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Mirchev MB, Boeva I, Peshevska-Sekulovska M, Stoitsov V, Peruhova M. Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms. World J Clin Cases 2023; 11:3408-3417. [PMID: 37383909 PMCID: PMC10294181 DOI: 10.12998/wjcc.v11.i15.3408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/26/2023] [Accepted: 04/17/2023] [Indexed: 05/25/2023] Open
Abstract
High rates of extrapancreatic malignancies, in particular colorectal cancer (CRC), have been detected in patients with intraductal papillary mucinous neoplasm (IPMN). So far, there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with IPMN. In the past few years, some data related to common genetic alterations in IPMN and other affiliated cancers have been published. This review elucidated the association between IPMN and CRC, shedding light on the most relevant genetic alterations that may explain the possible relationship between these entities. In keeping with our findings, we suggested that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken. Presently, there are no specific guidelines regarding colorectal screening programs for patients with IPMN. We recommend that patients with IPMNs are at high-risk for CRC, and a more rigorous colorectal surveillance program should be implemented.
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Affiliation(s)
| | - Irina Boeva
- Department of Gastroenterology, Heart and Brain Hospital, Burgas 8000, Bulgaria
| | | | - Veselin Stoitsov
- Department of Gastroenterology, Heart and Brain Hospital, Burgas 8000, Bulgaria
| | - Milena Peruhova
- Department of Gastroenterology, Heart and Brain Hospital, Burgas 8000, Bulgaria
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Ardeshna DR, Rangwani S, Cao T, Pawlik TM, Stanich PP, Krishna SG. Intraductal Papillary Mucinous Neoplasms in Hereditary Cancer Syndromes. Biomedicines 2022; 10:1475. [PMID: 35884779 PMCID: PMC9313108 DOI: 10.3390/biomedicines10071475] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 11/16/2022] Open
Abstract
Hereditary pancreatic cancer, which includes patients with familial pancreatic cancer (FPC) and hereditary pancreatic cancer syndromes, accounts for about 10% of all pancreatic cancer diagnoses. The early detection of pre-cancerous pancreatic cysts has increasingly become a focus of interest in recent years as a potential avenue to lower pancreatic cancer incidence and mortality. Intraductal papillary mucinous cystic neoplasms (IPMNs) are recognized precursor lesions of pancreatic cancer. IPMNs have high prevalence in patients with hereditary pancreatic cancer and their relatives. While various somatic mutations have been identified in IPMNs, certain germline mutations associated with hereditary cancer syndromes have also been identified in IPMNs, suggesting a role in their formation. While the significance for the higher prevalence of IPMNs or similar germline mutations in these high-risk patients remain unclear, IPMNs do represent pre-malignant lesions that need close surveillance. This review summarizes the available literature on the incidence and prevalence of IPMNs in inherited genetic predisposition syndromes and FPC and speculates if IPMN and pancreatic cancer surveillance in these high-risk individuals needs to change.
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Affiliation(s)
- Devarshi R. Ardeshna
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (D.R.A.); (S.R.)
| | - Shiva Rangwani
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (D.R.A.); (S.R.)
| | - Troy Cao
- College of Medicine, Ohio State University, Columbus, OH 43210, USA;
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Peter P. Stanich
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
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Pseudomyxoma Peritonei After a Total Pancreatectomy for Intraductal Papillary Mucinous Neoplasm With Colloid Carcinoma in Lynch Syndrome. Pancreas 2019; 48:135-138. [PMID: 30531244 DOI: 10.1097/mpa.0000000000001201] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
We report a case of pseudomyxoma peritonei (PMP) arising in a 62-year-old male patient with Lynch syndrome (LS). The patient's medical history included an adenocarcinoma of the colon for which a right hemicolectomy was performed and a pancreatectomy due to an intraductal papillary mucinous neoplasm (IPMN) with invasive colloid carcinoma. It was considered that the PMP could be a metastasis of the earlier colonic or pancreatic carcinoma. The pancreatic carcinoma, colon carcinoma, and PMP tissues were examined, and immunohistochemical and molecular analyses were performed to determine the PMP origin. Histopathologic examination revealed morphological similarities with the pancreatic colloid carcinoma, and further immunohistochemical and molecular analyses, including a shared GNAS mutation, confirmed the pancreatic origin of the PMP. In conclusion, this is a unique case of a patient with LS presenting with PMP originating from an IPMN with invasive colloid carcinoma, several years after pancreatectomy. The present case has important diagnostic implications. The IPMN should be considered as a rare extracolonic manifestation of LS, and pancreatic carcinoma origin should be considered in patients presenting with PMP. This case report highlights the added value of molecular diagnostics in daily pathology practice.
