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Bahrizadeh M, Fotros D, Chegini M, Sadeghi A, Hekmatdoost A, Yari Z. Association of dietary glycemic index and glycemic load with pancreatic steatosis: a case control study. BMC Endocr Disord 2025; 25:89. [PMID: 40165222 PMCID: PMC11956228 DOI: 10.1186/s12902-025-01909-0] [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: 09/24/2024] [Accepted: 03/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Carbohydrate intake, its type and characteristics including glycemic index (GI) and glycemic load (GL) may be associated with the risk of pancreatic steatosis (PS), but there is no conclusive evidence. The aim of the present study was to investigate whether the intake of carbohydrates, GI and GL were associated with an increased risk of PS. METHODS To conduct this study, 278 patients with common bile duct stones (CBD) underwent endoscopic ultrasound, including 89 patients with PS (case group) and 189 healthy individuals (control group). In addition to demographic and anthropometric information, a 168-item questionnaire of food frequency was completed to calculate GL and GI. RESULTS With the increase of GI and GL, the number of patients with PS increased significantly (P = 0.013, P < 0.001, respectively) and the risk of PS increased significantly. A similar increase in risk of PS was found with increased risk of carbohydrate, simple sugar and fructose intake. After adjusting all the confounders, the risk of PS with increasing simple sugar and fructose intake was 4.3 times (OR T3 vs. T1 = 4.3, 95% CI: 1.7-10.6, P trend < 0.001) and 5.3 times (OR T3 vs. T1 = 5.3, 95% CI: 2.2-12.9, P trend < 0.001), respectively, compared to the first tertile. Conversely, increased fiber intake showed a reverse association with the PS, so that those in the second and third tertiles of fiber intake were 84% (OR = 0.16, 95% CI: 0.05-0.45) and 87% (OR = 0.13, 95% CI: 0.04-0.39) less at risk of developing PS, respectively (P trend = 0.001). CONCLUSIONS These findings support the hypothesis of direct associations between GI and GL increased risk of PS.
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Affiliation(s)
- Mohammad Bahrizadeh
- Student Research Committee, Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Danial Fotros
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Maedeh Chegini
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran
| | - Amir Sadeghi
- Research Institute for Gastroenterology and Liver Diseases of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, West Arghavan St. Farahzadi Blvd., Sharake Qods, Tehran, Iran.
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Wu Z, Li J. Correlation Between Fatty Pancreas Disease and Pancreatic Diseases, Perioperative Complications of Pancreatic Surgery. Cancer Manag Res 2025; 17:723-730. [PMID: 40177416 PMCID: PMC11963821 DOI: 10.2147/cmar.s508567] [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: 11/26/2024] [Accepted: 03/18/2025] [Indexed: 04/05/2025] Open
Abstract
Fatty pancreas disease (FPD) refers to excessive fat accumulation and fat infiltration in pancreatic tissue. Factors such as obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and alcohol consumption can contribute to the development of FPD. Patients with FPD typically lack obvious clinical symptoms or signs, and diagnosis primarily relies on imaging techniques. Currently, there is limited attention to this disease both domestically and internationally. FPD is closely associated with pancreatic-related diseases (eg, diabetes, pancreatitis, pancreatic cancer). Pancreatic cancer, characterized by high mortality and low survival rates, has been linked to FPD in terms of its occurrence, progression, and patient prognosis. FPD is considered a potential early clinical manifestation of pancreatic cancer and may promote distant metastasis. However, the mechanisms by which FPD contributes to pancreatic carcinogenesis remain unclear. Additionally, Studies have found that FPD can lead to perioperative complications (postoperative pancreatic fistula, postoperative nonalcoholic fatty liver, endoscopic retrograde cholangiopancreatography pancreatitis), which are closely related to the prognosis of patients after pancreatic surgery.Although FPD is challenging to diagnose, its instability allows for clinical management through early dietary interventions, oral medications, and, when necessary, bariatric surgery to alter disease progression. Whether targeting adipocytes, lipid metabolism, or adipocyte-related cytokines could serve as novel intervention strategies for pancreatic cancer remains a critical area for further investigation.
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Affiliation(s)
- Zhejing Wu
- Department of Hepatobiliary Surgery, Institute of Hepatobiliary and Intestinal Diseases, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan,People’s Republic of China
| | - Jingdong Li
- Department of Hepatobiliary Surgery, Institute of Hepatobiliary and Intestinal Diseases, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan,People’s Republic of China
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Vlăduț C, Steiner C, Löhr M, Gökçe DT, Maisonneuve P, Hank T, Öhlund D, Sund M, Hoogenboom SA. High prevalence of pancreatic steatosis in pancreatic cancer patients: A meta-analysis and systematic review. Pancreatology 2025; 25:98-107. [PMID: 39706752 DOI: 10.1016/j.pan.2024.11.010] [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: 08/29/2024] [Revised: 11/09/2024] [Accepted: 11/12/2024] [Indexed: 12/23/2024]
Abstract
OBJECTIVE In the last decade there has been increasing interest in defining pancreatic steatosis (PS) and establishing its association with pancreatic ductal adenocarcinoma (PDAC). However, no consensus guidelines have yet been published on the management of PS. In this systematic review and meta-analysis performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we investigated the association between PS and PDAC. DESIGN Medical literature between 2007 and 2023 was reviewed for eligible trials investigating the prevalence of PS in patients with PDAC. Eligible studies reporting on PS, assessed via imaging or histology, were included. The primary objective was to determine the association between PDAC and PS by comparing the prevalence of PS in individuals with- and without PDAC. Secondary, an evaluation was conducted to establish whether the method of assessment correlated with the association of PDAC and PS, and the prevalence of PDAC in individuals with PS. Measures of effect size were determined using odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CI). RESULTS The systematic review identified a total of 23 studies, of which seventeen studies examined PS prevalence among PDAC patients and were included in the meta-analysis. Overall, the pooled prevalence of PS in patients with PDAC was 53.6 % (95 % CI 40.9-66.2). No significant difference in PS prevalence was observed across various diagnostic methods or geographical regions. Overall, the pooled OR for PS in patients with PDAC compared to controls was 3.23 (95 % CI 1.86-5.60). CONCLUSIONS PDAC patients have a high prevalence of PS, and they are significantly more likely to have PS compared to controls. These findings emphasize the need to prioritize a standardized approach to the diagnosis, follow-up, and treatment of PS, with future studies focusing on identifying patients who would benefit from PDAC surveillance programs.
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Affiliation(s)
- Cătălina Vlăduț
- Department of Gastroenterology, "Prof Dr Agrippa Ionescu" Clinical Emergency Hospital, 011356 Bucharest, Romania; Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
| | | | - Matthias Löhr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.
| | - Dilara Turan Gökçe
- Department of Gastroenterology, Ankara Bilkent City Hospital, Ankara, Turkey.
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy.
| | - Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
| | - Daniel Öhlund
- Department of Diagnostics and Intervention (oncology) and Wallenberg Centre of Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.
| | - Malin Sund
- Department of Diagnostics and Intervention (surgery), Umeå University, Umeå, Sweden; Department of Surgery, University of Helsinki and Helsinki, University Hospital, Helsinki, Finland.
| | - Sanne A Hoogenboom
- Department of Gastroenterology, HagaZiekenhuis Hospital, The Hague, Netherlands.
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Ibrahim RM, Solanki S, Qiao W, Hwang H, Singh BS, Cazacu IM, Saftoiu A, Katz MHG, Kim MP, McAllister F, Bhutani MS. Fatty pancreas on EUS: Risk factors, correlation with CT/MRI, and implications for pancreatic cancer screening. Endosc Ultrasound 2025; 14:13-19. [PMID: 40151596 PMCID: PMC11939939 DOI: 10.1097/eus.0000000000000109] [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: 09/15/2024] [Accepted: 01/02/2025] [Indexed: 03/29/2025] Open
Abstract
Background and Objectives Fatty pancreas (FP), traditionally perceived as a benign finding, has been undergoing scrutiny lately due to growing evidence linking it to various disease states, including increased risk for pancreatic cancer (PC). Methods A retrospective study of patients who underwent EUS at a single institution from August 2007 to October 2023, conducted by one endosonographer with more than 25 years of experience. Focusing on individuals identified with FP during EUS, we compared these findings with corresponding findings on computed tomography/magnetic resonance imaging (CT/MRI) conducted within 3 months or 1 year prior to or following EUS. Results Ninety-one patients were included and identified as having FP on their EUS exams. The most common indication for EUS was PC screening in high-risk patients (35.16%). At the time of conducting EUS, 65.93% of patients had a body mass index (BMI) ≥30, 63.73% had hypertension, and 32.96% had type 2 diabetes mellitus (DM). Of the 91 patients, 70 had CT or MRI done within 3 months of the EUS date, and only 15 (21.43%) had FP reported on imaging. All 91 patients had CT or MRI within 1 year, and only 16 (17.58%) had FP reported on imaging. Conclusion Only 21.43% of patients had FP on their CT/MRI within 3 months despite EUS findings, suggesting either lower accuracy of CT/MRI compared to EUS in identifying FP or potential underreporting in a real-world setting, even in a tertiary care center. This discrepancy in reporting is noteworthy considering FP's role as a potential precursor to several important conditions and promoting pancreatic carcinogenesis pathways.
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Affiliation(s)
- Ramez M. Ibrahim
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shantanu Solanki
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wei Qiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hyunsoo Hwang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ben S. Singh
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Irina M. Cazacu
- Department of Oncology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Adrian Saftoiu
- Department of Gastroenterology and Hepatology, Elias Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest 050474, Romania
| | - Matthew H. G. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael P. Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Florencia McAllister
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Manoop S. Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Diao B, Fan Z, Zhou B, Zhan H. Crosstalk between pancreatic cancer and adipose tissue: Molecular mechanisms and therapeutic implications. Biochem Biophys Res Commun 2024; 740:151012. [PMID: 39561650 DOI: 10.1016/j.bbrc.2024.151012] [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: 08/03/2024] [Revised: 11/02/2024] [Accepted: 11/14/2024] [Indexed: 11/21/2024]
Abstract
The incidence rate of pancreatic cancer, a fatal illness with a meager 5-year survival rate, has been on the rise in recent times. When individuals accumulate excessive amounts of adipose tissue, the adipose organ becomes dysfunctional due to alterations in the adipose tissue microenvironment associated with inflammation and metabolism. This phenomenon may potentially contribute to the aberrant accumulation of fat that initiates pancreatic carcinogenesis, thereby influencing the disease's progression, resistance to treatment, and metastasis. This review presents a summary of the impact of pancreatic steatosis, visceral fat, cancer-associated adipocytes and lipid diets on the advancement of pancreatic cancer, as well as the reciprocal effects of pancreatic cancer on adipose tissue. Understanding the molecular mechanisms underlying the relationship between dysfunctional adipose tissue and pancreatic cancer better may lead to the discovery of new therapeutic targets for the disease's prevention and individualized treatment. This is especially important given the rising global incidence of obesity, which will improve the pancreatic cancer treatment options that are currently insufficient.
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Affiliation(s)
- Boyu Diao
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Bin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Department of Retroperitoneal Tumor Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
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Della Pepa G, Salamone D, Testa R, Bozzetto L, Costabile G. Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches. Nutr Rev 2024; 82:1820-1834. [PMID: 38153345 DOI: 10.1093/nutrit/nuad159] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023] Open
Abstract
Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.
