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To describe clinical characteristics and outcomes of a large cohort of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas affecting the main pancreatic duct.IPMNs are being diagnosed with increasing frequency. Preoperative determination of malignancy remains problematic, and reported results of long-term survival following resection are conflicting.The combined databases from the Massachusetts General Hospital and the Pancreatic Unit of the University of Verona were analyzed. To avoid confusing overlap with mucinous cystic neoplasms, only patients with tumors of the main pancreatic duct (with or without side branch involvement) were included. A total of 140 tumors consecutively resected between 1990 and 2002 were classified as either benign (adenoma and borderline tumors) or malignant (carcinoma in situ or invasive cancer) to compare their characteristics and survival.Men and women were equally affected (mean age 65 years). Seven patients (12%) had adenomas, 40 (28%) borderline tumors, 25 (18%) carcinoma in situ, and 58 (42%) invasive carcinoma. The median age of patients with benign IPMN was 6.4 years younger than those with malignant tumors (P = 0.04). The principal symptoms were abdominal pain (65%), weight loss (44%), acute pancreatitis (23%), jaundice (17%), and onset or worsening of diabetes (12%); 27% of patients were asymptomatic. Jaundice and diabetes were significantly associated with malignant tumors. Five- and 10-year cancer-specific survival for patients with noninvasive tumors was 100%, and comparable survival of the 58 patients with invasive carcinoma was 60% and 50%.Cancer is found in 60% of patients with main-duct IPMNs. Patients with malignant tumors are 6 years older than their benign counterparts and have a higher likelihood of presenting with jaundice or new onset diabetes. No patients with benign tumors or carcinoma in situ died of their disease following resection, and those with invasive cancer had a markedly better survival (60% at 5 years) than pancreatic ductal adenocarcinoma. These findings support both the concept of progression of benign IPMNs to invasive cancer and an aggressive policy of resection at diagnosis.

s / Pancreatolog S4 Aims: To evaluate the long-term outcome after surgical resection of sporadic, asymptomatic NF-pNET < 2 cm, stratifying the results by resection type and histopathologic features. Patients & methods: Patients resected between June 1997 and November 2008 at our institution (minimum follow-up of 60months) were retrieved from a prospectively maintained electronic database and analyzed retrospectively. Results: Study population consisted of 49 patients (27 females and 22 males), with amedian age of 59 years (range 38-61). 31 patients underwent parenchyma-sparing resections (15 enucleations, 15 middle pancreatectomies, 1 spleen-preserving distal pancreatectomies), while 18 patients underwent formal resections (8 pancreaticoduodenectomies, 10 distal pancreactomies with splenectomy). Mean lymph node yielding was 1.35 (0-9) in atypical resections and 19 (7-32) in formal resections (p1⁄40.0001). Lymph node metastases were found in only one patient undergoing pancreaticoduodenectomy. The median tumor size was 16 mm. 48 tumors were G1, one was G2, none was G3 (2010 WHO classification). The final pathologic report showed microscopic local invasion (perineural invasion, lymph vascular invasion or fat invasion) in 8 patients. At a median followup of 80 months (60-193), 4 patients died of other causes, 4 were lost to follow-up the remaining 37 patients did not develop recurrence and are alive and disease-free. Conclusion: Long-term outcome of surgically resected asymptomatic sporadic NF-pNET < 2 cm is excellent. Atypical resections with limited lymph node dissection may be oncologically adequate. Microscopic local invasion did not impact on the natural history of the disease.

