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Chen X, Sun F, Wang X, Feng X, Aref AR, Tian Y, Ashrafizadeh M, Wu D. Inflammation, microbiota, and pancreatic cancer. Cancer Cell Int 2025; 25:62. [PMID: 39987122 PMCID: PMC11847367 DOI: 10.1186/s12935-025-03673-6] [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: 10/14/2024] [Accepted: 02/04/2025] [Indexed: 02/24/2025] Open
Abstract
Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life of people around the world. In spite of the advances in the treatment of PC, the overall survival of this disease in advanced stage is less than 12%. Moreover, PC cells have aggressive behaviour in proliferation and metastasis as well as capable of developing therapy resistance. Therefore, highlighting the underlying molecular mechanisms in PC pathogenesis can provide new insights for its treatment. In the present review, inflammation and related pathways as well as role of gut microbiome in the regulation of PC pathogenesis are highlighted. The various kinds of interleukins and chemokines are able to regulate angiogenesis, metastasis, proliferation, inflammation and therapy resistance in PC cells. Furthermore, a number of molecular pathways including NF-κB, TLRs and TGF-β demonstrate dysregulation in PC aggravating inflammation and tumorigenesis. Therapeutic regulation of these pathways can reverse inflammation and progression of PC. Both chronic and acute pancreatitis have been shown to be risk factors in the development of PC, further highlighting the role of inflammation. Finally, the composition of gut microbiota can be a risk factor for PC development through affecting pathways such as NF-κB to mediate inflammation.
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Affiliation(s)
- XiaoLiang Chen
- Department of General Surgery and Integrated Traditional Chinese and Western Medicine Oncology, Tiantai People'S Hospital of Zhejiang Province(Tiantai Branch of Zhejiang Provincial People'S Hospital), Hangzhou Medical College, Taizhou, Zhejiang, China
| | - Feixia Sun
- Nursing Department, Shandong First Medical University Affiliated Occupational Disease Hospital (Shandong Provincial Occupational Disease Hospital), Jinan, China
| | - Xuqin Wang
- Department of Oncology, Chongqing General Hospital, Chongqing University, Chongqing, 401120, China
| | - Xiaoqiang Feng
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, China
| | - Amir Reza Aref
- VitroVision Department, DeepkinetiX, Inc, Boston, MA, USA
| | - Yu Tian
- Research Center, the Huizhou Central People'S Hospital, Guangdong Medical University, Huizhou, Guangdong, China.
- School of Public Health, Benedictine University, No. 5700 College Road, Lisle, IL, 60532, USA.
| | - Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, Shandong, China.
| | - Dengfeng Wu
- Department of Emergency, The People'S Hospital of Gaozhou, No. 89 Xiguan Road, Gaozhou, 525200, Guangdong, China.
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Liu L, Wang X, Guo D, Ma R, Gong H, Wang C. Hormone replacement therapy and risk of pancreatic cancer in postmenopausal women: Evidence from the US National Inpatient Sample 2008-2018. Heliyon 2024; 10:e37588. [PMID: 39309886 PMCID: PMC11415697 DOI: 10.1016/j.heliyon.2024.e37588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 09/04/2024] [Accepted: 09/05/2024] [Indexed: 09/25/2024] Open
Abstract
Background Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancreatic cancer has yielded mixed results. This study aimed to investigate the potential association between HRT and the risk of pancreatic cancer in postmenopausal women. Methods This population-based, retrospective study extracted data from the US National Inpatient Sample (NIS) 2008-2018. Hospitalized females aged ≥55 years were eligible for inclusion. Associations between HRT, other study variables, and pancreatic cancer diagnosis were determined using univariate and multivariable regression analyses. Results After 1:4 matching by age, data of postmenopausal women with (n = 35,309) and without (n = 141,236) HRT were included in the analysis. The mean age was 73.4 years. Multivariable analyses showed that women with HRT had significantly decreased odds of pancreatic cancer (adjusted OR [aOR], 0.69, 95 % CI: 0.53-0.90). Compared to patients without HRT, patients with HRT in the 55-64-year-old group (aOR 0.48, 95 % CI: 0.32-0.74), 65-74-year-old group (aOR 0.49, 95 % CI: 0.34-0.71), non-hypertensive group (aOR 0.55, 95 % CI: 0.38-0.79), and non-hyperlipidemia group (aOR 0.59, 95 % CI: 0.42-0.82) had significantly decreased odds of pancreatic cancer. Conclusions In US postmenopausal women, HRT is associated with a reduced risk of pancreatic cancer, especially those aged 55-74 year. Further study is needed to clarify the mechanisms underlying the associations.
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Affiliation(s)
- Lei Liu
- Department of Digestive Surgery, Songjiang Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201600, China
| | - Xinyu Wang
- Division of Biology, University of California San Diego, 9500 Gilman Dr. La Jolla, CA, 92093, USA
| | - Dekai Guo
- Department of Digestive Surgery, Songjiang Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201600, China
| | - Ruirui Ma
- Department of Digestive Surgery, Songjiang Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201600, China
| | - Haibing Gong
- Department of Digestive Surgery, Songjiang Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201600, China
| | - Congjun Wang
- Department of Biliary and Pancreatic Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, 160 Pujian Road, Shanghai, 200127, China
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Ma DM, Dong XW, Han X, Ling Z, Lu GT, Sun YY, Yin XD. Pancreatitis and Pancreatic Cancer Risk. Technol Cancer Res Treat 2023; 22:15330338231164875. [PMID: 36972517 PMCID: PMC10052482 DOI: 10.1177/15330338231164875] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023] Open
Abstract
Purpose: The present retrospective study aimed to explore the relationship between pancreatitis and pancreatic cancer in the population cohort of the UK Biobank (UKB) (https://www.ukbiobank.ac.uk). Methods: From the 500 thousand population cohort of UKB, according to the age and gender of patients with pancreatic cancer 1:10, matching the control without pancreatic cancer, the binary Logistic regression model was used to analyze the relationship between pancreatitis and pancreatic cancer, and subgroup analyses were used to identify potential effect modifiers. Results: A total of 1538 patients with pancreatic cancer were compared with 15 380 controls. In the fully adjusted model, patients with pancreatitis had a significantly increased risk of pancreatic cancer compared with no pancreatitis. The risk of pancreatitis and pancreatic cancer increased with the age of pancreatitis, and the risk of pancreatic cancer was highest in the 61 to 70 age group. In addition, in the first 3 years of acute pancreatitis, the risk of pancreatic cancer increased significantly with the increase in the duration of the disease (odds ratio [OR] 29.13, 95% confidence interval [CI]: 16.34-51.93), after 3 years, the trend of increase decreased. After more than 10 years, there was no significant correlation between the risk of acute pancreatitis and pancreatic cancer. However, patients with chronic pancreatitis were significantly associated with an increased risk of pancreatic cancer only in the first 3 years (OR 28.14, 95% CI: 14.86-53.31). Conclusion: Pancreatitis may associate with an increased risk of pancreatic cancer. The older the age of pancreatitis, the higher the risk of pancreatic cancer. The risk of pancreatic cancer increases significantly in the first 3 years of the course of pancreatitis. This may provide an alternative strategy for the early identification of individuals at high risk of pancreatic cancer.
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Affiliation(s)
- Dong-Mei Ma
- Department of Oncology, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Xiao-Wu Dong
- Pancreatic Center, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Yangzhou Key Laboratory of Pancreatic Diseases, Yangzhou, China
| | - Xiao Han
- Department of Oncology, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Zhi Ling
- Department of Oncology, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Guo-Tao Lu
- Pancreatic Center, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Yangzhou Key Laboratory of Pancreatic Diseases, Yangzhou, China
| | - Yun-Yun Sun
- Pancreatic Center, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Yangzhou Key Laboratory of Pancreatic Diseases, Yangzhou, China
| | - Xu-Dong Yin
- Department of Oncology, 587863Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
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Lim CY, Min JH, Hwang JA, Choi SY, Ko SE. Assessment of main pancreatic duct cutoff with dilatation, but without visible pancreatic focal lesion on MDCT: a novel diagnostic approach for malignant stricture using a CT-based nomogram. Eur Radiol 2022; 32:8285-8295. [PMID: 35726102 DOI: 10.1007/s00330-022-08928-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/29/2022] [Accepted: 05/30/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To identify useful features to predict hidden pancreatic malignancies in patients with main pancreatic duct (MPD) abrupt cutoff and dilatation, but without visible focal pancreatic lesions on CT. METHODS This retrospective study included 92 patients (mean age, 63.4 ± 10.6 years, 63 men and 29 women) with MPD abrupt cutoff and dilatation, but without visible focal pancreatic lesion on contrast-enhanced CT between 2009 and 2021. Two radiologists independently evaluated the CT imaging features. Multivariable logistic regression analysis was performed to identify clinical and CT imaging features for hidden pancreatic malignancies. A nomogram was developed based on these results and assessed its performance. RESULTS Thirty-eight (41.3%) and 54 (58.7%) were classified into the malignant and benign groups, respectively. In the multivariable analysis, CA19-9 elevation (odds ratio [OR] 7.5, p = 0.003), duct cutoff site at the head/neck (OR 7.6, p = 0.006), parenchymal contour abnormality at the duct cutoff site (OR 13.7, p < 0.001), and presence of acute pancreatitis (OR 11.5, p = 0.005) were independent predictors of pancreatic malignancy. A combination of any two significant features showed an accuracy of 77.2%, and a combination of any three features exhibited a specificity of 100%. The CT-based nomogram showed an area under the curve (AUC) of 0.84 (95% confidence interval, 0.77-0.90). CONCLUSIONS The three CT imaging features and CA19-9 elevation translated into a nomogram permit a reliable estimation of hidden pancreatic malignancies in patients with MPD abrupt cutoff without visible focal pancreatic lesion. It may facilitate determining whether to proceed to further diagnostic tests. KEY POINTS • Isoattenuating pancreatic ductal adenocarcinoma can manifest only as an isolated main pancreatic duct (MPD) dilatation with abrupt cutoff, making it difficult to distinguish from benign strictures. • Along with the serum CA 19-9 elevation, MPD cutoff site at the pancreas head or neck, parenchymal contour abnormality at the duct cutoff site, and associated acute pancreatitis indicated a higher probability of the malignant MPD strictures. • The CT-based nomogram provided excellent diagnostic performance (AUC of 0.84) for hidden pancreatic malignancies in patients with MPD abrupt cutoff and dilatation.