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Affiliation(s)
- Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council-CNR, Pisa, Italy
| | - Dominic Salamone
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Roberta Testa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Lutgarda Bozzetto
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppina Costabile
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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Fotros D, Tabar MS, Chegini M, Bahrizadeh M, Sadeghi A, Rabbani A, Yari Z, Hekmatdoost A. Adherence to the dietary approaches to stop hypertension (DASH) and risk of pancreatic steatosis. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:190. [PMID: 39567983 PMCID: PMC11580558 DOI: 10.1186/s41043-024-00628-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 08/20/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND The Dietary Approach to Stop Hypertension (DASH) has shown positive effects on various health factors that may be related to pancreatic steatosis (PS). This study aimed to investigate the association between adherence to the DASH diet and the risk of developing PS. METHODS This case-control study was conducted on 278 patients diagnosed with gallstone disease and referred to Taleghani Hospital (Tehran, Iran). Among the participants, 89 were diagnosed with PS based on an endoscopic ultrasound (EUS) examination, while 189 patients did not exhibit this condition. The dietary intake of patients was assessed using a validated food frequency questionnaire (FFQ). Participants were classified based on the DASH diet score. Multiple logistic regression models estimated crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS The mean ± SD of DASH score in PS patients and controls was 23.68 ± 4.38 and 25.27 ± 4.2, respectively (P = 0.006). The risk of PS in the highest tertile of DASH score was 64% lower than the lowest tertile (OR = 0.36, 95%CI: 0.17-0.75, P = 0.005) after full adjustment for confounders. Also, more intake of vegetables and whole grains and less intake of sodium, red and processed meat were each significantly associated with reduced risk of PS. CONCLUSIONS Our data prove that adherence to the DASH diet was associated with a lower risk of PS. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms.
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Affiliation(s)
- Danial Fotros
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Shaygan Tabar
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maedeh Chegini
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Bahrizadeh
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Research Institute for Gastroenterology and Liver Diseases of Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhassan Rabbani
- Department of General Surgery, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Solsona-Vilarrasa E, Vousden KH. Obesity, white adipose tissue and cancer. FEBS J 2024. [PMID: 39496581 DOI: 10.1111/febs.17312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 09/27/2024] [Accepted: 10/17/2024] [Indexed: 11/06/2024]
Abstract
White adipose tissue (WAT) is crucial for whole-body energy homeostasis and plays an important role in metabolic and hormonal regulation. While healthy WAT undergoes controlled expansion and contraction to meet the body's requirements, dysfunctional WAT in conditions like obesity is characterized by excessive tissue expansion, alterations in lipid homeostasis, inflammation, hypoxia, and fibrosis. Obesity is strongly associated with an increased risk of numerous cancers, with obesity-induced WAT dysfunction influencing cancer development through various mechanisms involving both systemic and local interactions between adipose tissue and tumors. Unhealthy obese WAT affects circulating levels of free fatty acids and factors like leptin, adiponectin, and insulin, altering systemic lipid metabolism and inducing inflammation that supports tumor growth. Similar mechanisms are observed locally in an adipose-rich tumor microenvironment (TME), where WAT cells can also trigger extracellular matrix remodeling, thereby enhancing the TME's ability to promote tumor growth. Moreover, tumors reciprocally interact with WAT, creating a bidirectional communication that further enhances tumorigenesis. This review focuses on the complex interplay between obesity, WAT dysfunction, and primary tumor growth, highlighting potential targets for therapeutic intervention.
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Abboud Y, Gaddam S. The Role of Endoscopic Ultrasound-Guided Shear Wave Elastography in Pancreatic Diseases. Diagnostics (Basel) 2024; 14:2329. [PMID: 39451652 PMCID: PMC11507009 DOI: 10.3390/diagnostics14202329] [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: 09/04/2024] [Revised: 10/15/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024] Open
Abstract
Elastography is a non-invasive imaging modality that has been developed for the evaluation of the stiffness of various organs. It is categorized into two main types: strain elastography and shear wave elastography. While strain elastography offers valuable information on the mechanical properties of the organ being studied, it is limited by the qualitative nature of its measurements and its reliance on operator skills. On the other hand, shear wave elastography overcomes these limitations as it provides a quantitative assessment of tissue stiffness, offers more reproducibility, and is less operator-dependent. Endoscopic ultrasound-guided shear wave elastography (EUS-SWE) is an emerging technique that overcomes the limitations of transabdominal ultrasound in the evaluation of the pancreas. A growing body of literature has demonstrated its safety and feasibility in the evaluation of pancreatic parenchyma. This article provides a comprehensive review of the current state of the literature on EUS-SWE, including its technical aspects, clinical applications in the evaluation of various pancreatic conditions, technological limitations, and future directions.
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Affiliation(s)
- Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA;
| | - Srinivas Gaddam
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Habas E, Farfar K, Habas E, Rayani A, Elzouki AN. Extended Review and Updates of Nonalcoholic Fatty Pancreas Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2024; 12:284-291. [PMID: 39539795 PMCID: PMC11556510 DOI: 10.4103/sjmms.sjmms_526_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.
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Affiliation(s)
- Elmukhtar Habas
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
| | - Kalifa Farfar
- Department of Medicine, Alwakra General Hospital, Alwakra, Qatar
| | - Eshrak Habas
- Department of Medicine, Tripoli Central Hospital, Tripoli, Libya
| | - Amnna Rayani
- Tripoli Children Hospital, Medical College, Tripoli University, Tripoli, Libya
| | - Abdul-Naser Elzouki
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
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Kalisz K, Navin PJ, Itani M, Agarwal AK, Venkatesh SK, Rajiah PS. Multimodality Imaging in Metabolic Syndrome: State-of-the-Art Review. Radiographics 2024; 44:e230083. [PMID: 38329901 DOI: 10.1148/rg.230083] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024]
Abstract
Metabolic syndrome comprises a set of risk factors that include abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, low high-density lipoprotein levels, and high blood pressure, at least three of which must be fulfilled for diagnosis. Metabolic syndrome has been linked to an increased risk of cardiovascular disease and type 2 diabetes mellitus. Multimodality imaging plays an important role in metabolic syndrome, including diagnosis, risk stratification, and assessment of complications. CT and MRI are the primary tools for quantification of excess fat, including subcutaneous and visceral adipose tissue, as well as fat around organs, which are associated with increased cardiovascular risk. PET has been shown to detect signs of insulin resistance and may detect ectopic sites of brown fat. Cardiovascular disease is an important complication of metabolic syndrome, resulting in subclinical or symptomatic coronary artery disease, alterations in cardiac structure and function with potential progression to heart failure, and systemic vascular disease. CT angiography provides comprehensive evaluation of the coronary and systemic arteries, while cardiac MRI assesses cardiac structure, function, myocardial ischemia, and infarction. Liver damage results from a spectrum of nonalcoholic fatty liver disease ranging from steatosis to fibrosis and possible cirrhosis. US, CT, and MRI are useful in assessing steatosis and can be performed to detect and grade hepatic fibrosis, particularly using elastography techniques. Metabolic syndrome also has deleterious effects on the pancreas, kidney, gastrointestinal tract, and ovaries, including increased risk for several malignancies. Metabolic syndrome is associated with cerebral infarcts, best evaluated with MRI, and has been linked with cognitive decline. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Pickhardt in this issue.
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Affiliation(s)
- Kevin Kalisz
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Patrick J Navin
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Malak Itani
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Amit Kumar Agarwal
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Sudhakar K Venkatesh
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
| | - Prabhakar Shantha Rajiah
- From the Duke University School of Medicine, Durham, NC (K.K.); Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 559905 (P.J.N., S.K.V., P.S.R.); Mallinckrodt Institute of Radiology, Washington University, St. Louis, Mo (M.I.); and Mayo Clinic, Jacksonville, Fla (A.K.A.)
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12
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Yamazaki H, Streicher SA, Wu L, Fukuhara S, Wagner R, Heni M, Grossman SR, Lenz HJ, Setiawan VW, Le Marchand L, Huang BZ. Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study. Cell Rep Med 2024; 5:101391. [PMID: 38280379 PMCID: PMC10897551 DOI: 10.1016/j.xcrm.2023.101391] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 11/24/2023] [Accepted: 12/29/2023] [Indexed: 01/29/2024]
Abstract
Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.
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Affiliation(s)
- Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan.
| | - Samantha A Streicher
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Shunichi Fukuhara
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Róbert Wagner
- Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Martin Heni
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University, Ulm, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Steven R Grossman
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Heinz-Josef Lenz
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Veronica Wendy Setiawan
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Loïc Le Marchand
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Brian Z Huang
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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13
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Kiemen AL, Dbouk M, Diwan EA, Forjaz A, Dequiedt L, Baghdadi A, Madani SP, Grahn MP, Jones C, Vedula S, Wu P, Wirtz D, Kern S, Goggins M, Hruban RH, Kamel IR, Canto MI. Magnetic Resonance Imaging-Based Assessment of Pancreatic Fat Strongly Correlates With Histology-Based Assessment of Pancreas Composition. Pancreas 2024; 53:e180-e186. [PMID: 38194643 PMCID: PMC10872776 DOI: 10.1097/mpa.0000000000002288] [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] [Indexed: 01/11/2024]
Abstract
OBJECTIVE The aim of the study is to assess the relationship between magnetic resonance imaging (MRI)-based estimation of pancreatic fat and histology-based measurement of pancreatic composition. MATERIALS AND METHODS In this retrospective study, MRI was used to noninvasively estimate pancreatic fat content in preoperative images from high-risk individuals and disease controls having normal pancreata. A deep learning algorithm was used to label 11 tissue components at micron resolution in subsequent pancreatectomy histology. A linear model was used to determine correlation between histologic tissue composition and MRI fat estimation. RESULTS Twenty-seven patients (mean age 64.0 ± 12.0 years [standard deviation], 15 women) were evaluated. The fat content measured by MRI ranged from 0% to 36.9%. Intrapancreatic histologic tissue fat content ranged from 0.8% to 38.3%. MRI pancreatic fat estimation positively correlated with microanatomical composition of fat (r = 0.90, 0.83 to 0.95], P < 0.001); as well as with pancreatic cancer precursor ( r = 0.65, P < 0.001); and collagen ( r = 0.46, P < 0.001) content, and negatively correlated with pancreatic acinar ( r = -0.85, P < 0.001) content. CONCLUSIONS Pancreatic fat content, measurable by MRI, correlates to acinar content, stromal content (fibrosis), and presence of neoplastic precursors of cancer.