University of Pittsburgh, Pittsburgh, PA, USA Background: There is growing concern over rising healthcare costs, which are primarily driven by hospital (re)admissions. The cost of pancreatitis care in the US was $3.7 billion in 2004. We recently reported on the absolute risk of readmission after initial hospitalization for AP and CP in Allegheny County, PA. Aim: To evaluate the overall burden and pattern of readmissions in these cohorts. Methods: We identified all unique White or Black Allegheny County residents with first hospital admission for AP or CP from 1996-2005 using Pennsylvania Health Care Cost Containment Council (PHC4) dataset. Final study population consisted of patients (AP: 6010; CP: 868) who survived index admission and had follow up data available. Etiology was determined using associated diagnosis (Dx) codes. We analyzed pancreatitis related readmission data (type, number, patterns) until 3rd quarter 2007 (median follow up w40 months). Results: Readmission with Primary AP or CP (PriAPCP) or any pancreatitis (AnyPanc) Dx was noted in 24% and 33% in AP; 45% and 58% in CP cohort respectively. In patients with readmissions, total (average) number of readmissions with PriAPCP and AnyPanc Dx were 3757 (2.7) and 6543 (3.4) in AP; 1836 (4.7) and 3485 (6.9) in CP cohort respectively. Readmission burden was disproportionately high due to alcohol (etiology in 20% AP and 32% CP cohorts respectively which accounted for a readmission burden of w40-50%). Readmission patterns during follow up differed by etiology (more frequent and wider distribution in alcoholic; less frequent, occurring closer to index admission in non-alcoholic etiologies); type of pancreatitis (readmissions related to CP and in CP patients more frequent than AP) and age (more frequent and wider distribution in patients aged

To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs).Case series.Academic hospital.Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009.Operative morbidity and survival after resection.A total of 139 patients with median age of 56 years (range, 21-85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P = .01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P.001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival.Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning PETs should undergo tumor resection and careful postoperative surveillance, even if surgical pathologic findings suggest benign disease.

Pancreatic cancer is the fourth leading cause of cancer death in the United States and is frequently lethal despite aggressive medical and surgical treatment. Better forms of treatment are needed. One promising area of investigational treatment for patients with pancreatic cancer involves the use of immunotherapy. Approaches to cancer immunotherapy have evolved over the past 20 years resulting in improved response rates to therapy. This form of treatment was founded on the adoptive transfer of tumor-infiltrating lymphocytes in the treatment of melanoma. More recently, innovative strategies involving genetic modification of peripheral blood lymphocytes to express T cell receptors targeting tumor antigens have been developed and show promise in generating anti-tumor responses against a wide range of malignancies beyond melanoma. Vaccines and immunomodulatory agents also exist. MAGE-A3 is a cancer-testis antigen (CTA) and is expressed in up to 40% of pancreatic cancer tumors thus may be a suitable target in the treatment of this malignancy. It has a favorable expression profile, which is limited to neoplastic tissue and non-MHC bearing germ cell tissues. Furthermore, expression of MAGE-A3 (and other CTA) may be up-regulated in cancer cells by treatment with chromatin remodeling agents. Vaccines targeting MAGE-A3 are currently in use. The goal of these studies was to explore epigenetic mechanisms to enhance expression of the MAGE-A3 CTA in pancreatic cancer in an effort to improve recognition of these tumors by MAGE-A3-specific T lymphocytes as a basis for combined therapy against this disease. Pancreatic cancer cell lines were cultured with chromatin remodeling agents 5-aza-2′-deoxycytidine (5-AZA), Valproate (VALP), 5-AZA + VALP, or with the chemotherapeutic agent Gemcitabine (Gem). Expression of MAGE-A3 (and other CTA) was assayed at the mRNA or protein level. Untreated and treated pancreatic cancer cell lines were co-cultured with antigen-specific T lymphocytes (generated by transduction of lymphocytes with MAGE-A3-specific T cell receptors) and reactivity was measured via interferon gamma release. Treatment of pancreatic cancer cell lines with chromatin remodeling agents resulted in increased levels of CTAs (including MAGE-A3) and was synergistic when used in combination. The increased MAGE-A3 expression was associated with improved recognition by antigen-specific T lymphocytes. Treatment with Gemcitabine had no effect on CTA expression or antigen-specific recognition. These findings suggest that expression of CTA and MAGE-A3 in pancreatic cancer cells may be upregulated via treatment with chromatin remodeling agents, rendering them more susceptible to antigen-specific T lymphocytes. These data provide the groundwork for further studies addressing combined epigenetic therapy and immunotherapy for pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4796.

