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1
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Motta RV, Culver EL. IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease. Front Immunol 2024; 15:1272084. [PMID: 38433835 PMCID: PMC10904653 DOI: 10.3389/fimmu.2024.1272084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 01/25/2024] [Indexed: 03/05/2024] Open
Abstract
Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.
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Affiliation(s)
- Rodrigo V. Motta
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Emma L. Culver
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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2
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Xuan M, Gu X, Liu Y, Yang L, Li Y, Huang D, Li J, Xue C. Intratumoral microorganisms in tumors of the digestive system. Cell Commun Signal 2024; 22:69. [PMID: 38273292 PMCID: PMC10811838 DOI: 10.1186/s12964-023-01425-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/06/2023] [Indexed: 01/27/2024] Open
Abstract
Tumors of the digestive system pose a significant threat to human health and longevity. These tumors are associated with high morbidity and mortality rates, leading to a heavy economic burden on healthcare systems. Several intratumoral microorganisms are present in digestive system tumors, and their sources and abundance display significant heterogeneity depending on the specific tumor subtype. These microbes have a complex and precise function in the neoplasm. They can facilitate tumor growth through various mechanisms, such as inducing DNA damage, influencing the antitumor immune response, and promoting the degradation of chemotherapy drugs. Therefore, these microorganisms can be targeted to inhibit tumor progression for improving overall patient prognosis. This review focuses on the current research progress on microorganisms present in the digestive system tumors and how they influence the initiation, progression, and prognosis of tumors. Furthermore, the primary sources and constituents of tumor microbiome are delineated. Finally, we summarize the application potential of intratumoral microbes in the diagnosis, treatment, and prognosis prediction of digestive system tumors. Video Abstract.
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Affiliation(s)
- Mengjuan Xuan
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Xinyu Gu
- Department of Oncology, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China
| | - Yingru Liu
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Li Yang
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Yi Li
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China
| | - Di Huang
- Department of Child Health Care, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Juan Li
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China.
| | - Chen Xue
- Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, China.
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3
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Chai Y, Huang Z, Shen X, Lin T, Zhang Y, Feng X, Mao Q, Liang Y. Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response. Microorganisms 2023; 11:1240. [PMID: 37317214 PMCID: PMC10221276 DOI: 10.3390/microorganisms11051240] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/02/2023] [Accepted: 05/04/2023] [Indexed: 06/16/2023] Open
Abstract
The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.
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Affiliation(s)
- Yihan Chai
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Zhengze Huang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xuqiu Shen
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Tianyu Lin
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Yiyin Zhang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xu Feng
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Qijiang Mao
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
| | - Yuelong Liang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
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4
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Temel HY, Kaymak Ö, Kaplan S, Bahcivanci B, Gkoutos GV, Acharjee A. Role of microbiota and microbiota-derived short-chain fatty acids in PDAC. Cancer Med 2023; 12:5661-5675. [PMID: 36205023 PMCID: PMC10028056 DOI: 10.1002/cam4.5323] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/08/2022] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive lethal diseases among other cancer types. Gut microbiome and its metabolic regulation play a crucial role in PDAC. Metabolic regulation in the gut is a complex process that involves microbiome and microbiome-derived short-chain fatty acids (SCFAs). SCFAs regulate inflammation, as well as lipid and glucose metabolism, through different pathways. This review aims to summarize recent developments in PDAC in the context of gut and oral microbiota and their associations with short-chain fatty acid (SCFA). In addition to this, we discuss possible therapeutic applications using microbiota in PDAC.
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Affiliation(s)
- Hülya Yılmaz Temel
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Öznur Kaymak
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Seren Kaplan
- Department of Bioengineering, Faculty of EngineeringEge UniversityIzmirTurkey
| | - Basak Bahcivanci
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
| | - Georgios V. Gkoutos
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
- National Institute for Health Research Surgical Reconstruction, Queen Elizabeth Hospital BirminghamBirminghamUK
- MRC Health Data Research UK (HDR UK)BirminghamUK
| | - Animesh Acharjee
- Institute of Cancer and Genomic Sciences, University of BirminghamBirminghamUK
- National Institute for Health Research Surgical Reconstruction, Queen Elizabeth Hospital BirminghamBirminghamUK
- MRC Health Data Research UK (HDR UK)BirminghamUK
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5
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Dong S, Li W, Li X, Wang Z, Chen Z, Shi H, He R, Chen C, Zhou W. Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression. Front Immunol 2022; 13:1038650. [PMID: 36578477 PMCID: PMC9792100 DOI: 10.3389/fimmu.2022.1038650] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.
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Affiliation(s)
- Shi Dong
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Wancheng Li
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Xin Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Zhengfeng Wang
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhou Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Huaqing Shi
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Ru He
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Chen Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Wence Zhou
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
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6
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Panthangi V, Cyril Kurupp AR, Raju A, Luthra G, Shahbaz M, Almatooq H, Foucambert P, Esbrand FD, Zafar S, Khan S. Association Between Helicobacter pylori Infection and the Risk of Pancreatic Cancer: A Systematic Review Based on Observational Studies. Cureus 2022; 14:e28543. [PMID: 36185865 PMCID: PMC9518818 DOI: 10.7759/cureus.28543] [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: 06/26/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal data. Little is known about the risk factors involved with this malignancy. In this systematic review, we aimed to examine the relationship between H. pylori infection and pancreatic cancer based on the evidence from the existing observational studies across the world. We searched major electronic databases such as PubMed, MEDLINE, Science Direct, and Cochrane Library. After a careful and thorough screening process, we selected 15 observation studies for this systematic review. Six of 15 studies found a significant association between H. pylori infection and pancreatic cancer. Additionally, four of these studies found a significant relationship between the cytotoxin-associated gene A strain of H. pylori and pancreatic cancer. Based on the evidence from the selected studies, a weak association was observed between H. pylori infection and cancer of the pancreas, especially in European and Asian populations compared to the North American population. The cross-sectional evidence from the case-control studies only suggests the existence of an association but does not provide substantial evidence of the causative relationship. Further large-scale, prospective cohort studies are warranted in the future to understand this contradictory relationship better.
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Affiliation(s)
- Venkatesh Panthangi
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Anjumol Raju
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Gaurav Luthra
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mahrukh Shahbaz
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Halah Almatooq
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Paul Foucambert
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Faith D Esbrand
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sana Zafar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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7
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The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review. Biomedicines 2022; 10:biomedicines10071511. [PMID: 35884816 PMCID: PMC9312496 DOI: 10.3390/biomedicines10071511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
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8
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Gupta I, Pedersen S, Vranic S, Al Moustafa AE. Implications of Gut Microbiota in Epithelial-Mesenchymal Transition and Cancer Progression: A Concise Review. Cancers (Basel) 2022; 14:2964. [PMID: 35740629 PMCID: PMC9221329 DOI: 10.3390/cancers14122964] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 12/04/2022] Open
Abstract
Advancement in the development of molecular sequencing platforms has identified infectious bacteria or viruses that trigger the dysregulation of a set of genes inducing the epithelial-mesenchymal transition (EMT) event. EMT is essential for embryogenesis, wound repair, and organ development; meanwhile, during carcinogenesis, initiation of the EMT can promote cancer progression and metastasis. Recent studies have reported that interactions between the host and dysbiotic microbiota in different tissues and organs, such as the oral and nasal cavities, esophagus, stomach, gut, skin, and the reproductive tract, may provoke EMT. On the other hand, it is revealed that certain microorganisms display a protective role against cancer growth, indicative of possible therapeutic function. In this review, we summarize recent findings elucidating the underlying mechanisms of pathogenic microorganisms, especially the microbiota, in eliciting crucial regulator genes that induce EMT. Such an approach may help explain cancer progression and pave the way for developing novel preventive and therapeutic strategies.