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Affiliation(s)
- Ashley L. Kiemen
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Mohamad Dbouk
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Department of Medicine, Washington University St. Louis, St. Louis, USA; 1 Brookings Dr, St. Louis, MO 63130
| | - Elizabeth Abou Diwan
- Department of Medicine, Washington University St. Louis, St. Louis, USA; 1 Brookings Dr, St. Louis, MO 63130
| | - André Forjaz
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Lucie Dequiedt
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Azarakhsh Baghdadi
- Radiology and Radiological Science, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Seyedeh Panid Madani
- Radiology and Radiological Science, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Mia P. Grahn
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Craig Jones
- Computer Science, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
- Malone Center for Engineering in Healthcare, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Swaroop Vedula
- Malone Center for Engineering in Healthcare, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - PeiHsun Wu
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Denis Wirtz
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Departments of Chemical and Biomolecular Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Materials Science and Engineering, The Johns Hopkins University; 3400 N Charles St, Baltimore, Maryland 21218, USA
| | - Scott Kern
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Michael Goggins
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Ralph H. Hruban
- Departments of Pathology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Ihab R. Kamel
- Radiology and Radiological Science, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - Marcia Irene Canto
- Oncology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine; 600 North Wolfe Street, Baltimore, Maryland 21287, USA
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14
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Pagkali A, Makris A, Brofidi K, Agouridis AP, Filippatos TD. Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease. Diabetes Metab Syndr Obes 2024; 17:283-294. [PMID: 38283640 PMCID: PMC10813232 DOI: 10.2147/dmso.s397643] [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: 08/09/2023] [Accepted: 12/29/2023] [Indexed: 01/30/2024] Open
Abstract
Non-Alcoholic Fatty Pancreas disease (NAFPD), characterized by fat accumulation in pancreatic tissue, is an emerging clinical entity. However, the clinical associations, the underlying molecular drivers, and the pathophysiological mechanisms of NAFPD have not yet been characterized in detail. The NAFPD spectrum not only includes infiltration and accumulation of fat within and between pancreatic cells but also involves several inflammatory processes, dysregulation of physiological metabolic pathways, and hormonal defects. A deeper understanding of the underlying molecular mechanisms is key to correlate NAFPD with clinical entities including non-alcoholic fatty liver disease, metabolic syndrome, diabetes mellitus, atherosclerosis, as well as pancreatic cancer and pancreatitis. The aim of this review is to examine the pathophysiological mechanisms of NAFPD and to assess the possible causative/predictive risk factors of NAFPD-related clinical syndromes.
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Affiliation(s)
- Antonia Pagkali
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasios Makris
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Kalliopi Brofidi
- Department of Internal Medicine, School of Medicine, University of Crete, Heraklion, Greece
| | - Aris P Agouridis
- School of Medicine, European University Cyprus, Nicosia, Cyprus
- Department of Internal Medicine, German Oncology Center, Limassol, Cyprus
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15
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Caldart F, de Pretis N, Luchini C, Ciccocioppo R, Frulloni L. Pancreatic steatosis and metabolic pancreatic disease: a new entity? Intern Emerg Med 2023; 18:2199-2208. [PMID: 37462859 PMCID: PMC10635967 DOI: 10.1007/s11739-023-03364-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 06/30/2023] [Indexed: 08/24/2023]
Abstract
Overweight and obesity are some of the most important health challenges. Many diseases are related to these metabolic disorders, and, among them, the pancreatic fat accumulation, also called "pancreatic steatosis" or "nonalcoholic fatty pancreas", seems to have an emerging role in different conditions. There are different method to evaluate the fat content in the pancreas, such as histology, different imaging techniques and endoscopic ultrasound, but there is no gold standard for the correct diagnosis and for the identification of "inter/intralobular" and "intra-acinar" pancreatic fat. However, the fat storage in the pancreas is linked to chronic inflammation and to several conditions, such as acute and chronic pancreatitis, type 2 diabetes mellitus and pancreatic cancer. In addition, pancreatic fat accumulation has also been demonstrated to play a role in surgical outcome after pancreatectomy, in particular for the development of postoperative pancreatic fistula. Different possible therapeutic approaches have been proposed, but there is still a lack of evidence. The aim of this review is to report the current evidence about the relationship between the obesity, the pancreatic fat accumulation and its potential role in pancreatic diseases.
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Affiliation(s)
- Federico Caldart
- Gastroenterology B Unit, University of Verona-Verona Hospital, Verona, Italy.
| | - Nicolò de Pretis
- Gastroenterology B Unit, University of Verona-Verona Hospital, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology B Unit, University of Verona-Verona Hospital, Verona, Italy
| | - Luca Frulloni
- Gastroenterology B Unit, University of Verona-Verona Hospital, Verona, Italy
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16
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Lipp M, Tarján D, Lee J, Zolcsák Á, Szalai E, Teutsch B, Faluhelyi N, Erőss B, Hegyi P, Mikó A. Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients. Cancers (Basel) 2023; 15:4876. [PMID: 37835570 PMCID: PMC10571813 DOI: 10.3390/cancers15194876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/29/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.
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Affiliation(s)
- Mónika Lipp
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Dorottya Tarján
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
| | - Jimin Lee
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Medical School, Semmelweis University, 1085 Budapest, Hungary
| | - Ádám Zolcsák
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary
| | - Eszter Szalai
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Restorative Dentistry and Endodontics, Semmelweis University, 1088 Budapest, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Nándor Faluhelyi
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Department of Medical Imaging, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Bálint Erőss
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Péter Hegyi
- Institute of Pancreatic Diseases, Semmelweis University, 1083 Budapest, Hungary; (M.L.); (D.T.); (B.E.); (P.H.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, 6725 Szeged, Hungary
| | - Alexandra Mikó
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (J.L.); (Á.Z.); (E.S.); (B.T.); (N.F.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- Department of Medical Genetics, Medical School, University of Pécs, 7624 Pécs, Hungary
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17
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Xu T, Xu X, Liu D, Chang D, Li S, Sun Y, Xie J, Ju S. Visual Investigation of Tumor-Promoting Fibronectin Potentiated by Obesity in Pancreatic Ductal Adenocarcinoma Using an MR/NIRF Dual-Modality Dendrimer Nanoprobe. Adv Healthc Mater 2023; 12:e2300787. [PMID: 37057680 DOI: 10.1002/adhm.202300787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Indexed: 04/15/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by dense stroma. Obesity is an important metabolic factor that greatly increases PDAC risk and mortality, worsens progression and leads to poor chemotherapeutic outcomes. With omics analysis, magnetic resonance and near-infrared fluorescence (MR/NIRF) dual-modality imaging and molecular functional verification, obesity as an important risk factor is proved to modulate the extracellular matrix (ECM) components and enhance Fibronectin (FN) infiltration in the PDAC stroma, that promotes tumor progression and worsens response to chemotherapy by reducing drug delivery. In the study, to visually evaluate FN in vivo and guide PDAC therapy, an FN-targeted nanoprobe, NP-CREKA, is synthesized by conjugating gadolinium chelates, NIR797 and fluorescein isothiocyanate to a polyamidoamine dendrimer functionalized with targeting peptides. A dual-modality strategy combining MR and NIRF imaging is applied, allowing effective visualization of FN in orthotopic PDAC with high spatial resolution, ideal sensitivity and excellent penetrability, especially in obese mice. In conclusion, the findings provide new insights into the potential of FN as an ideal target for therapeutic evaluation and improving treatment efficacy in PDAC, hopefully improving the specific management of PDAC in lean and obese hosts.
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Affiliation(s)
- Tingting Xu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Xiaoxuan Xu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Dongfang Liu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Di Chang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Siqi Li
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Yeyao Sun
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Jinbing Xie
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
| | - Shenghong Ju
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China
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18
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Marti-Aguado D, Ten-Esteve A, Baracaldo-Silva CM, Crespo A, Coello E, Merino-Murgui V, Fernandez-Paton M, Alfaro-Cervello C, Sánchez-Martín A, Bauza M, Jimenez-Pastor A, Perez-Girbes A, Benlloch S, Pérez-Rojas J, Puglia V, Ferrández A, Aguilera V, Latorre M, Monton C, Escudero-García D, Bosch-Roig I, Alberich-Bayarri Á, Marti-Bonmati L. Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease. Front Endocrinol (Lausanne) 2023; 14:1213441. [PMID: 37600695 PMCID: PMC10436077 DOI: 10.3389/fendo.2023.1213441] [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: 04/27/2023] [Accepted: 07/18/2023] [Indexed: 08/22/2023] Open
Abstract
Objective To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases. Method A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated. Results In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD. Conclusion Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
| | - Amadeo Ten-Esteve
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Department of Technologies for Health and Well-Being, Polytechnic University of Valencia, Valencia, Spain
| | | | - Ana Crespo
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Elena Coello
- Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Merino-Murgui
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Matias Fernandez-Paton
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
| | - Clara Alfaro-Cervello
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Alba Sánchez-Martín
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Mónica Bauza
- Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Ana Jimenez-Pastor
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, Valencia, Spain
| | | | - Salvador Benlloch
- Digestive Disease Department, Hospital Arnau de Vilanova, Valencia, Spain
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Judith Pérez-Rojas
- Pathology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Víctor Puglia
- Pathology Department, Hospital Arnau de Vilanova, Valencia, Spain
| | - Antonio Ferrández
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Victoria Aguilera
- Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Mercedes Latorre
- Hepatology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
| | - Cristina Monton
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
| | - Desamparados Escudero-García
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain
- Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Ignacio Bosch-Roig
- Universitat Politècnica de València, Institute of Telecommunications and Multimedia Applications (iTEAM), Valencia, Spain
| | - Ángel Alberich-Bayarri
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, Valencia, Spain
| | - Luis Marti-Bonmati
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), Valencia, Spain
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
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19
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Janssens LP, Takahashi H, Nagayama H, Nugen F, Bamlet WR, Oberg AL, Fuemmeler E, Goenka AH, Erickson BJ, Takahashi N, Majumder S. Artificial intelligence assisted whole organ pancreatic fat estimation on magnetic resonance imaging and correlation with pancreas attenuation on computed tomography. Pancreatology 2023; 23:556-562. [PMID: 37193618 DOI: 10.1016/j.pan.2023.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/18/2023] [Accepted: 04/20/2023] [Indexed: 05/18/2023]
Abstract
BACKGROUND Fatty pancreas is associated with inflammatory and neoplastic pancreatic diseases. Magnetic resonance imaging (MRI) is the diagnostic modality of choice for measuring pancreatic fat. Measurements typically use regions of interest limited by sampling and variability. We have previously described an artificial intelligence (AI)-aided approach for whole pancreas fat estimation on computed tomography (CT). In this study, we aimed to assess the correlation between whole pancreas MRI proton-density fat fraction (MR-PDFF) and CT attenuation. METHODS We identified patients without pancreatic disease who underwent both MRI and CT between January 1, 2015 and June 1, 2020. 158 paired MRI and CT scans were available for pancreas segmentation using an iteratively trained convolutional neural network (CNN) with manual correction. Boxplots were generated to visualize slice-by-slice variability in 2D-axial slice MR-PDFF. Correlation between whole pancreas MR-PDFF and age, BMI, hepatic fat and pancreas CT-Hounsfield Unit (CT-HU) was assessed. RESULTS Mean pancreatic MR-PDFF showed a strong inverse correlation (Spearman -0.755) with mean CT-HU. MR-PDFF was higher in males (25.22 vs 20.87; p = 0.0015) and in subjects with diabetes mellitus (25.95 vs 22.17; p = 0.0324), and was positively correlated with age and BMI. The pancreatic 2D-axial slice-to-slice MR-PDFF variability increased with increasing mean whole pancreas MR-PDFF (Spearman 0.51; p < 0.0001). CONCLUSION Our study demonstrates a strong inverse correlation between whole pancreas MR-PDFF and CT-HU, indicating that both imaging modalities can be used to assess pancreatic fat. 2D-axial pancreas MR-PDFF is variable across slices, underscoring the need for AI-aided whole-organ measurements for objective and reproducible estimation of pancreatic fat.
