 5546 with RAP, 8898 with CP, and 18,182 with pancreatic cancer. The cumulative incidence of pancreatitis (acute and chronic) during the study period was 0.80% (95% CI, 0.79%-0.80%). The transition incidence rates to CP were 12.1 (95% CI, 8.1-18.1) from AP, 46.8 (95% CI, 31.6-69.3) from RAP, and 0.07 (95% CI, 0.04-0.13) from a healthy state. Similar patterns were observed for transitions to pancreatic cancer. Most patients diagnosed with CP (64.2%) and pancreatic cancer (96.4%) transitioned directly from a healthy state. Among patients with pancreatitis, 41.0% (95% CI, 40.5%-41.5%) died during follow-up. CONCLUSIONS The study findings revealed an increased risk of CP and pancreatic cancer in patients with a history of AP. However, most patients with CP and pancreatic cancer transitioned directly from a healthy state.
Collapse
Affiliation(s)
- Mathias Ellgaard Cook
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Niels Henrik Bruun
- Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark
| | - Line Davidsen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Schou Olesen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
| |
Collapse
|
31
|
Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, Araújo-Vilar D. Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain. Front Endocrinol (Lausanne) 2023; 14:1250203. [PMID: 38034001 PMCID: PMC10687442 DOI: 10.3389/fendo.2023.1250203] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 10/10/2023] [Indexed: 12/02/2023] Open
Abstract
The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.
Collapse
Affiliation(s)
- Antía Fernández-Pombo
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Sofía Sánchez-Iglesias
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Ana I. Castro-Pais
- Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain
| | - Maria José Ginzo-Villamayor
- Department of Estatística, Análise Matemática e Optimización, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Silvia Cobelo-Gómez
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Teresa Prado-Moraña
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Everardo Josué Díaz-López
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Felipe F. Casanueva
- CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain
| | - Lourdes Loidi
- Galician Public Foundation for Genomic Medicine (SERGAS-Xunta de Galicia), Santiago de Compostela, Spain
| | - David Araújo-Vilar
- Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CiMUS, University of Santiago de Compostela, Santiago de Compostela, Spain
- Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| |
Collapse
|
32
|
Sun Q, Ren Q, Du L, Chen S, Wu S, Zhang B, Wang B. Cardiometabolic Index (CMI), Lipid Accumulation Products (LAP), Waist Triglyceride Index (WTI) and the risk of acute pancreatitis: a prospective study in adults of North China. Lipids Health Dis 2023; 22:190. [PMID: 37946249 PMCID: PMC10633920 DOI: 10.1186/s12944-023-01948-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/16/2023] [Indexed: 11/12/2023] Open
Abstract
OBJECTIVE To investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population. METHODOLOGY The present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI < 24 kg/m2), overweight group (BMI 24-28 kg /m2), and obesity group (BMI ≥ 28 kg/m2). The data were subjected to analysis in order to investigate the correlation between these anthropometric indexes and the incidence of AP. Cox regression models were employed to assess the relative risk of AP while accounting for known risk factors through appropriate adjustments. OUTCOMES Over the course of a median follow-up duration of 12.59 ± 0.98 years, we documented 401 incident AP cases. Incidence density and cumulative incidence rates of AP increased with the increase of CMI, LAP, and WTI. After multivariate adjustment, the fourth quartile of CMI, LAP, and WTI exhibited the greatest risk of AP [CMI: hazard ratio (HR) 1.93, 95% confidential interval (CI) (1.45-2.57); LAP: HR 2.00, 95% CI(1.49-2.68); WTI: HR 2.13,95% CI (1.59-2.83)]. In comparison to the normal weight group, the obesity group (BMI ≥ 28 kg/m2) had an elevated risk of AP (HR = 1.58, 95% CI: 1.21-2.05). Furthermore, the incremental effect of BMI combined with CMI on the prognostic value of AP was greater than that of BMI alone (the C statistics demonstrated a result of 0.607 versus 0.546; the integrated discrimination improvement revealed a result of 0.321%; net reclassification improvement was 1.975%). CONCLUSION We found that CMI, LAP, and WTI were positively and independently connected to the risk of AP. Additionally, CMI demonstrates a superior prognostic capacity than other indexes in anticipating AP.
Collapse
Affiliation(s)
- Qiu Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, 154 Anshan Road, Heping District, Tianjin, 300052, China
- Department of Hepatobiliary, Kailuan General Hospital, No.57 Xinhua East Street, Tangshan, 063000, China
| | - Qingshuai Ren
- Deparment of Cardiovascular Surgery, North China University of Science and Technology, Tangshan, 063000, China
| | - Liming Du
- Department of Hepatobiliary, Kailuan General Hospital, No.57 Xinhua East Street, Tangshan, 063000, China
| | - Shuohua Chen
- Department of Cardiology, Kailuan General Hospital, North China University of Science and Technology, No.57 Xinhua East Street, Tangshan, 063000, China
| | - Shouling Wu
- Department of Cardiology, Kailuan General Hospital, North China University of Science and Technology, No.57 Xinhua East Street, Tangshan, 063000, China
| | - Bing Zhang
- Department of Hepatobiliary, Kailuan General Hospital, No.57 Xinhua East Street, Tangshan, 063000, China.
