Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging （MRI）/magnetic resonance cholangio pancreatography （MRCP） and computer tomography （CT） scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms （IPMN）. While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

International guidelines for the management of pancreatic intraductal papillary mucinous neoplasms

The management of intraductal papillary mucinous neoplasms(IPMN) is presently evolving as a result of the improved understanding of the natural history and biological behavior of the different pancreatic cystic neoplasms; and better preoperative diagnosis of these neoplasms due to advancement in preoperative diagnostic tools. International consensus guidelines for the management of IPMN were first formulated in 2006 and subsequently revised in 2012. Both these guidelines were constructed based on expert opinion and not on robust clinical data. The main limitation of the original Sendai guidelines was that it had a low positive predictive value resulting in many benign neoplasms being resected. Hence,these guidelines were revised in 2012. However,although the updated guidelines resulted in an improvement in the positive predictive value over the Sendai Guidelines,the results of several studies validating these guidelines demonstrated that its positive predictive value remained low. Furthermore,although both guidelines were associated with high negative predictive values,several investigators have demonstrated that some malignant IPMNs may be missed. Finally,it is imperative to emphasize that major considerations when managing a patient with IPMN including the patient's surgical risk,life-expectancy and even cost of investigations are not taken into account in current guidelines. The management of a patient with IPMN should be individualized and tailored according to a patient's risk benefit profile for resection vs surveillance.     

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.     

Epidemiology,clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey

IntroductionA prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines.MethodsAn online data sheet was built.ResultsFifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up.ConclusionsThis prospective study offers a reliable real-life picture of the diagnostic work-up CPN.     

Resection of pancreatic cystic neoplasms in recurrent acute pancreatitis prevents recurrent pancreatitis but does not identify more malignancies

BACKGROUNDRecurrent acute pancreatitis (RAP) may be a presenting feature of and an indication for resection of pancreatic cysts, including intra-ductal papillary mucinous neoplasm (IPMN). Few data are available regarding the prevalence of malignancy and post-operative RAP in this population.AIMTo study the role of resection to help prevent RAP and analyze if presentation as RAP would be a predictor for malignancy.METHODSThis retrospective study assessed 172 patients who underwent surgical resection of pancreatic cystic neoplasms at a university hospital between 2002 and 2016. The prevalence of preoperative high-risk cyst features, and of neoplasia was compared between patients with and without RAP. To identify the cause of pancreatitis, all the patients had a detailed history of alcohol, smoking, medications obtained, and had cross-sectional imaging (contrast-enhanced computed tomography/magnetic resonance imaging) and endoscopic ultrasound to look for gallstone etiology and other structural causes for pancreatitis. The incidence of RAP post-resection was the primary outcome.RESULTSIPMN accounted for 101 cases (58.7%) {[branch duct (BD) 59 (34.3%), main duct (MD) 42] (24.4%)}. Twenty-nine (16.9%) presented with RAP (mean 2.2 episodes): 15 had BD-IPMN, 8 MD-IPMN, 5 mucinous cystic neoplasm and 1 serous cystic neoplasm. Malignancy was similar among those with vs without RAP for all patients [6/29 (20.7%) vs 24/143 (16.8%)] and IPMN patients [6/23 (26.1%) vs 23/78 (29.5%)], although tended to be higher with RAP in BD-IPMN, [5/15 (33.3%) vs 3/44 (6.8%), P = 0.04]. At mean follow-up of 7.2 years, 1 (3.4%) RAP patient had post-resection RAP. The mean episodes of acute pancreatitis before vs after surgery were 3.4 vs 0.02 (P < 0.0001). CONCLUSIONMalignancy was not increased in patients with pancreatic cystic neoplasms who have RAP compared to those without RAP. In addition, specific cyst charac-teristics were not clearly associated with RAP. The incidence of RAP was markedly decreased in almost all patients following cyst resection.     

Prevalence,Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed.     

Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas （IPMNs）. IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ＂new＂ but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head （75%） while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year- old male diagnosed with IPMN （carcinoma in situ） in the pancreatic head and a branch duct type IPMN （duct atypia） in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.     

Pancreatic incidentalomas: Investigation and management

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management.     