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Affiliation(s)
- Laurens P Janssens
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Fred Nugen
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - William R Bamlet
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Ann L Oberg
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Eric Fuemmeler
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Shounak Majumder
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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20
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Otsuka N, Shimizu K, Taniai M, Tokushige K. Risk factors for fatty pancreas and effects of fatty infiltration on pancreatic cancer. Front Physiol 2023; 14:1243983. [PMID: 37664430 PMCID: PMC10470060 DOI: 10.3389/fphys.2023.1243983] [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: 06/21/2023] [Accepted: 07/25/2023] [Indexed: 09/05/2023] Open
Abstract
Objective: This study clarified the risk factors and pathophysiology of pancreatic cancer by examining the factors associated with fatty pancreas. Methods: The degree of fatty pancreas, background factors, and incidence of pancreatic cancer were examined among nonalcoholic fatty liver disease (NAFLD) patients (n = 281) and intraductal papillary mucinous neoplasm (IPMN) patients with a family history of pancreatic cancer (n = 38). The presence of fatty pancreas was confirmed by the pancreatic CT value/splenic CT value ratio (P/S ratio). Immunohistochemical staining was performed on 10 cases with fatty pancreas, confirmed via postoperative pathology. Results: Fatty pancreas occurred in 126 patients (44.8%) in the NAFLD group who were older (p = 0.0002) and more likely to have hypertension (p < 0.0001). The IPMN group had 18 patients (47.4%) with fatty pancreas, included more men than women (p = 0.0056), and was more likely to have patients with hypertension (p = 0.0010). On histological examination, a significant infiltration of adipocytes into the acini from the pancreatic interstitium induced atrophy of the pancreatic parenchyma, and both M1 and M2 macrophages were detected in the area where adipocytes invaded the pancreatic parenchyma. Accumulation of p62 and increased positive staining of NQO1 molecules related to autophagy dysfunction were detected in pancreatic acinar cells in the fatty area, acinar-ductal metaplasia, and pancreatic cancer cells. The rate of p62-positive cell area and that of NQO1-positive cell area were significantly higher in the fatty pancreatic region than those in the control lesion (pancreatic region with few adipocyte infiltration). Furthermore, the rate of p62-positive cell area or that of NQO1-positive cell area showed strong positive correlations with the rate of fatty pancreatic lesion. These results suggest that adipocyte invasion into the pancreatic parenthyme induced macrophage infiltration and autophagy substrate p62 accumulation. High levels of NQO1 expression in the fatty area may be dependent on p62 accumulation. Conclusion: Hypertension was a significant risk factor for fatty pancreas in patients with NAFLD and IPMN. In fatty pancreas, fatty infiltration into the pancreatic parenchyme might induce autophagy dysfunction, resulting in activation of antioxidant proteins NQO1. Thus, patients with fatty pancreas require careful follow-up.
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Affiliation(s)
- Nao Otsuka
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Kyoko Shimizu
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
- Shinjuku Mitsui Building Clinic, Tokyo, Japan
| | - Makiko Taniai
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
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21
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Lin YC, Hou YC, Wang HC, Shan YS. New insights into the role of adipocytes in pancreatic cancer progression: paving the way towards novel therapeutic targets. Theranostics 2023; 13:3925-3942. [PMID: 37554282 PMCID: PMC10405844 DOI: 10.7150/thno.82911] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 06/21/2023] [Indexed: 08/10/2023] Open
Abstract
Pancreatic cancer (PC) remains one of the most lethal malignancies across the world, which is due to delayed diagnosis and resistance to current therapies. The interactions between pancreatic tumor cells and their tumor microenvironment (TME) allow cancer cells to escape from anti-cancer therapies, leading to difficulties in treating PC. With endocrine function and lipid storage capacity, adipose tissue can maintain energy homeostasis. Direct or indirect interaction between adipocytes and PC cells leads to adipocyte dysfunction characterized by morphological change, fat loss, abnormal adipokine secretion, and fibroblast-like transformation. Various adipokines released from dysfunctional adipocytes have been reported to promote proliferation, invasion, metastasis, stemness, and chemoresistance of PC cells via different mechanisms. Additional lipid outflow from adipocytes can be taken into the TME and thus alter the metabolism in PC cells and surrounding stromal cells. Besides, the trans-differentiation potential enables adipocytes to turn into various cell types, which may give rise to an inflammatory response as well as extracellular matrix reorganization to modulate tumor burden. Understanding the molecular basis behind the protumor functions of adipocytes in PC may offer new therapeutic targets.
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Affiliation(s)
- Yu-Chun Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
| | - Ya-Chin Hou
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Department of Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
| | - Hao-Chen Wang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Medical Imaging Center, Innovation Headquarter, National Cheng Kung University; Tainan 704, Taiwan
| | - Yan-Shen Shan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
- Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
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22
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Tanabe M, Higashi M, Tanabe M, Kawano Y, Inoue A, Narikiyo K, Kobayashi T, Ueda T, Ito K. Automated whole-volume measurement of CT fat fraction of the pancreas: correlation with Dixon MR imaging. Br J Radiol 2023; 96:20220937. [PMID: 37017644 PMCID: PMC10230395 DOI: 10.1259/bjr.20220937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 03/06/2023] [Accepted: 03/07/2023] [Indexed: 04/06/2023] Open
Abstract
OBJECTIVES This study aimed to assess the feasibility of pancreatic steatosis quantification by automated whole-volume measurement of the fat fraction of the pancreas on CT in comparison to MRI using proton-density fat fraction (PDFF) techniques. METHODS Fifty-nine patients who underwent both CT and MRI were analyzed. Automated whole-volume measurement of pancreatic fat on unenhanced CT was performed by a histogram analysis with local thresholding. Three sets of CT fat volume fraction (FVF) (%) values with thresholds of -30 Hounsfield unit (HU), -20 HU and -10 HU were compared to MR-FVF (%) values measured on a PDFF map. RESULTS The median -30 HU CT-FVF, -20 HU CT-FVF, -10 HU CT-FVF and MR-FVF values of the pancreas were 8.6% (interquartile range (IQR), 11.3), 10.5% (IQR, 13.2), 13.4% (IQR, 16.1) and 10.9% (IQR, 9.7), respectively. The -30 HU CT-FVF (%), -20 HU CT-FVF (%) and -10 HU CT-FVF (%) of the pancreas showed a significant positive correlation with the MR-FVF (%) of the pancreas (ρ = 0.898, p < 0.001, ρ = 0.905, p < 0.001, ρ = 0.909, p < 0.001, respectively). The -20 HU CT-FVF (%) displayed reasonable agreement with the MR-FVF (%) with a low absolute fixed bias (mean difference, 0.32%; limit of agreement from -10.1 to 10.7%). CONCLUSION The automated whole-volume measurement of the CT fat fraction of the pancreas using the threshold CT attenuation value of -20 HU may be a feasible, non-invasive, and convenient technique for quantifying pancreatic steatosis. ADVANCES IN KNOWLEDGE CT-FVF value of the pancreas had a positive correlation with the MR-FVF value. The -20 HU CT-FVF may be a convenient technique for quantifying pancreatic steatosis.
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Affiliation(s)
- Masahiro Tanabe
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Mayumi Higashi
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Masaya Tanabe
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Yosuke Kawano
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Atsuo Inoue
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Koji Narikiyo
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Taiga Kobayashi
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Takaaki Ueda
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Katsuyoshi Ito
- Department of Radiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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23
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Koiwai A, Hirota M, Matsuura T, Itoh T, Kin R, Katayama T, Endo K, Takasu A, Kogure T, Murakami K, Satoh K. Diffuse pancreatic parenchymal atrophy, an imaging finding predictive of the development of pancreatic ductal adenocarcinoma: A case-control study. JGH Open 2023; 7:445-452. [PMID: 37359111 PMCID: PMC10290266 DOI: 10.1002/jgh3.12930] [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: 10/27/2022] [Revised: 05/21/2023] [Accepted: 05/22/2023] [Indexed: 06/28/2023]
Abstract
Background and Aim Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer, partly because its early detection is difficult. This study aimed to identify computed tomography (CT) findings associated with PDAC prior to diagnosis. Methods Past CT images were retrospectively collected from the PDAC group (n = 54) and the control group (n = 90). The following imaging findings were compared: pancreatic mass, main pancreatic duct (MPD) dilatation with or without cutoff, cyst, chronic pancreatitis with calcification, partial parenchymal atrophy (PPA), and diffuse parenchymal atrophy (DPA). In the PDAC group, CT findings were examined during the pre-diagnostic period and 6-36 months and 36-60 months before diagnosis. Multivariate analyses were performed using logistic regression. Results MPD dilatation with cutoff (P < 0.0001) and PPA (P = 0.023) were identified as significant imaging findings 6-36 months before diagnosis. DPA was identified as a novel imaging finding at 6-36 months (P = 0.003) and 36-60 months (P = 0.009) before diagnosis. Conclusion DPA, MPD dilatation with cutoff, and PPA were identified as imaging findings associated with pre-diagnostic PDAC.
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Affiliation(s)
- Akinobu Koiwai
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Morihisa Hirota
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Tomonori Matsuura
- Division of RadiologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Takehito Itoh
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Ryo Kin
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Tomofumi Katayama
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Katsuya Endo
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Atsuko Takasu
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Takayuki Kogure
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Kazuhiro Murakami
- Division of PathologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
| | - Kennichi Satoh
- Division of GastroenterologyTohoku Medical and Pharmaceutical UniversitySendaiJapan
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24
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Ibrahim MK, Simon TG, Rinella ME. Extrahepatic Outcomes of Nonalcoholic Fatty Liver Disease: Nonhepatocellular Cancers. Clin Liver Dis 2023; 27:251-273. [PMID: 37024206 DOI: 10.1016/j.cld.2023.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, including isolated steatosis, steatohepatitis, and cirrhosis. The overall global prevalence of NAFLD is estimated to be 30%, and the associated clinical and economic burden will continue to increase. NAFLD is a multisystemic disease with established links to cardiovascular disease, type 2 diabetes, metabolic syndrome, chronic kidney disease, polycystic ovarian syndrome, and intra- and extrahepatic malignancies. In this article the authors review the potential mechanisms and current evidence for the association between NAFLD and extrahepatic cancers and the resultant impact on clinical outcomes.
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Affiliation(s)
- Maryam K Ibrahim
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Tracey G Simon
- Harvard Medical School, Boston, MA, USA; Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, MA, USA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Mary E Rinella
- University of Chicago Pritzker School of Medicine; University of Chicago Hospitals.
