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Pancreatic Cystic Neoplasms: Management and Unanswered Questions

2013; Elsevier BV; Volume: 144; Issue: 6 Linguagem: Inglês

10.1053/j.gastro.2013.01.073

1528-0012

James J. Farrell, Carlos Fernández‐del Castillo,

Neuroendocrine Tumor Research Advances

Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts. Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts. View Large Image Figure ViewerDownload Hi-res image Download (PPT)There has recently been a large increase in the number of patients with IPMNs, partially because of increased awareness of their existence but mostly because of increased use of cross-sectional imaging technologies, which led to the incidental discovery of many pancreatic cysts. Computed tomography (CT) and magnetic resonance imaging (MRI) studies have shown that the prevalence of pancreatic cysts (in individuals without history of symptoms of pancreatic disease) is about 2.5%1de Jong K. Nio C. Mearadji B. et al.Disappointing interobserver agreement among radiologists for a classifying diagnosis of pancreatic cysts using magnetic resonance imaging.Pancreas. 2012; 41: 278-282Crossref PubMed Scopus (56) Google Scholar, 2Laffan T.A. Horton K.M. Klein A.P. et al.Prevalence of unsuspected pancreatic cysts on MDCT.Am J Roentgenol. 2008; 191: 802-807Crossref PubMed Scopus (625) Google Scholar and that this increases with age, to the point that 10% of persons 70 years or older have a pancreatic cyst.1de Jong K. Nio C. Mearadji B. et al.Disappointing interobserver agreement among radiologists for a classifying diagnosis of pancreatic cysts using magnetic resonance imaging.Pancreas. 2012; 41: 278-282Crossref PubMed Scopus (56) Google Scholar It is believed that most of these are small, branch duct IPMNs (BD-IPMNs), but there is no firm pathology data to support this. Regardless, because of the malignant potential of BD-IPMNs, their identification generates anxiety, subsequent imaging analyses, and sometimes invasive tests or surgery. We do not have a clear picture of how BD-IPMNs progress, so management recommendations are in a state of flux.We review our knowledge of cystic neoplasms of the pancreas (CNPs), discussing the most common types, management strategies, and important areas for future study. We focus separately on BD-IPMNs, which are likely to be the majority of CNPs, and the role of endoscopic ultrasound (EUS) in the diagnosis and management of patients with incidentally discovered pancreatic cysts.Presentation, Radiologic Features, Progression, and ManagementMucinous Cystic NeoplasmsMucinous cystic neoplasms (MCNs) are relatively uncommon tumors that comprise about 25% of all resected cystic neoplasms of the pancreas, based on data from a large surgical series.3Valsangkar N.P. MoralesOyarvide V. Thayer S.P. et al.851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts General Hospital.Surgery. 2012; 152: S4-S12Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar They occur most frequently in women (>95%), in the distal pancreas (>95%), and, unlike BD-IPMNs, are always a single lesion.4Crippa S. Salvia R. Warshaw A.L. et al.Mucinous cystic neoplasm of the pancreas is not an aggessive entity: lessons from 163 resected patients.Ann Surg. 2008; 247: 571-579Crossref PubMed Scopus (316) Google Scholar, 5Yamao K. Yanagisawa A. Takahashi K. et al.Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan Pancreas Society.Pancreas. 2011; 40: 67-71Crossref PubMed Scopus (173) Google Scholar, 6Le Baleur Y. Couvelard A. Vullierme M.P. et al.Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions.Pancreatology. 2011; 11: 495-499Abstract Full Text PDF PubMed Scopus (48) Google Scholar They are characterized by a dense, ovarian-like stroma that surrounds the tumor, and an inner-epithelial layer with tall, mucin-producing cells. This layer can exhibit various degrees of atypia, from adenoma to invasive carcinoma, which frequently coexist. Median age of diagnosis was reported to be 45 and 48 years (range, 16–84 years) in 2 large series studies; most patients presented either incidentally or with vague symptoms, although about 10% have presented with acute pancreatitis and 12% with a palpable mass.4Crippa S. Salvia R. Warshaw A.L. et al.Mucinous cystic neoplasm of the pancreas is not an aggessive entity: lessons from 163 resected patients.Ann Surg. 2008; 247: 571-579Crossref PubMed Scopus (316) Google Scholar, 5Yamao K. Yanagisawa A. Takahashi K. et al.Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan Pancreas Society.Pancreas. 