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, 154 Anshan Road, Heping District, Tianjin, 300052, China.
| |
Collapse
|
33
|
Park SM, Kim KB, Han JH, Kim N, Kang TU, Swan H, Kim HJ. Incidence and risk of pancreatic cancer in patients with acute or chronic pancreatitis: a population-based cohort study. Sci Rep 2023; 13:18930. [PMID: 37919344 PMCID: PMC10622573 DOI: 10.1038/s41598-023-45382-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 10/18/2023] [Indexed: 11/04/2023] Open
Abstract
We aimed to evaluate the incidence and risk of pancreatic cancer (PC) in pancreatitis. We identified patients with acute pancreatitis (AP) (n = 225,811, 50.0%) and chronic pancreatitis (CP) (n = 225,685, 50.0%) from Korean population-based data and matched them with age- and sex-matched controls (n = 4,514,960). We analyzed the incidence and adjusted hazard ratios (aHRs) of PC among patients followed for more than 2 years or 5 years, and assessed risk changes over time in single episode of AP (SAP), recurrent AP (RAP), CP with AP, and CP without AP groups. We also performed subgroup analysis for both sexes. The incidences (per 104 person-years) and risks (aHR) of PC were higher in the RAP (12.69, 5.00) or CP with AP (12.12, 5.74) groups compared to the SAP (2.31, 1.32) or CP without AP (2.28, 1.57) groups. The risks of PC decreased over time, however, the risk of PC remained elevated in the RAP and CP with AP groups for more than 8 years. Females with RAP, SAP, and CP with AP had higher risks of PC than males. The risk of PC is higher and persists for longer duration in patients with RAP and CP with AP compared to those with SAP or CP without AP.
Collapse
Affiliation(s)
- Seon Mee Park
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Ki Bae Kim
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Joung-Ho Han
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seungnam, Republic of Korea
| | - Tae Uk Kang
- Health and Wellness College, Sungshin Women's University, Seoul, Republic of Korea
| | - Heather Swan
- Department of Preventive Medicine, Korea University College of Medicine, 126-1, 5-ga, Inchon-ro, Seoul, 136-705, Republic of Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, 126-1, 5-ga, Inchon-ro, Seoul, 136-705, Republic of Korea.
- Department of Public Health, Graduate School, Korea University, Seoul, Republic of Korea.
| |
Collapse
|
34
|
Thompson DA, Tsaava T, Rishi A, George SJ, Hepler TD, Hide D, Pavlov VA, Brines M, Chavan SS, Tracey KJ. Galantamine ameliorates experimental pancreatitis. Mol Med 2023; 29:149. [PMID: 37907853 PMCID: PMC10617083 DOI: 10.1186/s10020-023-00746-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/19/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND Acute pancreatitis is a common and serious inflammatory condition currently lacking disease modifying therapy. The cholinergic anti-inflammatory pathway (CAP) is a potent protective anti-inflammatory response activated by vagus nerve-dependent α7 nicotinic acetylcholine receptor (α7nAChR) signaling using splenic CD4+ T cells as an intermediate. Activating the CAP ameliorates experimental acute pancreatitis. Galantamine is an acetylcholinesterase inhibitor (AChEI) which amplifies the CAP via modulation of central muscarinic ACh receptors (mAChRs). However, as mAChRs also activate pancreatitis, it is currently unknown whether galantamine would be beneficial in acute pancreatitis. METHODS The effect of galantamine (1-6 mg/kg-body weight) on caerulein-induced acute pancreatitis was evaluated in mice. Two hours following 6 hourly doses of caerulein (50 µg/kg-body weight), organ and serum analyses were performed with accompanying pancreatic histology. Experiments utilizing vagotomy, gene knock out (KO) technology and the use of nAChR antagonists were also performed. RESULTS Galantamine attenuated pancreatic histologic injury which was mirrored by a reduction in serum amylase and pancreatic inflammatory cytokines and an increase the anti-inflammatory cytokine IL-10 in the serum. These beneficial effects were not altered by bilateral subdiaphragmatic vagotomy, KO of either choline acetyltransferase+ T cells or α7nAChR, or administration of the nAChR ganglionic blocker mecamylamine or the more selective α7nAChR antagonist methyllycaconitine. CONCLUSION Galantamine improves acute pancreatitis via a mechanism which does not involve previously established physiological and molecular components of the CAP. As galantamine is an approved drug in widespread clinical use with an excellent safety record, our findings are of interest for further evaluating the potential benefits of this drug in patients with acute pancreatitis.
Collapse
Affiliation(s)
- Dane A Thompson
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA
- Department of Surgery, Northshore University Hospital, Northwell Health, Feinstein Institutes for Medical Research, Manhasset, NY, USA
| | - Tea Tsaava
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Arvind Rishi
- Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Sam J George
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Tyler D Hepler
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Daniel Hide
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Valentin A Pavlov
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA
| | - Michael Brines
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Sangeeta S Chavan
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.
- The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA.
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA.
| | - Kevin J Tracey
- Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.
- The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA.
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA.
| |
Collapse
|
35
|
Thapa S, Allakky A, Turaga A. OCP-driven hypertriglyceridaemia and recurrent acute pancreatitis. BMJ Case Rep 2023; 16:e257067. [PMID: 37798042 PMCID: PMC10565274 DOI: 10.1136/bcr-2023-257067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/07/2023] Open
Abstract
Recurrent acute pancreatitis poses a significant challenge in clinical management. In this case, a young, obese woman with metabolic syndrome presented with her third episode of acute pancreatitis within a span of 4 months. Due to unavailability, plasmapheresis could not be performed, and the patient was managed solely with pharmacological therapy. Initial evaluation revealed abdominal pain, tenderness and elevated laboratory markers. CT scan findings indicated pancreatic and peripancreatic oedema. Further investigations highlighted the presence of hypertriglyceridaemia and hypocalcaemia. As the patient was using oral contraceptive pills (OCP), it was crucial to consider their potential role in causing hypertriglyceridaemia. Consequently, the patient was advised to discontinue OCP use. Despite the lack of plasmapheresis, intensive medical management, including medication and lifestyle modifications, showed positive results. This case underscores the importance of recognising the association between OCP, hypertriglyceridaemia and recurrent pancreatitis in patients with metabolic syndrome.