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25
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Yamazaki H, Streicher SA, Wu L, Fukuhara S, Wagner R, Heni M, Grossman SR, Lenz HJ, Setiawan VW, Marchand LL, Huang BZ. Genetic Evidence Causally Linking Pancreas Fat to Pancreatic Cancer: A Mendelian Randomization Study. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.04.20.23288770. [PMID: 37163062 PMCID: PMC10168411 DOI: 10.1101/2023.04.20.23288770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Background & Aims Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and any clues to understanding its elusive etiology could lead to breakthroughs in prevention, early detection, or treatment. Observational studies have shown a relationship between pancreas fat accumulation and PDAC, but the causality of this link is unclear. We therefore investigated whether pancreas fat is causally associated with PDAC using two-sample Mendelian randomization. Methods We leveraged eight genetic variants associated with pancreas fat (P<5×10 -8 ) from a genome-wide association study (GWAS) in the UK Biobank (25,617 individuals), and assessed their association with PDAC in the Pancreatic Cancer Cohort Consortium I-III and the Pancreatic Cancer Case-Control Consortium dataset (8,275 PDAC cases and 6,723 non-cases). Causality was assessed using the inverse-variance weighted method. Although none of these genetic variants were associated with body mass index (BMI) at genome-wide significance, we further conducted a sensitivity analysis excluding genetic variants with a nominal BMI association in GWAS summary statistics from the UK Biobank and the Genetic Investigation of Anthropometric Traits consortium dataset (806,834 individuals). Results Genetically determined higher levels of pancreas fat using the eight genetic variants was associated with increased risk of PDAC. For one standard deviation increase in pancreas fat levels (i.e., 7.9% increase in pancreas fat fraction), the odds ratio of PDAC was 2.46 (95%CI:1.38-4.40, P=0.002). Similar results were obtained after excluding genetic variants nominally linked to BMI (odds ratio:3.79, 95%CI:1.66-8.65, P=0.002). Conclusions This study provides genetic evidence for a causal role of pancreas fat in the pathogenesis of PDAC. Thus, reducing pancreas fat could lower the risk of PDAC.
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26
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Wang G, Gao H, Dai S, Gao Y, Yin L, Li M, Zhang K, Zhang J, Jiang K, Miao Y, Lu Z. Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice. Cancer Lett 2023; 562:216155. [PMID: 37030634 DOI: 10.1016/j.canlet.2023.216155] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/10/2023]
Abstract
Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/- (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1β. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.
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Affiliation(s)
- Guangfu Wang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Hao Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Shangnan Dai
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Yong Gao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Lingdi Yin
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Mingna Li
- Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China
| | - Kai Zhang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Jingjing Zhang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Kuirong Jiang
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China
| | - Yi Miao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China; Pancreas Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210019, China.
| | - Zipeng Lu
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China; Pancreas Institute, Nanjing Medical University, Nanjing, 210000, China.
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Ruze R, Song J, Yin X, Chen Y, Xu R, Wang C, Zhao Y. Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review. Signal Transduct Target Ther 2023; 8:139. [PMID: 36964133 PMCID: PMC10039087 DOI: 10.1038/s41392-023-01376-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 01/31/2023] [Accepted: 02/15/2023] [Indexed: 03/26/2023] Open
Abstract
Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers. The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence, which is partially responsible for the slight but constant increase in pancreatic cancer (PC) occurrence. PC is a highly lethal malignancy characterized by its insidious symptoms, delayed diagnosis, and devastating prognosis. The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent whole-body systemic changes that are suitable for cancer initiation. The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways. Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment (TME) for carcinogenesis, which can be exacerbated by several crucial pathophysiological processes and TME components, such as autophagy, endoplasmic reticulum stress, oxidative stress, epithelial-mesenchymal transition, and exosome secretion. This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity- and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Jianlu Song
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Xinpeng Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Yuan Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Chengcheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China.
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China.
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Mukherjee S, Maheshwari D, Pal R, Sachdeva N. Pancreatic fat in type 2 diabetes: Causal or coincidental? World J Meta-Anal 2023; 11:68-78. [DOI: 10.13105/wjma.v11.i3.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/27/2022] [Accepted: 02/15/2023] [Indexed: 03/01/2023] Open
Abstract
Type 2 diabetes (T2D) is a multifactorial metabolic disorder affecting more than 450 million people across the globe. With the increasing prevalence of T2D and obesity, the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D. Over the past decade and a half, a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease. While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism, a few reports suggest a lack of such association. Pancreatic fat has also been linked with genetic risk of developing T2D, prediabetes, reduced insulin secretion, and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome. With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function, our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved. This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.
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Affiliation(s)
- Soham Mukherjee
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Deep Maheshwari
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rimesh Pal
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Naresh Sachdeva
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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Möller K, Jenssen C, Braden B, Hocke M, Hollerbach S, Ignee A, Faiss S, Iglesias-Garcia J, Sun S, Dong Y, Carrara S, Dietrich CF. Pancreatic changes with lifestyle and age: What is normal and what is concerning? Endosc Ultrasound 2023; 12:213-227. [PMID: 37148135 PMCID: PMC10237602 DOI: 10.4103/eus-d-22-00162] [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: 09/26/2022] [Accepted: 01/03/2023] [Indexed: 05/07/2023] Open
Abstract
During the aging process, typical morphological changes occur in the pancreas, which leads to a specific "patchy lobular fibrosis in the elderly." The aging process in the pancreas is associated with changes in volume, dimensions, contour, and increasing intrapancreatic fat deposition. Typical changes are seen in ultrasonography, computed tomography, endosonography, and magnetic resonance imaging. Typical age-related changes must be distinguished from lifestyle-related changes. Obesity, high body mass index, and metabolic syndrome also lead to fatty infiltration of the pancreas. In the present article, age-related changes in morphology and imaging are discussed. Particular attention is given to the sonographic verification of fatty infiltration of the pancreas. Ultrasonography is a widely used screening examination method. It is important to acknowledge the features of the normal aging processes and not to interpret them as pathological findings. Reference is made to the uneven fatty infiltration of the pancreas. The differential diagnostic and the differentiation from other processes and diseases leading to fatty infiltration of the pancreas are discussed.
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Affiliation(s)
- Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Maerkisch-Oderland, D-15344 Strausberg, Germany
- Brandenburg Institute of Clinical Medicine at Medical University Brandenburg, Neuruppin, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Michael Hocke
- Medical Department II, Helios Klinikum Meiningen, Meiningen, Germany
| | - Stephan Hollerbach
- Department of Medicine and Gastroenterology, Allgemeines Krankenhaus, Celle, Germany
| | - André Ignee
- Department of Medical Gastroenterology, Julius-Spital Würzburg, Germany
| | - Siegbert Faiss
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Siyu Sun
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Liaoning Province, China
| | - Yi Dong
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Siliva Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
| | - Christoph F. Dietrich
- Department of Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
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Ookura R, Usuki N. Visual assessment of pancreatic fat deposition: useful grading system and the relation to BMI and diabetes. Jpn J Radiol 2023; 41:172-179. [PMID: 36097235 PMCID: PMC9889527 DOI: 10.1007/s11604-022-01334-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 09/01/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE To establish a simple and clinically useful method for the visual assessment of pancreatic fat deposition using computed tomography (CT) images, and to evaluate the relationship of the pancreatic fat deposition with body mass index (BMI) and type 2 diabetes mellitus (DM). MATERIALS AND METHODS We used a four-scale grading system as the visual assessment criteria for pancreatic fat deposition using CT images. Pancreatic fat deposition was assessed for 200 patients and the results were compared with the CT attenuation-based assessment. In addition, the relationships of pancreatic fat deposition with BMI and type 2 DM were investigated. RESULTS The visual and CT attenuation-based assessments were considered consistent. The results of the visual assessment suggested that mild and moderate pancreatic fat deposition correlated with BMI and presence of type 2 DM while severe fat deposition did not correlate with them. No correlation between pancreatic fat deposition and HbA1c level was found. CONCLUSION The visual assessment criteria we used were consistent with CT attenuation-based assessment and may be useful for clinical application of pancreatic fat deposition. According to the visually assessment, mild or moderate pancreatic fat deposition correlated with BMI and the presence of type 2 DM, but severe fat deposition did not correlate with them.
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Affiliation(s)
- Ryusuke Ookura
- Department of Diagnostic and Interventional Radiology, Japan Community Healthcare Organization Osaka Hospital, 4-2-78, Fukushima, Fukushima-ku, Osaka, 553-0003, Japan.
| | - Noriaki Usuki
- Department of Diagnostic and Interventional Radiology, Japan Community Healthcare Organization Osaka Hospital, 4-2-78, Fukushima, Fukushima-ku, Osaka, 553-0003, Japan
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Rugivarodom M, Geeratragool T, Pausawasdi N, Charatcharoenwitthaya P. Fatty Pancreas: Linking Pancreas Pathophysiology to Nonalcoholic Fatty Liver Disease. J Clin Transl Hepatol 2022; 10:1229-1239. [PMID: 36381092 PMCID: PMC9634764 DOI: 10.14218/jcth.2022.00085] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 12/04/2022] Open
Abstract
Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.
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Affiliation(s)
| | | | | | - Phunchai Charatcharoenwitthaya
- Correspondence to: Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Medicine Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkok 10700, Thailand. ORCID: https://orcid.org/0000-0002-8334-0267. Tel: +66-2-4197282, Fax: +66-2-4115013, E-mail:
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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.
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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.
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Wang F, Deng Y, Yu L, Zhou A, Wang J, Jia J, Li N, Ding F, Lian W, Liu Q, Yang Y, Lin X. A Macrophage Membrane-Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis. Pharmaceutics 2022; 14:pharmaceutics14112341. [PMID: 36365160 PMCID: PMC9698601 DOI: 10.3390/pharmaceutics14112341] [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: 09/20/2022] [Revised: 10/23/2022] [Accepted: 10/26/2022] [Indexed: 11/16/2022] Open
Abstract
The clinical translation of therapeutic peptides is generally challenged by multiple issues involving absorption, distribution, metabolism and excretion. In this study, a macrophage membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanodelivery system was developed to enhance the bioavailability of the somatostatin (SST) peptide, which faces the hurdles of short half-life and potential side effects in the treatment of chronic pancreatitis. Using a facile nanoprecipitation strategy, SST was loaded in the nanoparticles with an encapsulation efficiency (EE) and a loading efficiency (LE) of 73.68 ± 3.56% and 1.47 ± 0.07%, respectively. The final formulation of SST-loaded nanoparticles with the camouflage of macrophage membrane (MP-SST) showed a mean diameter of 151 ± 4 nm and an average zeta potential of −29.6 ± 0.3 mV, which were stable long term during storage. With an above 90% cell viability, a hemolysis level of about 2% (<5%) and a preference for being ingested by activated endothelial cells compared to macrophages, the membrane−polymer hybrid nanoparticle showed biocompatibility and targeting capability in vitro. After being intravenously administered to mice with chronic pancreatitis, the MP-SST increased the content of SST in the serum (123.6 ± 13.6 pg/mL) and pancreas (1144.9 ± 206.2 pg/g) compared to the treatment of (Dulbecco’s phosphate-buffered saline) DPBS (61.7 ± 6.0 pg/mL in serum and 740.2 ± 172.4 pg/g in the pancreas). The recovery of SST by MP-SST downregulated the expressions of chronic pancreatitis-related factors and alleviated the histologic severity of the pancreas to the greatest extent compared to other treatment groups. This augmentation of SST therapeutic effects demonstrated the superiority of integrating the synthetic polymer with biological membranes in the design of nanoplatforms for advanced and smart peptide delivery. Other peptides like SST can also be delivered via the membrane−polymer hybrid nanosystem for the treatment of diseases, broadening and promoting the potential clinical applications of peptides as therapeutics.
