Intraductal Papillary Mucinous Neoplasms of the Pancreas

OBJECTIVE: To update the authors' experience with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND DATA: IPMNs are intraductal mucin-producing cystic neoplasms of the pancreas with clear malignant potential. Since the authors' 2001 report, the number of IPMNs resected at our institution has more than doubled, providing an opportunity to define the clinical features of this distinct neoplasm. METHODS: All patients undergoing pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and March 2003 were evaluated. Noninvasive IPMNs were classified as "adenoma," "borderline," or "carcinoma-in situ" (CIS) depending on the degree of dysplasia within the specimen. Invasive cancers were classified as tubular, colloid, mixed, or anaplastic types. Pathology was retrospectively reviewed to identify main-duct or branch-duct origin of the tumors. Long-term overall survival for patients having IPMNs with invasive cancer was compared with those patients having IPMNs without an invasive component. RESULTS: Between January 1987 and March 2003, inclusive, 136 pancreatic resections were performed for patients with IPMNs, with 78 resections performed since January 2001. The mean age of the patients was 66.8 +/- 1.1 years, with 57% being male and 89% white. Pancreaticoduodenectomy was performed in 71% of patients, total pancreatectomy in 15%, distal pancreatectomy in 12%, and central pancreatic resection in 2%. IPMNs without evidence of invasive cancer were identified in 62% (n = 84) of patients (17% adenoma, 28% borderline, or 55% CIS). The remaining 38% (n = 52) of patients had IPMNs with associated invasive cancer (60% tubular, 27% colloid, 7% mixed, and 6% anaplastic). The mean age of patients with IPMN adenoma was 63.2 years, 66.7 years for those with borderline/CIS IPMNs, and 68.1 years for those with invasive cancer (P = 0.08, adenomas vs. invasive cancer). In those patients with invasive cancers, 15% had invasive cancer at the final surgical margin, 23% had IPMN without invasive cancer at the margin, and 54% had lymph node metastases. Residual IPMN was identified at the neck or uncinate margin in 24% of patients with noninvasive IPMNs. The overall 5-year survival for patients having IPMNs without invasive cancer was 77% (several deaths secondary to metachronous invasive cancer), compared with 43% in those patients with an invasive component (P < 0.0001). There were no differences in survival when comparing adenomas, borderline neoplasms, and CIS. Similarly, there were no statistically significant differences in survival when comparing branch-duct, main-duct, and combined variants; however, the branch-duct variants were more often noninvasive. For those patients with invasive IPMNs, 2-year survival was 40% when margins were positive for invasive cancer or for IPMN without invasive cancer, and 60% when margins were tumor-free (P = 0.15). Those patients with colloid carcinomas (n = 14) had improved survival compared with those with tubular carcinomas (n = 31), with 5-year survival rates of 83% and 24%, respectively. IPMN recurrences and deaths from cancer occurred in patients with both invasive and noninvasive IPMNs at initial resection. CONCLUSIONS: IPMNs continue to be recognized with increasing frequency. Five-year survival for those patients following resection of IPMNs with invasive cancer (43%) is improved compared with those patients with resected pancreatic ductal adenocarcinoma in the absence of IPMN (averages 15%-25%). Survival following resection of IPMNs without invasive cancer (regardless of degree of dyplasia) is good, but recurrent disease in the residual pancreas suggests that long-term surveillance is critical. Based on the age at resection data, there appears to be a 5-year lag time from IPMN adenoma (63.2 years) to invasive cancer (68.1 years).