Disease spectrum of intraductal papillary mucinous neoplasm with an associated invasive carcinoma: Invasive IPMN versus pancreas ductal adenocarcinoma-associated IPMN

204 Background: Previous studies have analyzed that inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI), associated with the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN). This study aimed to evaluate the correlation between the inflammatory markers and the invasive carcinoma in IPMN and propose a nomogram including inflammatory markers for predicting invasive IPMN. Methods: From 1995 to 2016, total 468 patients who underwent surgical resection at four institutions for histologically confirmed IPMN and the data were reviewed retrospectively. The patients with history of pancreatitis, other malignancies and without CA19-9 data or lymphocyte counts were excluded, the study cohort consisted of 365 patients. Variables with P < 0.05 in risk factor analysis were included in the nomogram. Results: Of 365 patients, 98 (26.8%) patients had invasive IPMN. In univariate analysis, high body mass index (BMI) ( P = 0.037), pre-operative bilirubin level ( P = 0.001), CA19-9 ( P < 0.001), NLR ( P = 0.019), PLR ( P = 0.002), ALI ( P = 0.001), main duct type (P < 0.001), the presence of solid portion ( P < 0.001) and tumor size (P = 0.086) were identified as risk factors for invasive IPMN. In multivariate analysis, pre-operative bilirubin level (P = 0.003), CA19-9 (P = 0.002), main duct type (P = 0.034) and the presence of solid portion (P < 0.001) were independent predictive markers for invasive IPMN. The nomogram was developed including all factors of risk factor analysis. Conclusions: The inflammatory markers were the risk factors for the presence of IPMN-associated invasive carcinoma. This nomogram may be useful in identifying patients with IPMN at risk of malignancy and for selecting which patients should undergo surgery. Further validation studies are needed to assess the predictive ability of nomogram including inflammatory markers.

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Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement

ULTRASONOGRAPHY ◽

10.14366/usg.16039 ◽

2017 ◽

Vol 36 (3) ◽

pp. 260-269

Author(s):

Masato Saito ◽

Naoki Hirokawa ◽

Yoko Usami ◽

Masanori Someya ◽

Koh-ichi Sakata

Keyword(s):

Differential Diagnosis ◽

Pancreatic Ductal Adenocarcinoma ◽

Contrast Enhancement ◽

Intraductal Papillary Mucinous Neoplasm ◽

Invasive Carcinoma ◽

Ductal Adenocarcinoma ◽

Echo Intensity ◽

Mucinous Neoplasm

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Intraductal Papillary Mucinous Neoplasm of the Pancreas: An Update

Scientifica ◽

10.6064/2012/893632 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 5

Author(s):

Shu-Yuan Xiao

Keyword(s):

Intraductal Papillary Mucinous Neoplasm ◽

Invasive Carcinoma ◽

Ductal Adenocarcinoma ◽

Cystic Tumor ◽

Main Duct ◽

Branch Duct ◽

Mucinous Neoplasm ◽

Invasive Component ◽

Small Branch ◽

Asymptomatic Patients

Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas. The etiology is unknown, but increasing evidence suggests the involvement of several tumorigenesis pathways, including an association with hereditary syndromes. IPMN occurs more commonly in men, with the mean age at diagnosis between 64 and 67 years old. At the time of diagnosis, it may be benign, with or without dysplasia, or frankly malignant with an invasive carcinoma. Tumors arising from the main pancreatic duct are termed main-duct IPMNs, those involving the branch ducts, branch-duct IPMNs. In general, small branch-duct IPMNs are benign, particularly in asymptomatic patients, and can be safely followed. In contrast, main-duct tumors should be surgically resected and examined carefully for an invasive component. In the absence of invasion, patient’s survival is excellent, from 94 to 100%. For patients with an IPMN-associated invasive carcinoma, the prognosis overall is better than those with ade novopancreatic ductal adenocarcinoma, with a 5-year survival of 40% to 60% in some series. However, no survival advantage can be demonstrated if the invasive component in an IPMN patient is that of the conventional tubular type (versus mucinous carcinoma). Several histomorphologic variants are recognized, although the clinical significance of this “subtyping” is not well defined.

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MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

International Journal of Molecular Sciences ◽

10.3390/ijms22063221 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3221

Author(s):

Natsuhiko Kuratomi ◽

Shinichi Takano ◽

Mitsuharu Fukasawa ◽

Shinya Maekawa ◽

Makoto Kadokura ◽

...

Keyword(s):

Pancreatic Juice ◽

Intraductal Papillary Mucinous Neoplasm ◽

Invasive Carcinoma ◽

Sequence Data ◽

Mirna Sequence ◽

Tissue Analysis ◽

Mucinous Neoplasm ◽

Paired Samples ◽

Mirna Sequencing ◽

Invasive Ipmn

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.

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Clinical-relevant model of intraductal papillary mucinous neoplasm induced by ARID1A loss.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14696 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14696-e14696

Author(s):

Tao Wei ◽

Qi Chen ◽

Tingbo Liang ◽

Xueli Bai

Keyword(s):

Intraductal Papillary Mucinous Neoplasm ◽

Invasive Carcinoma ◽

Pancreatic Neoplasm ◽

Significant Proportion ◽

Ductal Adenocarcinoma ◽

Cystic Tumor ◽

Mouse Strains ◽

Cystic Neoplasm ◽

Low Grade ◽

Mucinous Neoplasm

e14696 Background: Intraductal papillary mucinous neoplasm (IPMN) constitutes a precursor lesion for malignancy of pancreas. Genes encoding subunits of SWI/SNF chromatin-remodeling complexes like ARID1A are collectively mutated in a significant proportion of patients with pancreatic neoplasm. In the present study, we characterize the role of ARID1A in pancreatic tumorigenesis using genetic engineering mouse models. Methods: Various mouse strains were interbred to obtain pancreas-specific Arid1aflox, KrasLSL-G12D/+; Arid1aflox, KrasLSL-G12D/+; Tgfbr2flox; Arid1aflox, and various littermate control animals. Tissue microarrays were used to determine the expression of ARID1A in human pancreatic ductal adenocarcinoma and IPMN. Results: Arid1a loss in pancreas of mice incurred pancreatic duct dilation and development of cystic lesions. Concomitant Kras mutation and Arid1a inactivation accelerated formation of cystic neoplasm resembling human IPMN. These lesions were reminiscent of specific subtype of IPMN given their morphology and expression pattern of mucin proteins. Histological examination further revealed the step-wise progression of these neoplasm from low-grade to high-grade dysplasia and even invasive carcinoma. TGFBR2 deletion promoted the malignant transformation of IPMN to invasive carcinoma in the background of Kras and Arid1a alterations. Analysis of human tissues consistently showed negative or low expression of ARID1A in over half of IPMN patients. Moreover, patients with pancreatic adenocarcinoma also exhibited downregulated ARID1A expression, and reduced expression correlated with worse prognosis. Conclusions: We have established a preclinical mouse model of pancreatic cystic tumor closely resembling human IPMN. This is helpful for the further understanding of biology of IPMN and highlight therapeutic niches for patient tailored treatment in those with altered SWI/SNF function.

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