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Lee SH, Kim WY, Hwang DY, Han HS. Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report. World J Gastroenterol 2015; 21:7916-7920. [PMID: 26167093 PMCID: PMC4491980 DOI: 10.3748/wjg.v21.i25.7916] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 03/20/2015] [Accepted: 04/17/2015] [Indexed: 02/06/2023] Open
Abstract
We report a case of intraductal papillary mucinous neoplasm (IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer (HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature.
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MESH Headings
- Adenocarcinoma/genetics
- Adenocarcinoma/pathology
- Adenocarcinoma/surgery
- Biomarkers, Tumor/analysis
- Biopsy
- Choristoma
- Colectomy
- Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
- Colorectal Neoplasms, Hereditary Nonpolyposis/pathology
- Colorectal Neoplasms, Hereditary Nonpolyposis/surgery
- Female
- Genetic Predisposition to Disease
- Heredity
- Humans
- Ileal Neoplasms/chemistry
- Ileal Neoplasms/pathology
- Ileal Neoplasms/surgery
- Immunohistochemistry
- Middle Aged
- Neoplasms, Cystic, Mucinous, and Serous/chemistry
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/surgery
- Pancreas
- Pancreatic Neoplasms
- Phenotype
- Tomography, X-Ray Computed
- Tumor Burden
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Abstract
Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.
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Clinical implications of mismatched repair gene promoter methylation in pancreatic cancer. Med Oncol 2011; 29:970-6. [PMID: 21660619 DOI: 10.1007/s12032-011-9968-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2011] [Accepted: 04/21/2011] [Indexed: 12/25/2022]
Abstract
To investigate the relationship between the hypermethylation statuses of the mismatch repair genes (hMLH1 and hMSH2) promoters and explore the correlation between it and the development of pancreatic cancer and the biological behavior of pancreatic cancer. We selected 90 patients who were diagnosed with pancreatic cancer and underwent radical operations in the First Affiliated Hospital of the Dalian Medical University between January 2002 and June 2008. The methylation status of the hMLH1 and hMSH2 promoters was detected by methylation-specific polymerase chain reaction (MSP). Meanwhile, the expression of hMLH1 and hMSH2 protein was detected by Western blot and immunohistochemistry, and its correlation with biological behavior of pancreatic cancer was explored. Of the 90 cases, hMLH1 promoter methylation was detected in 54 (60.0%) patients, while none of the paracancerous tissues indicated methylation. In the study, the hMLH1-methylated tumors lost hMLH1 protein expression, but the non-hMLH1-methylated tumors were not seen to have a loss of hMLH1 protein expression (P < 0.001). On the other hand, there were four cases of hMSH2 promoter methylation. However, no significant difference was found between hMSH2 promoter methylation and non-hMSH2 promoter methylation cases (P > 0.05). After universal analysis, hMLH1 expression was significantly related to tumor differentiation, lymph node metastasis, and tumor location (P < 0.05) while not related to the age, sex, and tumor size (P > 0.05). Our study suggests that the mismatch repair genes play an important role in pancreatic cancer carcinogenesis and progression through epigenetic modification, and it may be regarded as a potential target for the management of pancreatic cancer.
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Souza LR, Fonseca-Silva T, Pereira CS, Santos EP, Lima LC, Carvalho HA, Gomez RS, Guimarães ALS, De Paula AMB. Immunohistochemical analysis of p53, APE1, hMSH2 and ERCC1 proteins in actinic cheilitis and lip squamous cell carcinoma. Histopathology 2011; 58:352-60. [PMID: 21323960 DOI: 10.1111/j.1365-2559.2011.03756.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
AIMS This study has compared the tissue expression of the p53 tumour suppressor protein and DNA repair proteins APE1, hMSH2 and ERCC1 in normal, dysplastic and malignant lip epithelium. METHODS AND RESULTS Morphological analysis and immunohistochemistry were performed on archived specimens of normal lip mucosa (n=15), actinic cheilitis (AC) (n=30), and lip squamous cell carcinoma (LSCC) (n=27). AC samples were classified morphologically according to the severity of epithelial dysplasia and risk of malignant transformation. LSCC samples were morphologically staged according to WHO and invasive front grading (IFG) criteria. Differences between groups and morphological stages were determined by bivariate statistical analysis. Progressive increases in the percentage of epithelial cells expressing p53 and APE1 were associated with increases in morphological malignancy from normal lip mucosa to LSCC. There was also a significant reduction in epithelial cells expressing hMSH2 and ERCC1 proteins in the AC and LSCC groups. A higher percentage of malignant cells expressing APE1 was found in samples with an aggressive morphological IFG grade. CONCLUSIONS Our data showed that epithelial cells from premalignant to malignant lip disease exhibited changes in the expression of p53, APE1, hMSH2 and ERCC1 proteins; these molecular change might contribute to lip carcinogenesis.