胰腺癌前病变诊断和治疗

目的 通过对7例胰腺癌前病变患者的临床诊断和治疗分析,探讨此类疾病诊断方法的应用及治疗策略.方法 收集2006年1月-2007年12月92例手术治疗胰腺肿瘤中有癌前病变的7例患者,其中黏液囊腺瘤(MCN)1例、导管内乳头状黏液瘤(IPMN)2例、胰腺内分泌肿瘤1例、胰腺上皮内瘤变(PanIN)Ⅰ级、Ⅱ级及Ⅲ级各1例.采用免疫荧光分析法测定患者血清CA19-9.7例上腹部均行超声和螺旋CT检查;1例行超声内镜检查及穿刺;2例行逆行胰胆管造影检查.结果 胰腺癌前病变临床表现不典型,影像学检查常无实质性肿块,但PanIN可伴有胰管扩张、狭窄;IPMN在胰头处可表现为囊性扩张的胰管;囊腺瘤等在胰体尾处可表现为单个孤立的囊肿.肿瘤指标CA19-9在此类疾病中可轻度增高.但对诊断作用有限.手术切除可治愈,并可防止肿瘤的进一步癌变.结论 对疑为胰腺癌前病变患者需积极选用多种影像学方法进行诊断,并予以积极的手术探查及切除.     

Repeated pancreatectomy after pancreato-duodenectomy for a intraductal papillary mucinous tumour: advantage of pancreatico-gastrostomy with a gastric partition

Background

Regular follow-up and monitoring of intraductal papillary mucinous neoplasms (IPMN) is important as there is a risk of recurrence in both the non-invasive and invasive IPMN.

Methods

Three patients developed pancreatic remnant recurrence after a pancreatico-duodenectomy for IPMN. Pancreatico-gastrostomy anastomosis was performed in all patients. Long-term follow-up was performed with radiographical surveillance and by endoscopic gastroscopy.

Results

Magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) revealed in one patient, 2 years after surgery, a 3-cm mass at the site of the anastomosis and dilatation of the Wirsung duct >6 mm in two other patients (2 and 3 years after surgery, respectively). The diagnosis of recurrence was confirmed endoscopically by the presence of a large amount of mucin at the anastomotic site. Cytological examination revealed moderate dysplasia. Opacification of the Wirsung duct after endoscopic retrograde cholangiopancreatography (ERCP) was only possible in one patient in whom an irregular stenosis of the duct was observed.

Conclusions

Long-term follow-up of the pancreatic remnant after pancreato-duodenectomy for IPMN is better achieved with pancreatico-gastrostomy anastomosis.     

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.     

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective Resection

Due to the widespread use of high-quality cross-sectional imaging, pancreatic cystic neoplasms are being diagnosed with increasing frequency. Clinicians are therefore asked to counsel a growing number of patients with pancreatic cysts diagnosed incidentally at an early, asymptomatic stage. Over the last two decades, accumulating knowledge on the biologic behavior of these neoplasms along with improved diagnostics through imaging and endoscopic cyst fluid analysis have allowed for a selective therapeutic approach toward these neoplasms. On one end of the management spectrum, observation is recommended for typically benign lesions (serous cystadenoma), and on the other end, upfront resection is recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma, solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In between, management of premalignant lesions (branch duct IPMN) is dictated by the presence of high-risk features. In general, resection should be considered whenever the risk of malignancy is higher than the risk of the operation. This review aims to describe the evolution and current status of evidence guiding the selection of patients with pancreatic cystic neoplasms for surgical resection, along with a specific discussion on the type of resection required and expected outcomes.     

Decreased CT-number in the pancreatic parenchyma is a reliable imaging biomarker of the presence of malignancies in patients with high-risk intraductal papillary mucinous neoplasm

