Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-hypersecreting IPNB achieved clinical success.The patient with polypoid type IPNB achieved curative resection.There were no PTCS-BP-related serious adverse events.CONCLUSION PTCS-BP appears to be feasible,efficacious,and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Surgically treating a rare and asymptomatic intraductal papillary neoplasm of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasms of the bile duct(IPNBs)are rare and characterized by papillary growth within the bile duct lumen.IPNB is similar to obstructive biliary pathology.In this report,we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this condition.Integrating relevant literature contributes to a more comprehensive understanding of the disease.CASE SUMMARY A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical examination.Preoperative imaging revealed a lesion on the left side of the liver,which raised the suspicion of IPNB.A laparoscopic left hemihepatectomy was performed,and subsequent histopathological examination confirmed the diagnosis of IPNB.At the 3-mo postoperative follow-up,the patient reported good recovery and no metastasis.IPNB can manifest both latently and asymptomatically.Radical surgical resection is the most effective treatment for IPNB.CONCLUSION Hepatic and biliary masses,should be considered to diagnose IPNB.Prompt surgery and vigilant follow-up are crucial in determining prognosis.

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.

Intraductal papillary neoplasm of the bile duct:The new frontier of biliary pathology

Intraductal papillary neoplasms of the bile duct(IPNBs)represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen.Since their first description in 2001,several classifications have been proposed,mainly based on histopathological,radiological and clinical features,although no specific guidelines addressing their management have been developed.Bile duct neoplasms generally develop through a multistep process,involving different precursor pathways,ranging from the initial lesion,detectable only microscopically,i.e.biliary intraepithelial neoplasia,to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma.Complex and advanced investigations,mainly relying on magnetic resonance imaging(MRI)and cholangioscopy,are required to reach a correct diagnosis and to define an adequate bile duct mapping,which supports proper treatment.The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB,as well as their natural evolution with a particular focus on prognosis and survival.Aggressive surgical resection,including hepatectomy,pancreaticoduodenectomy or both,represents the treatment of choice,yielding optimal results in terms of survival,although several endoscopic approaches have been described.IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential.The novel subclassification of types 1 and 2 defines the histological and clinical aspects,prognosis and survival.Diagnosis is mainly based on MRI and cholangioscopy.Surgical resection represents the mainstay of treatment,although endoscopic resection is currently applied to nonsurgically fit patients.New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB,to identify targeted therapies.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

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.

Intraductalpapillarymucinousneoplasmofthebileductwithgastricand duodenalfistulas

Intraductal papillary mucinous neoplasm (IPMN) of the bile duct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowl-edge, only two cases of IPMN of the bile duct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bile duct penetrating into two neighboring organs of the stom-ach and duodenum presenting with abdominal pain and jaundice. Endoscopy showed thick mucin extruding from two openings of the fistulas. Endoscopic suction of thick mucin using direct peroral cholangioscopy with ultra-slim endoscope through choledochoduodenal fis-tula was very difficult and ineffective because of very thick mucin and next endoscopic suction through the stent after prior insertion of biliary metal stent into cho-ledochogastric fistula also failed. Pathologic specimen obtained from the proximal portion of the choledocho-gastric fistula near left intrahepatic bile duct through the metal stent showed a low grade adenoma. The pa-tient declined the surgical treatment due to her old age and her abdominal pain with jaundice was improved af-ter percutaneous transhepatic biliary drainage with the irrigation of N-acetylcysteine three times daily for 10 d.

Intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.

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.

Intraductal papillary neoplasm of the bile ducts: A case report and literature review

Intraductal papillary neoplasm of the bile duct(IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries,it is very rare and the etiology is unknown. In this article,we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-yearold female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB,gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of Pub Med database,we collected 354 IPNB patients reported in 22 articles. In these patients,52.8% were from Japan and 27.7% were from western countries including the United States(11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically,57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically,pancreato-biliary subtype accounted for 41.8%,intestinal 28.0%,gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies,diagnosis of IPNB is still challenging,especially in western countries due to its rarity. Defined clinicopathologic features are in demand for the accurate diagnosis and proper treatment.

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.

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.

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.

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.

Current status of diagnosis and therapy for intraductal papillary neoplasm of the bile duct

Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts.Clinicopathological images of these tumours are distinctive and diverse,including histological images with a low to high grade dysplasia,infiltrating and noninfiltrating characteristics,excessive mucus production,and similarity to intraductal papillary mucinous neoplasm(IPMN)of the pancreas.The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features,intraductal papillary neoplasm of the bile duct(IPNB),as precancerous lesion of biliary carcinoma.IPNB is currently classified into type 1 that is similar to IPMN,and type 2 that is not similar to IPMN.Many of IPNB spreads superficially,and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression.Prognosis of IPNB is said to be better than normal bile duct cancer.

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.

Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data revealed jaundice and liver injury.Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary growth.Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated orifice.Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic imaging.Therefore,the initial diagnosis was IPNB.After endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was performed.Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type IPNB.In addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident.Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET.

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.