Collapse
Affiliation(s)
- Samriddha Thapa
- Internal Medicine, Lower Bucks Hospital, Bristol, Pennsylvania, USA
| | - Akhil Allakky
- Internal Medicine, Lower Bucks Hospital, Bristol, Pennsylvania, USA
| | - Anjani Turaga
- Surgery, Gandhi Medical College, Secunderabad-Padmarao Nagar, India
| |
Collapse
|
36
|
Alalawi Y, Daghriri AA, Alkhudairy AI, Ali AA, Alahmari MN, Alahmari FN, Khan RG, Al-Zayed A, Alamri M. Pancreatitis Prevention in Tabuk City, Kingdom of Saudi Arabia: Evaluating Public Knowledge and Raising Awareness of Risk Factors and Symptoms. Cureus 2023; 15:e47069. [PMID: 38021830 PMCID: PMC10645396 DOI: 10.7759/cureus.47069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2023] [Indexed: 12/01/2023] Open
Abstract
INTRODUCTION Pancreatitis is an inflammation of the pancreas. The pancreas is a flat, elongated gland situated in the upper abdomen, beyond the stomach. It produces digestive enzymes and hormones that regulate glucose absorption in the body. Pancreatitis can be acute, developing rapidly and lasting for several days, or chronic, persisting over an extended period and affecting specific individuals. While treatment can improve mild cases of pancreatitis, severe cases can be fatal. METHOD This study utilizes a cross-sectional survey design with 549 participants, allowing data collection from a representative sample of Tabuk City's adult population. RESULTS The participants' knowledge about the risk factors and symptoms of pancreatitis was inadequate. Among those who did not receive any information about pancreatitis and its risk factors, the count was 352 (64.1%). On the other hand, there was increased awareness of pancreatitis and its risk factors, which would lead to early detection and prevention. A total of 483 participants (88%) expressed adequate agreement, and 305 participants (55.6%) demonstrated an adequate response regarding seeking medical attention if they experienced any symptoms of pancreatitis. CONCLUSION Our findings revealed a lack of knowledge about the risk factors and symptoms of pancreatitis. Furthermore, there was inadequate awareness regarding governmental initiatives or programs that support access to pancreatitis knowledge and awareness in Tabuk City.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Afnan Al-Zayed
- Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, SAU
| | - Mohammed Alamri
- College of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
| |
Collapse
|
37
|
Lee B, Jones EK, Manohar M, Li L, Yadav D, Conwell DL, Hart PA, Vege SS, Fogel EL, Serrano J, Andersen D, Bellin MD, Topazian MD, Van Den Eeden SK, Pandol SJ, Forsmark CE, Fisher WE, Park WG, Husain SZ, Habtezion A. Distinct Serum Immune Profiles Define the Spectrum of Acute and Chronic Pancreatitis From the Multicenter Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) Study. Gastroenterology 2023; 165:173-186. [PMID: 37061168 PMCID: PMC10330331 DOI: 10.1053/j.gastro.2023.03.236] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/21/2023] [Accepted: 03/30/2023] [Indexed: 04/17/2023]
Abstract
BACKGROUND & AIMS Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. METHODS Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). RESULTS A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. CONCLUSIONS Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.
Collapse
Affiliation(s)
- Bomi Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California.
| | - Elaina K Jones
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California
| | - Murli Manohar
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California
| | - Liang Li
- Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Darwin L Conwell
- Department of Internal Medicine, University of Kentucky, Lexington, Kentucky
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Santhi Swaroop Vege
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Evan L Fogel
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Jose Serrano
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Dana Andersen
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Melena D Bellin
- Division of Pediatric Endocrinology, University of Minnesota, Minneapolis, Minnesota
| | - Mark D Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Stephen J Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California
| | - Chris E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida
| | - William E Fisher
- Division of General Surgery, Baylor College of Medicine, Houston, Texas
| | - Walter G Park
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Sohail Z Husain
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, School of Medicine, Stanford University, Stanford, California
| | - Aida Habtezion
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California.
| |
Collapse
|
38
|
Tu X, Liu Q, Chen L, Li J, Yu X, Jiao X, Wang N, Hu L, Yuan Y, Gong W, Ding Y, Shi X, Xiao W, Lu G. Number of recurrences is significantly associated with the post-acute pancreatitis diabetes mellitus in a population with hypertriglyceridemic acute pancreatitis. Lipids Health Dis 2023; 22:82. [PMID: 37386421 DOI: 10.1186/s12944-023-01840-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 05/31/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND Twenty-three percent of patients are diagnosed with diabetes mellitus after the first episode of acute pancreatitis. The incidence of post-acute pancreatitis diabetes mellitus is significantly higher than that of type 1 diabetes mellitus. Some studies have concluded that the all-cause mortality and worse prognosis of diabetes after pancreatitis are higher. We predicted that number of recurrences of pancreatitis would be significantly associated with the incidences of metabolic syndrome, abdominal obesity, and post-acute pancreatitis diabetes mellitus. METHODS Patients admitted to our hospital for hypertriglyceridemic acute pancreatitis from 2013-2021 were selected for a cross-sectional study. Statistical analysis methods were used to analyze the effect of recurrences on the long-term prognosis of patients with hypertriglyceridemic acute pancreatitis. RESULTS In this study, 101 patients with hypertriglyceridemic acute pancreatitis were included: 60 (59.41%) in the recurrent acute pancreatitis group and 41 (40.59%) in the only one episode of acute pancreatitis group. Among all hypertriglyceridemic acute pancreatitis patients, approximately 61.4% were diagnosed with abdominal obesity, 33.7% of patients are diagnosed with metabolic syndrome, 34.7% of patients are diagnosed with diabetes mellitus, and 21.8% of patients are diagnosed with post-acute pancreatitis diabetes mellitus. Recurrent acute pancreatitis were independent risk factors for post-acute pancreatitis diabetes mellitus in patients with hypertriglyceridemic acute pancreatitis (odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.230-12.774) and the risk of post-acute pancreatitis diabetes mellitus in patients with three or more recurrent episodes was 6.607 times higher than that in patients without recurrent episodes (OR = 6.607, 95% CI = 1.412-30.916). CONCLUSIONS Recurrence is an independent risk factor for the development of post-acute pancreatitis diabetes mellitus and is significantly associated with the number of recurrences.