2011; 40: 67-71Crossref PubMed Scopus (173) Google Scholar The typical radiologic presentation is that of a thick-walled single cyst located in the neck, body, or tail of the pancreas, often with septations, and occasionally with nodules or calcifications.6Le Baleur Y. Couvelard A. Vullierme M.P. et al.Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions.Pancreatology. 2011; 11: 495-499Abstract Full Text PDF PubMed Scopus (48) Google Scholar The risk of malignancy is 17.5% and in 1 series all malignant tumors had either nodules or were >4 cm.4Crippa S. Salvia R. Warshaw A.L. et al.Mucinous cystic neoplasm of the pancreas is not an aggessive entity: lessons from 163 resected patients.Ann Surg. 2008; 247: 571-579Crossref PubMed Scopus (316) Google Scholar Because malignant MCNs are significantly larger (8.2 cm vs 4.5 cm) and are diagnosed in older patients (49.5 years vs 44 years), they are presumed to grow slowly over time. However, the relatively low frequency of cancer in patients with MCNs indicates that not all progress; identifying patients whose MCNs are at risk greatest risk of progressing could spare many patients from surgery.Patients are presently treated by surgical resection and have excellent prognoses unless invasive carcinomas with either extracapsular or diffuse intracapsular infiltration are detected.4Crippa S. Salvia R. Warshaw A.L. et al.Mucinous cystic neoplasm of the pancreas is not an aggessive entity: lessons from 163 resected patients.Ann Surg. 2008; 247: 571-579Crossref PubMed Scopus (316) Google Scholar Patients with small presumed MCNs (unilocular, in pancreatic body or tail locations, in female middle-age patients, with increased levels of cyst fluid, and expression of carcinoembryonic antigen [CEA]) that are devoid of nodules can potentially be managed with observation, but lifelong close surveillance is mandatory. The high incidence of MCNs in women, their location in the body or tail of the pancreas, and the presence of ovarian-like stroma indicate that hormones such as human chorionic gonadotropin are involved in pathogenesis, and might be managed therapeutically.7Izumo A. Yamaguchi K. Eguchi T. et al.Mucinous cystic tumor of the pancreas: immunohistochemical assessment of “ovarian-type stroma.”.Oncol Rep. 2003; 10: 515-525PubMed Google ScholarSerous CystadenomasSerous cystadenomas (SCAs) account for about 16% of resected cystic tumors of the pancreas. SCAs are benign, slow-growing tumors that also predominantly affect women (approximately 75%). Mean age of patients who underwent surgery for SCAs was 62 years in 2 large US series8Galanis C. Zamani A. Cameron J.L. et al.Resected serous cystic neoplasms of the pancreas: a review of 158 patients with recommendations for treatment.J Gastrointest Surg. 2007; 11: 820-826Crossref PubMed Scopus (156) Google Scholar, 9Tseng J.F. Warshaw A.L. Sahani D.V. et al.Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment.Ann Surg. 2005; 242 (discussion 419–421): 413-419PubMed Google Scholar and 52 and 56 years in 2 European series.10Le Borgne J. de Calan L. Partensky C. Cystadenomas and cystadenocarcinomas of the pancreas: a multiinstitutional restrospective study of 398 cases.Ann Surg. 1999; 230: 152-161Crossref PubMed Scopus (426) Google Scholar, 11Bassi C. Salvia R. Molinari E. et al.Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa?.World J Surg. 2003; 27: 319-323Crossref PubMed Scopus (175) Google Scholar The typical SCA is formed by many tiny cysts lined by a cuboidal epithelium that is glycogen rich and has a honeycomb appearance, but a variant that is oligo- or macrocystic has been described and comprises about 10% of cases.9Tseng J.F. Warshaw A.L. Sahani D.V. et al.Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment.Ann Surg. 2005; 242 (discussion 419–421): 413-419PubMed Google Scholar, 12Hochwald S.N. Rofsky N.M. Dobryansky M. et al.Magnetic resonance imaging with magnetic resonance cholangiopancreatography accurately predicts resectability of pancreatic carcinoma.J Gastrointest Surg. 1999; 3: 506-511Crossref PubMed Scopus (30) Google Scholar Very few cases of malignant SCA (on the basis of presence of concomitant tumors in the liver or other extrapancreatic sites) have been described; they represent <1% of cases.8Galanis C. Zamani A. Cameron J.L. et al.Resected serous cystic neoplasms of the pancreas: a review of 158 patients with recommendations for treatment.J Gastrointest Surg. 2007; 11: 820-826Crossref PubMed Scopus (156) Google ScholarSCAs can form anywhere in the pancreas and can occasionally involve the entire organ. Most are diagnosed incidentally but, depending on their location and size, they