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Affiliation(s)
- Chae Young Lim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Seo-Youn Choi
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Seong Eun Ko
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Republic of Korea
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Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022. [DOI: https://doi.org/10.5306/wjco.v13.i11.907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022; 13:907-917. [PMID: 36483975 PMCID: PMC9724185 DOI: 10.5306/wjco.v13.i11.907] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/08/2022] [Accepted: 11/07/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Epidemiological studies of chronic pancreatitis (CP) and its association with pancreatic ductal adenocarcinoma (PDAC) are limited. Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.
AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC. The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.
METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases. Patients included in the study had ICD-10 codes for CP and PDAC. The ethnic, socioeconomic, and racial backgrounds of patients with CP and PDAC were analyzed.
RESULTS Hospital admissions for CP was 29 per 100000, and 2890 (0.78%) had PDAC. Blacks [adjusted odds ratio (aOR) 1.13], men (aOR 1.35), age 40 to 59 (aOR 2.60), and being overweight (aOR 1.34) were significantly associated with CP (all with P < 0.01). In patients with CP, Whites (aOR 1.23), higher income, older age (aOR 1.05), and being overweight (aOR 2.40) were all significantly associated with PDAC (all with P < 0.01). Men (aOR 1.81) and Asians (aOR 15.19) had significantly increased mortality (P < 0.05). Hispanics had significantly increased hospital length of stay (aOR 5.24) (P < 0.05).
CONCLUSION Based on this large, nationwide analysis, black men between 40-59 years old and overweight are at significantly increased risk for admission with CP. White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC. This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.
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Affiliation(s)
- Daniel Lew
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Fatima Kamal
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Khiem Phan
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Karamvir Randhawa
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Sam Cornwell
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Ayrton I Bangolo
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Simcha Weissman
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Stephen J Pandol
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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D’Alterio C, Giardino A, Scognamiglio G, Butturini G, Portella L, Guardascione G, Frigerio I, Montella M, Gobbo S, Martignoni G, Napolitano V, De Vita F, Tatangelo F, Franco R, Scala S. CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients. Cells 2022; 11:3340. [PMID: 36359736 PMCID: PMC9655815 DOI: 10.3390/cells11213340] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/15/2022] [Accepted: 10/17/2022] [Indexed: 04/21/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5-20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12's poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches.
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Affiliation(s)
- Crescenzo D’Alterio
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Alessandro Giardino
- Unit of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy
| | - Giosuè Scognamiglio
- Pathology Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Giovanni Butturini
- Unit of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy
| | - Luigi Portella
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Giuseppe Guardascione
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Isabella Frigerio
- Unit of HPB Surgery, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy
| | - Marco Montella
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Stefano Gobbo
- Department of Pathology, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Guido Martignoni
- Department of Pathology, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy
| | - Vincenzo Napolitano
- Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Ferdinando De Vita
- Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Fabiana Tatangelo
- Pathology Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Renato Franco
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Stefania Scala
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
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Paley EL. Towards Understanding COVID-19: Molecular Insights, Co-infections, Associated Disorders, and Aging. J Alzheimers Dis Rep 2021; 5:571-600. [PMID: 34514341 PMCID: PMC8385430 DOI: 10.3233/adr-210010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND COVID-19 can be related to any diseases caused by microbial infection(s) because 1) co-infection with COVID-19-related virus and other microorganism(s) and 2) because metabolites produced by microorganisms such as bacteria, fungi, and protozoan can be involved in necrotizing pneumonia and other necrotizing medical conditions observed in COVID-19. OBJECTIVE By way of illustration, the microbial metabolite of aromatic amino acid tryptophan, a biogenic amine tryptamine inducing neurodegeneration in cell and animal models, also induces necrosis. METHODS This report includes analysis of COVID-19 positivity by zip codes in Florida and relation of the positivity to population density, possible effect of ecological and social factors on spread of COVID-19, autopsy analysis of COVID-19 cases from around the world, serum metabolomics analysis, and evaluation of autoantigenome related to COVID-19. RESULTS In the present estimations, COVID-19 positivity percent per zip code population varied in Florida from 4.65% to 44.3% (February 2021 data). COVID-19 analysis is partially included in my book Microbial Metabolism and Disease (2021). The autoantigenome related to COVID-19 is characterized by alterations in protein biosynthesis proteins including aminoacyl-tRNA synthetases. Protein biosynthesis alteration is a feature of Alzheimer's disease. Serum metabolomics of COVID-19 positive patients show alteration in shikimate pathway metabolism, which is associated with the presence of Alzheimer's disease-associated human gut bacteria. CONCLUSION Such alterations in microbial metabolism and protein biosynthesis can lead to toxicity and neurodegeneration as described earlier in my book Protein Biosynthesis Interference in Disease (2020).
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Affiliation(s)
- Elena L. Paley
- Expert BioMed, Inc. and Nonprofit Public Charity Stop Alzheimers Corp., Miami-Dade, FL, USA
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Monroy-Iglesias MJ, Dolly S, Sarker D, Thillai K, Van Hemelrijck M, Santaolalla A. Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies. J Clin Med 2021; 10:1665. [PMID: 33924591 PMCID: PMC8069449 DOI: 10.3390/jcm10081665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/19/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa.
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Affiliation(s)
- Maria J. Monroy-Iglesias
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Saoirse Dolly
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Debashis Sarker
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
- School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
| | - Kiruthikah Thillai
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Mieke Van Hemelrijck
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Aida Santaolalla
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
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Al Manasra ARA, Tawalbeh RA, Al-Qaoud DI, Ayesh MH, Al-Omari MH, Manasreh T, Fataftah J. Migrated Inferior Vena Cava (IVC) Filter Strut: A Rare Cause of Chronic Distal Pancreatitis with Likely Malignant Transformation. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e929599. [PMID: 33707408 PMCID: PMC7957838 DOI: 10.12659/ajcr.929599] [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] [Indexed: 12/05/2022]
Abstract
Patient: Female, 44-year-old Final Diagnosis: Pancreatic adenocarcinoma Symptoms: Abdominal pain Medication:— Clinical Procedure: Neoplasm Specialty: Surgery
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Affiliation(s)
- Abdel Rahman A Al Manasra
- Departmet of General Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ra'fat A Tawalbeh
- Departmet of General Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Doaa I Al-Qaoud
- Departmet of Pediatrics, Faculty of Medicine, Hashemite University, Zarqa, Jordan
| | - Mahmoud H Ayesh
- Departmet of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Mamoon H Al-Omari
- Departmet of Radiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Tarek Manasreh
- Department of General Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Jehad Fataftah
- Department of Radiology, Faculty of Medicine, Hashemite University, Zarqa, Jordan
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Takahashi R, Macchini M, Sunagawa M, Jiang Z, Tanaka T, Valenti G, Renz BW, White RA, Hayakawa Y, Westphalen CB, Tailor Y, Iuga AC, Gonda TA, Genkinger J, Olive KP, Wang TC. Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte-mediated immune suppression. Gut 2021; 70:330-341. [PMID: 32393543 DOI: 10.1136/gutjnl-2019-319912] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 03/25/2020] [Accepted: 04/18/2020] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Long-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression. DESIGN We crossed LSL-Kras+/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples. RESULTS KC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12D pancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+ T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+ B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival. CONCLUSION We show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.
