Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients

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Abstract

The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN.

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Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis.

Matthew Rutter, Brian Saunders, Kay Wilkinson … (2004)

Patients with ulcerative colitis are at increased risk of colorectal cancer. It is widely believed that this is secondary to colonic inflammation. However, the severity of colonic inflammation has never been shown to be a risk factor. We devised a case-control study of patients with long-standing extensive ulcerative colitis to examine various potential risk factors for neoplasia. All cases of colorectal neoplasia detected from our surveillance program between January 1, 1988, and January 1, 2002, were studied (n = 68). Each patient was matched with 2 control patients from the same surveillance population (n = 136). Matching was for sex, colitis extent, age at onset, duration of colitis, and year of index surveillance colonoscopy. Segmental colonoscopic and histological inflammation was recorded by using a simple score (0, normal; 1, quiescent/chronic inflammation; and 2, 3, and 4, mild, moderate, and severe active inflammation, respectively). Other data collected included history of primary sclerosing cholangitis, family history of colorectal cancer, and smoking and drug history (mesalamine 5-aminosalicylic acid, azathioprine, and folate). Univariate analysis showed a highly significant correlation between the colonoscopic (odds ratio, 2.5; P = 0.001) and histological (odds ratio, 5.1; P < 0.001) inflammation scores and the risk of colorectal neoplasia. No other factors reached statistical significance. On multivariate analysis, only the histological inflammation score remained significant (odds ratio, 4.7; P < 0.001). In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia. Endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs.

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International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

Marcia Irene Canto, Femme Harinck, Ralph H. Hruban … (2012)

Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed. Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended. Conclusions Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

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Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.

R. Gupta, Sierra Matula, Noam Harpaz … (2007)

Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Sci

Journal ID (iso-abbrev): Cancer Sci

Journal ID (publisher-id): cas

Title: Cancer Science

Publisher: John Wiley & Sons, Ltd (Chichester, UK )

ISSN (Print): 1347-9032

ISSN (Electronic): 1349-7006

Publication date (Print): October 2015

Publication date (Electronic): 04 September 2015

Volume: 106

Issue: 10

Pages: 1408-1413

Affiliations

[1 ]Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital Seongnam, Korea

[2 ]Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital Seongnam, Korea

[3 ]Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center Daegu, Korea

[4 ]Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital Seongnam, Korea

Author notes

Correspondence Jin-Hyeok Hwang, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Korea., Tel: +82-31-787-7017; Fax: +82-31-787-4051;, E-mail: woltoong@ 123456snu.ac.kr

Funding InformationNo sources of funding were declared for this study.

[*]

In Kyeom Hwang and Haeryoung Kim contributed equally to this work as 1st authors.

Article

DOI: 10.1111/cas.12744

PMC ID: 4638021

PubMed ID: 26183380

SO-VID: 0ad67338-b2d9-4630-a4cf-05df42c7a085

License:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

History

Date received : 16 February 2015

Date revision received : 01 July 2015

Date accepted : 12 July 2015

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Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients

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Most cited references 13

Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis.

International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study.

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