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Affiliation(s)
- Ishita Gupta
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Shona Pedersen
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
| | - Ala-Eddin Al Moustafa
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (S.P.); (S.V.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
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9
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Yang Q, Zhang J, Zhu Y. Potential Roles of the Gut Microbiota in Pancreatic Carcinogenesis and Therapeutics. Front Cell Infect Microbiol 2022; 12:872019. [PMID: 35463649 PMCID: PMC9019584 DOI: 10.3389/fcimb.2022.872019] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/14/2022] [Indexed: 11/28/2022] Open
Abstract
The intestinal microenvironment is composed of normal gut microbiota and the environment in which it lives. The largest microecosystem in the human body is the gut microbiota, which is closely related to various diseases of the human body. Pancreatic cancer (PC) is a common malignancy of the digestive system worldwide, and it has a 5-year survival rate of only 5%. Early diagnosis of pancreatic cancer is difficult, so most patients have missed their best opportunity for surgery at the time of diagnosis. However, the etiology is not entirely clear, but there are certain associations between PC and diet, lifestyle, obesity, diabetes and chronic pancreatitis. Many studies have shown that the translocation of the gut microbiota, microbiota dysbiosis, imbalance of the oral microbiota, the interference of normal metabolism function and toxic metabolite products are closely associated with the incidence of PC and influence its prognosis. Therefore, understanding the correlation between the gut microbiota and PC could aid the diagnosis and treatment of PC. Here, we review the correlation between the gut microbiota and PC and the research progresses for the gut microbiota in the diagnosis and treatment of PC.
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Affiliation(s)
- Qiaoyu Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
- Queen Mary College, Nanchang University, Nanchang, China
| | - Jihang Zhang
- Institute of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
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10
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Abstract
IgG4-related conditions affecting the digestive tract are part of a multi-organ fibro-inflammatory disorder termed IgG4-related disease (IgG4-RD), with autoimmune pancreatitis and IgG4-related cholangitis being the most prominent manifestations. Gastrointestinal symptoms include jaundice, weight loss, abdominal pain, biliary strictures, and pancreatic and hepatic masses that mimic malignant diseases. IgG4-RD manifestations occur less frequently elsewhere in the digestive tract, namely in the oesophagus, retroperitoneum or intestine. Evidence-based European guidelines frame the current state-of-the-art in the diagnosis and management of IgG4-related digestive tract disease. Diagnosis is based on histology (if available), imaging, serology, other organ involvement and response to therapy (HISORt criteria). Few biomarkers beyond serum IgG4 concentrations are reliable. The first-line therapy (glucocorticoids) is swiftly effective but disease flares are common at low doses or after tapering. Second-line therapy might consist of other immunosuppressive drugs such as thiopurines or rituximab. Further trials, for example, of anti-CD19 drugs, are ongoing. Although an association between IgG4-RD and the development of malignancies has been postulated, the true nature of this relationship remains uncertain at this time.
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11
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Grochowska M, Perlejewski K, Laskus T, Radkowski M. The Role of Gut Microbiota in Gastrointestinal Tract Cancers. Arch Immunol Ther Exp (Warsz) 2022; 70:7. [PMID: 35112169 PMCID: PMC8810472 DOI: 10.1007/s00005-021-00641-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium (Helicobacter pylori) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: Helicobacter pylori, Escherichia coli, and Porphyromonas gingivalis as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.
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Affiliation(s)
- Marta Grochowska
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Karol Perlejewski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Laskus
- Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Marek Radkowski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
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12
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Permuth JB, Rahman S, Chen DT, Waterboer T, Giuliano AR. A Case Control Study of the Seroprevalence of Helicobacter pylori Proteins and Their Association with Pancreatic Cancer Risk. J Pancreat Cancer 2021; 7:57-64. [PMID: 34901696 PMCID: PMC8655807 DOI: 10.1089/pancan.2021.0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2021] [Indexed: 12/12/2022] Open
Abstract
Background: The association between Helicobacter pylori (H. pylori) infection and pancreatic cancer (PC) risk remains inconclusive. We examined the association between H. pylori antibodies and PC risk in a case-control study at a comprehensive cancer center. Methods: Multiplex serology using a glutathione S-transferase capture immunosorbent assay in conjunction with fluorescent bead technology was used to measure antibodies to 15 H. pylori proteins in serum or plasma from 131 incident cases with PC or a PC precursor and 131 healthy controls. Reactivity to ≥4 H. pylori proteins was defined as the overall seroprevalence. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at diagnosis/interview, gender, and race. Results: The majority of the sample was 50 years or older, and from the white race group. Half of the sample were women. Seroprevalence ≥4 of H. pylori proteins was 11.1%. Overall, H. pylori seroprevalence was not associated with PC risk (OR: 0.59; 95% CI: 0.25–1.40). The prevalence of several H. pylori-specific proteins HP537 (OR: 1.78; 95% CI: 0.30–10.51), HP305 (OR: 1.38; 95% CI: 0.61–3.16), and HP410 (OR: 1.31; 95% CI: 0.44–3.96) increased the odds of PC. Similarly, H. pylori-specific proteins HP522 (OR: 0.25; 95% CI: 0.04–1.66), HyuA (OR: 0.49; 95% CI: 0.21–1.14), and HP1564 (OR: 0.63; 95% CI: 0.27–1.51) decreased the odds of PC. However, these findings were not statistically significant at α = 0.05. Conclusions: Our findings do not support an association between H. pylori and PC risk. Further evaluation of this lack of association is recommended.
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Affiliation(s)
- Jennifer B Permuth
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Shams Rahman
- Department of Public Health and Health Equity, College of Nursing and Health Sciences, Bethune-Cookman University, Daytona, Florida, USA
| | - Dung-Tsa Chen
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Tim Waterboer
- Division of Infections and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Anna R Giuliano
- Center of Infection Research in Cancer, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
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13
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Gut microbiome linked to pancreatitis. CURRENT OPINION IN PHYSIOLOGY 2021. [DOI: 10.1016/j.cophys.2021.100470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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14
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Bellotti R, Speth C, Adolph TE, Lass-Flörl C, Effenberger M, Öfner D, Maglione M. Micro- and Mycobiota Dysbiosis in Pancreatic Ductal Adenocarcinoma Development. Cancers (Basel) 2021; 13:cancers13143431. [PMID: 34298645 PMCID: PMC8303110 DOI: 10.3390/cancers13143431] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/30/2021] [Accepted: 07/05/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Dysbiosis of the intestinal flora has emerged as an oncogenic contributor in different malignancies. Recent findings suggest a crucial tumor-promoting role of micro- and mycobiome alterations also in the development of pancreatic ductal adenocarcinoma (PDAC). METHODS To summarize the current knowledge about this topic, a systematic literature search of articles published until October 2020 was performed in MEDLINE (PubMed). RESULTS An increasing number of publications describe associations between bacterial and fungal species and PDAC development. Despite the high inter-individual variability of the commensal flora, some studies identify specific microbial signatures in PDAC patients, including oral commensals like Porphyromonas gingivalis and Fusobacterium nucleatum or Gram-negative bacteria like Proteobacteria. The role of Helicobacter spp. remains unclear. Recent isolation of Malassezia globosa from PDAC tissue suggest also the mycobiota as a crucial player of tumorigenesis. Based on described molecular mechanisms and interactions between the pancreatic tissue and the immune system this review proposes a model of how the micro- and the mycobial dysbiosis could contribute to tumorigenesis in PDAC. CONCLUSIONS The presence of micro- and mycobial dysbiosis in pancreatic tumor tissue opens a fascinating perspective on PDAC oncogenesis. Further studies will pave the way for novel tumor markers and treatment strategies.