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Affiliation(s)
- Ryota Takahashi
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Marina Macchini
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Masaki Sunagawa
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Zhengyu Jiang
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Takayuki Tanaka
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Giovanni Valenti
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Bernhard W Renz
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of General, Visceral and Transplantation Surgery, Hospital of the University of Munich, Munich, Germany
- German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ruth A White
- Division of Hematology and Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Yoku Hayakawa
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - C Benedikt Westphalen
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany
- Comprehensive Cancer Center Munich and German Cancer Consortium (DKTK), partner site Munich, Munich, Germany
| | - Yagnesh Tailor
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Alina C Iuga
- Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Tamas A Gonda
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Jeanine Genkinger
- Mailman School of Public Health, Columbia University, New York, New York, USA
| | - Kenneth P Olive
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Timothy C Wang
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
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12
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The Epidemiology of Pancreatic Cancer and the Association With Acetylsalicylic Acid in the United States: A Population-Based Study. Pancreas 2020; 49:1207-1212. [PMID: 32898007 DOI: 10.1097/mpa.0000000000001659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Pancreatic cancer (PaC) is the third leading cause of cancer-related death in the United States. Multiple studies have investigated the epidemiology and the association between PaC and acetylsalicylic acid (ASA) use, revealing mixed results. Using a large database, we sought to investigate the epidemiology of PaC. METHODS Using a commercial database (Explorys Inc, Cleveland, Ohio), which includes electronic health record data from 26 major integrated US health care systems, all patients 18 years and older diagnosed with PaC for 5 years were identified based on Systematized Nomenclature Of Medicine-Clinical Terms. We determined the prevalence of PaC and the potential associated factors using univariable and multivariable analysis. RESULTS Of the 32,970,850 individuals, we identified 30,250 individuals with PaC with an overall prevalence of 0.08%. Individuals with PaC were more likely to be males, seniors (age, >65 years), and White, compared with patients without PaC. In subgroup analysis of chronic pancreatitis, individuals on ASA, individuals >65 years, White, and White males were less likely to have PaC, and non-White females were more likely to have PaC. CONCLUSIONS This is the largest population-based study evaluating the epidemiology of PaC. We observed a protective association of ASA on a subgroup of patients with PaC and chronic pancreatitis.
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13
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De Jesus-Acosta A, Narang A, Mauro L, Herman J, Jaffee EM, Laheru DA. Carcinoma of the Pancreas. ABELOFF'S CLINICAL ONCOLOGY 2020:1342-1360.e7. [DOI: 10.1016/b978-0-323-47674-4.00078-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Pasquale V, Dugnani E, Liberati D, Marra P, Citro A, Canu T, Policardi M, Valla L, Esposito A, Piemonti L. Glucose metabolism during tumorigenesis in the genetic mouse model of pancreatic cancer. Acta Diabetol 2019; 56:1013-1022. [PMID: 30989379 DOI: 10.1007/s00592-019-01335-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 03/28/2019] [Indexed: 12/11/2022]
Abstract
AIM More than 40% of pancreatic ductal adenocarcinoma (PDAC) patients have glucose intolerance or diabetes. The association has led to two hypotheses: PDAC causes diabetes or diabetes shares risk factors for the development of PDAC. In order to elucidate the relationship between diabetes and PDAC, we investigated the glucose metabolism during tumorigenesis in the LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre (KPC) mouse, a genetically engineered model of PDAC. METHODS Male and female KPCs have been fed with standard diet (SD) or high-fat diet (HFD). The imaging-based 4-class tumor staging was used to follow pancreatic cancer development. Not fasting glycemia, 4-h fasting glycemia, insulin, C-peptide, glucose tolerance after OGTT and abdominal fat volume were measured during tumorigenesis. RESULTS PDAC development did not lead to an overt diabetic phenotype or to any alterations in glucose tolerance in KPC fed with SD. Consumption of HFD induced higher body weight/abdominal fat volume and worsened glucose homeostasis both in control CRE mice and only in early tumorigenesis stages of the KPC mice, excluding that the cancer development itself acts as a trigger for the onset of dysmetabolic features. CONCLUSION Our data demonstrate that carcinogenesis in KPC mice is not associated with paraneoplastic diabetes.
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Affiliation(s)
- Valentina Pasquale
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Erica Dugnani
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Daniela Liberati
- Division of Genetics and Cell biology, Genomic Unit for the diagnosis of human pathologies, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
| | - Paolo Marra
- Department of Radiology, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
| | - Antonio Citro
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Tamara Canu
- Department of Radiology, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
| | - Martina Policardi
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Libera Valla
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy
| | - Antonio Esposito
- Department of Radiology, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Lorenzo Piemonti
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
- Vita-Salute San Raffaele University, Milan, Italy.
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15
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Long-term Outcome and Causes of Death for Working-age Patients Hospitalized Due to Acute Pancreatitis With a Median Follow-up of 10 Years. Ann Surg 2019; 269:932-936. [DOI: 10.1097/sla.0000000000002612] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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16
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Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol 2019; 10:10-27. [PMID: 30834048 PMCID: PMC6396775 DOI: 10.14740/wjon1166] [Citation(s) in RCA: 1483] [Impact Index Per Article: 247.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 11/14/2018] [Indexed: 12/24/2022] Open
Abstract
Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
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Affiliation(s)
- Prashanth Rawla
- Department of Internal Medicine, SOVAH Health, Martinsville, VA 24112, USA
| | - Tagore Sunkara
- Department of Gastroenterology and Hepatology, Mercy Medical Center, Des Moines, IA 50314, USA
| | - Vinaya Gaduputi
- Division of Gastroenterology, SBH Health System, Bronx, NY, USA
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17
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Sadr-Azodi O, Oskarsson V, Discacciati A, Videhult P, Askling J, Ekbom A. Pancreatic Cancer Following Acute Pancreatitis: A Population-based Matched Cohort Study. Am J Gastroenterol 2018; 113:1711-1719. [PMID: 30315287 DOI: 10.1038/s41395-018-0255-9] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 08/06/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute pancreatitis is linked to pancreatic cancer, but the direction of this association is not fully elaborated. METHODS This was a population-based cohort study including all Swedish residents diagnosed with a first-time episode of acute pancreatitis between 1997 and 2013 and corresponding matched pancreatitis-free individuals from the general population. Hazard ratios for the association between acute pancreatitis and pancreatic cancer were estimated using multivariable Cox regression models. RESULTS Overall, 49,749 individuals with acute pancreatitis and 138,750 matched individuals without acute pancreatitis were followed up for 1,192,134 person-years (median 5.3 years). A total of 769 individuals developed pancreatic cancer, of whom 536 (69.7%) had a history of acute pancreatitis. The risk of pancreatic cancer was substantially increased during the first few years after a diagnosis of acute pancreatitis but declined gradually over time, reaching a level comparable to the pancreatitis-free population after >10 years of follow-up. In those with non-gallstone-related acute pancreatitis, the risk of pancreatic cancer declined to a level comparable to the pancreatitis-free population only when follow-up time was censored for a second episode of acute pancreatitis or a diagnosis of chronic pancreatitis. Increasing number of recurrent episodes of acute pancreatitis was associated with increased risk of pancreatic cancer. CONCLUSION These findings imply a delay in the diagnosis of pre-existing pancreatic cancer, if clinically presented as acute pancreatitis. Any association between non-gallstone-related acute pancreatitis and pancreatic cancer in the long-term (>10 years) could be mediated through recurrent acute pancreatitis or chronic pancreatitis.
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Affiliation(s)
- Omid Sadr-Azodi
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden.,Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden.,Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
| | - Viktor Oskarsson
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
| | - Andrea Discacciati
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
| | - Per Videhult
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
| | - Johan Askling
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
| | - Anders Ekbom
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgery, Västerås County Hospital, Västerås, Sweden
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18
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Feng L, Qi Q, Wang P, Chen H, Chen Z, Meng Z, Liu L. Serum levels of IL-6, IL-8, and IL-10 are indicators of prognosis in pancreatic cancer. J Int Med Res 2018; 46:5228-5236. [PMID: 30304975 PMCID: PMC6300928 DOI: 10.1177/0300060518800588] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Early detection and prognosis prediction are critical to improve patient survival in pancreatic cancer. This study aimed to investigate whether interleukins could serve as indicators of prognosis in pancreatic cancer. METHODS Sixty-eight patients with pancreatic cancer were enrolled in the study during the period between 2012 and 2014. The serum levels of a broad spectrum of interleukins in these patients were determined, including IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-15, and IL-23. RESULTS IL-6, IL-8, and IL-10 showed significant positive correlations with each other. Moreover, high levels of serum IL-6, IL-8, and IL-10 were independently strongly associated with poor survival of patients with pancreatic cancer. CONCLUSIONS Our results suggest that serum levels of IL-6, IL-8, and IL-10 could be useful markers for prediction of prognosis in patients with pancreatic cancer.
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Affiliation(s)
- Lanyun Feng
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Qi Qi
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Peng Wang
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Hao Chen
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Zhen Chen
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Zhiqiang Meng
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
| | - Luming Liu
- 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,2 Department of Oncology, Shanghai Medical College, Shanghai, China
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19
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Song Y, Wang Q, Wang D, Junqiang Li, Yang J, Li H, Wang X, Jin X, Jing R, Yang JH, Su H. Label-Free Quantitative Proteomics Unravels Carboxypeptidases as the Novel Biomarker in Pancreatic Ductal Adenocarcinoma. Transl Oncol 2018; 11:691-699. [PMID: 29631213 PMCID: PMC6154863 DOI: 10.1016/j.tranon.2018.03.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 03/13/2018] [Accepted: 03/13/2018] [Indexed: 01/26/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a high mortality rate and poor prognosis. However, little is known concerning the molecular mechanism of PDAC at the proteomics level. Here we report a proteomics analysis of PDAC tumor and adjacent tissues by shotgun proteomics followed by label-free quantification, and in total, 3031 and 3306 proteins were identified in three pairs of PDAC tumor and adjacent tissues, respectively; 40 of them were differentially expressed for at least three-fold in PDAC tumor tissues. Ontological and interaction network analysis highlighted the dysregulation of a set of four proteins in the carboxypeptidase family: carboxypeptidase A1 (CPA1), A2 (CPA2), B1 (CPB1), and chymotrypsin C (CTRC). Western blotting confirmed the downregulation of the carboxypeptidase network in PDAC. Immunohistochemistry of tissue microarray from 90 PDAC patients demonstrated that CPB1 was downregulated 7.07-fold (P < .0001, n = 81) in tumor comparing with the peritumor tissue. Further 208 pancreatic tissues from PDAC tumor, peritumor, and pancreatis confirmed the downregulation of CPB1 in the PDAC patients. In summary, our results displayed that the expression of carboxypeptidase is significantly downregulated in PDAC tumor tissues and may be novel biomarker in the patient with PDAC.