can cause jaundice, pancreatitis, abdominal pain, or present as a palpable mass. Because SCAs are benign, treatment (surgical resection) should be determined based on the presence of symptoms. Patients managed without surgery should undergo imaging analysis at periodic intervals to ensure there is no rapid growth, which increases chances for symptoms and can lead to bigger or more complex procedures.13Malleo G. Bassi C. Rossini R. et al.Growth pattern of serous cystic neoplasms of the pancreas: observational study with long-term magnetic resonance surveillance and recommendations for treatment.Gut. 2012; 61: 746-751Crossref PubMed Scopus (81) Google Scholar Management by observation with or without serial imaging is contingent on an accurate diagnosis. The diagnosis can be made based on the lesion's radiologic appearance (a spongy, multilobular mass, often with a central calcifications) or by EUS-guided biopsy and analysis of fluid. Fluid from SCAs characteristically has low levels of CEA (typically <5 ng/mL) but can often be difficult to acquire from the microcystic variant compared with the oligocystic variant. The oligocystic variant is harder to diagnose because its radiologic features overlap with those of MCNs and BD-IPMNs.Patients with von Hippel-Lindau syndrome often have multiple oligocystic SCAs, and sporadic SCAs have been shown to have genetic alterations, including those that cause overexpression of vascular endothelial growth factor, which is also associated with this syndrome.14Panarelli N.C. Park K.J. Hruban R.H. et al.Microcystic serous cystadenoma of the pancreas with subtotal cystic degeneration: another neoplastic mimic of pancreatic pseudocyst.Am J Surg Pathol. 2012; 36: 726-731Crossref PubMed Scopus (19) Google Scholar It is a challenge to predict the rate of growth of SCAs in individual patients, and nonsurgical ablative therapies, which might include vascular endothelial growth factor inhibitors, require investigation.Solid Pseudopapillary NeoplasmsSolid pseudopapillary neoplasms (SPNs) of the pancreas are uncommon and comprise 80%) at median ages of 30 or 38 years, based on 2 recent series.15Reddy S. Cameron J.L. Scudiere J. et al.Surgical management of solid-pseudopapillary neoplasms of the pancreas (Franz or Hamoudi tumors): a single-institutional series.J Am Coll Surg. 2009; 208: 950-959Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar, 16Butte J.M. Brennan M.F. Gonen M. et al.Solid pseudopapillary tumors of the pancreas Clinical features, surgical outcomes, and long-term survival in 45 consecutive patients from a signle center.J Gastrointest Surg 2011. 2011; 15: 350-357Crossref PubMed Scopus (131) Google Scholar SPNs can be located throughout the pancreas; they are detected as incidental findings or because they cause symptoms, such as abdominal pain, pancreatitis, jaundice, or a palpable mass. In radiology examinations, SPNs appear as a well-demarcated heterogeneous mass with solid and cystic components. They can be diagnosed using EUS-guided fine-needle aspiration (FNA) or core biopsy analysis, based on the presence of cells that form microadenoid structures and branching papillary clusters with delicate fibrovascular cores. Patients are treated by surgical resection. Most SPNs are benign; 85% survive long term.18Gaujoux S. Tang L. Klimstra D. et al.The outcome of resected cystic pancreatic endocrine neoplasms: a case-matched analysis.Surgery. 2012; 151: 518-525Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 19Boninsegna L. Partelli S. D'Innocenzio M.M. et al.Pancreatic cystic endocrine tumors: a different morphological entity associated with a less aggressive behavior.Neuroendocrinology. 2010; 92: 246-251Crossref PubMed Scopus (58) Google Scholar, 20Bordeianou L. Vagefi P.A. Sahani D.V. et al.Cystic pancreatic endocrine neoplams: a distinct tumor type?.J Am Coll Surg. 2008; 206: 1154-1158Abstract Full Text Full Text PDF PubMed Scopus (103) Google ScholarSolid and cystic pancreatic endocrine tumors are discovered incidentally with increasing frequency. Although the conventional wisdom has been to resect all of these lesions, given their uncertain behavior, this approach has been challenged. However, outcomes of 77 patients with small, nonfunctioning PENs who were only observed did not differ from outcomes of patients who underwent surgery.22Lee L.C. Grant C.S. Salomao D.R. et al.Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management.Surgery. 