BACKGROUND & AIMS: Mucin-producing neoplasms (MPNs) of the pancreas include mucinous cystic neoplasms (MCNs) and main-duct, branch-duct, and combined intraductal papillary mucinous neoplasms (IPMNs). MCNs and branch-duct IPMNs are frequently confused; it is unclear whether main-duct, combined, and branch-duct IPMNs are a different spectrum of the same disease. We evaluated their clinical and epidemiologic characteristics. METHODS: Patients who underwent resection for histologically confirmed MPNs were identified (N = 557); specimens were reviewed and eventually reclassified. RESULTS: One hundred sixty-eight patients (30\%) had MCNs, 159 (28.5\%) had branch-duct IPMNs, 149 (27\%) had combined IPMNs, and 81 (14.5\%) had main-duct IPMNs. Patients with MCNs were significantly younger and almost exclusively women; 44\% of patients with main-duct or combined IPMNs and 57\% of those with branch-duct IPMNs were women. MCNs were single lesions located in the distal pancreas (95\%); 11\% were invasive. IPMNs were more frequently found in the proximal pancreas; invasive cancer was found in 11\%, 42\%, and 48\% of branch-duct, combined, and main-duct IPMNs, respectively (P = .001). Patients with invasive MCN and those with combined and main-duct IPMNs were older than those with noninvasive tumors. The 5-year disease-specific survival rate approached 100\% for patients with noninvasive MPNs. The rates for those with invasive cancer were 58\%, 56\%, 51\%, and 64\% for invasive MCNs, branch-duct IPMNs, main-duct IPMNs, and combined IPMNs, respectively. CONCLUSIONS: MPNs comprise 3 different neoplasms: MCNs, branch-duct IPMNs, and main-duct IPMNs, including the combined type. These tumors have specific clinical, epidemiologic, and morphologic features that allow a reasonable degree of accuracy in preoperative diagnosis.

Objective To define how patients with pancreatic cysts are being diagnosed and treated. Design Retrospective case series. Setting University-affiliated tertiary care center. Patients Four hundred one patients evaluated in the Department of Surgery between January 2004 and December 2007. Main Outcome Measures Clinical management, histological diagnosis, and results of surveillance. Results Pancreatic cysts were incidentally discovered in 71% (284 of 401) of patients. There was no statistically significant difference in age (60.4 vs 63.1 years; P = .10), cyst size (31 vs 27 mm; P = .12), or histological diagnosis between symptomatic patients and patients with incidentally discovered cysts. Whereas the majority of symptomatic patients had their cystic neoplasms resected on diagnosis, 50% (142 of 284) of incidentally discovered cysts were initially managed nonoperatively. Of the patients who were managed with surveillance, 13 (8%) subsequently underwent resection after a median of 2.1 years because of an increase in cyst size, development of symptoms, increasing tumor markers, worrisome endoscopic ultrasonography findings, or patient anxiety. The most common diagnosis among resected lesions was either main-duct intraductal papillary mucinous neoplasm (25%) or branch-duct intraductal papillary mucinous neoplasm (23%). Invasive cancer was found in 29 of 256 (11%) resected cystic neoplasms, 9 of which were incidentally discovered, and in 7% (1 of 13) of patients who underwent watchful waiting prior to resection. Conclusions Incidentally discovered pancreatic cystic neoplasms composed 71% of our series, of which 50% were immediately resected. Subsequent morphologic changes or development of symptoms prompted an operation in 8% of patients after a period of surveillance. Invasive malignancy was present in 11% of all resected specimens but in 38% of main-duct intraductal papillary mucinous neoplasms.

G A A b st ra ct s reported abdominal complaints as opposed to 7.6% of those without PC(s) (p = 0.589). None of the individuals with PC(s) had pancreatic disease in their medical history. Conclusion: In individuals undergoing preventive medical examination with MRI, the prevalence of PCs was 2.2%. Of these PCs, 5.3% were ≥30 mm, 8% were multilocular and in 10% of cases may represent side-branch IPMN. Cyst presence correlated with increasing age, no difference of prevalence by sex was found. Abdominal complaints did not correlate with PC presence.