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Affiliation(s)
- Yang Song
- Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Qing Wang
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Desheng Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Junqiang Li
- Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Jing Yang
- Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Hong Li
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Xiang Wang
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Xuerong Jin
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China
| | - Ruirui Jing
- Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China
| | - Jing-Hua Yang
- Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China; Departments of Surgery and Urology, VA Boston Healthcare System, Boston University School of Medicine, Boston, 510660, MA, USA.
| | - Haichuan Su
- Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shaanxi, China.
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20
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Andersson G, Borgquist S, Jirström K. Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study. Int J Cancer 2018; 143:52-62. [PMID: 29424426 PMCID: PMC5969235 DOI: 10.1002/ijc.31302] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 12/13/2017] [Accepted: 02/05/2018] [Indexed: 12/30/2022]
Abstract
The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered. What's new? Female hormones appear to protect against pancreatic cancer, at least in Sweden. Numerous studies have investigated the relationship between the two, but no clear picture has yet emerged. These authors used data from the Malmö Diet and Cancer study, looking for correlations between hormone levels and cancer risk. They found that a younger start to menstruation—indicating an earlier boost in estrogen—correlated with less chance of developing pancreatic cancer. Use of hormone replacement therapy, particularly estrogen‐only therapy, significantly reduced risk among postmenopausal women. Breastfeeding, oral contraceptive use and parity did not appear to affect pancreatic cancer risk.
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Affiliation(s)
- Gustav Andersson
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Signe Borgquist
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.,Clinical Trial Unit, Skåne University Hospital, Lund, Sweden
| | - Karin Jirström
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
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21
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Andersson G, Wennersten C, Borgquist S, Jirström K. Pancreatic cancer risk in relation to sex, lifestyle factors, and pre-diagnostic anthropometry in the Malmö Diet and Cancer Study. Biol Sex Differ 2016; 7:66. [PMID: 27980714 PMCID: PMC5148828 DOI: 10.1186/s13293-016-0120-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 12/03/2016] [Indexed: 02/06/2023] Open
Abstract
Background Lifestyle factors may influence the risk of developing pancreatic cancer. Whereas cigarette smoking is an established risk factor, the effects of high alcohol intake and obesity are more uncertain. The aim of the present study was to examine the associations of pre-diagnostic anthropometry, alcohol consumption, and smoking habits with pancreatic cancer risk in a Swedish prospective, population-based cohort, with particular reference to potential sex differences. Methods The studied cohort consists of 28,098 participants, including all incident cases of pancreatic cancer, in the Malmö Diet and Cancer Study up until December 31, 2013 (n = 163). Non-parametric and chi-squared tests were applied to compare the distribution of risk factors between cases and non-cases. Cox regression proportional hazards models were used to estimate the relationship between investigative factors and pancreatic cancer risk. Anthropometric factors included height, weight, body mass index (BMI), waist and hip circumference, waist-hip ratio (WHR), and body fat percentage. Results BMI was not a significant risk factor for pancreatic cancer, but a higher WHR was significantly associated with an increased risk in the entire cohort (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.28–4.35, p for trend = 0.009). Regular smoking was a significant risk factor among both women (HR 2.62, 95% CI 1.61–4.27) and men (HR 3.57, 95% CI 1.70–7.47), whereas occasional smoking was a significant risk factor only in women (HR 3.29, 95% CI 1.50–7.19). Passive smoking at work for >20 years was significantly associated with an increased risk in the entire cohort (HR 1.73, 95% CI 1.15–2.58) and in women selectively (HR 2.01, 95% CI 1.21–3.31). Alcohol consumption was not a significant risk factor. A significant interaction was found between female sex and age (p = 0.045), but no other factor, in relation to pancreatic cancer risk. Conclusions WHR was the only pre-diagnostic anthropometric factor associated with pancreatic cancer risk, with no sex-related differences. Regular smoking was confirmed as a significant risk factor in both sexes, whereas occasional and passive smoking were significant risk factors only in women. Despite the lack of a significant interaction between smoking and sex in relation with pancreatic cancer risk, potential sex differences should be considered in future epidemiological studies.
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Affiliation(s)
- Gustav Andersson
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden
| | - Christoffer Wennersten
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden
| | - Signe Borgquist
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden
| | - Karin Jirström
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, 221 85 Lund, Sweden
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Hu ZH, Connett JE, Yuan JM, Anderson KE. Role of survivor bias in pancreatic cancer case-control studies. Ann Epidemiol 2015; 26:50-6. [PMID: 26688282 DOI: 10.1016/j.annepidem.2015.11.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 11/02/2015] [Accepted: 11/03/2015] [Indexed: 10/22/2022]
Abstract
PURPOSE The purpose of this study was to evaluate the impact of survivor bias on pancreatic cancer case-control studies. METHODS The authors constructed five case-loss scenarios based on the Iowa Women's Health Study cohort to reflect how case recruitment in population-based studies varies by case survival time. Risk factors for disease incidence included smoking, body mass index (BMI), waist circumference, diabetes, and alcohol consumption. Odds ratios (ORs) were estimated by conditional logistic regression and quantitatively compared by the interactions between risk factors and 3-month survival time. Additionally, Kaplan-Meier estimates for overall survival were compared within the subset cohort of pancreatic cancer cases. RESULTS BMI and waist circumference showed a significant inverse relationship with survival time. Decreasing trends in ORs for BMI and waist circumference were observed with increasing case survival time. The interaction between BMI and survival time based on a cutpoint of 3 months was significant (P < .01) as was the interaction between waist circumference and survival time (P < .01). CONCLUSIONS The findings suggested that case losses could result in survivor bias causing underestimated odds ratios for both BMI and waist circumference, whereas other risk factors were not significantly affected by case losses.
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Affiliation(s)
- Zhen-Huan Hu
- Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee.
| | - John E Connett
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis
| | - Jian-Min Yuan
- University of Pittsburgh Cancer Institute and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
| | - Kristin E Anderson
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis
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Abstract
OBJECTIVE To evaluate the long-term outcome of autoimmune pancreatitis. METHODS Patients with at least 2 years of follow-up were included. Information was collected regarding disease characteristics, treatment outcome, diagnosed malignancies, and mortality. In addition, pancreatic function and quality of life were assessed prospectively. RESULTS 107 patients were included (87% men, 90% with type 1), with a median follow-up of 74 (interquartile range, 49-108) months. One third was operated for suspected pancreatic cancer (32%). Most patients were (successfully) treated with steroids (83%), but relapses were common (52%), for which no risk factors could be identified. Pancreatic carcinoma was not observed.Prospective data were obtained from 64%, as 17% had died, 7% were lost to follow-up, and 13% refused to participate. After a median of 75 (interquartile range, 50-106) months, 46% still used active treatment. Exocrine and endocrine insufficiencies were highly prevalent (82% and 57%, respectively). Quality of life and survival were not impaired, as compared with a reference population. CONCLUSIONS Despite an excellent initial treatment response, relapses are common, even in type 2, and almost half of the patients require maintenance therapy. Pancreatic insufficiency is highly prevalent, which calls for active screening. Pancreatic cancer was not observed, and quality of life and survival are not impaired.
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Lea CS, Holly EA, Bracci PM. Cigarette smoking and risk of pancreatic cancer: a clinic-based case-control study in the San Francisco Bay Area. Ann Epidemiol 2015; 25:816-23. [PMID: 26475980 DOI: 10.1016/j.annepidem.2015.08.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 08/12/2015] [Accepted: 08/17/2015] [Indexed: 12/13/2022]
Abstract
PURPOSE Cigarette smoking is an established risk factor for pancreatic cancer (PC). We examined the association between cigarette smoking and PC in a San Francisco Bay Area clinic-based, case-control study. METHODS A total of 536 cases and sex and age frequency-matched controls (n = 869) were recruited predominately from the University of California San Francisco (UCSF) medical clinics between 2006 and 2011. Participants were interviewed in-person using structured questionnaires. Adjusted odds ratios (ORs) were computed. RESULTS Forty-eight percent of cases and controls reported never having smoked cigarettes; 39% of cases and 40% of controls were former smokers; 13% of cases and 12% of controls were current smokers. No association was found for either former (OR = 0.85, 95% confidence interval [CI] = 0.66-1.1) or current cigarette smoking (men: OR = 1.0, 95% CI = 0.60-1.7; women: OR = 1.2, 95% CI = 0.73-2.1). No dose-response relationships were detected with number of cigarettes/day, smoking intensity, duration, or years since last smoked. Comparisons with a 1995-1999 population-based UCSF study demonstrated a significantly increased proportion of never smokers in this study (P < .001). CONCLUSIONS This study revealed no significant associations between cigarette smoking and PC in the San Francisco Bay Area during 2006-2011. Data suggest a reduction in the duration of smoking within the referral population.