2012; 152: 965-974Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar It is not clear if this approach also applies to patients with CPEN. Ablative therapies, guided by EUS or percutaneous, could also be studied.IPMNsFor many years, the term mucinous ductal ectasia was used to describe gross dilation of the pancreatic duct resulting from overproduction of mucus from a proliferative epithelium with papillary growth. It is not uncommon for these tumors to erode into the duodenum or bile duct, and patients often have pancreatitis-like symptoms for years. Although these tumors can become malignant, they are often confined to the duct or are minimally invasive. These tumors are now recognized as an advanced form of main duct IPMN (M-IPMN). Neoplastic proliferation can occur in either just the side branches of the pancreatic ductal system (BD-IPMN) or a combination of side branches and the main duct (mixed or combined IPMN).23Fernández-del Castillo C. Adsay N.V. Intraductal papillary mucinous neooplasms of the pancreas.Gastroenterology. 2010; 139: 708-713Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar For a long time BD-IPMNs were confused with mucinous cystic neoplasms. They have different epidemiologic features and cancer risk than main duct or combined IPMN, based primarily on differing histologic subtypes, which can only be determined by surgical pathology.24Crippa S. Fernández-del Castillo C. Salvia R. et al.Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics.Clin Gastroenterol Hepatol. 2010; 8: 213-219Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar, 25Furukawa T. Hatori T. Fujita I. et al.Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas.Gut. 2011; 60: 509-516Crossref PubMed Scopus (210) Google ScholarThe epithelial lining of most M-IPMNs has an intestinal phenotype and expresses typical intestinal lineage markers, such as CDX2 and MUC2.23Fernández-del Castillo C. Adsay N.V. Intraductal papillary mucinous neooplasms of the pancreas.Gastroenterology. 2010; 139: 708-713Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar M-IPMNs have a wide degree of heterogeneity in dysplastic areas, similar to villous adenomas of the colon. The risk of harboring malignancy is high, with invasive carcinoma found in 45% of cases and high-grade dysplasia (ie, carcinoma in situ) in an additional 20%.24Crippa S. Fernández-del Castillo C. Salvia R. et al.Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics.Clin Gastroenterol Hepatol. 2010; 8: 213-219Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar The invasive carcinomas that arise from intestinal-type IPMN are often colloid, which have a more indolent behavior.17Abraham S.C. Klimstra D. Wilentz R.E. et al.Solid-pseudopapillary tumors of teh pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations.Am J Pathol. 2002; 160: 1361-1369Abstract Full Text Full Text PDF PubMed Scopus (388) Google Scholar, 26Mino-Kenudson M. Fernández-del Castillo C. Baba Y. et al.Prognosis of invasive IPMN depends on histological and precursor epithelial subtypes.Gut. 2011; 60: 1712-1720Crossref PubMed Scopus (208) Google ScholarMost BD-IPMNs have a gastric-type epithelium: they are MUC5AC positive and MUC1 negative, with MUC2 detected in only scattered goblet cells. However, there are other histologic subtypes of BD-IPMNs, such as oncocytic, intestinal, and pancreaticobiliary.26Mino-Kenudson M. Fernández-del Castillo C. Baba Y. et al.Prognosis of invasive IPMN depends on histological and precursor epithelial subtypes.Gut. 2011; 60: 1712-1720Crossref PubMed Scopus (208) Google Scholar, 27Furukawa T. Klöppel G. Adsay N.V. et al.Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study.Virchows Arch. 2005; 447: 794-799Crossref PubMed Scopus (532) Google Scholar, 28Sadakari Y. Ohuchida K. Nakata K. et al.Invasive carcinoma derived from the nonintestinal type intraductal papillary mucinous neoplasm of the pancreas has a poorer prognosis than that derived from the intestinal type.Surgery. 2010; 147: 812-817Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Gastric-type BD-IPMNs are typically (of) low grade; in a small percentage, a tubular-type adenocarcinoma develops, which has the same bad prognosis as conventional pancreatic ductal adenocarcinoma (PDAC). It has been proposed that pancreatic duct glands give rise to pancreatic intraepithelial neoplasms (the precursors of PDAC) and gastric-type BD-IPMN and that they have similar biology and outcomes.17Abraham S.C. Klimstra D. Wilentz R.E. et al.Solid-pseudopapillary tumors of teh pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations.Am J Pathol. 