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Affiliation(s)
- Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (R.B.); (D.Ö.)
| | - Cornelia Speth
- Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.S.); (C.L.-F.)
| | - Timon E. Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Metabolism & Endocrinology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (T.E.A.); (M.E.)
| | - Cornelia Lass-Flörl
- Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (C.S.); (C.L.-F.)
| | - Maria Effenberger
- Department of Internal Medicine I, Gastroenterology, Hepatology, Metabolism & Endocrinology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (T.E.A.); (M.E.)
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (R.B.); (D.Ö.)
| | - Manuel Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria; (R.B.); (D.Ö.)
- Correspondence: ; Tel.: +43-504-51280 (ext. 809)
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Youssefi M, Tafaghodi M, Farsiani H, Ghazvini K, Keikha M. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:359-369. [PMID: 32891538 DOI: 10.1016/j.jmii.2020.08.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 07/07/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Masoud Youssefi
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Tafaghodi
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hadi Farsiani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kiarash Ghazvini
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
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Pancreatic Cancer Meets Human Microbiota: Close Encounters of the Third Kind. Cancers (Basel) 2021; 13:cancers13061231. [PMID: 33799784 PMCID: PMC7998494 DOI: 10.3390/cancers13061231] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/26/2021] [Accepted: 03/07/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary The microorganisms colonizing the epithelial surfaces of the human body, called microbiota, have been shown to influence the initiation, progression and response to therapy of many solid tumors, including pancreatic ductal adenocarcinoma, the most prominent form of pancreatic cancer. Here, we summarize the current knowledge about the influence of oral, gut and intratumoral microbiota on pancreatic ductal adenocarcinoma development and chemoresistance. Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer with a dismal prognosis. The five-year survival rate has not changed significantly in over 40 years. Current first-line treatments only offer a modest increase in overall survival in unselected populations, and there is an urgent need to personalize treatment in this aggressive disease and develop new therapeutic strategies. Evolving evidence suggests that the human microbiome impacts cancerogenesis and cancer resistance to therapy. The mechanism of action and interaction of microbiome and PDAC is still under investigation. Direct and indirect effects have been proposed, and the use of several microbiome signatures as predictive and prognostic biomarkers for pancreatic cancer are opening new therapeutic horizons. In this review, we provide an overview for the clinicians of studies describing the influence and associations of oral, gastrointestinal and intratumoral microbiota on PDAC development, progression and resistance to therapy and the potential use of microbiota as a diagnostic, prognostic and predictive biomarker for PDAC.
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Abstract
ABSTRACT Microorganisms can help maintain homeostasis in humans by providing nutrition, maintaining hormone balance, and regulating inflammatory responses. In the case of imbalances, these microbes can cause various diseases, even malignancy. Pancreatic cancer (PC) is characterized by high tumor invasiveness, distant metastasis, and insensitivity to traditional chemotherapeutic drugs, and it is confirmed that PC is closely related to microorganisms. Recently, most studies based on clinical samples or case reports discussed the positive or negative relationships between microorganisms and PC. However, the specific mechanisms are blurry, especially the involved immunological pathways, and the roles of beneficial flora have usually been ignored. We reviewed studies published through September 2020 as identified using PubMed, MEDLINE, and Web of Science. We mainly introduced the traits of oral, gastrointestinal, and intratumoral microbes in PC and summarized the roles of these microbes in tumorigenesis and tumoral development through immunological pathways, in addition to illustrating the relationships between metabolic diseases with PC by microorganism. In addition, we identified microorganisms as biomarkers for early diagnosis and immunotherapy. This review will be significant for greater understanding the effect of microorganisms in PC and provide more meaningful guidance for future clinical applications.
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Affiliation(s)
- Xin Wei
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Chunlei Mei
- Institute of Reproductive Health, Huazhong University of Science and Technology, Wuhan, China
| | - Xixi Li
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Yingjun Xie
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
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18
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Zhang W, Zhang K, Zhang P, Zheng J, Min C, Li X. Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer. Front Oncol 2021; 10:604531. [PMID: 33520714 PMCID: PMC7841623 DOI: 10.3389/fonc.2020.604531] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 11/30/2020] [Indexed: 12/16/2022] Open
Abstract
Pancreatic cancer is one of the most common digestive system cancers. Early diagnosis is difficult owing to the lack of specific symptoms and reliable biomarkers. The cause of pancreatic cancer remains ambiguous. Smoking, drinking, new-onset diabetes, and chronic pancreatitis have been proven to be associated with the occurrence of pancreatic cancer. In recent years, a large number of studies have clarified that a variety of microorganisms colonized in pancreatic cancer tissues are also closely related to the occurrence and development of pancreatic cancer, and the specific mechanisms include inflammatory induction, immune regulation, metabolism, and microenvironment changes caused by microorganism. The mechanism of action of the pancreatic colonized microbiome in the tumor microenvironment, as well as immunotherapy approaches require further study in order to find more evidence to explain the complex relationship between the pancreatic colonized microbiome and PDAC. Relevant studies targeting the microbiome may provide insight into the mechanisms of PDAC development and progression, improving treatment effectiveness and overall patient prognosis. In this article, we focus on the research relating to the microorganisms colonized in pancreatic cancer tissues, including viruses, bacteria, and fungi. We also highlight the microbial diversity in the occurrence, invasion, metastasis, treatment, and prognosis of pancreatic cancer in order to elucidate its significance in the early diagnosis and new therapeutic treatment of pancreatic cancer, which urgently need to be improved in clinical practice. The elimination or increase in diversity of the pancreatic microbiome is beneficial for prolonging the survival of PDAC patients, improving the response to chemotherapy drugs, and reducing tumor burden. The colonization of microorganisms in the pancreas may become a new hotspot in the diagnosis and treatment of pancreatic cancer.
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Affiliation(s)
| | | | | | | | | | - Xiaoyu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
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19
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Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives. J Clin Med 2020; 9:jcm9113535. [PMID: 33139601 PMCID: PMC7692447 DOI: 10.3390/jcm9113535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/28/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.