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Affiliation(s)
- C Suzanne Lea
- Department of Public Health, Brody School of Medicine, East Carolina University, Greenville, NC; Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA.
| | - Elizabeth A Holly
- Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA
| | - Paige M Bracci
- Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA
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Bassagañas S, Allende H, Cobler L, Ortiz MR, Llop E, de Bolós C, Peracaula R. Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines. Cytokine 2015; 75:197-206. [PMID: 25934648 DOI: 10.1016/j.cyto.2015.04.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 04/13/2015] [Accepted: 04/13/2015] [Indexed: 12/27/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma containing several pro-inflammatory cytokines, which are described to modulate the expression of important genes related to tumor promotion and progression. In the present work we have investigated the potential role of these cytokines in the biosynthesis of tumor-associated carbohydrate antigens such as sialyl-Lewis(x) (SLe(x)) through the regulation of specific glycosyltransferase genes. METHODS Two human PDAC cell lines MDAPanc-3 and MDAPanc-28 were treated with pro-inflammatory cytokines IL-1β, TNFα, IL-6 or IL-8, and the content of tumor-associated carbohydrate antigens at the cell membrane was analyzed by flow cytometry. In addition, variation in the mRNA expression of sialyltransferase (ST) and fucosyltransferase (FUT) genes, which codify for the ST and FucT enzymes involved in the carbohydrate antigens' biosynthesis, was determined. The inflammatory microenvironment of PDAC tissues and the expression of Lewis-type antigens were analyzed by immunohistochemistry to find a possible correlation between inflammation status and the presence of tumor-associated carbohydrate antigens. RESULTS IL-1β stimuli increased SLe(x) and α2,6-sialic acid levels in MDAPanc-28 cells and enhanced the mRNA levels of ST3GAL3-4 and FUT5-7, which codify for ST and FucT enzymes related to SLe(x) biosynthesis, and of ST6GAL1. IL-6 and TNFα treatments increased the levels of SLe(x) and Le(y) antigens in MDPanc-3 cells and, similarly, the mRNA expression of ST3GAL3-4, FUT1-2 and FUT6, related to these Lewis-type antigens' biosynthesis, were increased. Most PDAC tissues stained for SLe(x) and SLe(a) and tended to be expressed in the tumor samples with a higher presence of inflammatory immune cells. CONCLUSIONS The inflammatory microenvironment can modulate the glycosylation pattern of PDAC cells, increasing the expression of tumor-associated sialylated antigens such as SLe(x), which contributes to pancreatic tumor malignancy.
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Affiliation(s)
- Sònia Bassagañas
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain
| | - Helena Allende
- Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Lara Cobler
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
| | - M Rosa Ortiz
- Department of Pathology, Dr. Josep Trueta University Hospital, Girona, Spain
| | - Esther Llop
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain
| | - Carme de Bolós
- Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Rosa Peracaula
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
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Tong GX, Geng QQ, Chai J, Cheng J, Chen PL, Liang H, Shen XR, Wang DB. Association between pancreatitis and subsequent risk of pancreatic cancer: a systematic review of epidemiological studies. Asian Pac J Cancer Prev 2015; 15:5029-34. [PMID: 24998582 DOI: 10.7314/apjcp.2014.15.12.5029] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
This study aimed to summarize published epidemiological evidence for the relationship between pancreatitis and subsequent risk of pancreatic cancer (PC). We searched Medline and Embase for epidemiological studies published by February 5th, 2014 examining the risk of PC in pancreatitis patients using highly inclusive algorithms. Information about first author, year of publication, country of study, recruitment period, type of pancreatitis, study design, sample size, source of controls and attained age of subjects were extracted by two researchers and Stata 11.0 was used to perform the statistical analyses and examine publication bias. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the random effects model. A total of 17 articles documenting 3 cohort and 14 case-control studies containing 14,667 PC cases and 17,587 pancreatitis cases were included in this study. The pooled OR between pancreatitis and PC risk was 7.05 (95%CI: 6.42-7.75). However, the pooled ORs of case-control and cohort studies were 4.62 (95%CI: 4.08-5.22) and 16.3 (95%CI: 14.3-18.6) respectively. The risk of PC was the highest in patients with chronic pancreatitis (pooled OR=10.35; 95%CI: 9.13-11.75), followed by unspecified type of pancreatitis (pooled OR=6.41; 95%CI: 4.93-8.34), both acute and chronic pancreatitis (pooled OR=6.13; 95%CI: 5.00-7.52), and acute pancreatitis (pooled OR=2.12; 95%CI: 1.59-2.83). The pooled OR of PC in pancreatitis cases diagnosed within 1 year was the highest (pooled OR=23.3; 95%CI: 14.0-38.9); and the risk in subjects diagnosed with pancreatitis for no less than 2, 5 and 10 years were 3.03 (95%CI: 2.41-3.81), 2.82 (95%CI: 2.12-3.76) and 2.25 (95%CI: 1.59-3.19) respectively. Pancreatitis, especially chronic pancreatitis, was associated with a significantly increased risk of PC; and the risk decreased with increasing duration since diagnosis of pancreatitis.
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Affiliation(s)
- Gui-Xian Tong
- Center for Health Management, School of Health Services Management, Anhui Medical University, Hefei, China E-mail :
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Kimura Y, Kikuyama M, Kodama Y. Acute Pancreatitis as a Possible Indicator of Pancreatic Cancer: The Importance of Mass Detection. Intern Med 2015; 54:2109-14. [PMID: 26328633 DOI: 10.2169/internalmedicine.54.4068] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
OBJECTIVE The aims of this study were to assess the incidence of pancreatic cancer and the contributing factors for the diagnosis of tumors in patients with acute pancreatitis and to gain insight into how patients with acute pancreatitis should be followed up. METHODS Using the electronic medical database of Shizuoka General Hospital, 177 patients admitted for acute pancreatitis in the past 6 years were evaluated retrospectively for pancreatic cancer. RESULTS Twelve patients (6.8%) were newly diagnosed with pancreatic cancer. During the first hospitalization, 5 patients (41.7%) with a detected pancreatic mass underwent surgical treatment: the final tumor stages were IA, IIA, and IIB in 1, 2, and 2 patients, respectively. In 7 patients (58.3%) without a detected pancreatic mass at the first admission, a pancreatic mass was recognized on follow-up computed tomography (CT) in 2 patients with main pancreatic duct (MPD) dilatation, and 1 patient with recurrent acute pancreatitis. The tumor stages were IA, IIA, and IA, respectively. Among the remaining 4 patients without follow-up, the tumor stage was IV. The patient gender, age, MPD dilatation, tumor marker, and serum amylase level were not significantly associated with pancreatic cancer. The detection of a pancreatic mass on CT led to the diagnosis of pancreatic cancer. CONCLUSION Acute pancreatitis should be considered as a possible diagnostic indicator of pancreatic cancer. Various factors associated with acute pancreatitis and pancreatic cancer were not predictive of a diagnosis of pancreatic cancer. Only the detection of a pancreatic mass led to the early diagnosis of pancreatic cancer. Patients hospitalized for acute pancreatitis should be followed up with a diagnostic imaging modality.
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Affiliation(s)
- Yuto Kimura
- Department of Gastroenterology, Kyoto University Hospital, Japan
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Independent and joint effect of type 2 diabetes and gastric and hepatobiliary diseases on risk of pancreatic cancer risk: 10-year follow-up of population-based cohort. Br J Cancer 2014; 111:2180-6. [PMID: 25275365 PMCID: PMC4260037 DOI: 10.1038/bjc.2014.525] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Revised: 08/29/2014] [Accepted: 09/07/2014] [Indexed: 12/13/2022] Open
Abstract
Background: Type 2 diabetes mellitus, gastric and hepatobiliary comorbidities, and cancer share common risk factors: for example, tobacco, obesity, physical inactivity, high calorie intake, and metabolic disorders. Prior studies find type 2 diabetes and gastric and hepatobiliary comorbidities heightening risk of pancreatic cancer. Yet joint association of type 2 diabetes mellitus and gastric and hepatobiliary comorbidities on pancreatic cancer risk has not been assessed. Methods: This study rates independent/joint effects of type 2 diabetes as well as gastric and hepatobiliary comorbidity on pancreatic cancer risk for a retrospective population-based cohort of 166 850 type 2 diabetics identified in 1997–1998 and followed for 10–11 years, comparing their cancer incidence with that of 166 850 non-diabetics matched for age, gender, and locale. Time-dependent Cox's proportional hazards model evaluted joint association of type 2 diabetes and chronic conditions on pancreatic cancer risk. Results: A total of 1178 subjects were newly diagnosed with pancreatic cancer during follow-up, with incidence rates of 0.49 per 1000 person-years in type 2 diabetes and 0.26 per 1000 person-years in the non-diabetics. We observed greater magnitude of hazard ratios (HRs) of pancreatic cancer for patients with type 2 diabetes along with acute alcoholic hepatitis, acute pancreatitis, cholecystitis, and gastric ulcer compared with patients without type 2 diabetes or counterpart comorbidity (HR: 1.36, 95% confidence interval (CI): 1.19–1.56; 1.74, 1.23–2.45; 9.18, 7.44–11.33; and 2.31, 1.98–2.70, respectively). Main effects of type 2 diabetes were all statistically with narrow 95% CI and remained similar across risk stratification with various comorbidities: range 1.59–1.80. Conclusions: Our study demonstrates that pre-existing type 2 diabetes, acute alcoholic hepatitis, acute pancreatitis, cholecystitis, and gastric ulcer independently or jointly predict subsequent pancreatic cancer risk. Clinicians must recognise burden of these gastric and hepatobiliary comorbidities and keep clinically vigilant for their diagnosis.