Collapse
Affiliation(s)
- Xiamin Tu
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Qingxie Liu
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Lin Chen
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Jie Li
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Xiaoping Yu
- Health Management Centre, Yangzhou University Affiliated Hospital, Yangzhou, 225000, Jiangsu, China
| | - Xiuping Jiao
- Health Management Centre, Yangzhou University Affiliated Hospital, Yangzhou, 225000, Jiangsu, China
| | - Ningzhi Wang
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Lianghao Hu
- Department of Gastroenterology, Changhai Hospital of the Second Military Medical University, Shanghai, 200433, China
| | - Yuan Yuan
- Department of Nursing, Yangzhou University Affiliated Hospital, Yangzhou, 225000, Jiangsu, China
| | - Weijuan Gong
- College of Medicine, Yangzhou University, Yangzhou, 225000, Jiangsu, China
| | - Yanbing Ding
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China
| | - Xiaolei Shi
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China.
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China.
| | - Weiming Xiao
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China.
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China.
| | - Guotao Lu
- Pancreatic Center of Gastroenterology, Affiliated Hospital of Yangzhou University, No.368, Hanjiang Middle Road, Yangzhou, 225100, Jiangsu Province, China.
- Yangzhou Key Laboratory of Pancreas in Jiangsu Province, Yangzhou, 225000, Jiangsu, China.
| |
Collapse
|
39
|
Cook ME, Knoph CS, Fjelsted CA, Frøkjær JB, Bilgrau AE, Novovic S, Jørgensen MT, Mortensen MB, Nielsen LBJ, Hadi A, Berner-Hansen M, Rutkowski W, Vujasinovic M, Löhr M, Drewes AM, Olesen SS. Effects of a peripherally acting µ-opioid receptor antagonist for the prevention of recurrent acute pancreatitis: study protocol for an investigator-initiated, randomized, placebo-controlled, double-blind clinical trial (PAMORA-RAP trial). Trials 2023; 24:301. [PMID: 37127657 PMCID: PMC10150502 DOI: 10.1186/s13063-023-07287-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/31/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND Acute and chronic pancreatitis constitute a continuum of inflammatory disease of the pancreas with an increasing incidence in most high-income countries. A subset of patients with a history of pancreatitis suffer from recurrence of acute pancreatitis attacks, which accelerate disease progression towards end-stage chronic pancreatitis with loss of exocrine and endocrine function. There is currently no available prophylactic treatment for recurrent acute pancreatitis apart from removing risk factors, which is not always possible. Pain is the primary symptom of acute pancreatitis, which induces the endogenous release of opioids. This may further be potentiated by opioid administration for pain management. Increased exposure to opioids leads to potentially harmful effects on the gastrointestinal tract, including, e.g. increased sphincter tones and decreased fluid secretion, which may impair pancreatic ductal clearance and elevate the risk for new pancreatitis attacks and accelerate disease progression. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have been developed to counteract the adverse effects of opioids on the gastrointestinal tract. We hypothesize that the PAMORA naldemedine will reduce the risk of new pancreatitis attacks in patients with recurrent acute pancreatitis and hence decelerate disease progression. METHODS The study is a double-blind, randomized controlled trial with allocation of patients to either 0.2 mg naldemedine daily or matching placebo for 12 months. A total of 120 outpatients will be enrolled from five specialist centres in Denmark and Sweden. The main inclusion criteria is a history of recurrent acute pancreatitis (minimum of two confirmed pancreatitis attacks). The primary endpoint is time to acute pancreatitis recurrence after randomization. Secondary outcomes include changes in quality of life, gastrointestinal symptom scores, new-onset diabetes, exocrine pancreatic insufficiency, disease severity, health care utilization, adherence to treatment, and frequency of adverse events. Exploratory outcomes are included for mechanistic linkage and include the progression of chronic pancreatitis-related findings on magnetic resonance imaging (MRI) and changes in circulating blood markers of inflammation and fibrosis. DISCUSSION This study investigates if naldemedine can change the natural course of pancreatitis in patients with recurrent acute pancreatitis and improve patient outcomes. TRIAL REGISTRATION EudraCT no. 2021-000069-34. CLINICALTRIALS gov NCT04966559. Registered on July 8, 2021.