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20
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Zhao Z, Liu W. Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment. Technol Cancer Res Treat 2020; 19:1533033820962117. [PMID: 33357065 PMCID: PMC7768873 DOI: 10.1177/1533033820962117] [Citation(s) in RCA: 185] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 08/08/2020] [Accepted: 08/19/2020] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied malignant tumor. At present, we urgently need to identify high-risk patients with precancerous diseases through screening approaches, so that medical professionals and the general public may better understand prevention strategies or early detection measures. Pancreatic cancer is a highly invasive malignant tumor with a fatal risk, mainly seen in men and older adults (60-85 years old). Pancreatic cancer is now increasingly observed in young patients. Because the disease has no early symptoms and can quickly invade surrounding tissues and organs, it is one of the deadliest cancers. With a view to identify the important factors for the development of pancreatic cancer, previous studies have found that smoking, alcohol, and chronic pancreatitis are considered high-risk factors. Recent studies have shown that abnormal metabolism of human microorganisms, blood type, and glucose and lipid levels are also important factors in the development of pancreatic cancer. Identifying early diagnosis options is an important way to improve detection and survival rates of pancreatic cancer. None of the many tumor markers associated with pancreatic cancer are highly specific, which also indicates further research is required to improve the early detection rate. Future directions in terms of treatment evaluating the relationship between the microbiology-free system and immunotherapy will bring a major breakthrough and is expected to bring exciting clinical applications in improving the life-cycle of pancreatic cancer patients.
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Affiliation(s)
- ZhiYu Zhao
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Wei Liu
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Wei Liu, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
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21
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Sun Z, Xiong C, Teh SW, Lim JCW, Kumar S, Thilakavathy K. Mechanisms of Oral Bacterial Virulence Factors in Pancreatic Cancer. Front Cell Infect Microbiol 2019; 9:412. [PMID: 31867287 PMCID: PMC6904357 DOI: 10.3389/fcimb.2019.00412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 11/19/2019] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer is a highly lethal disease, and most patients remain asymptomatic until the disease enters advanced stages. There is lack of knowledge in the pathogenesis, effective prevention and early diagnosis of pancreatic cancer. Recently, bacteria were found in pancreatic tissue that has been considered sterile before. The distribution of flora in pancreatic cancer tissue was reported to be different from normal pancreatic tissue. These abnormally distributed bacteria may be the risk factors for inducing pancreatic cancer. Therefore, studies on combined effect of multi-bacterial and multi-virulence factors may add to the knowledge of pancreatic cancer pathogenesis and aid in designing new preventive and therapeutic strategies. In this review, we outlined three oral bacteria associated with pancreatic cancer and their virulence factors linked with cancer.
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Affiliation(s)
- Zhong Sun
- Department of Biomedical Science, Universiti Putra Malaysia, Serdang, Malaysia
| | - ChengLong Xiong
- Department of Public Health Microbiology, School of Public Health, Fudan University, Shanghai, China
| | - Seoh Wei Teh
- Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia
| | - Jonathan Chee Woei Lim
- Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Suresh Kumar
- Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia.,Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang, Malaysia.,UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia
| | - Karuppiah Thilakavathy
- Department of Biomedical Science, Universiti Putra Malaysia, Serdang, Malaysia.,Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang, Malaysia
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22
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The microbiota and microbiome in pancreatic cancer: more influential than expected. Mol Cancer 2019; 18:97. [PMID: 31109338 PMCID: PMC6526613 DOI: 10.1186/s12943-019-1008-0] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.
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Abstract
Chronic pancreatitis is a chronic inflammatory disease of the pancreas characterised by irreversible morphological change and typically causing pain and/or permanent loss of function. This progressive, irreversible disease results in destruction of healthy pancreatic tissue and the development of fibrous scar tissue. Gradual loss of exocrine and endocrine function follows, along with clinical manifestations such as steatorrhoea, abdominal pain and diabetes. Nutrition in chronic pancreatitis has been described as a problem area and, until recently, there was little research on the topic. It is often asserted that >90 % of the pancreas must be damaged before exocrine insufficiency occurs; however, an exploration of the original studies from the 1970s found that the data do not support this assertion. The management of steatorrhoea with pancreatic enzyme replacement therapy is the mainstay of nutritional management, and early identification and treatment is a key. The presence of steatorrhoea, coupled with poor dietary intake (due to intractable abdominal pain, gastrointestinal side effects and often alcoholism) renders the chronic pancreatitis patients at considerable risk for undernutrition, muscle depletion and fat-soluble vitamin deficiency. Premature osteoporosis/osteopenia afflicts two-thirds of patients as a consequence of poor dietary intake of calcium and vitamin D, low physical activity, low sunlight exposure, heavy smoking, as well as chronic low-grade inflammation. Bone metabolism studies show increased bone formation as well as bone resorption in chronic pancreatitis, indicating that bone turnover is abnormally high. Loss of the pancreatic islet cells occurs later in the disease process as the endocrine cells are diffusely distributed throughout the pancreatic parenchyma. Patients may develop type 3c (pancreatogenic) diabetes, which is complicated by concurrent decreased glucagon secretion, and hence an increased risk of hypoglycaemia. Diabetes control is further complicated by poor diet, malabsorption and (for some) alcoholism, and therefore those with type 3c diabetes have clinical characteristics and therapeutic goals that are different from that of type 1 and type 2 diabetes patients. This review describes emerging research and clinical guidelines for nutrition in chronic pancreatitis.
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24
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Culver EL, Smit WL, Evans C, Sadler R, Cargill T, Makuch M, Wang LM, Ferry B, Klenerman P, Barnes E. No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort. Pancreatology 2017; 17:395-402. [PMID: 28412148 PMCID: PMC5459459 DOI: 10.1016/j.pan.2017.04.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/02/2017] [Accepted: 04/04/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Helicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP. RESULTS 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1-4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.
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Affiliation(s)
- Emma L Culver
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
| | - Wouter L Smit
- Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Caroline Evans
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Ross Sadler
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Tamsin Cargill
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Mateusz Makuch
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK
| | - Lai-Mun Wang
- Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK
| | - Berne Ferry
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Paul Klenerman
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Eleanor Barnes
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
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Sarnecka AK, Zagozda M, Durlik M. An Overview of Genetic Changes and Risk of Pancreatic Ductal Adenocarcinoma. J Cancer 2016; 7:2045-2051. [PMID: 27877219 PMCID: PMC5118667 DOI: 10.7150/jca.15323] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 06/02/2016] [Indexed: 12/17/2022] Open
Abstract
The pancreatic carcinoma is a leading cause of death in cancer carriers worldwide. The early diagnostic is difficult due to late stage during diagnosis, lack of characteristic symptoms and also multifactor basis. In cancer development take part both, environmental and genetic factors, alone or in conjunction with each other. The nonspecific biomarkers of cancers are a reason for the search for more accurate factors which allow for fast and personalized diagnostics. Some of cancers have identified molecular (metabolic, biochemical or genetic) markers but in most cases the only clue is patient`s interview and abnormal levels of organ functions markers. Possible genetic basis of cancer suggests to widen studies on connection between environmental factors with both, nuclear and mitochondrial, genes changes.