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Abstract
OBJECTIVES Pancreatitis is considered a possible risk factor for and a presentation of pancreatic adenocarcinoma (PA). We aimed to evaluate a large PA patient registry to determine whether prior history of pancreatitis influenced survival. METHODS We retrospectively analyzed the Mayo Clinic Biospecimen Resource for Pancreas Research database from January 1992 to September 2011. Data collected included demographic characteristics, history of tobacco or alcohol use, diabetes mellitus (DM), cholelithiasis, pseudocyst, and details regarding PA. Clinical characteristics and outcomes of PA patients with pancreatitis were compared with PA patients without pancreatitis history. RESULTS We analyzed 2573 patients with PA diagnosis. Among these patients, 195 (8%) were identified who had pancreatitis diagnosis ≥ 10 days before PA diagnosis. The cohort with pancreatitis history included more patients with DM (30% vs. 18%; P<0.001) and more smokers (68% vs. 58%; P=0.02). Compared with patients without pancreatitis history, these patients received diagnoses of PA at a younger age (63 vs. 65 y; P=0.005) and earlier stage (stages I and II; 52% vs. 37%; P<0.001). A greater percentage had history of surgery with curative intent (50% vs. 43%; P=0.001) and significantly better survival [median (range), 387 d (314 to 460 d) vs. 325 d (306 to 344 d); P=0.003]. CONCLUSIONS Patients with PA and pancreatitis had more weight loss and DM, but had PA diagnosis at an earlier stage, were more likely to have pancreatic surgery, and therefore better survival than PA patients without pancreatitis, likely due to the earlier diagnosis. Further studies are needed to evaluate whether screening for PA in patients with pancreatitis history would provide survival benefit.
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He XD, Wu Q, Liu W, Hong T, Li JJ, Miao RY, Zhao HT. Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China. World J Gastroenterol 2014; 20:9541-9548. [PMID: 25071350 PMCID: PMC4110587 DOI: 10.3748/wjg.v20.i28.9541] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 02/22/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the risk factors for ampullary adenoma and ampullary cancer.
METHODS: This case-control study included ampullary tumor patients referred to Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of the same hospital. Data on metabolic syndromes, medical conditions, and family history were collected by retrospective review of the patients’ records and health examination reports, or by interview.
RESULTS: A total of 181 patients and 905 age- and sex-matched controls were enrolled. We found that a history of diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were significantly related to ampullary adenomas. Diabetes, cholecystolithiasis, chronic pancreatitis, total cholesterol, high-density lipoprotein, and apolipoprotein A were also significantly related to ampullary cancer.
CONCLUSION: Some metabolic syndrome components and medical conditions are potential risk factors for the development of ampullary tumors. Cholelithiasis, diabetes, and apolipoprotein A may contribute to the malignant transformation of benign ampullary adenomas into ampullary cancer.
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Ling S, Feng T, Jia K, Tian Y, Li Y. Inflammation to cancer: The molecular biology in the pancreas (Review). Oncol Lett 2014; 7:1747-1754. [PMID: 24932227 PMCID: PMC4049733 DOI: 10.3892/ol.2014.2003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 03/11/2014] [Indexed: 02/07/2023] Open
Abstract
Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from inflammation to pancreatic carcinogenesis, in support of the strategies for the prevention, diagnosis and treatment of PC.
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Affiliation(s)
- Sunbin Ling
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
| | - Tingting Feng
- Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
| | - Kaiqi Jia
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
| | - Yu Tian
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
| | - Yan Li
- Institute of Cancer Stem Cells, Dalian Medical University, Dalian, Liaoning 116044, P.R. China ; College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
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32
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Arora S, Joel A. Pancreatic cancer in a case of idiopathic chronic pancreatitis. Indian J Med Res 2013; 138:568. [PMID: 24434269 PMCID: PMC3868077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Affiliation(s)
- Shalabh Arora
- Department of Medical Oncology, Christian Medical College Hospital, Vellore, Tamil Nadu 632 004, India,For correspondence:
| | - Anjana Joel
- Department of Medical Oncology, Christian Medical College Hospital, Vellore, Tamil Nadu 632 004, India
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Lai HC, Tsai IJ, Chen PC, Muo CH, Chou JW, Peng CY, Lai SW, Sung FC, Lyu SY, Morisky DE. Gallstones, a cholecystectomy, chronic pancreatitis, and the risk of subsequent pancreatic cancer in diabetic patients: a population-based cohort study. J Gastroenterol 2013; 48:721-7. [PMID: 23053420 DOI: 10.1007/s00535-012-0674-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Accepted: 08/21/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND The causal association between diabetes and pancreatic cancer remains unclear in Asian populations. This study examined whether gallstones, a cholecystectomy, chronic pancreatitis and the treatment of antidiabetic agents affect the risk of subsequent pancreatic cancer for patients with diabetes in a Taiwanese population. METHODS Using claims data from the universal health insurance program in Taiwan, 449,685 newly diagnosed diabetic cases among insured people from 2000 to 2003 were identified as the case group. The comparison group, matched for gender, age, and the index year of the diabetes cohort, consisted of 325,729 persons without diabetes. Pancreatic cancer incidence was measured in both groups until the end of 2008. Other risk factors associated with this cancer were also measured. RESULTS The incidence of pancreatic cancer in the diabetic cohort was 2-fold greater than that in the comparison group (1.46 vs. 0.71 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.75 [95 % confidence interval (CI) 1.45-2.10]. The risk slightly increased for diabetic patients with gallstones, cholecystitis, and a cholecystectomy (HR 1.92, 95% CI 1.18-3.11), but greatly increased for those with comorbidity of chronic pancreatitis (HR 22.9, 95% CI 12.6-41.4). Pancreatic cancer risk also increased significantly for those patients who used more insulin for treating diabetes (OR 2.20, 95% CI 1.40-3.45). CONCLUSION Our data suggest that the risk of pancreatic cancer is moderately increased in patients with diabetes, especially those using insulin therapy. The risk is greatly increased for diabetic patients with chronic pancreatitis.
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Affiliation(s)
- Hsueh-Chou Lai
- School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
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Does autoimmune pancreatitis increase the risk of pancreatic carcinoma?: a retrospective analysis of pancreatic resections. Pancreas 2013; 42:506-10. [PMID: 23271394 DOI: 10.1097/mpa.0b013e31826bef91] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES To estimate the risk of malignancy in autoimmune pancreatitis (AIP). METHODS We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases. RESULTS The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3 PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP. CONCLUSIONS These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.
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Danielsson K, Ansari D, Andersson R. Personalizing Pancreatic Cancer Medicine: What are the Challenges? Per Med 2013; 10:45-59. [DOI: 10.2217/pme.12.111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Krissi Danielsson
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, SE-221 85, Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, SE-221 85, Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, SE-221 85, Lund, Sweden
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Duell EJ, Lucenteforte E, Olson SH, Bracci PM, Li D, Risch HA, Silverman DT, Ji BT, Gallinger S, Holly EA, Fontham EH, Maisonneuve P, Bueno-de-Mesquita HB, Ghadirian P, Kurtz RC, Ludwig E, Yu H, Lowenfels AB, Seminara D, Petersen GM, La Vecchia C, Boffetta P. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23:2964-2970. [PMID: 22767586 PMCID: PMC3477881 DOI: 10.1093/annonc/mds140] [Citation(s) in RCA: 166] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Accepted: 03/27/2012] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
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Affiliation(s)
- E J Duell
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
| | - E Lucenteforte
- Department of Epidemiology, Institute for Pharmacological Research 'Mario Negri', Milan; Department of Preclinical and Clinical Pharmacology 'Mario Aiazzi Mancini', University of Florence, Florence, Italy
| | - S H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York
| | - P M Bracci
- Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco
| | - D Li
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston
| | - H A Risch
- Department of Epidemiology and Public Health, School of Public Health, School of Medicine, Yale University, New Haven
| | - D T Silverman
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA
| | - B T Ji
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA
| | - S Gallinger
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - E A Holly
- Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco
| | - E H Fontham
- School of Public Health, Louisiana State University, New Orleans, USA
| | - P Maisonneuve
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| | - H B Bueno-de-Mesquita
- National Institute for Public Health and the Environment, Bilthoven; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
| | - P Ghadirian
- Epidemiology Research Unit, Research Centre of the University of Montreal Hospital Centre (CRCHUM), Montreal, Canada
| | - R C Kurtz
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York
| | - E Ludwig
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York
| | - H Yu
- Department of Epidemiology and Public Health, School of Public Health, School of Medicine, Yale University, New Haven; Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu
| | - A B Lowenfels
- Department of Surgery, New York Medical College, Valhalla
| | - D Seminara
- Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda
| | - G M Petersen
- Departments of Health Science Research, Gastroenterology, and Medical Genetics, Mayo Clinic College of Medicine, Rochester, USA
| | - C La Vecchia
- Department of Epidemiology, Institute for Pharmacological Research 'Mario Negri', Milan; Department of Occupational Health, University of Milan, Milan, Italy
| | - P Boffetta
- The Tisch Cancer Institute and Institute for Translational Epidemiology, Mt Sinai School of Medicine, New York, USA
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Bosetti C, Lucenteforte E, Silverman DT, Petersen G, Bracci PM, Ji BT, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Bertuccio P, Gao YT, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Boffetta P, La Vecchia C. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann Oncol 2012; 23:1880-8. [PMID: 22104574 PMCID: PMC3387822 DOI: 10.1093/annonc/mdr541] [Citation(s) in RCA: 279] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Revised: 10/06/2011] [Accepted: 10/10/2011] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.
