Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas

In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.

Expression of the tumor suppressor gene maspin and its significance in intraductal papillary mucinous neoplasms of the pancreas

BACKGROUND: Maspin is a member of the serpin family of protease inhibitors and is thought to inhibit carcinoma invasion, metastasis, and angiogenesis and induce apoptosis. We examined maspin expression immunohistochemically and assessed its significance in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: We examined 39 surgically resected specimens of IPMN that included 17 adenomas (IPMAs), 5 borderline tumors (IPMBs), 4 non-invasive carcinomas (non-invasive IPMCs), and 13 invasive carcinomas (invasive IPMCs). Immunostaining was performed according to the EnVision ChemMate method. The degree of maspin expression was scored and assessed according to the percentage and staining intensity of positive cells. RESULTS: Maspin expression was minimal in normal pancreatic duct epithelium, whereas in IPMNs, maspin was expressed in neoplasms of all stages. Maspin expression increased with increasing grade from IPMAs, IPMBs, to non-invasive IPMCs but decreased significantly in invasive IPMCs. No specific association between maspin expression and mucin type was found. Analysis of maspin expression with respect to clinicopathologic factors in cases of invasive IPMC revealed a greater extent of invasion in cases of low maspin expression and significantly fewer apoptotic cells in the tumor.CONCLUSIONS: Maspin was expressed at high levels in IPMNs at various stages from adenoma to invasive carcinoma, and our results suggest that maspin may be involved in the occurrence and progression of IPMN. In addition, our data suggest that the apoptosis-inducing action of maspin suppresses invasion and progression of IPMN.

molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

Imaging considerations in intraductal papillary mucinous neoplasms of the pancreas

With the widespread use of cross-sectional imaging,particularly computed tomography(CT) and magnetic resonance imaging(MRI),and the continuous improvement in the image quality of these techniques,the diagnosis of incidental pancreatic cysts has increased dramatically in the last decades.While the vast majority of these cysts are not clinically relevant,a small percentage of them will evolve into an invasive malignant tumor making their management challenging.Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms(IPMN) are the most common pancreatic cystic lesions with malignant potential.Imaging findings on CT and MRI correlate tightly with the presence of malignant degeneration in these neoplasms.IPMN can be classified based on their distribution as main duct,branch duct or mixed type lesions.MRI is superior to CT in demonstrating the communication of a branch duct IPMN with the main pancreatic duct(MPD).Most branch duct lesions are benign whereas tumors involving the MPD are frequently associated with malignancy.The presence of solid nodules,thick enhancing walls and/or septae,a wide(> 1 cm) connection of a side-branch lesion with the MPD and the size of the tumor > 3 cm are indicative of malignancy in a branch and mixed type IPMN.A main pancreatic duct > 6 mm,a mural nodule > 3 mm and an abnormal attenuating area in the adjacent pancreatic parenchyma on CT correlates with malignant disease in main duct and mixed type IPMN.An accurate characterization of these neoplasms by imaging is thus crucial for selecting the best management options.In this article,we review the imaging findings of IPMN including imaging predictors of malignancy and surgical resectability.We also discuss follow-up strategies for patients with surgically resected IPMN and patients with incidental pancreatic cysts.

Extrapancreatic malignancies and intraductal papillary mucinous neoplasms of the pancreas

Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identified in 10%-52% of patients with IPMNs.The majority of these additional cancers occur before or concurrent with the diagnosis of IPMN.The gastrointestinal tract is most commonly involved in secondary malignancies,with benign colon polyps and colon cancer commonly seen in western countries and gastric cancer commonly seen in Asian countries.Other extrapancreatic malignancies associated with IPMNs include benign and malignant esophageal neoplasms,gastrointestinal stromal tumors,carcinoid tumors,hepatobiliary cancers,breast cancers,prostate cancers,and lung cancers.There is no clear etiology for the development of secondary malignancies in patients with IPMN.Although population-based studies have shown different results from single institution studies regarding the exact incidence of additional primary cancers in IPMN patients,both have reached the same conclusion:there is a higher incidence of extrapancreatic malignancies in patients with IPMNs than in the general population.This f inding has signif icant clinical implications for both the initial evaluation and the subsequent long-term followup of patients with IPMNs.If a patient has not had recent colonoscopy,this should be performed during the evaluation of a newly diagnosed IPMN.Upper endoscopy should be performed in patients from Asian countries or for those who present with symptoms suggestive of upper gastrointestinal disease.Routine screening studies(breast and prostate) should be carried out as currently recommended for patient's age both before and after the diagnosis of IPMN.

Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography

AIM:To retrospectively evaluate the imaging features of pancreatic intraductal papillary mucinous neoplasms (IPMNs) in multi-detector row computed tomography (MDCT).METHODS: A total of 20 patients with pathologically-confirmed intraductal papillary mucinous neoplasms (IPMNs) were included in this study. Axial MDCT images combined with CT angiography (CTA) and multiplanar volume reformations (MPVR) or curved reformations (CR) were preoperatively acquired. Two radiologists (Tan L and Wang DB) reviewed all the images in consensus using an interactive picture archiving and communication system. The disputes in readings were resolved through consultation with a third experienced radiologist (Chen KM). Finally, the findings and diagnoses were compared with the pathologic results.RESULTS: The pathological study revealed 12 malignant IPMNs and eight benign IPMNs. The diameters of the cystic lesions and main pancreatic ducts (MPDs) were significantly larger in malignant IPMNs compared with those of the benign IPMNs (P<0.05). The combined-type IPMNs had a higher rate of malignancy than the other two types of IPMNs (P<0.05). Tumors with mural nodules and thick septa had a significantly higher incidence of malignancy than tumors without these features (P<0.05). Communication of side-branch IPMNs with the MPD was present in nine cases at pathologic examination. Seven of them were identified from CTA and MPVR or CR images. From comparison with the pathological diagnosis, the sensitivity, specificity, and accuracy of MDCT in characterizing the malignancy of IPMN of the pancreas were determined to be 100%, 87.5% and 95%, respectively.CONCLUSION: MDCT with CTA and MPVR or CR techniques can elucidate the imaging features of IPMNs and help predict the malignancy of these tumors.

Prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasms(IPMN) are mucin producing cystic neoplasms of the pancreas histologically classified as having non-invasive and invasive components.The five-year survival rates for non-invasive and associated invasive carcinoma are 90% and 40%,respectively in resected IPMN lesions.Invasive carcinoma within IPMN lesions can be further classified by histological subtype into colloid carcinoma and tubular carcinoma.Estimated five-year survival rates following resection of colloid carcinoma range from 57%-83% and estimated five-year survival following resection of tubular carcinoma range from 24%-55%.The difference in survival outcome between invasive colloid and tubular IPMN appears to be a function of disease biology,as patients with the tubular subtype tend to have larger tumors with a propensity for metastasis to regional lymph nodes.When matched to resected conventional pancreatic adenocarcinoma lesions by the Memorial Sloan Kettering Cancer Center pancreatic adenocarcinoma nomogram,the colloid carcinoma histological subtype has an improved estimated five-year survival outcome compared to conventional pancreatic adenocarcinoma,87% and 23%(P = 0.0001),respectively.Resected lesions with the tubular carcinoma subtype overall have a similar five-year survival outcome compared to conventional pancreatic adenocarcinoma.However,when these groups were stratified by regional lymph node status patients with negative regional lymph nodes and the tubular subtype experienced significantly better survival than patients with a similar nodal status and ductal adenocarcinoma with estimated five-year survival rates of 73% and 27%(P = 0.01),respectively.

Nomograms predicting long-term survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: A population-based study

BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas.METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance,Epidemiology,and End Results database,and randomly divided into the training(n=853)and the validation(n=366)cohorts.Based on the Cox regression model,nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient.The performance of the nomograms was measured according to discrimination,calibration,and clinical utility.Moreover,we compared the predictive accuracy of the nomograms with that of the traditional staging system.RESULTS In the training cohort,age,marital status,histological type,T stage,N stage,M stage,and chemotherapy were selected to construct nomograms.Compared with the American Joint Committee on Cancer 7th staging system,the nomograms were generally more discriminative.The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction.Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system.With respect to decision curve analyses,the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities.CONCLUSION The nomograms show improved predictive accuracy,discrimination capability,and clinical utility,which can be used as reliable tools for risk classification and treatment recommendations.

Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas

AIM:To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas(IPMN).METHODS:Over a 14-year period,50 patients who did not undergo surgery for resectable main-duct or mixed IPMN,for reasons of precluding comorbidities,age and/or refusal,were compared with 74 patients who underwent resection to assess differences in rates of survival,recurrence/occurrence of malignancy,and prognostic factors.All study participants had dilatation of the main pancreatic duct by ≥ 5 mm,with or without dilatation of the branch ducts.Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration.For the surgical patients,pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct.Clinical and biologic follow-ups were conducted for all patients at least annually,through hospitalization or consultation every six months during the first year of follow-up,together with abdominal imaging analysis(magnetic resonance cholangiopancreatography or computed tomography) and,if necessary,endoscopic ultrasound with or without fine needle aspiration.RESULTS:The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients(74% vs 58%; P =0.019).The parameters of age(< 70 years) and absence of a nodule were associated with better survival(P < 0.05); however,the parameters of main pancreatic duct diameter > 10 mm,branch ductdiameter > 30 mm,or presence of extra pancreatic cancers did not significantly influence the prognosis.In the nonsurgical patients,pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo(median:29 mo; range:8-141 mo).Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age,sex,symptoms,subtype of IPMN,or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups,with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis(> 10 mm).CONCLUSION:Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.

Evolution of incidental branch-duct intraductal papillary mucinous neoplasms of the pancreas: A study with magnetic resonance imaging cholangiopancreatography

AIM To investigate the type and timing of evolution of incidentally found branch-duct intraductal papillary mucinous neoplasms(bd-IPMN) of the pancreas addressed to magnetic resonance imaging cholangiopancreatography(MRCP) follow-up.METHODS We retrospectively evaluated 72 patients who underwent, over the period 2006-2016, a total of 318 MRCPs(mean 4.4) to follow-up incidental, presumed bdIPMN without signs of malignancy, found or confirmedat a baseline MRCP examination. Median follow-up time was 48.5 mo(range 13-95 mo). MRCPs were acquired on 1.5T and/or 3.0T systems using 2D and/or 3D technique. Image analysis assessed the rates of occurrence over the follow-up of the following outcomes:(1) imaging evolution, defined as any change in cysts number and/or size and/or appearance; and(2) alert findings, defined as worrisome features and/or high risk stigmata(e.g., thick septa, parietal thickening, mural nodules and involvement of the main pancreatic duct). Time to outcomes was described with the Kaplan-Meir approach. Cox regression model was used to investigate clinical or initial MRCP findings predicting cysts changes.RESULTS We found a total of 343 cysts(per-patient mean 5.1) with average size of 8.5 mm(range 5-25 mm). Imaging evolution was observed in 32/72 patients(44.4%; 95%CI: 32-9-56.6), involving 47/343 cysts(13.7%). There was a main trend towards small(< 10 mm) increase and/or decrease of cysts size at a median time of 22.5 mo. Alert findings developed in 6/72 patients(8.3%; 95%CI: 3.4-17.9) over a wide interval of time(13-63 mo). No malignancy was found on endoscopic ultrasound with fine-needle aspiration(5/6 cases) or surgery(1/6 cases). No clinical or initial MRCP features were significantly associated with changes in bd-IPMN appearance(P > 0.01).CONCLUSION Changes in MRCP appearance of incidental bd-IPNM were frequent over the follow-up(44.4%), with relatively rare(8.3%) occurrence of non-malignant alert findings that prompted further diagnostic steps. Changes occurred at a wide interval of time and were unpredictable, suggesting that imaging followup should be not discontinued, though MRCPs might be considerably delayed without a significant risk of missing malignancy.