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Affiliation(s)
- Agnieszka K Sarnecka
- Department of Surgical Research & Transplantology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.; Central Clinical Hospital, Ministry of Internal Affairs, Warsaw, Poland
| | - Malgorzata Zagozda
- Department of Surgical Research & Transplantology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.; Central Clinical Hospital, Ministry of Internal Affairs, Warsaw, Poland
| | - Marek Durlik
- Department of Surgical Research & Transplantology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.; Central Clinical Hospital, Ministry of Internal Affairs, Warsaw, Poland
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26
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Shi ZD. Recent advances in research of immunoglobulin G4-related autoimmune pancreatits. Shijie Huaren Xiaohua Zazhi 2016; 24:3946-3952. [DOI: 10.11569/wcjd.v24.i28.3946] [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
Autoimmune pancreatitis (AIP) is a rare type of chronic pancreatitis that belongs to the spectrum of immunoglobulin G4 (IgG4) related diseases. AIP is characterized by lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells. Patients with AIP present clinically with recurrent pancreatitis and obstructive jaundice, symptoms involving bile ducts and salivary glands and so on. Serum IgG4 level is often elevated. The main imaging manifestation of AIP is a "sausage-shaped pancreas" and multiple strictures of the main pancreatic duct. AIP responds sensitively to glucocorticosteroids but relapses easily. In relapsed cases, re-administration of glucocorticosteroids alone or in combination with immune modulators is effective.
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Abstract
IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers. Novel assays - such as the serum IgG4:IgG1 ratio and IgG4:IgG RNA ratio (which distinguish IgG4-SC from PSC with high serum IgG4 levels), and plasmablast expansion to recognize IgG4-SC with normal serum IgG4 levels - require further validation. Steroids and other immunosuppressive therapies can lead to clinical and radiological improvement when given in the inflammatory phase of the disease, but evidence for the efficacy of treatment regimens is limited. Progressive fibrosclerotic disease, liver cirrhosis and an increased risk of malignancy are now recognized outcomes. Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system.
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28
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Baysal B, İnce AT, Gültepe B, Gücin Z, Malya FÜ, Tozlu M, Şentürk H, Bağcı P, Çelikel ÇA, Aker F, Özkara S, Paşaoğlu E, Dursun N, Özgüven BY, Tunçel D. Helicobacter pylori is undetectable in intraductal papillary mucinous neoplasm. Pancreatology 2016; 16:865-8. [PMID: 27320723 DOI: 10.1016/j.pan.2016.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 06/08/2016] [Accepted: 06/09/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND About half of the world population is infected with Helicobacter pylori (H. pylori), a bacterium associated with gastric cancer and considered to be a risk factor for pancreatic ductal adenocarcinoma. Whether the bacterium is associated with intraductal papillary mucinous neoplasm, believed to be a precursor of pancreatic ductal adenocarcinoma, is unknown. The aim of this study was to investigate the presence of H. pylori DNA in tissue sections of intraductal papillary mucinous neoplasm. METHODS The presence of H. pylori DNA was tested in a retrospective controlled study of formalin-fixed, paraffin-embedded pancreatic tissues from 24 patients who underwent surgery for intraductal papillary mucinous neoplasm. Histologically normal tissues surrounding neoplasms were used as control. H. pylori DNA was evaluated after deparaffinization, DNA extraction, and purification, and results were evaluated statistically. RESULTS Samples were collected from 13 males and 11 females with mean age 59 years (range 44-77), and consisted of 19 cases of main-duct and three cases of branched-duct intraductal papillary mucinous neoplasm. Two patients were diagnosed with pancreatic cancer and main-duct intraductal papillary mucinous neoplasm. H. pylori DNA was not detected either in intraductal papillary mucinous neoplasm tissue, or in surrounding normal tissue. CONCLUSIONS Although H. pylori has been implicated in pancreatic ductal adenocarcinoma, it may not play a key role in the development of intraductal papillary mucinous neoplasm.
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Affiliation(s)
- Birol Baysal
- Gastroenterology Department, Bezmialem Vakıf University, Istanbul, Turkey
| | - Ali Tüzün İnce
- Gastroenterology Department, Bezmialem Vakıf University, Istanbul, Turkey.
| | - Bilge Gültepe
- Microbiology Division, Bezmialem Vakıf University, Istanbul, Turkey
| | - Zuhal Gücin
- Pathology Division, Bezmialem Vakıf University, Istanbul, Turkey
| | - Fatma Ümit Malya
- Surgery Department, Bezmialem Vakıf University, Istanbul, Turkey
| | - Mukaddes Tozlu
- Gastroenterology Department, Bezmialem Vakıf University, Istanbul, Turkey
| | - Hakan Şentürk
- Gastroenterology Department, Bezmialem Vakıf University, Istanbul, Turkey
| | - Pelin Bağcı
- Pathology Division, Marmara University, Istanbul, Turkey
| | | | - Fügen Aker
- Pathology Division, Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey
| | - Selvinaz Özkara
- Pathology Division, Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey
| | - Esra Paşaoğlu
- Pathology Division, İstanbul Education and Research Hospital, Istanbul, Turkey
| | - Nevra Dursun
- Pathology Division, İstanbul Education and Research Hospital, Istanbul, Turkey
| | - Banu Yılmaz Özgüven
- Pathology Division, Şişli Etfal Education and Research Hospital, Istanbul, Turkey
| | - Deniz Tunçel
- Pathology Division, Şişli Etfal Education and Research Hospital, Istanbul, Turkey
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Cheng C, Li CP. Influence of Helicobacter pylori infection on extra-gastric diseases. Shijie Huaren Xiaohua Zazhi 2016; 24:2010-2018. [DOI: 10.11569/wcjd.v24.i13.2010] [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
The discovery of Helicobacter pylori (H. pylori) colonization of the stomach and its pathogenic effects is a crucial landmark in modern gastroenterology. There have been many studies reporting that the natural history of many disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma are linked with the presence of this bacterium. Moreover, H. pylori is often involved in the pathogenic processes of a variety of extra-gastric diseases, especially those characterized by persistent and low grade systemic inflammation. The proposed mechanisms ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This paper will review the results of the most important studies on the association of H. pylori infection with extra-gastric diseases, such as autoimmune, neoplastic, cardiovascular and other related disorders, as well as possible mechanisms implicated in the pathogenesis of these extra-gastric diseases.
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Ai F, Hua X, Liu Y, Lin J, Feng Z. Preliminary study of pancreatic cancer associated with Helicobacter pylori infection. Cell Biochem Biophys 2016; 71:397-400. [PMID: 25146335 DOI: 10.1007/s12013-014-0211-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Little is known about the relationship about Helicobacter pylori (H. pylori) infection and pancreatic, and this study was set to investigate how H. pylori infection is correlated with pancreatic cancer and provide references for the clinical prevention and treatment of pancreatic cancer. 56 cases of pancreatic cancer patients admitted to the hospital from August 2012 to August 2013 were collected as the observation group. The anti-Hp IgG (H. pylori-specific antibodies), Hp IgM (H. pylori antibodies), and CagA-Hp-IgG (H. pylori serotoxin-associated protein a antibody) in the serum were measured and compared with the related indicators of control group (60 cases of healthy subjects). The H. pylori infection rate was 64.29% in the observation group, and that in the control group was 46.67%. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P < 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53% in the control group, for which the observation group was significantly higher than the control group (P < 0.05). The occurrence of H. pylori infection in patients with pancreatic cancer was also positively correlated with the smoking history and the history of chronic pancreatitis (P < 0.05). Helicobacter pylori infection is one of the risk factors for pancreatic cancer, and the patients with positive CagA-Hp have the higher risk, so the prevention and treatment of H. pylori infection would be beneficial for the prevention and treatment of pancreatic cancer.