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Affiliation(s)
- C Bosetti
- Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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Gastrectomy and risk of pancreatic cancer: systematic review and meta-analysis of observational studies. Cancer Causes Control 2012; 23:1279-88. [PMID: 22674223 DOI: 10.1007/s10552-012-0005-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Accepted: 05/25/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE To investigate the association between gastrectomy and risk of pancreatic cancer (PaC). METHODS We identified eligible studies in Medline and EMBASE up to 11 February 2012 and the reference lists of original studies and review articles on this topic. Summary relative risks with their 95 % confidence intervals were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochran Q and I (2) statistics. RESULTS Fifteen studies (11 case-control studies and 4 cohort studies) met eligibility criteria. The current data suggest that gastrectomy is associated with a 54 % excess risk of PaC (SRRs = 1.54; 95 % CI, 1.25-1.90; test for heterogeneity Q = 17.94, p < 0.001, I (2) = 22 %). There was no publication bias in the present meta-analysis. CONCLUSION A significant increased risk of PaC exists in patients who have undergone gastrectomy, particularly those receiving Billroth II resection with a long postoperative interval.
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Stroma and pancreatic ductal adenocarcinoma: an interaction loop. Biochim Biophys Acta Rev Cancer 2012; 1826:170-8. [PMID: 22521638 DOI: 10.1016/j.bbcan.2012.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 04/06/2012] [Accepted: 04/08/2012] [Indexed: 02/07/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDA) has two exceptional features. First, it is a highly lethal disease, with a median survival of less than 6 months and a 5-year survival rate less than 5%. Second, PDA tumor cells are surrounded by an extensive stroma, which accounts for up to 90% of the tumor volume. It is well recognized that stromal microenvironment can accelerate malignant transformation, tumor growth and progression. More importantly, the interaction loop between PDA and its stroma greatly contributes to tumor growth and progression. We propose that the extensive stroma of PDA is closely linked to its poor prognosis. An improved understanding of the mechanisms that contribute to pancreatic tumor growth and progression is therefore urgently needed. Targeting the stroma may thus provide novel prevention, earlier detection and therapeutic options to this deadly malignancy. Accordingly, in this review, we will summarize the mechanism of PDA stroma formation, the role of the stroma in tumor progression and therapy resistance and the potential of stroma-targeted therapeutics strategies.
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Liang CC, Yao P, Zhao ZH. Investigation of risk factors for pancreatic carcinoma and chronic pancreatitis. Shijie Huaren Xiaohua Zazhi 2012; 20:870-874. [DOI: 10.11569/wcjd.v20.i10.870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare risk factors for pancreatic cancer and chronic pancreatitis to find clues to the early diagnosis of pancreatic cancer.
METHODS: The clinical data for 265 patients with pancreatic carcinoma and 294 patients with chronic pancreatitis who were treated at our hospital from January 2005 to October 2010 were analyzed comparatively. Univariate and multivariate analyses were performed to examine factors affecting the incidence of pancreatic carcinoma using logistic regression models.
RESULTS: Univariate analysis showed that age, nation, smoking, smoking >20 cigarettes/day, drinking, alcohol >40 g/d, alcohol >10 years, diabetes, cholelithiasis, blood and urine amylase, fasting blood sugar level, AST level, ALT level, CA19-9 level differed significantly between the two groups. Multivariate analysis showed that age (OR = 1.607, P < 0.05), CA19-9 >35 KU/L (OR = 1.004, P < 0.05), and fasting blood sugar level >6.4 mmol/L (OR = 1.453, P < 0.05) were independent risk factors for pancreatic carcinoma. Using regression analysis, 251 (94.7%) of 265 cases of pancreatic carcinoma and 282 (95.9%) of 294 cases of chronic pancreatitis were predicted. The total accuracy is 95.3%.
CONCLUSION: Chronic pancreatitis patients with significant risk factors for pancreatic cancer should be regularly monitored for early detection of pancreatic cancer.
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Olson SH. Selected medical conditions and risk of pancreatic cancer. Mol Carcinog 2012; 51:75-97. [PMID: 22162233 DOI: 10.1002/mc.20816] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
We review the current evidence for associations of several medical conditions with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy. There are consistent findings of reduced risk associated with presence of self-reported allergies, particularly hay fever but not asthma; data on other allergies are limited and inconclusive. Several studies provide evidence that patients with pancreatic cancer are more likely than comparison groups to report pancreatitis. Those studies that investigated the time between onset of pancreatitis and diagnosis of pancreatic cancer found that risk estimates declined with longer periods of time; however, increased risks were noted for long-term pancreatitis, indicating that this condition is both a risk factor and a sign of early disease. Increased risk was reported in association with cholelithiasis, but the few studies that considered time before diagnosis of cancer did not find increased risk for cholelithiasis diagnosed in the more distant past. There is weak evidence that cholecystectomy 2 or more years before cancer diagnosis is related to risk, but this is based on only a few studies. There is no consistent association between ulcers and risk, while gastrectomy may increase risk. Overall, study of these conditions, particularly those that are rare, presents methodologic challenges. Time between diagnoses is likely to be important but is not considered in most studies. Lack of adequate control in several studies for risk factors such as smoking and heavy alcohol use also makes it difficult to draw firm conclusions about these results.
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Affiliation(s)
- Sara H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
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Eggers JP, Grandgenett PM, Collisson EC, Lewallen ME, Tremayne J, Singh PK, Swanson BJ, Andersen JM, Caffrey TC, High RR, Ouellette M, Hollingsworth MA. Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras. Clin Cancer Res 2011; 17:6140-50. [PMID: 21825040 DOI: 10.1158/1078-0432.ccr-10-2288] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. EXPERIMENTAL DESIGN We used genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer. RESULTS Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35, and p39 were rarely expressed in pancreatic ducts whereas more than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35, and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels. CONCLUSION These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells.
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Affiliation(s)
- John P Eggers
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
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Stratégies de dépistage de l’adénocarcinome pancréatique chez les patients à haut risque. Bull Cancer 2011; 98:827-36. [DOI: 10.1684/bdc.2011.1396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Bertuccio P, La Vecchia C, Silverman DT, Petersen GM, Bracci PM, Negri E, Li D, Risch HA, Olson SH, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham ET, Bamlet WR, Holly EA, Lucenteforte E, Hassan M, Yu H, Kurtz RC, Cotterchio M, Su J, Maisonneuve P, Duell EJ, Bosetti C, Boffetta P. Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2011; 22:1420-1426. [PMID: 21245160 PMCID: PMC3139985 DOI: 10.1093/annonc/mdq613] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2010] [Revised: 09/08/2010] [Accepted: 09/10/2010] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.
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Affiliation(s)
- P Bertuccio
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; Department of Occupational Health, Section of Medical Statistics, University of Milan, Milan, Italy
| | - C La Vecchia
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; Department of Occupational Health, Section of Medical Statistics, University of Milan, Milan, Italy
| | | | | | | | - E Negri
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
| | - D Li
- The University of Texas M.D Anderson Cancer Center, Houston
| | - H A Risch
- Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven
| | - S H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA
| | | | - A B Miller
- Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
| | - H B Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven; Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - R Talamini
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico (CRO), Aviano, Italy
| | - J Polesel
- Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico (CRO), Aviano, Italy
| | - P Ghadirian
- Epidemiology Research Unit, Research Centre (CRCHUM), Montréal, Canada
| | - P A Baghurst
- Public Health, Women's and Children's Hospital, Adelaide, Australia
| | - W Zatonski
- Cancer Center & Institute of Oncology, Warsaw, Poland
| | - E T Fontham
- Louisiana State University, School of Public Health, New Orleans
| | | | - E A Holly
- University of California, San Francisco
| | - E Lucenteforte
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; Department of Occupational Health, Section of Medical Statistics, University of Milan, Milan, Italy
| | - M Hassan
- The University of Texas M.D Anderson Cancer Center, Houston
| | - H Yu
- Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven
| | - R C Kurtz
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
| | - M Cotterchio
- Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Cancer Care Ontario, Toronto, Canada
| | - J Su
- National Cancer Institute, Bethesda
| | | | - E J Duell
- Catalan Institute of Oncology (ICO), Barcelona, Spain
| | - C Bosetti
- Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
| | - P Boffetta
- International Prevention Research Institute, Lyon, France; The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA.