BackgroundIntraductal papillary mucinous neoplasm (IPMN) is a premalignant cystic neoplasm of the pancreas and is frequently detected in imaging investigations. A proportion of the patients with IPMN develop malignancies including high-grade dysplasia and invasive carcinoma. To predict the presence of malignancies in IPMN, constant imaging follow-up is usually required. Pancreatic steatosis (PS) has been recently identified as a facilitating factor for pancreatic cancer, and can be predicted through computed tomography (CT). We hypothesized that the CT-number of the pancreatic parenchyma could be a new reliable imaging biomarker for IPMN patients.MethodsEighty-six patients undergoing pancreatectomy for IPMN were investigated. Using preoperative CT, the pancreatic index (PI) was calculated by dividing the CT-number of the pancreas by that of the spleen.ResultsMalignancies were pathologically detected in 63 cases (73.3%). Patients were divided into two cohorts according to the presence of malignancies and were compared for various factors including the PI scores. The comparison of the two cohorts detected significant differences in two parameters (CA19-9 and PI score), and the PI score was the most sensitive biomarker to predict the presence of malignancies in patients showing high-risk stigmata of IPMN.ConclusionsPancreatic CT-number is an additional reliable imaging biomarker in distinguishing patients with IPMN having malignancies when investigating the patients showing high-risk stigmata.     

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.     

多层螺旋CT对胰腺囊性肿瘤的诊断价值

目的探讨多层螺旋CT对胰腺囊性肿瘤的表现和诊断价值,以提高对该类疾病的认识。方法回顾性分析谷城县人民医院2010年1月-2013年1月18例经手术或穿刺活检标本病理证实的胰腺囊性肿瘤患者的CT资料。结果浆液性囊腺瘤8例,7例小囊型,1例大囊型,小囊型病灶较小,囊内有分隔,强化是呈海绵状,1例可见中央星状瘢痕伴钙化,大囊型病灶呈薄壁大囊,无囊壁结节及分隔,增强扫描囊壁轻度强化;黏液性腺瘤6例,2例表现为单房囊性病灶,4例表现为多房分隔囊性病灶,增强后壁有强化;黏液性囊腺癌2例,1例伴有肝转移;实性假乳头状瘤2例,均为囊实混合型。结论多层螺旋CT对胰腺囊性肿瘤具有高度敏感性,不同病变有其特征表现,对术前诊断有一定价值。     

Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

Pancreatic cysts are increasingly diagnosed due to the widespread use of cross-sectional imaging, and some of these lesions harbor malignant potential. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are the major premalignant cystic neoplasms of the pancreas. A variety of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients with pancreatic cystic neoplasms.     

Intraductal papillary mucinous tumors and mucinous cystic tumors of the pancreas: imaging

Most cystic lesions of the pancreas are nonneoplastic and inflammatory in nature. However, approximately 5%–15% of cystic pancreatic masses may be neoplastic. Among the cystic neoplasms are the mucin-producing tumors, both the intraductal papillary mucinous neoplasms and the mucinous cystic neoplasms. Their imaging features on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) can assist in the differentiation of these lesions. The imaging findings of both intraductal papillary mucinous neoplasm and mucinous cystic neoplasm are reviewed with attention to CT and MRI.     

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer

Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.     

Pancreatic CT density is an optimal imaging biomarker for earlier detection of malignancy in the pancreas with intraductal papillary mucinous neoplasm

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are typically detected as incidental findings by computed tomography (CT); however, the conventional surveillance is not valid for the early detection of concomitant pancreatic cancer. The pancreas of IPMN is often accompanied by fatty infiltration in the parenchyma, and pancreatic fatty infiltration could be evaluated by pancreatic CT density (pancreatic index, PI). We aimed to investigate whether PI could be an imaging biomarker for the early prediction of malignancies in the pancreas with IPMN.MethodsTwo different cohorts were investigated. (Investigation cohort): A total of 1137 patients with initially low-risk IPMN were compensated by initial IPMN findings, and 2 groups (malignancy/possible benign, 50 cases each) were investigated for yearly changes in PI and for the cutoff value of PI indicating the development of malignancies. (Validation cohort): To validate the cutoff value, 256 patients radiologically suspected of having IPMNs were investigated.Results(Investigation-cohort): The malignancy group showed a gradual decrease in PI every year, and PI significantly differed among the 2 groups 1 year prior to the last investigation. The cutoff value of PI was set at 0.65. (Validation-cohort): A total of 55% of the patients with a PI below the cutoff value had malignancy in the pancreas, including concomitant pancreatic cancer, and the cutoff value was the most significant risk factors for the development of malignancies in the pancreas compared to the conventional risk factors for IPMN.ConclusionsDecreasing PI would be an optimal imaging biomarker for earlier detection of malignancies in the pancreas with IPMN.