Factors Associated With Invasive Intraductal Papillary Mucinous Carcinoma of the Pancreas
Authors: Seiko Hirono, Manabu Kawai, Ken-ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Masaki Ueno, Akio Yanagisawa, Hiroki Yamaue
Journal: JAMA Surgery (2017)

<h3>Importance</h3> Invasive intraductal papillary mucinous carcinoma has aggressive malignant behavior, including lymph node metastasis. It is important to identify factors associated with invasive intraductal papillary mucinous carcinoma to determine operative procedures, but they remain unclear. <h3>Objective</h3> To identify the specific factors associated with invasive intraductal papillary mucinous neoplasms for branch duct, main duct, and mixed type carcinomas. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of 286 consecutive patients who underwent surgical resection for intraductal papillary mucinous neoplasm from July 1999 to December 2015 at a tertiary institute. We compared clinical features between 96 patients (33.6%) with invasive intraductal papillary mucinous carcinoma and 190 patients (66.4%) with noninvasive intraductal papillary mucinous neoplasm for each morphological type. <h3>Main Outcomes and Measures</h3> Factors associated with invasive intraductal papillary mucinous carcinoma. Mural nodule size was measured by endoscopic ultrasonography. <h3>Results</h3> Of the 286 patients included in the cohort, the median (range) age was 71 (28-86) years, and 162 (56.6%) were male. High mural nodule size was independently associated with invasive intraductal papillary mucinous carcinoma in all types (branch duct: odds ratio [OR], 1.992; 95% CI, 1.177-3.367;<i>P </i>=<i> </i>.01; main duct: OR, 1.443; 95% CI, 1.094-1.905;<i>P </i>=<i> </i>.01; and mixed: OR, 1.178; 95% CI, 1.057-1.312;<i>P </i>=<i> </i>.04). The cutoff values for intraductal papillary mucinous neoplasms, determined by a receiver operating characteristic, were 9 mm for branch duct and 6 mm for mixed and main duct carcinoma. A high carcinoembryonic antigen level in the pancreatic juice was independently associated with mixed (OR, 1.002; 95% CI, 1.000-1.003;<i>P </i>=<i> </i>.01) and main duct (OR, 1.002; 95% CI, 1.000-1.003;<i>P </i>=<i> </i>.048) carcinomas, and the cutoff values were determined to be 150 and 300 ng/mL, respectively (to convert to micrograms per liter, multiply by 1). In addition, both being female and having an elevated serum carbohydrate antigen 19-9 level were also found to be independently associated with mixed type invasive intraductal papillary mucinous carcinoma, and using any 2 among 4 identified factors yielded the highest accuracy (79.0%) for mixed type carcinomas. For all types, the accuracy for these factors was 86.0% for differentiating between invasive and noninvasive intraductal papillary mucinous neoplasms, which was superior to the accuracies using the "high-risk stigmata" factors or "worrisome features" suggested by the international consensus guideline in 2012 (66.1% and 39.9%, respectively). <h3>Conclusions and Relevance</h3> The measurement of mural nodule size in all types of carcinomas and carcinoembryonic antigen level in the pancreatic juice in mixed and main duct carcinomas might play important roles in predicting invasive intraductal papillary mucinous carcinoma, but further large studies are needed to confirm these results.