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Affiliation(s)
- Ludmilla R Souza
- Health Science Programme, State University of Montes Claros, Montes Claros, MG, Brazil
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Verbeke CS. Intraductal papillary-mucinous neoplasia of the pancreas: Histopathology and molecular biology. World J Gastrointest Surg 2010; 2:306-13. [PMID: 21160835 PMCID: PMC2999203 DOI: 10.4240/wjgs.v2.i10.306] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2010] [Revised: 09/12/2010] [Accepted: 09/19/2010] [Indexed: 02/07/2023] Open
Abstract
Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer, characterized by gradual progression through a sequence of neoplastic changes. Based on the nature of the constituting neoplastic epithelium, degree of dysplasia and location within the pancreatic duct system, IPMNs are divided in several types which differ in their biological properties and clinical outcome. Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.
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Affiliation(s)
- Caroline S Verbeke
- Caroline S Verbeke, Department of Histopathology, St James's University Hospital, Leeds LS9 7TF, United Kingdom
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Hussein MRA, Aref EEM, Yassen DG, Ramadan MO. Analysis of hMSH2 Mismatch Repair Protein Expression in Dysplasia, CarcinomaIn Situand Invasive Squamous Cell Carcinoma of the Vocal Folds. Cancer Invest 2009; 27:38-46. [DOI: 10.1080/07357900802139951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Intraductal papillary mucinous neoplasm of the pancreas with loss of mismatch repair in a patient with Lynch syndrome. Am J Surg Pathol 2009; 33:309-12. [PMID: 18987546 DOI: 10.1097/pas.0b013e3181882c3d] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precancerous lesion with a well-described progression to carcinoma. This case report describes a 61-year-old woman with a history significant for multiple cancers and a confirmed germline mutation of MSH2, a mismatch repair gene responsible for Lynch syndrome, who was also found to have an IPMN of the pancreas. Phenotypic manifestations of Lynch syndrome in this patient included multiple adenomas and adenocarcinomas of the colon and also several other Lynch syndrome-associated cancers. The patient's adenocarcinoma of the colon and IPMN of the pancreas showed identical immunohistochemical staining profiles with loss of expression of MSH2 and MSH6 proteins and high levels of microsatellite instability. The immunohistochemical staining and microsatellite instability patterns of the adenocarcinoma of the colon and IPMN gives strong evidence to support the consideration of IPMN as part of the spectrum of lesions found in Lynch syndrome.
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Xiao GZ, Liu XS. Expression of DNA mismatch repair gene hMLH1 and its significance in gastric cancer and premalignant lesions. Shijie Huaren Xiaohua Zazhi 2006; 14:2093-2097. [DOI: 10.11569/wcjd.v14.i21.2093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression of DNA mismatch repair gene hMLH1 and its clinical significances in gastric cancer and premalignant lesions.
METHODS: Immunohistochemical technique was used to detect the expression of hMLH1 protein in 20 cases of chronic superficial gastritis, 20 cases of chronic atrophic gastritis complicated with intestinal metaplasia, 8 cases of adenomatous polyp, 58 cases of gastric cancer and the corresponding cancer-adjacent mucosa.
RESULTS: The hMLH1 protein was expressed mostly in epithelial cytoplasm and a little in cell nucleus. The positive rate of hMLH1 expression in chronic superficial gastritis and chronic atrophic gastritis with intestinal metaplasia were all 90%, which were significantly higher (χ2 = 9.741, P = 0.02) than those in adenomatous polyp (62.5%) and the corresponding cancer-adjacent mucosa (62.1%). The positive rate of hMLH1 expression was not significantly different between gastric cancer (72.4%) and the others (P > 0.05). Of 58 cases of cancer-adjacent mucosa, 21 (36.2%) were with chronic superficial gastritis, and 37 (63.8%) with chronic atrophic gastritis and intestinal metaplasia. The positive rates of hMLH1 expression were similar between the 21 and 37 cases, but they were both markedly lower than those in the nonneoplastic mucosa (χ2 = 9.885, P = 0.02).