Objective To assess changing patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms (PNENs). Design Retrospective review from May 21, 1977, through September 16, 2005. Setting Massachusetts General Hospital, a tertiary care center. Patients We evaluated 168 patients (51% male; mean age, 56 years) who underwent surgery for histologically confirmed PNENs. Main Outcome Measures Surgical outcomes, survival, and changes in presentation of PNENs in 2 time groups: 1977-1999 (77 patients) and 2000-2005 (91 patients). Results Ninety-eight patients (58.3%) had nonfunctioning PNENs, 86 of which were incidental. Insulinomas were the most common type of functional neoplasm (33.3%), followed by gastrinomas and glucagonomas; 12 patients (7.1%) had multiple endocrine neoplasia type 1. Of the neoplasms, 107 (63.7%) were located in the pancreatic body or tail. A pancreaticoduodenectomy was performed in 37 patients (22.0%), distal pancreatectomy was done in 88 (52.4%), and the rest had either middle segment pancreatectomy or enucleation. There were no operative deaths. We classified 76.8% of neoplasms as benign; of those classified as malignant, 25.6% had liver metastases. Of the patients, 10.1% received adjuvant therapy. Complete follow up was available in 90.5% of patients (mean, 63.3 months). Five- and 10-year actuarial survival rates were 77% and 62%, respectively. Incidentally discovered nonfunctioning neoplasms were significantly more frequent in the last 5 years (60.4% vs 40.3%; = .007), with a trend toward smaller neoplasms (mean, 4.2 cm vs 5.6 cm; = .19) and lesser likelihood of malignancy (21.8% vs 40.0%; = .08). Conclusions We report a large single-center experience with PNENs. Increasing numbers of PNENs are being resected, largely owing to the incidental detection of nonfunctioning neoplasms. This may lead to the treatment of smaller and less malignant neoplasms.

4034 Background: Staging systems and nomograms attempt to better stratify patients with pancreatic adenocarcinoma by evaluating different prognostic factors. The purpose of this study is to determi...

Hypothesis: Widespread use of computed tomography and ultrasound has led to the identification of increasing numbers of patients with asymptomatic cystic lesions of the pancreas. Design: Retrospective case series of patients with pancreatic cystic lesions. Setting: University-affiliated tertiary care referral center. Patients: Two hundred twelve patients with pancreatic cystic lesions seen in our surgical practice during 5 years (April 1997-March 2002). Main Outcome Measures: Presence or absence of symptoms, cyst size and location, cytologic or pathologic diagnosis, surgical treatment, and outcome. Results: Seventy-eight (36.7%) of 212 patients were asymptomatic. Incidental cysts were smaller (3.3 3 ±1.9 vs 4.6 ±2.7 cm; P

OBJECTIVE: The objective of this study is to assess lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) in identifying malignant nodal involvement in patients with pancreatic ductal adenocarcinoma. METHODS: Magnetic resonance imaging was performed in 13 patients with known or high index of suspicion of pancreatic cancer and who were scheduled for surgical resection. Protocols included T2*-weighted imaging before and after administration of Ferumoxytol (Feraheme) for the evaluation of lymph node involvement. Eleven of the 13 patients underwent a Whipple procedure and lymph node dissection. Nodes that lacked contrast uptake were deemed malignant, and those that demonstrated homogeneous uptake were deemed benign. RESULTS: A total of 264 lymph nodes were resection, of which 17 were malignant. The sensitivity and specificity of LNMRI was 76.5% and 98.4% at a nodal level and 83.3% and 80% at a patient level. CONCLUSION: LNMRI demonstrated high sensitivity and specificity in patients with pancreatic ductal adenocarcinoma.

In the year 2005, an estimated 31,800 people will die of pancreatic cancer in the United States. This disease is the fourth most common cause of cancer-related death among men in the United States. Its peak incidence occurs in the seventh and eighth decades of life. Although incidence is roughly equal in the two sexes, African Americans appear to have a higher incidence of pancreatic cancer than white Americans. In these NCCN Pancreatic Adenocarcinoma guidelines, only tumors of the exocrine pancreas are discussed; endocrine tumors from the islets of Langerhans and carcinoid tumors are not included. For the most recent version of the guidelines, please visit NCCN.org

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.