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Affiliation(s)
- Fang Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Yu Deng
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Luying Yu
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Ao Zhou
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Jieting Wang
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Jingyan Jia
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Ning Li
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Fadian Ding
- Center for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
| | - Wei Lian
- Center for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
| | - Qicai Liu
- Center for Reproductive Medicine, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China
| | - Yu Yang
- Department of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Juqian Road 185, Changzhou 213000, China
- Correspondence: (Y.Y.); (X.L.)
| | - Xinhua Lin
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
- Correspondence: (Y.Y.); (X.L.)
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Chan TT, Tse YK, Lui RNS, Wong GLH, Chim AML, Kong APS, Woo J, Yeung DKW, Abrigo JM, Chu WCW, Wong VWS, Tang RSY. Fatty Pancreas Is Independently Associated With Subsequent Diabetes Mellitus Development: A 10-Year Prospective Cohort Study. Clin Gastroenterol Hepatol 2022; 20:2014-2022.e4. [PMID: 34571257 DOI: 10.1016/j.cgh.2021.09.027] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/12/2021] [Accepted: 09/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although the association between fatty pancreas and metabolic syndrome has been suggested in retrospective studies, long-term prospective data on the effect of fatty pancreas on various metabolic outcomes are lacking. We aimed to prospectively investigate the association between fatty pancreas and the development of major metabolic outcomes. METHODS A total of 631 subjects from a population study using fat-water magnetic resonance imaging to quantify pancreatic and liver fat content during 2008 to 2010 were followed up prospectively until December 2020 (mean follow-up time, 11.1 ± 1.1 y). Subjects with significant alcohol intake and diabetes mellitus (DM) at baseline were excluded. Incidence of newly diagnosed DM, hypertension, dyslipidemia, ischemic heart disease, cardiovascular accidents, pancreatic cancer, and mortality were evaluated. RESULTS Among the 631 subjects (mean age, 48 ± 11 y), 93 (14.7%) had fatty pancreas. The fatty pancreas group had a higher incidence of DM (33.3% vs 10.4%; P < .001), hypertension (37.7% vs 22.7%; P = .003), and dyslipidemia (37.7% vs 14.6%; P < .001) during long-term follow-up evaluation. Individuals with both fatty liver and pancreas had the highest DM incidence, followed by fatty liver only and fatty pancreas only groups (P < .001). Fatty pancreas was associated independently with DM (adjusted hazard ratio, 1.81; 95% CI, 1.10-3.00; P = .020), but not hypertension or dyslipidemia on multivariate analysis. Each percentage increase of pancreatic fat increased the risk of incident DM by 7% (adjusted hazard ratio, 1.07; 95% CI, 1.01-1.13; P = .016). No participants developed pancreatic cancer during the follow-up period. CONCLUSIONS Fatty pancreas is associated independently with subsequent DM development, but not hypertension or dyslipidemia.
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Affiliation(s)
- Ting Ting Chan
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China
| | - Yee Kit Tse
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Medical Data Analytic Centre, Hong Kong Special Administrative Region, China
| | - Rashid Nok-Shun Lui
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China; Medical Data Analytic Centre, Hong Kong Special Administrative Region, China
| | - Angel Mei-Ling Chim
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China
| | - Jean Woo
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China
| | - David Ka-Wai Yeung
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Jill M Abrigo
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Winnie Chiu-Wing Chu
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China; Medical Data Analytic Centre, Hong Kong Special Administrative Region, China.
| | - Raymond Shing-Yan Tang
- Department of Medicine and Therapeutics, Hong Kong Special Administrative Region, China; Institute of Digestive Disease, Hong Kong Special Administrative Region, China.
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Wang Q, Wang H, Ding Y, Wan M, Xu M. The Role of Adipokines in Pancreatic Cancer. Front Oncol 2022; 12:926230. [PMID: 35875143 PMCID: PMC9305334 DOI: 10.3389/fonc.2022.926230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/13/2022] [Indexed: 12/24/2022] Open
Abstract
In modern society, inappropriate diets and other lifestyle habits have made obesity an increasingly prominent health problem. Pancreatic cancer (PC), a kind of highly aggressive malignant tumor, is known as a silent assassin and is the seventh leading cause of cancer death worldwide, pushing modern medicine beyond help. Adipokines are coming into notice because of the role of the intermediate regulatory junctions between obesity and malignancy. This review summarizes the current evidence for the relationship between highly concerning adipokines and the pathogenesis of PC. Not only are classical adipokines such as leptin and adiponectin included, but they also cover the recognized chemerin and osteopontin. Through a summary of the biological functions of these adipokines as well as their receptors, it was discovered that in addition to their basic function of stimulating the biological activity of tumors, more studies confirm that adipokines intervene in the progression of PC from the viewpoint of tumor metabolism, immune escape, and reprogramming of the tumor microenvironment (TME). Besides endocrine function, the impact of white adipose tissue (WAT)-induced chronic inflammation on PC is briefly discussed. Furthermore, the potential implication of the acknowledged endocrine behavior of brown adipose tissue (BAT) in relation to carcinogenesis is also explored. No matter the broad spectrum of obesity and the poor prognosis of PC, supplemental research is needed to unravel the detailed network of adipokines associated with PC. Exploiting profound therapeutic strategies that target adipokines and their receptors may go some way to improving the current worrying prognosis of PC patients.
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Chen Y, Zhang P, Lv S, Su X, Du Y, Xu C, Jin Z. Ectopic fat deposition and its related abnormalities of lipid metabolism followed by nonalcoholic fatty pancreas. Endosc Ultrasound 2022; 11:407-413. [PMID: 35848656 DOI: 10.4103/eus-d-21-00167] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background and Objectives The positive energy balance between caloric intake and caloric output increasing storage of triglycerides (TG) in adipocytes has made nonalcoholic fatty liver disease (NAFLD) one of the major public health problems in China. Excessive lipid deposition in the pancreas is referred to as nonalcoholic fatty pancreas disease (NAFPD). Early assessment of pancreatic fat infiltration will have an increasing role in the clinical management of the metabolic dysregulation and prevention pancreatic complications. Subjects and Methods We retrospectively collected data of inpatients with NAFPD from EUS database between September 2012 and August 2020 at our endoscopic center. The prevalence of NAFPD and factors associated with its development were statistically analyzed. The echogenicity of the pancreas was compared to that of the left renal cortex during the EUS examination by using an existing criterion. Results Four thousand, seven hundred and four consecutive individuals underwent EUS were enrolled. The prevalence of NAFPD was 1.2% (57/4704) . Factors independently associated with NAFPD on multivariate analysis were increasing TG (odds ratios [OR] 4.65, P = 0.014), NAFLD (OR 16.76, P = 0.005) and decreasing apolipoprotein A-1 (OR 0.002, P = 0.0127). We found no association between NAFPD and age, sex, total cholesterol or hypertension. Conclusions We found a meaningful relationship between NAFLD, dyslipidemia, and NAFPD in Chinese. We hypothesized that NAFPD was strongly correlated with ectopic fat deposition and its related abnormalities of lipid metabolism. Early diagnosis of NAFLD provides opportunities to control the progression of NAFPD.
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Affiliation(s)
- Yan Chen
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Pingping Zhang
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Shunli Lv
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xiaoju Su
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Yiqi Du
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Can Xu
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhendong Jin
- Department of Gastroenterology and Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
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Sotozono H, Kanki A, Yasokawa K, Yamamoto A, Sanai H, Moriya K, Tamada T. Value of 3-T MR imaging in intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma. Eur Radiol 2022; 32:8276-8284. [PMID: 35665843 DOI: 10.1007/s00330-022-08881-6] [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: 03/08/2022] [Revised: 04/26/2022] [Accepted: 05/12/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To examine the value of 3-T MRI for evaluating the difference between the pancreatic parenchyma of intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma (IPMN-IC) and the pancreatic parenchyma of patients without an IPMN-IC. METHODS A total of 132 patients underwent abdominal 3-T MRI. Of the normal pancreatic parenchymal measurements, the pancreas-to-muscle signal intensity ratio in in-phase imaging (SIR-I), SIR in opposed-phase imaging (SIR-O), SIR in T2-weighted imaging (SIR-T2), ADC (×10-3 mm2/s) in DWI, and proton density fat fraction (PDFF [%]) in multi-echo 3D DIXON were calculated. The patients were divided into three groups (normal pancreas group: n = 60, intraductal papillary mucinous neoplasm (IPMN) group: n = 60, IPMN-IC group: n = 12). RESULTS No significant differences were observed among the three groups in age, sex, body mass index, prevalence of diabetes mellitus, and hemoglobin A1c (p = 0.141 to p = 0.657). In comparisons among the three groups, the PDFF showed a significant difference (p < 0.001), and there were no significant differences among the three groups in SIR-I, SIR-O, SIR-T2, and ADC (p = 0.153 to p = 0.684). The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group (p < 0.001 and p < 0.001, respectively), with no significant difference between the normal pancreas group and the IPMN group (p = 0.916). CONCLUSIONS These observations suggest that the PDFF of the pancreas is associated with the presence of IPMN-IC. KEY POINTS • The cause and risk factors of IPMN with a concomitant invasive carcinoma have not yet been clarified. • The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group. • Pancreatic PDFF may be a potential biomarker for the development of IPMN with a concomitant invasive carcinoma.
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Affiliation(s)
- Hidemitsu Sotozono
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan.
| | - Akihiko Kanki
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Kazuya Yasokawa
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Akira Yamamoto
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Hiroyasu Sanai
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Kazunori Moriya
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Tsutomu Tamada
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
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Truong E, Pandol S, Jeon C. Uniting epidemiology and experimental models: pancreatic steatosis and pancreatic cancer. EBioMedicine 2022; 79:103996. [PMID: 35405390 PMCID: PMC9010750 DOI: 10.1016/j.ebiom.2022.103996] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/07/2022] [Accepted: 03/28/2022] [Indexed: 02/07/2023] Open
Abstract
Research from epidemiologic studies and experimental animal models provide insights into the role of pancreatic steatosis in the development of pancreatic cancer. Epidemiologic data demonstrate that pancreatic steatosis is widely prevalent and significantly associated with both development and progression of pancreatic cancer. By focusing on current experimental models, this review elucidates potential cellular mechanisms underlying not only the pathophysiology of pancreatic steatosis itself, but also the pathogenesis behind pancreatic steatosis's role in changing the tumour microenvironment and accelerating the development of pancreatic cancer. This review further explores the impact of bariatric surgery on pancreatic steatosis and pancreatic cancer. Synthesizing knowledge from both epidemiologic studies and experimental animal models, this review identifies gaps in current knowledge regarding pancreatic steatosis and its role in carcinogenesis and proposes future research directions to elucidate the possible mechanisms underlying other obesity-associated cancers.