2002; 160: 1361-1369Abstract Full Text Full Text PDF PubMed Scopus (388) Google Scholar, 26Mino-Kenudson M. Fernández-del Castillo C. Baba Y. et al.Prognosis of invasive IPMN depends on histological and precursor epithelial subtypes.Gut. 2011; 60: 1712-1720Crossref PubMed Scopus (208) Google Scholar, 29Strobel O. Rosow D.E. Rakhlin E.Y. et al.Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia.Gastroenterology. 2010; 138: 1166-1177Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar This concept is supported by the increased prevalence of pancreatic cysts (presumed to be BD-IPMNs) in families at high risk for pancreatic cancer.30Canto M.I. Hruban R.H. Fishman E.K. et al.Frequent detection of pancreatic lesions in asymptomatic high-risk individuals.Gastroenterology. 2012; 142: 796-804Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar BD-IPMN is by far the most common type of cystic neoplasm of the pancreas.M-IPMN and combined-type IPMN occur more frequently in men worldwide, but the male-to-female ratio is highest in Asia (3:1).31Ingkakul T. Thayer S.P. Ferrone C.R. et al.Epidemiology of intraductal papillary mucinous neoplasms of the pancreas: gender differences between 3 geographic regions.Pancreas. 2011; 40: 779-780Crossref PubMed Scopus (21) Google Scholar In one large series, the median age at diagnosis was 66 years (range, 31–87 years).24Crippa S. Fernández-del Castillo C. Salvia R. et al.Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics.Clin Gastroenterol Hepatol. 2010; 8: 213-219Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar The most common presenting symptom is abdominal pain (55%), followed by weight loss (45%), jaundice (17%), and acute pancreatitis (15%); in about 17% of cases the diagnosis is made incidentally.24Crippa S. Fernández-del Castillo C. Salvia R. et al.Mucin-producing neoplasms of the pancreas: an analysis of distinguishing clinical and epidemiologic characteristics.Clin Gastroenterol Hepatol. 2010; 8: 213-219Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar In two-thirds of cases, the tumor is located in the proximal pancreas (the head), and in 8% it affects the entire gland. Radiologic analyses have shown that the pancreatic duct is dilated by >6 mm, often extending into secondary branches. Solid components can be observed within the lumen or duct wall, as well as calcifications, and the pancreas can either be enlarged or appear atrophic.23Fernández-del Castillo C. Adsay N.V. Intraductal papillary mucinous neooplasms of the pancreas.Gastroenterology. 2010; 139: 708-713Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar Bulging papilla-extruding mucus, which is considered pathognomonic of M-IPMN, can be seen by endoscopy in about one-third of cases. Endoscopic retrograde cholangiopancreatography can often be used to visualize the filling defects from the tumors or mucus, allow for brushings and fluid obtention, and, if pancreatoscopy is performed, can sometimes be used to visualize the papillary or villous growths. EUS demonstrates the dilated pancreatic duct, provides morphologic detail of the solid components within it, and allows for targeted collection of biopsies.23Fernández-del Castillo C. Adsay N.V. Intraductal papillary mucinous neooplasms of the pancreas.Gastroenterology. 2010; 139: 708-713Abstract Full Text Full Text PDF PubMed Scopus (138) Google ScholarM-IPMNs and combined-type IPMNs are treated by surgical resection. It is important to localize the tumor well before surgery, which is often difficult because the entire ductal system is dilated. Liberal use of frozen-section margins and intraoperative pancreatoscopy and/or ultrasound is recommended to ensure no tumor with high-grade dysplasia or worse is left behind.23Fernández-del Castillo C. Adsay N.V. Intraductal papillary mucinous neooplasms of the pancreas.Gastroenterology. 2010; 139: 708-713Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar Frequently, elderly patients with this tumor have had recurrent pancreatitis for 20 years or more. For these patients, the consequences of pancreatic resection need to be weighed carefully against the potential benefits.Areas of future research in IPMN include development of more models, which include newer information on pathology subtypes, to predict which tumors are likely to become invasive and patient survival times; registries to improve our understanding of the natural history of the disease, including factors associated with postoperative recurrence; and further evaluation of intraductal ablative procedures in patients who are deemed high-surgical risk. Figure 1 summarizes the key features of the most common cystic neoplasms of the pancreas and provides radiologic, endoscopic, macroscopic, and histologic examples. Table 1 pr