Collapse
Affiliation(s)
- Mathias E Cook
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
| | - Cecilie S Knoph
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Camilla A Fjelsted
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Jens B Frøkjær
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Anders E Bilgrau
- Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark
| | - Srdan Novovic
- Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Maiken Thyregod Jørgensen
- Department of Surgery, Odense Pancreas Centre (OPAC), HPB Section, Odense University Hospital, Odense, Denmark
| | - Michael B Mortensen
- Department of Surgery, Odense Pancreas Centre (OPAC), HPB Section, Odense University Hospital, Odense, Denmark
| | - Liv B J Nielsen
- Digestive Disease Centre K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Amer Hadi
- Digestive Disease Centre K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Mark Berner-Hansen
- Digestive Disease Centre K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Wiktor Rutkowski
- Department for Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department for Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Matthias Löhr
- Department for Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Asbjørn M Drewes
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Søren S Olesen
- Department of Gastroenterology and Hepatology, Centre for Pancreatic Diseases and Mech-Sense, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
| |
Collapse
|
40
|
Tomaszewska E, Świątkiewicz M, Muszyński S, Donaldson J, Ropka-Molik K, Arciszewski MB, Murawski M, Schwarz T, Dobrowolski P, Szymańczyk S, Dresler S, Bonior J. Repetitive Cerulein-Induced Chronic Pancreatitis in Growing Pigs-A Pilot Study. Int J Mol Sci 2023; 24:ijms24097715. [PMID: 37175426 PMCID: PMC10177971 DOI: 10.3390/ijms24097715] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.
Collapse
Affiliation(s)
- Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Małgorzata Świątkiewicz
- Department of Animal Nutrition and Feed Science, National Research Institute of Animal Production, 32-083 Balice, Poland
| | - Siemowit Muszyński
- Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa
| | - Katarzyna Ropka-Molik
- Department of Animal Molecular Biology, National Research Institute of Animal Production, 32-083 Balice, Poland
| | - Marcin B Arciszewski
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Maciej Murawski
- Department of Animal Nutrition, Biotechnology and Fisheries, Faculty of Animal Science, University of Agriculture in Kraków, 30-059 Kraków, Poland
| | - Tomasz Schwarz
- Department of Animal Genetics, Breeding and Ethology, Faculty of Animal Science, University of Agriculture in Kraków, 30-059 Kraków, Poland
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, 20-033 Lublin, Poland
| | - Sylwia Szymańczyk
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Sławomir Dresler
- Department of Analytical Chemistry, Medical University of Lublin, 20-059 Lublin, Poland
- Department of Plant Physiology and Biophysics, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Joanna Bonior
- Department of Medical Physiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Kraków, Poland
| |
Collapse
|
41
|
Avnat E, Shapira G, Shoval S, Israel-Elgali I, Alkelai A, Shuldiner AR, Gonzaga-Jauregui C, Zidan J, Maray T, Shomron N, Friedman E. Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening. Genes (Basel) 2023; 14:genes14040937. [PMID: 37107695 PMCID: PMC10137689 DOI: 10.3390/genes14040937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/24/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders. METHODS Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed whole exome sequencing (WES) of 118 Druze individuals: 38 trios and 2 couples, representing geographically distinct clans (WES-cohort). Rates of validated PV were compared with rates in worldwide and Middle Eastern populations, from the gnomAD and dbSNP datasets. RESULTS Overall, 34 PVs were identified: 30 PVs in genes underlying AR disorders, 3 additional PVs were associated with autosomal dominant (AD) disorders, and 1 PV with X-linked-dominant inherited disorder in the WES cohort. CONCLUSIONS The newly identified PVs associated with AR conditions should be considered for incorporation into prenatal-screening options offered to Druze individuals after an extension and validation of the results in a larger study.
Collapse
Affiliation(s)
- Eden Avnat
- Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Guy Shapira
- Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel
| | - Shelly Shoval
- The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sheba Medical Center, Ramat Gan 52621, Israel
| | - Ifat Israel-Elgali
- Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv 69978, Israel
| | - Anna Alkelai
- Regeneron Genetics Center, Tarrytown, NY 10591, USA
| | | | - Claudia Gonzaga-Jauregui
- Regeneron Genetics Center, Tarrytown, NY 10591, USA
- International Laboratory for Human Genome Research, Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Juriquilla 04510, Querétaro, Mexico
| | - Jamal Zidan
- The Oncology Department, Ziv Medical Center, and the Azrieli Faculty of Medicine, Bar-Ilan University, Zefat 13206, Israel
| | - Taiseer Maray
- Golan for Development, Majdal Shams 1243800, Golan Heights
| | - Noam Shomron
- Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel
- Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv 69978, Israel
| | - Eitan Friedman
- Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
- The Meirav High Risk Clinic, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, Israel
| |
Collapse
|
42
|
Litvinova M, Khafizov K, Speranskaya A, Matsvay A, Asanov A, Nikolskaya K, Vinokurova L, Dubtsova E, Ipatova M, Mukhina T, Karnaushkina M, Bordin D. Spectrum of PRSS1, SPINK1, CTRC, CFTR, and CPA1 Gene Variants in Chronic Pancreatitis Patients in Russia. Sovrem Tekhnologii Med 2023; 15:60-70. [PMID: 37389024 PMCID: PMC10306969 DOI: 10.17691/stm2023.15.2.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Indexed: 07/01/2023] Open
Abstract
UNLABELLED The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation. MATERIALS AND METHODS The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. RESULTS Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes. CONCLUSION Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.