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Affiliation(s)
- Fulu Ai
- Department of Hepato-Biliary-Pancreatic Surgery, Liaoning Cancer Hospital & Institute, 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, China,
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Smit WL, Culver EL, Chapman RW. New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis. Clin Liver Dis 2016; 20:47-65. [PMID: 26593290 DOI: 10.1016/j.cld.2015.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the multisystem IgG4-related disease. IgG4-SC presents with biliary strictures and/or masses that can bear a striking similarity to other malignant and inflammatory diseases. Diagnosis is based on a combination of clinical, biochemical, radiological, and histologic findings with careful exclusion of malignant disease. Corticosteroids are the mainstay of treatment with good clinical, biochemical, and radiological responses. This review provides a comprehensive overview of the current knowledge of the prevalence, clinical features, radiology and histology findings, diagnosis, treatment, natural history, and pathophysiology of IgG4-SC.
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Affiliation(s)
- Wouter L Smit
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Roger W Chapman
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK.
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Bulajic M, Panic N, Löhr JM. Helicobacter pylori and pancreatic diseases. World J Gastrointest Pathophysiol 2014; 5:380-383. [PMID: 25400980 PMCID: PMC4231501 DOI: 10.4291/wjgp.v5.i4.380] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/14/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecular mimicry between H. pyloriα-carbonic anhydrase (α-CA) and human CA type II, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal and acinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pancreatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the genesis of such conditions could have a substantial impact on healthcare.
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Hagymási K, Tulassay Z. Helicobacter pylori infection: New pathogenetic and clinical aspects. World J Gastroenterol 2014; 20:6386-6399. [PMID: 24914360 PMCID: PMC4047324 DOI: 10.3748/wjg.v20.i21.6386] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/02/2013] [Accepted: 02/27/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial.
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Satoh Y, Ogawara H, Kawamura O, Shimoyama Y, Kusano M, Yokohama A, Saitoh T, Handa H, Tsukamoto N, Murakami H. Regulatory T cells percentage in peripheral blood before and after eradication of <i>Helicobacter pylori</i>. Health (London) 2014. [DOI: 10.4236/health.2014.64035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Risch HA, Lu L, Kidd MS, Wang J, Zhang W, Ni Q, Gao YT, Yu H. Helicobacter pylori seropositivities and risk of pancreatic carcinoma. Cancer Epidemiol Biomarkers Prev 2014; 23:172-8. [PMID: 24234587 PMCID: PMC3947155 DOI: 10.1158/1055-9965.epi-13-0447] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pathophysiologic actions of Helicobacter pylori colonization on gastric acidity have been hypothesized to modulate the effect of pancreatic carcinogens, through CagA-negative organism strain type, hyperchlorhydria and increased risk of pancreatic cancer, or CagA-positive strain, hypochlorhydria and decreased risk of pancreatic cancer. We aimed to determine H. pylori strain-specific associations with pancreatic cancer in a population in which colonization by CagA-positive strains is common. METHODS We carried out a large population-based case-control study of pancreatic carcinoma in Shanghai, China. Venipuncture specimens were obtained from a representative sample of 761 case patients and 794 randomly selected control subjects matched by category of age and gender. Antibody seropositivity for H. pylori and its virulence protein CagA were determined by commercial enzyme-linked immunosorbent IgG assays. RESULTS Compared with individuals seronegative for both H. pylori and CagA, decreased pancreas-cancer risk was seen for CagA seropositivity [adjusted OR, 0.68; 95% confidence interval (CI), 0.54-0.84], whereas some increased risk was suggested for CagA-negative H. pylori seropositivity (OR, 1.28; 95% CI, 0.76-2.13). No risk interactions were observed between CagA seropositivity and gender, cigarette smoking, or age-21 body mass index. CONCLUSIONS Similar to what has been seen in animal models, our results provide suggestive evidence in humans for the involvement of gastric acidity, through its bidirectional modification according to colonization by H. pylori CagA strain type, in the risk of pancreatic carcinoma. IMPACT H. pylori colonization may have diverse effects on cancer risk, depending on the organism strain type as well as on the particular cancer site.
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Affiliation(s)
- Harvey A. Risch
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut
| | - Lingeng Lu
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut
| | - Mark S. Kidd
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | - Jing Wang
- Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China
| | - Wei Zhang
- Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China
| | - Quanxing Ni
- Department of Pancreas and Hepatobiliary Surgery, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China
| | - Herbert Yu
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
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Felix K, Hauck O, Fritz S, Hinz U, Schnölzer M, Kempf T, Warnken U, Michel A, Pawlita M, Werner J. Serum protein signatures differentiating autoimmune pancreatitis versus pancreatic cancer. PLoS One 2013; 8:e82755. [PMID: 24349355 PMCID: PMC3857261 DOI: 10.1371/journal.pone.0082755] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Accepted: 11/04/2013] [Indexed: 12/24/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is defined by characteristic lymphoplasmacytic infiltrate, ductal strictures and a pancreatic enlargement or mass that can mimic pancreatic cancer (PaCa). The distinction between this benign disease and pancreatic cancer can be challenging. However, an accurate diagnosis may pre-empt the misdiagnosis of cancer, allowing the appropriate medical treatment of AIP and, consequently, decreasing the number of unnecessary pancreatic resections. Mass spectrometry (MS) and two-dimensional differential gel electrophoresis (2D-DIGE) have been applied to analyse serum protein alterations associated with AIP and PaCa, and to identify protein signatures indicative of the diseases. Patients' sera were immunodepleted from the 20 most prominent serum proteins prior to further 2D-DIGE and image analysis. The identity of the most-discriminatory proteins detected, was performed by MS and ELISAs were applied to confirm their expression. Serum profiling data analysis with 2D-DIGE revealed 39 protein peaks able to discriminate between AIP and PaCa. Proteins were purified and further analysed by MALDI-TOF-MS. Peptide mass fingerprinting led to identification of eleven proteins. Among them apolipoprotein A-I, apolipoprotein A-II, transthyretin, and tetranectin were identified and found as 3.0-, 3.5-, 2-, and 1.6-fold decreased in PaCa sera, respectively, whereas haptoglobin and apolipoprotein E were found to be 3.8- and 1.6-fold elevated in PaCa sera. With the exception of haptoglobin the ELISA results of the identified proteins confirmed the 2D-DIGE image analysis characteristics. Integration of the identified serum proteins as AIP markers may have considerable potential to provide additional information for the diagnosis of AIP to choose the appropriate treatment.
