Faculty Bibliography

BACKGROUND:Surgical resection remains the only potentially curative option for patients with pancreatic adenocarcinoma (PAC). Advances in surgical technique and perioperative care have reduced perioperative mortality; however, temporal trends in perioperative morbidity and the use of adjuvant therapy on a population basis remain ill-defined. STUDY DESIGN/METHODS:Using Surveillance, Epidemiology, and End Results-Medicare data, 2,461 patients with resected PAC were identified from 1991 to 2005. We examined trends in preoperative comorbidity indices, adjuvant treatment, type of pancreatic resection, and changes in morbidity and mortality during 4 time intervals (ie, 1991-1996, 1997-2000, 2001-2003, and 2003-2005). RESULTS:The majority of patients underwent pancreaticoduodenectomy (n = 1,945; 79%). There was a temporal increase in mean patient age (p < 0.05) and the number of patients with multiple preoperative comorbidities (Elixhauser comorbidities ≥3: 1991-1996, 10% vs 2003-2005, 26%; p < 0.001). Perioperative morbidity (53%) did not, however, change over time (p = 0.97) and 30-day mortality decreased by half (1991-1996: 6% vs 2003-2005: 3%; p = 0.04). Overall, 51% (n = 1,243) of patients received adjuvant therapy, with the majority receiving chemoradiation (n = 817; 33%). Among patients who received adjuvant therapy, factors associated with receipt of adjuvant chemotherapy alone relative to chemoradiation included older patient age (odds ratio = 1.75; p < 0.001) and ≥3 medical comorbidities (odds ratio = 1.57; p = 0.007). Receipt of adjuvant chemotherapy alone also increased over time (2003-2005 vs 1991-1996, odds ratio = 2.21; p < 0.001). CONCLUSIONS:Perioperative 30-day mortality associated with resection for PAC decreased by one-half from 1991 to 2005. Although patients undergoing resection for PAC were older and had more preoperative comorbidities, the incidence of perioperative complications remained stable. The relative use of adjuvant chemotherapy alone vs chemoradiation therapy for PAC has increased in the United States during the 15 years examined.

INTRODUCTION/BACKGROUND:Solid pseudopapillary neoplasms are rare pancreatic neoplasms with low malignant potential and favorable prognosis that are typically seen in young women. PRESENTATION OF CASE/METHODS:We report a case of two large solid pseudopapillary neoplasms in a 23-year old woman who was treated successfully with a total pancreatectomy. CONCLUSION/CONCLUSIONS:To the best of our knowledge, this is the first report of two discrete solid pseudopapillary neoplasms in the same patient.

OBJECTIVE:Autoimmune pancreatitis (AIP) is an inflammatory, IgG4-associated condition that often overlaps clinically and radiographically with pancreatic ductal adenocarcinoma. We reviewed our institutional experience with fine needle aspiration (FNA) cytology in patients subsequently diagnosed with AIP. STUDY DESIGN/METHODS:A retrospective review was conducted of FNA results correlating to all surgical pancreatic specimens diagnosed as AIP or lymphoplasmacytic sclerosing pancreatitis from 1984 to 2011. RESULTS:AIP was diagnosed in 15 cases by surgical resection and in 2 by combined clinical findings and nondiagnostic biopsies. Of 20 aspirates from 17 patients, 1 was diagnosed as malignant, 1 as neoplasm (mucinous), 10 as atypical, 5 as benign, and 3 as scant or nondiagnostic. Of the 10 aspirates diagnosed as atypical, 1 was suspicious for malignancy, 1 could not exclude neuroendocrine neoplasm, 1 was markedly atypical, and 7 demonstrated scattered ductal atypia. Common morphologic features included hypocellularity, focal-to-marked ductal epithelial atypia, fibrous tissue fragments, and a smear background lacking red blood cells. CONCLUSION/CONCLUSIONS:On FNA, AIP most often leads to an 'atypical' cytopathologic interpretation and rarely may be diagnosed as adenocarcinoma. Thus, caution is warranted to avoid overdiagnosis on FNA when a mass lesion is reported in a patient with clinical or radiographic suspicion of AIP.

PURPOSE:To analyze a single-center experience with locally advanced pancreatic cancer (LAPC) patients treated with chemoradiation (CRT) and to evaluate predictive variables of outcome. METHODS AND MATERIALS:LAPC patients at our institution between 1997 and 2009 were identified (n = 109). Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Cox proportional hazard models were used to evaluate predictive factors for survival. Patterns of failure were characterized, and associations between local progression and distant metastasis were explored. RESULTS:< .0001). CONCLUSIONS:LAPC patients who suffer local progression following definitive CRT may experience inferior OS and increased risk of metastasis, warranting efforts to improve control of local disease. However, patients with poor pretreatment performance status, elevated CA19-9 levels, and treatment interruptions may experience poor outcomes despite aggressive management with CRT, and may optimally be treated with induction chemotherapy or supportive care. Novel therapies aimed at controlling both local and systemic progression are needed for patients with LAPC.

More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10 ± 4.6, 27 ± 12, 16 ± 7.6, and 2.9 ± 2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of the von Hippel-Lindau gene (VHL), a key component of the VHL ubiquitin ligase complex that has previously been associated with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.