International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas

Tanaka, Masao; Chari, Suresh T.; Adsay, Volkan; Castillo, Carlos Fernández‐del; Falconi, Massimo; Shimizu, Michio; Yamaguchi, Koji; Yamao, Kenji; Matsuno, Seiki

doi:10.1159/000090023

Cited by 1,875 publications

(1,848 citation statements)

References 73 publications

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“…The major reason is the absence of factors that clearly predict malignancy. To overcome this issue, consensus conferences in Sendai1 and Fukuoka2 have defined combinations of risk factors that may predict malignancy more sensitively and specifically. A large number of mainly single‐centre analyses based on these criteria have been published, but a recent meta‐analysis3 of data from these publications demonstrated that both overall sensitivity and specificity of the most recent (Fukuoka) criteria were relatively low.…”

Section: Introductionmentioning

confidence: 99%

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas

et al. 2018

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BackgroundEstimation of the risk of malignancy in intraductal papillary mucinous neoplasia (IPMN) of the pancreas is a clinical challenge. Several routinely used clinical factors form the basis of the current consensus guidelines. This study aimed to determine the predictive values of the most commonly assessed risk factors.MethodsA meta‐analysis of individual risk factors of malignancy in IPMN was performed. Contingency tables were derived from these data, and sensitivity, specificity, negative and positive predictive values, and diagnostic odds ratios (DOR) were determined. Hierarchical summary receiver operating characteristic (HSROC) curves for each factor were calculated and the respective area under the curve (AUC) was assessed.ResultsA total of 3443 studies were screened initially. Analysis of recent literature revealed 60 studies with 13 relevant risk factors including clinical, serological and radiological parameters. The largest area under the HSROC curve was found for weight loss (0·84) and jaundice/raised bilirubin level (0·80), followed by increased carcinoembryonic antigen (CEA) (0·79) or carbohydrate antigen (CA) 19‐9 (0·78) levels. The most sensitive factors were patient age (71 per cent) and mural nodules (65 per cent), and jaundice/raised bilirubin level (97 per cent) and increased CEA level (95 per cent) were most specific. None of the analysed factors reached a positive or negative level of prediction beyond 90 per cent.ConclusionNone of the established criteria safely distinguishes malignant from non‐malignant lesions.

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Section: Introductionmentioning

confidence: 99%

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas

et al. 2018

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“…[4][5][6][7] Consequently, international consensus guidelines for the management of IPMNs and MCNs were established and recently updated. 8,9 Therefore, an accurate diagnosis is critical for proper patient management.…”

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Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts

et al. 2013

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With improvements in abdominal imaging, detection of incidental pancreatic cysts are becoming increasingly common. Analysis of pancreatic cyst fluid from fine-needle aspiration is particularly important in identifying intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), which have significant implications in clinical intervention and follow-up. Previous controlled studies have shown that KRAS mutations in cyst fluid are highly specific for mucinous differentiation in pancreatic cysts; however, this has not been examined in the clinical setting. Over a 6-year study period, 618 pancreatic cyst fluids obtained by fine-needle aspiration at the time of endoscopic ultrasound were tested for KRAS mutations as part of routine evaluation for a cystic neoplasm. Of the 618 specimens, 603 (98%) from 546 patients were satisfactory for molecular analysis. Patients ranged in age from 17 to 90 years (mean, 63.9 years) and were predominantly female (68%). Pancreatic cysts were relatively evenly distributed throughout the pancreas and ranged in size from 0.6 to 11.0 cm (mean, 2.3 cm). Mutations in KRAS were detected in 232 of 603 (38%) aspirates. Although sufficient for molecular analysis, 320 of 603 (53%) specimens were either less than optimal (38%) or unsatisfactory (15%) for cytopathologic diagnosis. Surgical follow-up information was available for 142 (26%) patients and consisted of 53 KRAS-mutated and 89 KRAS-wild-type cysts. Overall, KRAS mutations had a specificity of 100%, but a sensitivity of 54% for mucinous differentiation. When stratified by cyst type, KRAS had a sensitivity of 67% and 14% for IPMNs and MCNs, respectively. In summary, KRAS mutations were highly specific for mucinous differentiation, but were inadequate in identifying MCNs. Future molecular studies and the combination of other fluid markers are required to improve the detection and classification of pancreatic mucinous neoplasms by endoscopic ultrasound fine-needle aspiration.

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“…However, intestinal-type intraductal papillary mucinous neoplasms tend to be found in high-grade intraductal papillary mucinous neoplasms of borderline neoplasm and carcinoma, notably colloid carcinoma. 2 According to the International Consensus Guidelines, 6 all main duct intraductal papillary mucinous neoplasms, including mixed type, and branch duct intraductal papillary mucinous neoplasms suspected of malignancy are candidates for surgery. Although some clinical and imaging features, including dilatation of the main pancreatic duct, the presence of intramural nodules, cyst size of more than 30 mm, and the presence of symptoms, have been shown to predict malignancy in intraductal papillary mucinous neoplasms, it is sometimes difficult to accurately diagnose the grade of malignancy of intraductal papillary mucinous neoplasms preoperatively by these predictors.…”

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confidence: 99%

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

et al. 2011

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Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffinembedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (Po0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinaltype intraductal papillary mucinous neoplasms based on papillary subclassification (Po0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.

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International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas

Cited by 1,875 publications

References 73 publications

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas

Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts

Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas

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