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Affiliation(s)
- Emily Truong
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California.
| | - Stephen Pandol
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California
| | - Christie Jeon
- Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, California; UCLA Fielding School of Public Health, Los Angeles, CA
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Angrisani M, Ceresoli M, Ippolito D, Pagni F, Gandola D, Seminati D, Casati G, Sironi S, Braga M, Roccamatisi L, Uggeri F, Sandini M, Gianotti L. Estimating Fatty Pancreas-A Preoperative Bedside Assessment by Bioelectric Impedance Analysis: Implications for Pancreatic Surgery. Pancreas 2022; 51:345-350. [PMID: 35695762 DOI: 10.1097/mpa.0000000000002020] [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: 12/10/2022]
Abstract
OBJECTIVE The aim of the study was to evaluate whether fatty pancreas could be estimated by fat mass measurement by preoperative bioelectric impedance analysis. Preoperative computed tomography scan and pathologic evaluation were used as validation methods. Moreover, the 3 methodologies were tested for their ability in predicting postoperative pancreatic fistula. METHODS Seventy-five patients who underwent pancreatic resection were analyzed. Preoperative computed tomography attenuation in Hounsfield unit (CT-HU) was used to assess fatty pancreas. Bioelectric impedance analysis was performed the day before surgery and fat mass index (FMI) was calculated. Pancreatic steatosis was assessed by pathologists at the line of surgical transection. The ability of the methods in predicting postoperative pancreatic fistula was evaluated by the area under the receiver operating characteristics curves. RESULTS There was a strong correlation between CT-HU values and grade of pancreatic steatosis evaluated at histology ( r = -0.852, P < 0.001) and a moderate correlation between FMI and histologic pancreatic steatosis ( r = 0.612, P < 0.001) and between CT-HU value and FMI ( r = -0.659, P < 0.001) values. The area under the curve (95% confidence interval) was 0.942 (0.879-1) for histology, 0.924 (0.844-1) for CT-HU, and 0.884 (0.778-0.990) for FMI. CONCLUSIONS Bioelectric impedance analysis represents a valid alternative to assess pancreatic steatosis.
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Bhalla S, Kuchel GA, Pandol S, Bishehsari F. Association of Pancreatic Fatty Infiltration With Age and Metabolic Syndrome Is Sex-Dependent. GASTRO HEP ADVANCES 2022; 1:344-349. [PMID: 39131675 PMCID: PMC11308813 DOI: 10.1016/j.gastha.2022.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/25/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Fatty infiltration of the pancreas has been shown to be associated with both precancerous pancreatic lesions and pancreatic ductal adenocarcinoma. We aim to determine predictors of fatty infiltration of the pancreas in United States adults. Methods In this retrospective cohort study conducted at a large academic hospital in Chicago, Illinois, we calculated the relative fatty infiltration of the pancreas (corrected to spleen) of 265 cancer-free individuals based on their cross-sectional imaging. Demographic data and relevant laboratory results were obtained from medical records. Results We found that age was the strongest predictor of fatty infiltration of the pancreas in our series (P < .01). Fatty infiltration of the pancreas was also significantly associated with body mass index (P < .01) and hyperlipidemia (P < .05). In women, in addition to age (P < .05), elevated body mass index (P = .023), hyperlipidemia (P = .013), and fatty liver (P = .017) were predictors of fat in pancreas. We found a sex-dependent association between pancreatic fat and metabolic syndrome including fatty liver (P = .002). Conclusion Fatty infiltration of the pancreas increases by age and components of metabolic syndrome. These assertions could be sex-dependent.
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Affiliation(s)
- Sameer Bhalla
- Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois
| | - George A. Kuchel
- UConn Center on Aging, University of Connecticut, Farmington, Connecticut
| | - Stephen Pandol
- Division of Digestive and Liver Disease, Cedars-Sinai Medical Center, Los Angeles, California
| | - Faraz Bishehsari
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois
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Fatty Pancreas and Pancreatic Cancer: An Overlooked Association? J Clin Med 2022; 11:jcm11030763. [PMID: 35160214 PMCID: PMC8836883 DOI: 10.3390/jcm11030763] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 01/27/2022] [Accepted: 01/29/2022] [Indexed: 12/26/2022] Open
Abstract
Background: fatty pancreas (FP) is an old observation, but a new disease with clinical implications and several associated comorbid conditions, ranging from mild to life-threatening diseases. Herein, we aimed to assess the association between FP and pancreatic cancer (PC) development. Methods: we performed a retrospective cross-sectional study including all patients who underwent endoscopic ultrasound (EUS) for hepatobiliary indications. The study cohort was divided into patients with and without PC. Univariate and multivariate analysis were used to assess the association of several parameters with PC. Results: overall, 519 patients were included in the study. Of them, 48 had PC (PC group), and 471 did not (non-PC group). In univariate analysis, age (OR 1.04, 95% CI 1.01–1.07, p = 0.004), congestive heart failure (CHF) (OR 3.89, 95% CI 1.72–8.79, p = 0.001), ischemic heart disease (IHD) (OR 3.36, 95% CI 1.59–7.05, p = 0.001), hypertension (OR 2.42, 95% CI 1.33–4.41, p = 0.004) and fatty pancreas (FP) (OR 2.62, 95% CI 1.23–5.57, p = 0.01) were significantly associated with PC. In multivariate logistic regression analysis, only FP kept its association (OR 2.35, 95% CI 1.04–5.33, p = 0.04). Conclusion: FP was significantly associated with PC. A follow-up plan should be considered for individuals with FP.
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Filippatos TD, Alexakis K, Mavrikaki V, Mikhailidis DP. Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, "Prediabetes," Diabetes and Atherosclerosis. Dig Dis Sci 2022; 67:26-41. [PMID: 33469809 DOI: 10.1007/s10620-021-06824-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023]
Abstract
Fat accumulation in the pancreas associated with obesity and the metabolic syndrome (MetS) has been defined as "non-alcoholic fatty pancreas disease" (NAFPD). The aim of this review is to describe the association of NAFPD with obesity, MetS, type 2 diabetes mellitus (T2DM) and atherosclerosis and also increase awareness regarding NAFPD. Various methods are used for the detection and quantification of pancreatic fat accumulation that may play a significant role in the differences that have been observed in the prevalence of NAFPD. Endoscopic ultrasound provides detailed images of the pancreas and its use is expected to increase in the future. Obesity and MetS have been recognized as NAFPD risk factors. NAFPD is strongly associated with non-alcoholic fatty liver disease (NAFLD) and it seems that the presence of both may be related with aggravation of NAFLD. A role of NAFPD in the development of "prediabetes" and T2DM has also been suggested by most human studies. Accumulation of fat in pancreatic tissue possibly initiates a vicious cycle of beta-cell deterioration and further pancreatic fat accumulation. Additionally, some evidence indicates a correlation between NAFPD and atherosclerotic markers (e.g., carotid intima-media thickness). Weight loss and bariatric surgery decreases pancreatic triglyceride content but pharmacologic treatments for NAFPD have not been evaluated in specifically designed studies. Hence, NAFPD is a marker of local fat accumulation possibly associated with beta-cell function impairment, carbohydrate metabolism disorders and atherosclerosis.
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Affiliation(s)
- T D Filippatos
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece.
| | - K Alexakis
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - V Mavrikaki
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - D P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, NW3 2QG, UK.,Mohammed Bin Rashid University (MBRU) of Medicine and Health Sciences, Dubai, United Arab Emirates
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Khoury T, Mari A, Sbeit W. A Novel Clinical Score Predicting the Presence of Fatty Pancreas. J Clin Med 2021; 10:jcm10245843. [PMID: 34945139 PMCID: PMC8704931 DOI: 10.3390/jcm10245843] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/30/2021] [Accepted: 12/10/2021] [Indexed: 12/14/2022] Open
Abstract
Background: Fatty pancreas (FP) has become an increasingly encountered entity in recent years. Several studies have shown an association with several disease states. Aims: we aimed to generate a simple non-invasive scoring model to predict the presence of FP. Method: We performed a retrospective cross-sectional analysis at Galilee Medical Center. Inclusion criteria included patients who underwent endoscopic ultrasound (EUS) for hepatobiliary indications and who had either hyperechogenic pancreas consistent with FP or no sonographic evidence of fatty pancreas. Results: We included 569 patients. Among them, 78 patients had FP by EUS and 491 patients did not have FP. On univariate analysis, obesity (odds ratio (OR) 5.11, p < 0.0001), hyperlipidemia (OR 2.86, p = 0.0005), smoking (OR 2.02, p = 0.04), hypertension (OR 2.58, p = 0.0001) and fatty liver (OR 5.94, p < 0.0001) were predictive of FP. On multivariate analysis, obesity (OR 4.02, p < 0.0001), hyperlipidemia (OR 2.22, p = 0.01) and fatty liver (OR 4.80, p < 0.0001) remained significantly associated with FP. We developed a diagnostic score which included three parameters that were significant on multivariate regression analysis, with assignment of weights for each variable according to the OR estimate. A low cut-off score of ≤1 was associated with a negative predictive value (NPV) of 98.1% for FP, whereas a high cut-off score of ≥2 was associated with a positive predictive value (PPV) of 35–56%. Conclusion: We recommend incorporating this simple score as an aid to identify individuals with FP.
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Affiliation(s)
- Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel;
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 5290002, Israel;
- Correspondence:
| | - Amir Mari
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 5290002, Israel;
- Gastroenterology and Endoscopy Units, The Nazareth Hospital, EMMS, Nazareth 16100, Israel
| | - Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya 22100, Israel;
- Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 5290002, Israel;
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Kawamura A, Takakura K, Torisu Y, Kinoshita Y, Tomita Y, Nakano M, Yamauchi T, Suka M, Sumiyama K, Koido S, Saruta M. Impact of qualitative endoscopic ultrasonography on fatty pancreas at a referral medical center. JGH Open 2021; 6:44-49. [PMID: 35071787 PMCID: PMC8762627 DOI: 10.1002/jgh3.12692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/13/2021] [Accepted: 11/28/2021] [Indexed: 11/24/2022]
Abstract
Background Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. Methods The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut‐off point of the pancreas‐control (PC) ratio in EUS and liver‐control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. Results With the cut‐off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early‐stage group. Conclusion Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high‐risk patients.
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Affiliation(s)
- Atsushi Kawamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Kazuki Takakura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
- UnMed Clinic Motomachi Kanagawa Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Yuji Kinoshita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Yoichi Tomita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Takashi Yamauchi
- Department of Public Health and Environmental Medicine The Jikei University School of Medicine Tokyo Japan
| | - Machi Suka
- Department of Public Health and Environmental Medicine The Jikei University School of Medicine Tokyo Japan
| | - Kazuki Sumiyama
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Shigeo Koido
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
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Janssens LP, Weston AD, Singh D, Spears G, Harmsen WS, Takahashi N, Philbrick KA, Erickson BJ, Abu Dayyeh BK, Chari ST, Chandrasekhara V, Gleeson FC, Levy MJ, Pearson RK, Petersen BT, Vege SS, Majumder S. Determining age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk. Pancreatology 2021; 21:1524-1530. [PMID: 34507900 DOI: 10.1016/j.pan.2021.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 07/24/2021] [Accepted: 08/17/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Increased intrapancreatic fat is associated with pancreatic diseases; however, there are no established objective diagnostic criteria for fatty pancreas. On non-contrast computed tomography (CT), adipose tissue shows negative Hounsfield Unit (HU) attenuations (-150 to -30 HU). Using whole organ segmentation on non-contrast CT, we aimed to describe whole gland pancreatic attenuation and establish 5th and 10th percentile thresholds across a spectrum of age and sex. Subsequently, we aimed to evaluate the association between low pancreatic HU and risk of pancreatic ductal adenocarcinoma (PDAC). METHODS The whole pancreas was segmented in 19,456 images from 469 non-contrast CT scans. A convolutional neural network was trained to assist pancreas segmentation. Mean pancreatic HU, volume, and body composition metrics were calculated. The lower 5th and 10th percentile for mean pancreatic HU were identified, examining the association with age and sex. Pre-diagnostic CT scans from patients who later developed PDAC were compared to cancer-free controls. RESULTS Less than 5th percentile mean pancreatic HU was significantly associated with increase in BMI (OR 1.07; 1.03-1.11), visceral fat (OR 1.37; 1.15-1.64), total abdominal fat (OR 1.12; 1.03-1.22), and diabetes mellitus type 1 (OR 6.76; 1.68-27.28). Compared to controls, pre-diagnostic scans in PDAC cases had lower mean whole gland pancreatic HU (-0.2 vs 7.8, p = 0.026). CONCLUSION In this study, we report age and sex-specific distribution of pancreatic whole-gland CT attenuation. Compared to controls, mean whole gland pancreatic HU is significantly lower in the pre-diagnostic phase of PDAC.