CONCLUSION: Absence of hMLH1 expression may be one of the early molecular events in the carcinogenesis of gastric cancer. Timely visiting and monitoring chronic gastric patients with absence of hMLH1 protein expression may help to achieve early diagnosis of gastric cancer.
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Zen Y, Sasaki M, Fujii T, Chen TC, Chen MF, Yeh TS, Jan YY, Huang SF, Nimura Y, Nakanuma Y. Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct--an immunohistochemical study of 110 cases of hepatolithiasis. J Hepatol 2006; 44:350-8. [PMID: 16360234 DOI: 10.1016/j.jhep.2005.09.025] [Citation(s) in RCA: 172] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2005] [Revised: 08/29/2005] [Accepted: 09/05/2005] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Two types of neoplastic lesions preceding invasive intrahepatic cholangiocarcinoma (ICC) are identified: a flat-type neoplastic lesion called 'biliary intraepithelial neoplasia (BilIN)' and an intraductal papillary neoplasm of the bile duct (IPN-B). Multi-step carcinogenesis has been suggested in both lesions, although phenotypic changes during this process remain unclarified. METHODS We immunohistochemically examined expression patterns of MUC1, MUC2, MUC5AC, cytokeratin 7 (CK7), and CK20 in BilIN, IPN-B, and ICC in 110 cases of hepatolithiasis. RESULTS Thirty-seven cases of ICC in hepatolithiasis were divided into 18 tubular adenocarcinomas with BilIN, 10 tubular adenocarcinomas with IPN-B and nine colloid carcinomas with IPN-B. Carcinogenesis via BilIN was characterized by MUC2-/CK7+/CK20-with increasing MUC1 expression. IPN-B was characterized by the intestinal phenotype (MUC2+/CK20+), and carcinogenesis leading to tubular adenocarcinoma was associated with increasing MUC1 expression and that to colloid carcinoma with MUC1-negativity. Pathological stages of tubular adenocarcinoma of ICC with BilIN or IPN-B were more advanced than those of colloid carcinoma with IPN-B. CONCLUSIONS Immunophenotypes of MUCs and cytokeratins might characterize three cholangiocarcinogenetic pathways in hepatolithiasis. Increased expression of MUC1 in BilIN and also IPN-B is associated with tubular adenocarcinoma, while colloid carcinoma in IPN-B is characterized by MUC1-negativity and less advanced pathologic stages.
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Affiliation(s)
- Yoh Zen
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
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Goldstein NS, Bosler DS. Immunohistochemistry of the Gastrointestinal Tract, Pancreas, Bile Ducts, Gallbladder and Liver. DIAGNOSTIC IMMUNOHISTOCHEMISTRY 2006:442-508. [DOI: 10.1016/b978-0-443-06652-8.50019-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Garcea G, Dennison AR, Steward WP, Berry DP. Role of inflammation in pancreatic carcinogenesis and the implications for future therapy. Pancreatology 2005; 5:514-29. [PMID: 16110250 DOI: 10.1159/000087493] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The link between inflammation and pancreatic cancer has been observed for a number of gastrointestinal neoplasms. This review examines the role of inflammation in pancreatic carcinogenesis and how it can be utilised to develop new therapies against pancreatic cancer. METHODS A literature review of Pubmed, Medline and Web of Science databases was undertaken using the key words, pancreatic cancer, inflammation, inducible nitric oxide, interleukins, pro-inflammatory cytokines, cyclooxygenase-2, NF-kappa B, reactive oxygen species, DNA adducts, lipoxygenases, chemoprevention. RESULTS Epidemiological evidence and molecular studies both in vitro and in vivo all support the hypothesis that inflammation plays an important in the initiation and progression of pancreatic tumours. CONCLUSION Sustained damage caused by chronic inflammation may precede the onset of frank malignancy by a significant interval. As such, suppression of inflammatory changes and oxidative damage, may help delay or even prevent the inception of pancreatic neoplasia.
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Affiliation(s)
- G Garcea
- Cancer Studies and Molecular Medicine, Robert Kilpatrick Clinical Sciences Building, The Leicester Royal Infirmary, UK.
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