Collapse
Affiliation(s)
- M.M. Litvinova
- Associate Professor, Deputy Head for Research Work, Department of Medical Genetics1; Clinical Geneticist; The Loginov Moscow Clinical Scientific Center of Moscow Healthcare Department, 86 Entuziastov Shosse, Moscow, 111123, Russia
| | - K.F. Khafizov
- Head of the Laboratory of Genomic Research; Central Research Institute of Epidemiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 3A Novogireevskaya St., Moscow, 111123, Russia
| | - A.S. Speranskaya
- Senior Researcher, Head of the Laboratory of Multiomix Investigations; Scientific Research Institute for Systems Biology and Medicine, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 18 Nauchniy Proezd, Moscow, 117246, Russia; Researcher; Lomonosov Moscow State University, 1 Leninskiye Gory, Moscow, 119991, Russia
| | - A.D. Matsvay
- Researcher, Laboratory of Genomic Methods Development; Centre for Strategic Planning and Management of Biomedical Health Risks of FMBA of Russia
| | - A.Yu. Asanov
- Professor, Department of Medical Genetics; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia
| | - K.A. Nikolskaya
- Physician; The Loginov Moscow Clinical Scientific Center of Moscow Healthcare Department, 86 Entuziastov Shosse, Moscow, 111123, Russia
| | - L.V. Vinokurova
- Gastroenterologist; The Loginov Moscow Clinical Scientific Center of Moscow Healthcare Department, 86 Entuziastov Shosse, Moscow, 111123, Russia
| | - E.A. Dubtsova
- Head of the Department of Pathology of the Pancreas and Bile Ducts; The Loginov Moscow Clinical Scientific Center of Moscow Healthcare Department, 86 Entuziastov Shosse, Moscow, 111123, Russia
| | - M.G. Ipatova
- Associate Professor, Department of Hospital Pediatrics named after Academician V.A. Tabolin; Pirogov Russian National Research Medical University, 1 Ostrovitianova St., Moscow, 117997, Russia; Head of the Center for the Treatment of Developmental Anomalies and Diseases of the Hepatobiliary System in Children; N.F. Filatov Children’s City Hospital of Moscow Healthcare Department, 15 Sadovaya-Kudrinskaya St., Moscow, 123001, Russia
| | - T.F. Mukhina
- Gastroenterologist; Morozovskaya Children’s City Clinical Hospital of Moscow Healthcare Department, 1/9, 4 Dobrininskiy Pereulok, 119049, Moscow, Russia
| | - M.A. Karnaushkina
- Professor, Department of Internal Medicine with a Course of Cardiology and Functional Diagnostics named after Academician V.S. Moiseev; Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow, 117198, Russia
| | - D.S. Bordin
- Professor, Head of the Department of Pancreatic, Biliary and Upper Digestive Tract Disorders; The Loginov Moscow Clinical Scientific Center of Moscow Healthcare Department, 86 Entuziastov Shosse, Moscow, 111123, Russia; Professor, Department of Propaedeutic of Internal Diseases and Gastroenterology; A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 20/1 Delegatskaya St., Moscow, 127473, Russia; Professor, Department of General Medical Practice and Family Medicine; Tver State Medical University, 4 Sovetaskaya St., Tver, 170100, Russia
| |
Collapse
|
43
|
Zhang Y, Zhang WQ, Liu XY, Zhang Q, Mao T, Li XY. Immune cells and immune cell-targeted therapy in chronic pancreatitis. Front Oncol 2023; 13:1151103. [PMID: 36969002 PMCID: PMC10034053 DOI: 10.3389/fonc.2023.1151103] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 02/27/2023] [Indexed: 03/11/2023] Open
Abstract
In recent years, studies have attempted to understand the immune cells and mechanisms underlying the pathogenesis of chronic pancreatitis (CP) by constructing a model of CP. Based on these studies, the innate immune response is a key factor in disease pathogenesis and inflammation severity. Novel mechanisms of crosstalk between immune and non-immune pancreatic cells, such as pancreatic stellate cells (PSC), have also been explored. Immune cells, immune responses, and signaling pathways in CP are important factors in the development and progression of pancreatitis. Based on these mechanisms, targeted therapy may provide a feasible scheme to stop or reverse the progression of the disease in the future and provide a new direction for the treatment of CP. This review summarizes the recent advances in research on immune mechanisms in CP and the new advances in treatment based on these mechanisms.
Collapse
|
44
|
CAMARNEIRO RM, GOMES AP, CAIRES FG, SILVA CR, CAPUNGE IR, ROCHA RP, FERREIRA ÁE, NUNES VM. Transient hyperbilirubinemia as a risk factor for gallstones related events of the acute gallstone pancreatitis. Chirurgia (Bucur) 2023. [DOI: 10.23736/s0394-9508.22.05395-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
|
45
|
Radiomics analysis of contrast-enhanced T1W MRI: predicting the recurrence of acute pancreatitis. Sci Rep 2023; 13:2762. [PMID: 36797285 PMCID: PMC9935887 DOI: 10.1038/s41598-022-13650-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 05/26/2022] [Indexed: 02/18/2023] Open
Abstract
To investigate the predictive value of radiomics based on T1-weighted contrast-enhanced MRI (CE-MRI) in forecasting the recurrence of acute pancreatitis (AP). A total of 201 patients with first-episode of acute pancreatitis were enrolled retrospectively (140 in the training cohort and 61 in the testing cohort), with 69 and 30 patients who experienced recurrence in each cohort, respectively. Quantitative image feature extraction was obtained from MR contrast-enhanced late arterial-phase images. The optimal radiomics features retained after dimensionality reduction were used to construct the radiomics model through logistic regression analysis, and the clinical characteristics were collected to construct the clinical model. The nomogram model was established by linearly integrating the clinically independent risk factor with the optimal radiomics signature. The five best radiomics features were determined by dimensionality reduction. The radiomics model had a higher area under the receiver operating characteristic curve (AUC) than the clinical model for estimating the recurrence of acute pancreatitis for both the training cohort (0.915 vs. 0.811, p = 0.020) and testing cohort (0.917 vs. 0.681, p = 0.002). The nomogram model showed good performance, with an AUC of 0.943 in the training cohort and 0.906 in the testing cohort. The radiomics model based on CE-MRI showed good performance for optimizing the individualized prediction of recurrent acute pancreatitis, which provides a reference for the prevention and treatment of recurrent pancreatitis.