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Affiliation(s)
| | - Alexander D Weston
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA
| | - Dhruv Singh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Grant Spears
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - William S Harmsen
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | | | | | | | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Suresh T Chari
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Ferga C Gleeson
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael J Levy
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Randall K Pearson
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Bret T Petersen
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Santhi Swaroop Vege
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Shounak Majumder
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
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Pancreatic and hepatobiliary manifestations of nonalcoholic fatty pancreatic disease: a referral multi-center experience. Eur J Gastroenterol Hepatol 2021; 33:e297-e301. [PMID: 33600093 DOI: 10.1097/meg.0000000000002041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty pancreatic disease (NAFPD) is an increasingly recognized disease with accumulating evidence of associated co-morbidities. However, data linked with other pancreatic and hepatobiliary disorders are still being studied. AIMS To investigate the association of pancreato-hepato-biliary disorders with NAFPD. METHODS At two Israeli medical centers, a total of 569 patients were analyzed who underwent endoscopic ultrasound for hepatobiliary indications. They were divided into groups depending on the presence or absence of NAFPD. RESULTS Seventy-eight patients (13.7%) had NAFPD (NAFPD group) vs. 491 patients (86.3%) without (non-NAFPD group). NAFPD was significantly associated with obesity [odds ratio (OR) 4.98, 95% confidence interval (CI) 3.02-8.24, P < 0.0001], hypertension (OR 2.55, 95% CI 1.57-4.15, P = 0.0002), active smoking (OR 2.02, 95% CI 1.04-3.93, P = 0.03), and hyperlipidemia (OR 2.86, 95% CI 1.58-5.18, P = 0.0005). On multivariate regression analysis: fatty liver (OR 5.49, 95% CI 2.88-10.49, P < 0.0001), main duct intraductal papillary mucinous neoplasm (M-IPMN) (OR 2.69, 95% CI 1.05-6.9, P = 0.04), and gallstones (OR 1.93, 95% CI 1.1-3.38, P = 0.02) were the most endoscopically and ultrasonographically detected diseases that significantly correlated with NAFPD. CONCLUSION NAFPD was associated with several diseases, most importantly the premalignant M-IPMN. Further investigation for these coexisting diseases should be considered.
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Okada K, Watahiki T, Horie K, Takayama T, Aida Y, To K, Shida T, Ishige K, Nishiyama H, Shoda J, Suzuki H. The prevalence and clinical implications of pancreatic fat accumulation identified during a medical check-up. Medicine (Baltimore) 2021; 100:e27487. [PMID: 34731128 PMCID: PMC8519203 DOI: 10.1097/md.0000000000027487] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/15/2021] [Indexed: 01/05/2023] Open
Abstract
Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.
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Affiliation(s)
- Kosuke Okada
- Division of Medical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Takahisa Watahiki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Kaoru Horie
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Takako Takayama
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Yuka Aida
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Keii To
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Takashi Shida
- Division of Medical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Kazunori Ishige
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Hiroyuki Nishiyama
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Junichi Shoda
- Division of Medical Sciences, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
| | - Hideo Suzuki
- Tsukuba Preventive Medicine Research Center, University of Tsukuba Hospital, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki, Japan
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Koç U, Taydaş O. Evaluation of pancreatic steatosis prevalence and anthropometric measurements using non-contrast computed tomography. TURKISH JOURNAL OF GASTROENTEROLOGY 2021; 31:640-648. [PMID: 33090101 DOI: 10.5152/tjg.2020.19434] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Pancreatic steatosis (PS) is a subject of current interest and its prevalence has been reported to range from 16.1% to 30.7% using various radiological methods. This study aimed to evaluate PS prevalence with non-contrast computed tomography (CT). MATERIALS AND METHODS The non-contrast CT scans taken in 2016 and 2017 in our hospital were retrospectively screened. A total of 637 cases (320 males, 317 females) were included in the study. CT number measurements were performed from three anatomic regions of the pancreas using regions of interest (ROI) of approximately 1 cm2. The cases with a <0.7 ratio of the pancreatic over splenic CT number were accepted as quantitatively steatosis-positive. Anthropometric evaluations were undertaken by determining various parameters defined on CT. RESULTS PS was determined visually in 30.6% of the males and 29% of the females, and quantitatively in 32.8% and 30.6%, respectively. A positive agreement was determined between the quantitative and visual evaluations of steatosis (Cohen's kappa coefficient=0.587, p<0.001). Although PS was seen to be mostly diffuse, the tail region of the pancreas was determined to be the area with most steatosis. CONCLUSION PS is usually overlooked in radiology practice but it has a clinical presentation with non-insignificant prevalence. Current radiological methods are adequate in the evaluation of PS. The determination of the cut-off values for various criteria on non-contrast CT can provide more objective evaluations.
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Affiliation(s)
- Ural Koç
- Department of Radiology, Erzincan Mengucek Gazi Training and Research Hospital, Erzincan, Turkey
| | - Onur Taydaş
- Department of Radiology, Erzincan Mengucek Gazi Training and Research Hospital, Erzincan, Turkey
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Evrimler S, Yip-Schneider MT, Swensson J, Soufi M, Muraru R, Tirkes T, Schmidt CM, Akisik F. Magnetic resonance imaging-derived fat fraction predicts risk of malignancy in intraductal papillary mucinous neoplasm. Abdom Radiol (NY) 2021; 46:4779-4786. [PMID: 34086091 DOI: 10.1007/s00261-021-03146-0] [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: 04/21/2021] [Revised: 05/19/2021] [Accepted: 05/22/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Assess the relationship between MRI-derived pancreatic fat fraction and risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). METHODS MRIs of patients with IPMN who underwent pancreaticoduodenectomy were analyzed. IPMN with low-grade dysplasia (n = 29) were categorized as low-risk while IPMN at high risk of malignancy consisted of those with high-grade dysplasia/invasive carcinoma (n = 33). Pancreatic fat-fraction (FFmean) was measured using the 2-point Dixon-method. Images were evaluated for the high-risk stigmata and worrisome features according to the revised 2017 Fukuoka consensus criteria. Data on serum CA19-9, Diabetes Mellitus (DM) status, body mass index (BMI), and histological chronic pancreatitis were obtained. RESULTS A significant difference in FFmean was found between the high-risk IPMN (11.45%) and low-risk IPMN (9.95%) groups (p = 0.027). Serum CA19-9 level (p = 0.021), presence of cyst wall enhancement (p = 0.029), and solid mass (p = 0.008) were significantly associated with high-risk IPMN. There was a significant correlation between FFmean and mural nodule size (r = 0.36, p ˂ 0.01), type 2 DM (r = 0.34, p ˂ 0.01), age (r = 0.31, p ˂ 0.05), serum CA 19-9 (r = 0.30, p ˂ 0.05), cyst diameter (r = 0.30, p ˂ 0.05), and main pancreatic duct diameter (r = 0.26, p ˂ 0.05). Regression analysis revealed FFmean (OR 1.103, p = 0.035) as an independent predictive variable of high-risk IPMN. CONCLUSION FFmean is significantly associated with high-risk IPMN and an independent predictor of IPMN malignant risk. FFmean may have clinical utility as a biomarker to complement the current IPMN treatment algorithm and improve clinical decision making regarding the need for surgical resection or surveillance.
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Affiliation(s)
- Sehnaz Evrimler
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
- Department of Radiology, Suleyman Demirel University School of Medicine, 32260, Isparta, Turkey
| | - Michele T Yip-Schneider
- Department of Surgery, Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, 46202, USA
| | - Jordan Swensson
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Mazhar Soufi
- Department of Surgery, Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, 46202, USA
| | - Rodica Muraru
- Center for Outcomes Research in Surgery, Indiana University School of Medicine, 545 Barnhill Drive, EH 106E, Indianapolis, IN, 46202, USA
| | - Temel Tirkes
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - C Max Schmidt
- Department of Surgery, Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
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Tien YW, Chien HJ, Chiang TC, Chung MH, Lee CY, Peng SJ, Chen CC, Chou YH, Hsiao FT, Jeng YM, Tang SC. Local islet remodelling associated with duct lesion-islet complex in adult human pancreas. Diabetologia 2021; 64:2266-2278. [PMID: 34272581 DOI: 10.1007/s00125-021-05504-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 03/19/2021] [Indexed: 12/13/2022]
Abstract
AIMS/HYPOTHESIS Islets are thought to be stably present in the adult human pancreas to maintain glucose homeostasis. However, identification of the pancreatic intraepithelial neoplasia (PanIN)-islet complex in mice and the presence of PanIN lesions in adult humans suggest that similar remodelling of islet structure and environment may occur in the human pancreas. To identify islet remodelling in a clinically related setting, we examine human donor pancreases with 3D histology to detect and characterise the human PanIN-islet complex. METHODS Cadaveric donor pancreases (26-65 years old, n = 10) were fixed and sectioned (350 μm) for tissue labelling, clearing and microscopy to detect local islet remodelling for 3D analysis of the microenvironment. The remodelled microenvironment was subsequently examined via microtome-based histology for clinical assessment. RESULTS In nine pancreases, we identified the unique peri-lobular islet aggregation associated with the PanIN lesion (16 lesion-islet complexes detected; size: 3.18 ± 1.34 mm). Important features of the lesion-islet microenvironment include: (1) formation of intra-islet ducts, (2) acinar atrophy, (3) adipocyte association, (4) inflammation (CD45+), (5) stromal accumulation (α-SMA+), (6) increase in Ki-67 proliferation index but absence of Ki-67+ alpha/beta cells and (7) in-depth and continuous duct-islet cell contacts, forming a cluster. The duct-islet cell cluster and intra-islet ducts suggest likely islet cell neogenesis but not replication. CONCLUSIONS/INTERPRETATION We identify local islet remodelling associated with PanIN-islet complex in the adult human pancreas. The tissue remodelling and the evidence of inflammation and stromal accumulation suggest that the PanIN-islet complex is derived from tissue repair after a local injury.
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Affiliation(s)
- Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Jen Chien
- Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
| | - Tsai-Chen Chiang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsin Chung
- Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
- Department of Pathology, National Taiwan University Hospital - Hsinchu Branch, Hsinchu, Taiwan
| | - Chih-Yuan Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jung Peng
- Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Chien-Chia Chen
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Hsien Chou
- Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
- Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Fu-Ting Hsiao
- Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan
| | - Yung-Ming Jeng
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Shiue-Cheng Tang
- Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
- Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan.
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