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Affiliation(s)
- Klaus Felix
- Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany
- * E-mail: (KF)
| | - Oliver Hauck
- Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany
| | - Stefan Fritz
- Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany
| | - Ulf Hinz
- Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany
| | - Martina Schnölzer
- Functional Proteome Analysis, German Cancer Research Center (DKFZ), INF 580, Heidelberg, Germany
| | - Tore Kempf
- Functional Proteome Analysis, German Cancer Research Center (DKFZ), INF 580, Heidelberg, Germany
| | - Uwe Warnken
- Functional Proteome Analysis, German Cancer Research Center (DKFZ), INF 580, Heidelberg, Germany
| | - Angelika Michel
- Infection and Cancer Program, German Cancer Research Center (DKFZ), INF 260, Heidelberg, Germany
| | - Michael Pawlita
- Infection and Cancer Program, German Cancer Research Center (DKFZ), INF 260, Heidelberg, Germany
| | - Jens Werner
- Department of General Surgery, University of Heidelberg, INF 110, Heidelberg, Germany
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Huang YQ. Current status of research on autoimmune pancreatitis. Shijie Huaren Xiaohua Zazhi 2013; 21:3505-3513. [DOI: 10.11569/wcjd.v21.i32.3505] [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
Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterized clinically by frequent presentation with obstructive jaundice, histologically by lymphoplasmacytic infiltration with fibrosis, and therapeutically by a dramatic response to steroids. AIP have recently been classified into two subtypes, lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct centric pancreatitis (IDCP). The pathogenesis of AIP may involve genetic susceptibility, autoantibodies, molecular mimicry, imbalance of T-cell-mediated immune regulation, and gene mutation. In this article, we will systematically review typical and atypical clinical, imaging and histopathological features of AIP, with an emphasis placed on the advances in the diagnosis and treatment of this disease.
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Deng B, Li Y, Zhang Y, Bai L, Yang P. Helicobacter pylori infection and lung cancer: a review of an emerging hypothesis. Carcinogenesis 2013; 34:1189-95. [PMID: 23568955 DOI: 10.1093/carcin/bgt114] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (Hp) is one of the most common bacteria infecting humans. Recently, certain extragastric manifestations, linked to Hp infection, have been widely investigated, suggesting that Hp infection might be a 'systemic' disease. Accumulating, yet limited, evidence points to a potential association between Hp infection and lung cancer risk. Epidemiologic studies have shown that odds ratios (estimated relative risks) of lung cancer with Hp infection range from 1.24 to 17.78 compared with the controls, suggesting an increased lung cancer risk in the population exposed to Hp infection although far from supporting a causal relationship between Hp and lung cancer. Many studies have demonstrated the existence of Hp in the mucosa of the upper respiratory tract with no direct evidence of Hp-localization in lung tissue in the published literatures, rendering the possible functional mechanism underlying the association an open question. We followed the classic hypothesis-generating path, where we have thoroughly reviewed the publications on lung cancer and Hp infection from serological association to possible mechanisms as: (i) p130cas activated by Src kinase following Hp-host communication and p130cas-related carcinogenesis as in various malignancies; and (ii) gastroesophageal reflux and inhalation of urease or gastrin, which are Hp-related carcinogenic factors and present in lung tissues. We propose rigorous investigations regarding the Hp-lung cancer association and, if confirmed, the mechanisms of Hp infection leading to lung cancer development and progression. Clarification on Hp-lung cancer association is important for the understanding of lung cancer beyond tobacco-smoking-related carcinogenesis.
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Affiliation(s)
- Bo Deng
- Department of Health Sciences Research, Mayo Clinic, College of Medicine, Rochester, MN 55905, USA
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PCR-Based Detection and Genotyping of Helicobacter pylori in Endoscopic Biopsy Samples from Brazilian Patients. Gastroenterol Res Pract 2013; 2013:951034. [PMID: 23401678 PMCID: PMC3562691 DOI: 10.1155/2013/951034] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Revised: 12/16/2012] [Accepted: 12/23/2012] [Indexed: 12/16/2022] Open
Abstract
Helicobacter pylori (H. pylori) is considered the second most prevalent infection in man. A precise diagnosis is important for treating patients with the indicative gastrointestinal symptoms. The present study analyzes the effectiveness of a molecular biology method (PCR) comparing the results obtained with the histology and with the rapid urease tests. PCR was used in the detection and genotyping of the H. pylori urease-C gene and the patterns which were obtained from the patients studied. 141 biopsy samples from 131 patients were evaluated. 59 paraffin biopsies samples were positive for H. pylori according to the histological examination. Of those, 59/12 (20.3%) were amplified using PCR. Of the 82 samples from the fresh biopsies, 64 were positive for H. pylori according to the rapid urease test (78%); there was an agreement of 100% with PCR. Sixty positive H. pylori samples were genotyped (58 samples of fresh biopsies and 2 samples of paraffin biopsies) using two restriction enzymes. The patterns observed were analyzed with the computational program BIO 1D; 11 patterns with the enzyme HhaI and 12 patterns with the enzyme MboI were found. However, it was not possible to find a statistically significant correlation between the specific genotypes and digestive pathologies. Accordingly, future research should be performed to confirm a statistically significant relationship between genotyping and gastrointestinal symptoms.
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Fan Y, Zhang W, Shi CY, Cai DF. Associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk: evidence from a meta-analysis. Tumour Biol 2012. [PMID: 23184765 DOI: 10.1007/s13277-012-0598-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Glutathione S-transferases (GSTs), including glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), are multifunctional enzymes which play vital roles in the detoxification of a variety of carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 have been implicated in pancreatic cancer risk, but the results of published studies remain conflicting. Thus, a meta-analysis was conducted to estimate the effect of GSTM1 and GSTT1 polymorphisms on the risk of developing pancreatic cancer. A comprehensive search was performed in the PubMed, Embase, Web of Science, and Wanfang databases to identify the available studies on the associations of GSTM1 and GSTT1 polymorphisms with pancreatic cancer risk. The pooled odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) was used to estimate the associations. Stratified analyses by ethnicity and sensitivity analyses were performed to further identify the relationships. Overall, the null genotype of GSTT1 was associated with an increased risk of pancreatic cancer (OR = 1.61, 95 % CI 1.06-2.44, P OR = 0.025), but similar association was not found between the null genotype of GSTM1 and pancreatic cancer risk. Besides, a significant association of GSTT1 polymorphism with pancreatic cancer risk was identified in Asians (OR = 2.58, 95 % CI 1.67-3.98, P OR < 0.001), but not in Caucasians (OR = 1.16, 95 % CI 0.94-1.43, P OR = 0.170). Sensitivity analyses by sequential omission of individual study confirmed the stability of our results. Meta-analysis of available data thus far shows that the null genotype of GSTT1 is a risk factor for pancreatic cancer, particularly in the Asian population. The currently available data are not sufficient enough to identify the association between the GSTM1 polymorphism and pancreatic cancer risk.
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Affiliation(s)
- Yue Fan
- Department of Integrated TCM & Western Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road Fenglin Street, Shanghai, 200032, China
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Clinical Significance of Peripheral Blood T Lymphocyte Subsets in Helicobacter pylori-Infected Patients. Gastroenterol Res Pract 2012; 2012:819842. [PMID: 22536220 PMCID: PMC3320021 DOI: 10.1155/2012/819842] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2011] [Revised: 12/17/2011] [Accepted: 12/22/2011] [Indexed: 02/07/2023] Open
Abstract
Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4+ T cell, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio.