Reoperation for heterochronic intraductal papillary mucinous neoplasm of the pancreas after bile duct neoplasm resection:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)and intraductal papillary mucinous neoplasm(IPMN)of the pancreas have similar pathological manifestations.However,they often develop separately and it is rare for both to occur together.Patients presenting with heterochronic IPMN after IPNB are prone to be misdiagnosed with tumor recurrence.CASE SUMMARY A 67-year-old male patient was admitted 8.5 years after IPNB carcinoma and 4 years after the discovery of a pancreatic tumor.A left hepatic bile duct tumor with distal bile duct dilatation was found 8.5 years ago by the computed tomography;therefore,a left hepatectomy was performed.The postoperative pathological diagnosis was malignant IPNB with negative cutting edge and pathological stage T1N0M0.Magnetic resonance imaging 4 years ago showed cystic lesions in the pancreatic head with pancreatic duct dilatation,and carcinoembryonic antigen continued to increase.Positron emission tomography showed a maximum standard uptake value of 11.8 in the soft tissue mass in the pancreatic head,and a malignant tumor was considered.Radical pancreatoduodenectomy was performed.Postoperative pathological diagnosis was pancreatic head IPMN with negative cutting edge,pancreaticobiliary type,stage T3N0M0.He was discharged 15 d after the operation.Follow-up for 6 mo showed no tumor recurrence,and quality of life was good.CONCLUSION IPNB and IPMN are precancerous lesions with similar pathological characteristics and require active surgery and long-term follow-up.

Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms

High rates of extrapancreatic malignancies,in particular colorectal cancer(CRC),have been detected in patients with intraductal papillary mucinous neoplasm(IPMN).So far,there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with IPMN.In the past few years,some data related to common genetic alterations in IPMN and other affiliated cancers have been published.This review elucidated the association between IPMN and CRC,shedding light on the most relevant genetic alterations that may explain the possible relationship between these entities.In keeping with our findings,we suggested that once the diagnosis of IPMN is made,special consideration of CRC should be undertaken.Presently,there are no specific guidelines regarding colorectal screening programs for patients with IPMN.We recommend that patients with IPMNs are at high-risk for CRC,and a more rigorous colorectal surveillance program should be implemented.

The clinicopathologic features of intraductal papillary mucinous neoplasms of the pancreas

Since first described in 1982,intraductal papillary mucinous neoplasm(IPMN)has been the preferred term to describe the proliferation of the pancreatic ductal epithelium.It is totally different from pancreatic carcinoma in epi demiology,histology,pathology and prognosis.According to the site of involvement,IPMNs are classified into three categories,i.e.main duct type,branch duct type,and combined type.Most branch duct IPMNs are benign,whereas the other two types are often malignant.A large branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least.The additional existence of large mural nodules increases the possibility of malignancy in all types.The prognosis is more favorable after complete resection of benign and non-invasive malignant IPMNs.Malignant IPMNs that become more aggressive after parenchymal invasion necessitate adequate lymph node dissection.On the other hand,asymptomatic branch duct IPMNs without mural nodules can be observed without the need for resection for a considerable period of time.Our review addresses available data,current understanding,controversy,and future directions about IPMNs.

Clinical implications of the molecular characterization of intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm(IPMN)is a pre-malignant,mucin-producing epithelial lesion arising from pancreatic ducts.Observational reports define IPMN behavior as ranging from indolent,asymptomatic lesions to dysplasia that sometimes degenerate into pancreatic adenocarcinoma.The goal of IPMN management is risk-reducing surgery for high-risk cysts and observation of the remainder.Discriminating high-from low-risk IPMN disease still relies on imaging and clinical cyst characteristics.Here,we review the accepted classification of IPMN including the most common histological subtypes,their clinical features,and currently-accepted high-risk phenotypes.We then deeply examine the known molecular landscape of IPMN,which has largely been derived from post-resection analysis.This includes those gene variants unique to IPMN,chiefly GNAS and RNF43,but also examines the overlap between IPMN and conventional pancreatic adenocarcinoma.Utilizing molecular markers in the clinical setting relies on endoscopically-obtained cyst fluid and presumes that it accurately represents the molecular characteristics of the cystic epithelium.We synthesize existing data on mutational analysis from IPMN cyst fluid and consider the benefits and proper role of current commercially-available cyst fluid molecular analysis kits.We conclude that carefully interpreted molecular analysis of resected IPMN tissue reveals insights into its biology and natural history while cyst fluid analysis offers prognostication and data to guide treatment decisions.However,knowledge gaps remain,especially in characterizing IPMN molecular heterogeneity,time to progression,and correlating cyst fluid genotype data with surveillance strategies.As such,substantial additional research is required before the promise of true molecular guidance of IPMN management can be realized.

Simultaneous intraductal papillary neoplasms of the bile duct and pancreas treated with chemoradiotherapy

Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.