Collapse
|
46
|
Recurrent acute pancreatitis in an adult female with sickle cell disease: A case report. Ann Med Surg (Lond) 2023; 85:37-40. [PMID: 36742126 PMCID: PMC9893424 DOI: 10.1097/ms9.0000000000000178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 12/24/2022] [Indexed: 02/07/2023] Open
Abstract
Although risk factors such as cholelithiasis and vaso-occlusive crises exist in sickle cell disease, acute pancreatitis and its recurrence are considered rare complications manifesting as acute abdomen. Case Presentation A 33-year-old female with sickle cell disease and established cholelithiasis presented to the center with acute abdomen. After examination, investigation, and contrast enhanced computed tomography, acute pancreatitis was diagnosed. Conservative management was done and cholecystectomy was planned but delayed due to low hemoglobin. In the interval she presented again with similar features and diagnosed with of recurrence. After conservative management and after optimization of patient's hemodynamic status, laparoscopic cholecystectomy was finally performed. Postoperative period and follow-up visit after 2 months were uneventful. Clinical Discussion As the features of pancreatitis and vaso-occlusive crisis are similar, the former should be considered as a differential diagnosis of acute abdomen in sickle cell patients. Laparoscopic cholecystectomy is the treatment of choice for symptomatic cholelithiasis in these patients. However, some issues related to management such as preoperative transfusion and prophylactic cholecystectomy are still debated. This uncertainty caused delay in surgery which may have contributed to the recurrence of pancreatitis in our patient. As the risk of recurrence is possible after the first attack, standard guidelines are required for the definite management of the cause. Conclusion This case report adds to the limited literature on recurrent acute pancreatitis in sickle cell patients and points out the need for studies on developing management guidelines in such patients and need for prophylactic treatment.
Collapse
|
47
|
Xiao X, Wu X, Fu Q, Ren X, Pang X, Li Y, Zhang Q, Chen Y. Efficacy and safety of Dachaihu Decoction for acute pancreatitis: Protocol for a systematic review and meta-analysis. PLoS One 2023; 18:e0285661. [PMID: 37200279 DOI: 10.1371/journal.pone.0285661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 04/06/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Dachaihu Decoction (DCD) is a traditional herbal formula widely used for treating acute pancreatitis (AP) in China. However, the efficacy and safety of DCD has never been validated, limiting its application. This study will assess the efficacy and safety of DCD for AP treatment. METHODS Relevant randomized controlled trials of DCD in treating AP will be searched through Cochrane Library, PubMed, Embase, Web of Science, Scopus, CINAHL, China National Knowledge Infrastructure database, Wanfang Database, VIP Database, and Chinese Biological Medicine Literature Service System database. Only studies published between the inception of the databases and May 31, 2023 shall be considered. Searches will also be performed in the WHO International Clinical Trials Registry Platform, Chinese Clinical Trial Registry, and ClinicalTrials.gov. Preprint databases and grey literature sources such as OpenGrey, British Library Inside, ProQuest Dissertations & Theses Global, and BIOSIS preview will also be searched for relevant resources. The primary outcomes to be assessed will include mortality rate, rate of surgical intervention, proportion of patients with severe acute pancreatitis transferred to ICU, gastrointestinal symptoms, and the acute physiology and chronic health evaluation II score. Secondary outcomes will include systemic complications, local complications, the normalization period of C-reactive protein, length of stay in the hospital, TNF-α, IL-1, IL-6, IL-8, and IL-10 levels, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted independently by two reviewers using the Endnote X9 and Microsoft Office Excel 2016 software. The risk of bias of included studies will be assessed by the Cochrane "risk of bias" tool. Data analysis will be performed using the RevMan software (V.5.3). Subgroup and sensitivity analysis will be performed where necessary. RESULTS This study will provide high-quality current evidence of DCD for treating AP. CONCLUSION This systematic review will provide evidence of whether DCD is an effective and safe therapy for treating AP. TRIAL REGISTRATION PROSPERO registration number CRD42021245735. The protocol for this study was registered at PROSPERO, and is available in the S1 Appendix. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021245735.
Collapse
Affiliation(s)
- Xiang Xiao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xuanyu Wu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qinwei Fu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xuelei Ren
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiao Pang
- Southwest Medical University, Luzhou, Sichuan, China
| | - Yuanyuan Li
- Southwest Medical University, Luzhou, Sichuan, China
| | - Qinxiu Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yunhui Chen
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| |
Collapse
|
48
|
Muftah AA, Pecha RL, Riojas Barrett M, Abidi WM, Patel KK, Keihanian T, Othman MO. Pancreatic parenchymal changes seen on endoscopic ultrasound are dynamic in the setting of fatty pancreas: A short-term follow-up study. Pancreatology 2022; 22:1187-1194. [PMID: 36402715 DOI: 10.1016/j.pan.2022.10.006] [Citation(s) in RCA: 2] [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: 06/26/2022] [Revised: 10/17/2022] [Accepted: 10/31/2022] [Indexed: 11/05/2022]
Abstract
OBJECTIVES The impact of fatty pancreas on pancreatic parenchymal changes is unclear. The aim of this study is to assess parenchymal alterations over time in patients with fatty pancreas (FP). METHODS This is a retrospective study (2014-2021) of patients with FP identified on endoscopic ultrasound (EUS). Subjects with follow up imaging studies including Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), and EUS at least two years after the initial EUS were included. RESULTS A total of 39 patients with a mean age of 51.21 ± 12.34 years were included. Mean initial weight was 80.17 ± 17.75 kg. Diabetes, hepatic steatosis, and EPI were present in 15%, 46% and 33% of the patients at baseline, respectively. In 25 patients with available follow up EUS over 2.4 ± 0.76 years, 16% progressed to chronic pancreatitis (CP) and 24% had progressive parenchymal changes without meeting the criteria for CP. One patient progressed from focal to diffuse FP, while one patient had resolution of FP. In multivariate analysis, progressive parenchymal changes on EUS were associated with an increase in weight over time (p-value 0.04), independent of the effects of gender, alcohol, or tobacco. CONCLUSION Progressive parenchymal changes were noted in 44%. Our result suggests that FP is a dynamic process with the possibility of progression or regression over time.