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Tranah GJ, Holly EA, Wang F, Bracci PM. Cigarette, cigar and pipe smoking, passive smoke exposure, and risk of pancreatic cancer: a population-based study in the San Francisco Bay Area. BMC Cancer 2011; 11:138. [PMID: 21496267 PMCID: PMC3094325 DOI: 10.1186/1471-2407-11-138] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2010] [Accepted: 04/15/2011] [Indexed: 01/29/2023] Open
Abstract
Background To examine the influence of cigarette, cigar and pipe smoking, cessation of cigarette smoking and passive smoke exposure on the risk of pancreatic cancer. Methods Exposure data were collected during in-person interviews in a population-based case-control study of pancreatic cancer (N = 532 cases, N = 1701 controls) in the San Francisco Bay Area. Odds ratios (ORs) were adjusted for potential confounders. Results The adjusted odds ratio (OR) of pancreatic cancer among current smokers was 1.9 (95% confidence interval (CI), 1.4-2.7). A significant, positive trend in risk with increasing pack-years of smoking was observed (P-trend <0.0001). Compared with participants who continued to smoke, former smokers had no statistically significant elevation in risk of pancreatic cancer 10 years after smoking cessation, with risk reduced to that of never smokers regardless of prior smoking intensity. Both men and women experienced similar increased risk of pancreatic cancer with increasing smoking duration. Cigar and pipe smoking and exposure to passive smoke were not associated with pancreatic cancer. Conclusions Cigarette smoking is associated with an increased risk of pancreatic cancer. Smokers who had quit for ≥10 years no longer experienced an increased risk. Future work will help to determine the effect of declining smoking rates on pancreatic cancer incidence.
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Affiliation(s)
- Gregory J Tranah
- California Pacific Medical Center Research Institute, 94107, USA.
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Lipworth L, Zucchetto A, Bosetti C, Franceschi S, Talamini R, Serraino D, McLaughlin JK, La Vecchia C, Negri E. Diabetes mellitus, other medical conditions and pancreatic cancer: a case-control study. Diabetes Metab Res Rev 2011; 27:255-61. [PMID: 21309046 DOI: 10.1002/dmrr.1162] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Diabetes and other medical conditions have been related to pancreatic cancer, but time risk quantification is unsettled. METHODS We combined data from two case-control studies conducted in Italy, including 688 pancreatic cancer cases and 2204 controls. All subjects were interviewed by trained interviewers during their hospital stay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS Overall, 103 cases (15%) and 125 controls (5.7%) reported a history of diabetes. The OR for pancreatic cancer was more pronounced among those diagnosed with diabetes in the previous 2 years (OR = 5.17; 95% CI = 2.71-9.87) than among those with diabetes diagnosed more than 2 years ago (OR = 2.35; 95% CI = 1.70-3.26). The ORs remained significantly elevated 2-4 years (OR = 3.81; 95% CI = 2.07-7.04) and 5-9 years (OR = 3.75; 95% CI = 2.13-6.59) since diagnosis of diabetes, after which a non-significant 20% increased risk for pancreatic cancer was observed. As compared to non-diabetic non-smokers, the OR was 1.85 among non-diabetic current smokers, 2.17 among diabetic never/former smokers, and rose to 4.67 among diabetic current smokers, indicating a multiplicative effect between these two risk factors. Pancreatic cancer was significantly associated with pancreatitis, primarily among those diagnosed within 2 years (OR = 7.16; 95% CI = 2.25-22.78). In addition, the ORs were elevated for cholelithiasis (3.53; 95% CI = 1.67-7.45) and gastroduodenal ulcer (3.16; 95% CI = 1.14-8.73) only among those diagnosed within the past 2 years. CONCLUSIONS Diabetes is associated with heightened risk of pancreatic cancer. The association is significant for diabetes diagnosed up to 10 years before pancreatic cancer.
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Affiliation(s)
- Loren Lipworth
- International Epidemiology Institute, Rockville, MD, USA
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Wang W, Liao Z, Li G, Li ZS, Chen J, Zhan XB, Wang LW, Liu F, Hu LH, Guo Y, Zou DW, Jin ZD. Incidence of pancreatic cancer in chinese patients with chronic pancreatitis. Pancreatology 2011; 11:16-23. [PMID: 21311209 DOI: 10.1159/000322982] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2010] [Accepted: 11/19/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM It is suggested that patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer compared with the general population. This study was designed to determine the rate of pancreatic cancer in CP patients in China. METHODS This was a semiprospective, single-center study including 420 consecutive CP patients (285 males and 135 females, median age at onset 39.5 years), with the median follow-up time being 102.3 months (range 24-419 months). We calculated the standardized incidence ratio (SIR) based on the pancreatic cancer incidence in the general population of China. RESULTS Four cases of pancreatic cancer (0.9% of patients) were observed in 3,591 patient-years (expected number of cases 0.15; SIR 27.2, 95% CI 7.4-69.6). Similar results were seen in alcoholics and non-alcoholics, and in smokers and non-smokers. When patients lost to follow-up were considered to be followed up until the end point without having developed pancreatic cancer (4,280 patient-years), SIR was 22.8 (CI 6.2-58.4). Based on the Cox model, with inserting factors being sex, age at the time of CP clinical onset, type of pancreatitis, and presence or absence of diabetes, calcification, alcohol use and smoking status, only age was found to correlate positively with the occurrence of pancreatic cancer (>50 years, hazard ratio, 1.8 ± 0.5; p = 0.044). CONCLUSION The risk of pancreatic cancer is markedly increased in CP patients in China compared with the general population, especially in older patients. and IAP.
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Affiliation(s)
- Wei Wang
- Chronic Pancreatic Study Group, Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
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Béchade D. [Strategies for screening for pancreatic adenocarcinoma in high-risk patients: the place of endoscopic ultrasound]. Presse Med 2011; 40:230-8. [PMID: 21211938 DOI: 10.1016/j.lpm.2010.11.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Accepted: 11/04/2010] [Indexed: 12/19/2022] Open
Abstract
Screening high-risk individuals with imaging tests, such endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention results in decreased pancreatic cancer incidence and mortality in high-risk individuals.
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MESH Headings
- Adenocarcinoma/diagnosis
- Adenocarcinoma/genetics
- Adenocarcinoma/pathology
- Adenocarcinoma/surgery
- Adenocarcinoma, Mucinous/diagnosis
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adenocarcinoma, Papillary/diagnosis
- Adenocarcinoma, Papillary/genetics
- Adenocarcinoma, Papillary/pathology
- Adenocarcinoma, Papillary/surgery
- Atrophy
- Carcinoma in Situ/diagnosis
- Carcinoma in Situ/genetics
- Carcinoma in Situ/pathology
- Carcinoma in Situ/surgery
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Endosonography
- Female
- Genetic Predisposition to Disease/genetics
- Humans
- Male
- Mass Screening
- Middle Aged
- Neoplasm Staging
- Pancreas/pathology
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Pancreatitis, Chronic/diagnosis
- Pancreatitis, Chronic/genetics
- Pancreatitis, Chronic/pathology
- Pancreatitis, Chronic/surgery
- Precancerous Conditions/diagnosis
- Precancerous Conditions/genetics
- Precancerous Conditions/pathology
- Precancerous Conditions/surgery
- Prognosis
- Tomography, X-Ray Computed
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Affiliation(s)
- Dominique Béchade
- Institut Bergonié, oncologie digestive, 33076 Bordeaux cedex, France.
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Raimondi S, Lowenfels AB, Morselli-Labate AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010; 24:349-58. [PMID: 20510834 DOI: 10.1016/j.bpg.2010.02.007] [Citation(s) in RCA: 431] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2010] [Revised: 02/09/2010] [Accepted: 02/11/2010] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.
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Maisonneuve P, Lowenfels AB, Bueno-de-Mesquita HB, Ghadirian P, Baghurst PA, Zatonski WA, Miller AB, Duell EJ, Boffetta P, Boyle P. Past medical history and pancreatic cancer risk: Results from a multicenter case-control study. Ann Epidemiol 2010; 20:92-8. [PMID: 20123159 DOI: 10.1016/j.annepidem.2009.11.010] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2009] [Revised: 11/16/2009] [Accepted: 11/25/2009] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate risk factors that may be linked to pancreatic cancer. METHODS We designed a multicenter population-based case-control (823 cases, 1679 control patients) study with data collection by using a common protocol and questionnaire. Participating centers were located in Australia, Canada, the Netherlands, and Poland. RESULTS After adjustment for confounding factors, a positive history of pancreatitis was associated with pancreatic cancer (odds ratio [OR], 4.68; 95% confidence interval [95% CI], 2.23-9.84). The risk was especially high in heavy smokers (OR, 15.4; 95% CI, 3.18-74.9). Patients with diabetes had an increased risk of developing pancreatic cancer (OR, 2.16; 95% CI, 1.60-2.91). The risk was highest in the first year after the development of diabetes (OR, 6.68; 95% CI, 3.56-12.6) and decreased over time. A history of allergy was associated with a reduced risk of pancreas cancer (OR, 0.64; 95% CI, 0.50-0.82). CONCLUSIONS Patients with newly diagnosed diabetes and patients with pancreatitis, particularly in heavy smokers, have an increased risk for developing pancreatic cancer. In addition to being risk factors, these conditions could be early manifestations of underlying pancreatic cancer. A history of allergy decreases the risk of pancreatic cancer.
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