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.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm(IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucinproducing cells arising in the main duct(MD) and/or branch ducts(BD) of the pancreas.Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity.IPMN lacks ovarian-type stroma,unlike mucinous cystic neoplasm,and is defined as a grossly visible entity(≥ 5 mm),unlike pancreatic intraepithelial neoplasm.With the use of high-resolution imaging techniques,very small IPMNs are increasingly being identified.Most IPMNs are solitary and located in the pancreatic head,although 20%-40% are multifocal.Macroscopic classification in MD type,BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications.Based on cytoarchitectural atypia,IPMN is classified into low-grade,intermediategrade and high-grade dysplasia.Based on histological features and mucin(MUC) immunophenotype,IPMNs are classified into gastric,intestinal,pancreatobiliary and oncocytic types.These different phenotypes can be observed together,with the IPMN classified according to the predominant type.Two pathways have been suggested:gastric phenotype corresponds to less aggressive uncommitted cells(MUC1-,MUC2-,MUC5 AC +,MUC6 +) with the capacity to evolve to intestinal phenotype(intestinal pathway)(MUC1-,MUC2 +,MUC5 AC +,MUC6- or weak +) or pancreatobiliary /oncocytic phenotypes(pyloropancreatic pathway)(MUC1 +,MUC 2-,MUC5 AC +,MUC 6 +) becoming more aggressive.Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises(about 40% of IPMNs),except in some cases of minimal invasion.The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer.Once resected,they must be extensively sampled or,much better,submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms(IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree.Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning(FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive,in order to avoid an excessive pancreatic resection.Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease.FS accuracy averages 95%.Eroded epithelium on the main duct,severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results.FS results change the planned extent of resection in up to 30% of cases.The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatec-tomy if FS reveals:(1) at least IPMN adenoma on the main duct;or(2) at least borderline IPMN on branch ducts;or(3) invasive carcinoma.However,the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age,general condition and expected prognosis after resection.The main limitation of using FS is the existence of discontinuous("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

Intraductal papillary-mucinous neoplasia of the pancreas:Histopathology and molecular biology

Intraductal papillary-mucinous neoplasm(IPMN) of the pancreas is a clinically and morphologically distinctive precursor lesion of pancreatic cancer,characterized by gradual progression through a sequence of neoplastic changes.Based on the nature of the constituting neoplastic epithelium,degree of dysplasia and location within the pancreatic duct system,IPMNs are divided in several types which differ in their biological properties and clinical outcome.Molecular analysis and recent animal studies suggest that IPMNs develop in the context of a field-defect and reveal their possible relationship with other neoplastic precursor lesions of pancreatic cancer.

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas

AIM: As intraductal papillary mucinous neoplasm (IPMN)has a favorable prognosis, associated malignancies have potential significance in these patients. We examined the incidence and characteristics of pre-existing, coexisting and subsequent malignancies in patients with IPMN. METHODS: Seventy-nine cases of IPMN were diagnosed by detection of mucous in the pancreatic duct during endoscopic retrograde pancreatography. Histological diagnosis was confirmed in 30 cases (adenoma (n = 19)and adenocarcinoma (n = 11). Other primary malignancies associated with IPMN, occurring in the prediagnostic or postdiagnostic period, were investigated. Postdiagnostic follow-up period was 3.3±0.5 years (range, 0.2-20 years).RESULTS: Other 40 malignancies occurred in 28 patients (35%). They were found before (n = 15), at (n = 19) and after (n = 6) the diagnosis of IPMT. Major associated malignancies were gastric cancer (n = 12), colonic cancer (n = 7), esophageal cancer (n = 4), pulmonary cancer (n = 4), and independent pancreatic cancer (n = 3).Pancreatic cancer was synchronous with IPMN in two patients and metachronous in one (3 years after diagnosis of IPMN). Thirty-one lesions were treated surgically or endoscopically. Fourteen patients died of associated cancers. Development of other malignancies was related to age (71.9±8.2 vs66.8±9.3, P＜0.05), but not to gender or site of the tumor.CONCLUSION: IPMN is associated with a high incidence of other malignancies, particularly gastric and colonic cancers. Common genetic mechanisms between IPMN and other associated malignancies might be present. Clinicians should pay attention to the possibility of associated malignancies in preoperative screening and follow-up of patients with IPMN.