Results. The percentage of CD8+ T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05). The percentage of CD4+CD25+ T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.
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Bulajic M, Panic N, Stimec B, Isaksson B, Jesenofsky R, Schneider-Brachert W, Löhr JM. PCR in Helicobacter spp. diagnostic in extragastric malignancies of digestive system. Eur J Gastroenterol Hepatol 2012; 24:117-25. [PMID: 22081011 DOI: 10.1097/meg.0b013e32834dfde1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recognition of Helicobacter pylori as an important factor in genesis of gastric adenocarcinoma lead to a large number of studies concerning potential role of Helicobacter spp. in the development of extragastric digestive malignancies. The serological studies indicated possible localizations in the digestive system being from interest in enlightening Helicobacter spp. carcinogenic potential. The PCR obtruded itself as a gold standard in proving existence of actual correlation. In this review, the authors have examined studies conducted in the last 10 years examining Helicobacter spp. correlation with extragastric digestive carcinogenesis. Studies have been observed in four groups referring to hepatic carcinoma, bile duct cancer, pancreatic cancer, and colon cancer. The results of these researches have shown that there is a strong correlation between Helicobacter spp. colonization and primary liver tumors as well as bile duct tumors, whereas conclusions made by authors examining pancreatic cancer are contradictory and demands further investigation. No correlation between Helicobacter spp. and colon cancer have been proven. The PCR subtype most widely used in studies included in this review was nested PCR, whereas genes targeted most frequently for amplification are 16S rDNA of Helicobacter spp. and UreA gene or cagA gene of H. pylori. During the last 10 years PCR has proven itself as a sovereign method for Helicobacter spp. diagnostic in extragastric organs in the digestive system. Knowledge and experiences obtained in this domain could be encouraging for researchers in analogous fields of interest.
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Affiliation(s)
- Milutin Bulajic
- Medical Faculty of Belgrade, University Clinic Dr D. Misovic-Dedinje, Belgrade, Serbia
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Zhou D, Zhang Y, Gong W, Mohamed SO, Ogbomo H, Wang X, Liu Y, Quan Z. Are Helicobacter pylori and other Helicobacter species infection associated with human biliary lithiasis? A meta-analysis. PLoS One 2011; 6:e27390. [PMID: 22087306 PMCID: PMC3210793 DOI: 10.1371/journal.pone.0027390] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 10/16/2011] [Indexed: 02/06/2023] Open
Abstract
Background Since the isolation of Helicobacter species in biliary system, a hypothetical question was raised about the role of these agents in the development of cholelithiasis. This meta-analysis is to explore the association between the Helicobacter infection and biliary lithiasis. Methodology/Principal Findings A systematic literature search was performed to identify all eligible articles. Meta-analysis which was carried out using odds ratio and random effect model, 95% confidence intervals for odds ratio was calculated. Quantitative assessment of heterogeneity was explored by chi-square test with significance set at P value 0.10 and was measured using I2 statistic. Eighteen studies published between 1998 and 2011 were finally eligible for meta-analysis. H. Pylori, H. Bilis, H. Hepaticus, H. Pullorum and H. Ganmani were studied. With heterogeneity (I2 = 69.5%, P<0.0001), significantly higher pooled infection rates of H. Pylori (OR: 2.59, 35.82% versus 26.75%, P = 0.01) and H. Hepaticus (OR: 3.13, 31.30% versus 12.12%, P = 0.02) were observed in lithiasis group. Higher prevalence of H. Pylori in cholelithiasis patients were reported by studies from East Asia, South Asia and South America. Evidences supporting the higher presence of H. Pylori in cholelithiasis patients could be found by PCR for detecting 16s rRNA in bile, 26kDa protein gene in biliary tissue and immunohistochemistry. Using multiple detection tests could increase the detection rate of H. Pylori. Conclusions/Significances Our meta-analysis suggests a trend of higher presence of H. Pylori in cholelithiasis patients than control group and this trend was significant in the regions with higher prevalence of this agent. Evidences supporting the association between Helicobacter and cholelithiasis could be found by using different tests but the gold standard for the identification of these bacteria in biliary system has yet to be established. Considering obvious heterogeneity, a large multi-center study will facilitate us to further clarify the association between the Helicobacter infection and cholelithiasis.
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Affiliation(s)
- Di Zhou
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
| | - Yong Zhang
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
| | - Wei Gong
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
| | - Sayid Omar Mohamed
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
| | - Henry Ogbomo
- Departments of Oncology, Biochemistry and Molecular Biology, Faculty of Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Xuefeng Wang
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
| | - Yingbin Liu
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
- * E-mail: (ZWQ); (YBL)
| | - Zhiwei Quan
- Department of General Surgery, School of Medicine, Xinhua Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China
- * E-mail: (ZWQ); (YBL)
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Suzuki H, Franceschi F, Nishizawa T, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter 2011; 16 Suppl 1:65-9. [PMID: 21896088 DOI: 10.1111/j.1523-5378.2011.00883.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the previous year, some extragastric diseases, possibly linked to Helicobacter pylori infection, have been largely investigated. There are, in fact, several studies concerning cardiovascular diseases, lung diseases, hematologic diseases, eye and skin diseases, hepatobiliary diseases, diabetes mellitus, and neurological disorders. Among them, the relationship between bacterial CagA positivity and coronary heart disease is reportedly emphasized. Concerning normal tension glaucoma, new interesting data are playing in favor of the association with H. pylori infection. For other diseases, there are many interesting results, although more studies are needed to clarify the reality of the proposed association.
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Affiliation(s)
- Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
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Campuzano-Maya G. Cure of alopecia areata after eradication of Helicobacter pylori: a new association? World J Gastroenterol 2011; 17:3165-70. [PMID: 21912461 PMCID: PMC3158418 DOI: 10.3748/wjg.v17.i26.3165] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Revised: 03/05/2011] [Accepted: 03/12/2011] [Indexed: 02/06/2023] Open
Abstract
Alopecia areata is a disease of the hair follicles, with strong evidence supporting autoimmune etiology. Alopecia areata is frequently associated with immune-mediated diseases with skin manifestations such as psoriasis and lichen planus, or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura. Helicobacter pylori (H. pylori) infection is present in around 50% of the world's population and has been associated with a variety of immune-mediated extra-digestive disorders including autoimmune thyroiditis, idiopathic thrombocytopenic purpura, and psoriasis. A case of a 43-year old man with an 8-mo history of alopecia areata of the scalp and beard is presented. The patient was being treated by a dermatologist and had psychiatric support, without any improvement. He had a history of dyspepsia and the urea breath test confirmed H. pylori infection. The patient went into remission from alopecia areata after H. pylori eradication. If such an association is confirmed by epidemiological studies designed for this purpose, new therapeutic options could be available for these patients, especially in areas where infection with H. pylori is highly prevalent.
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Normalización de enzimas pancreáticas tras erradicación de Helicobacter pylori en un paciente de 7 años. An Pediatr (Barc) 2011; 75:77-8. [DOI: 10.1016/j.anpedi.2011.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 02/16/2011] [Accepted: 02/17/2011] [Indexed: 11/19/2022] Open
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