Collapse
Affiliation(s)
- Abdullah A Muftah
- Department of Internal Medicine, Baylor College of Medicine, Houston, Tx, USA
| | - Robert L Pecha
- Department of Internal Medicine, Baylor College of Medicine, Houston, Tx, USA
| | - Margarita Riojas Barrett
- Department of Medicine, Division of Gastroenterology, Baylor College of Medicine, Houston, Tx, USA
| | - Wasif M Abidi
- Department of Medicine, Division of Gastroenterology, Baylor College of Medicine, Houston, Tx, USA
| | - Kalpesh K Patel
- Department of Medicine, Division of Gastroenterology, Baylor College of Medicine, Houston, Tx, USA
| | - Tara Keihanian
- Department of Medicine, Division of Gastroenterology, Baylor College of Medicine, Houston, Tx, USA
| | - Mohamed O Othman
- Department of Medicine, Division of Gastroenterology, Baylor College of Medicine, Houston, Tx, USA.
| |
Collapse
|
49
|
Shah I, Bocchino R, Ahmed A, Freedman SD, Kothari DJ, Sheth SG. Impact of recurrent acute pancreatitis on the natural history and progression to chronic pancreatitis. Pancreatology 2022; 22:1084-1090. [PMID: 36150985 DOI: 10.1016/j.pan.2022.09.237] [Citation(s) in RCA: 2] [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: 06/24/2022] [Revised: 08/14/2022] [Accepted: 09/08/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS It is believed that acute pancreatitis (AP), recurrent AP (RAP) and chronic pancreatitis (CP) represent stages of the same disease spectrum. We aimed to identify risk factors, clinical presentation and outcomes in patients with prior RAP who develop CP. METHODS We retrospectively reviewed patients with CP who were seen at our Pancreas Center during 2016-2021. We divided them into two groups: with and without RAP (≥2 episodes of AP). We compared demographics, clinical presentation and resource utilization between the two groups. RESULTS We identified 440 patients with CP, of which 283 (64%) patients had preceding RAP. These patients were younger (55.6 vs 63.1 years), active smokers (36% vs 20%) and had alcohol-related CP (49% vs 25%) compared to those without RAP and CP (p < 0.05). More patients with RAP had chronic abdominal pain (89% vs 67.9%), nausea (43.3% vs 27.1%) and exocrine pancreatic insufficiency (65.8% vs 46.5%) (p < 0.05). More patients with RAP used opioids (58.4% vs 32.3%) and gabapentinoids (56.6% vs 34.8%) (p < 0.05). They also had more ED visits resulting in an opioid prescription (9.68% vs 2%) and more CP flares requiring hospitalization (3.09 vs 0.87) (p < 0.05). CONCLUSION Young age, smoking and alcohol use are seen in patients with RAP who progress to CP. These patients are highly symptomatic and use more healthcare resources, suggestive of an overall a more course compared to those patients who develop CP without preceding RAP. Early identification and counselling of these patients may slow down progression to CP.
Collapse
Affiliation(s)
- Ishani Shah
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA
| | - Rachel Bocchino
- Department of Internal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA
| | - Awais Ahmed
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA
| | - Steven D Freedman
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA
| | - Darshan J Kothari
- Division of Gastroenterology, Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA
| | - Sunil G Sheth
- Division of Gastroenterology, Department of Internal Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
50
|
Muacevic A, Adler JR, Arora JK, Soni RK. Comparative Evaluation of Harmless Acute Pancreatitis Score (HAPS) and Bedside Index of Severity in Acute Pancreatitis (BISAP) Scoring System in the Stratification of Prognosis in Acute Pancreatitis. Cureus 2022; 14:e32540. [PMID: 36654581 PMCID: PMC9840061 DOI: 10.7759/cureus.32540] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Acute pancreatitis is a common disease in patients presenting to the emergency room in any hospital. The most common causes are alcohol ingestion and gallstone disease. Diagnosis is usually based on clinical findings and elevated serum amylase and lipase levels. Imaging is often not necessary but may be used to confirm the diagnosis or rule out any other pathology or to evaluate for any complications. The majority of patients will have a mild, self-limiting disease but others may develop a severe fulminant course with organ failure. These patients are at high risk of developing complications, morbidity or mortality. Treatment of acute pancreatitis includes supportive treatment with antibiotics, fluids, analgesics and early enteral feeding. Several scores have been developed to predict the course of pancreatitis and help make informed decisions, monitoring and timely intervention. The majority of them are complicated, require extensive and expensive interventions or require time. Harmless acute pancreatitis score (HAPS) is one such score that is easy to calculate and is done at the time of admission, bedside index of severity in acute pancreatitis (BISAP) is another one requiring more parameters. The parameters used to calculate it are easily available and can be done at a majority of healthcare facilities in developing countries. HAPS thus seems to be a good option in aiding doctors in assessing acute pancreatitis. It may be considered as a standard scoring for acute pancreatitis for early and effective management. We have tried to study and compare the superiority of HAPS over BISAP in predicting prognosis in acute pancreatitis.
Collapse
|