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.

Common bile duct lesions-how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare variant of bile duct tumors,characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree,with morphological variations and occasional invasion.CASE SUMMARY We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography.Using the SpyGlass DS Ⅱ technology,we were able to define tumor extension and obtain targeted Spy-byte biopsies.After multidisciplinary evaluation,the patient was scheduled for surgical resection of the tumor,which was radically removed.CONCLUSION Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

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.

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.

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.

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.

Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy

BACKGROUND Intraductal papillary mucinous neoplasms(IPMNs)are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal adenocarcinoma.Currently,the International Consensus Guidelines(ICG)for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography(CT)imaging.Despite using the ICG,it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection.A supplementary quantitative radiological tool,radiomics,may improve diagnostic accuracy of radiological evaluation of IPMNs.We hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN histology.AIM To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus Guidelines.METHODS Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective cohort.Whole lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software(Healthmyne,Madison,WI).Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast phase.Univariate analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic regression.Conventional quantitative and qualitative CT measurements were also compared between groups,viaχ2(categorical)and Mann Whitney U(continuous)variables.RESULTS Twenty-nine subjects(15 males,age 71±9 years)with high grade or invasive tumor histology comprised the"malignant"cohort,while 22 subjects(11 males,age 70±7 years)with low grade tumor histology were included in the"benign"cohort.Radiomic analysis showed 18/39 precontrast,19/39 arterial phase,and 21/39 venous phase features differentiated malignant from benign IPMNs(P<0.05).Multivariate analysis including only ICG criteria yielded two significant variables:thickened and enhancing cyst wall and enhancing mural nodule<5 mm with an AUC(95%CI)of 0.817(0.709-0.926).Multivariable post contrast radiomics achieved an AUC(95%CI)of 0.87(0.767-0.974)for a model including arterial phase radiomics features and 0.834(0.716-0.953)for a model including venous phase radiomics features.Combined multivariable model including conventional variables and arterial phase radiomics features achieved an AUC(95%CI)of 0.93(0.85-1.0)with a 5-fold cross validation AUC of 0.90.CONCLUSION Multi-phase CT radiomics evaluation could play a role in improving predictive capability in diagnosing malignancy in IPMNs.Future larger studies may help determine the clinical significance of our findings.

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.

Pancreatic intraductal papillary mucinous neoplasms:Current diagnosis and management

Intraductal papillary mucinous neoplasms(IPMNs)represent approximately 1%of all pancreatic neoplasms and 25%of cystic neoplasms.They are divided into three types:main duct-IPMN(MD-IPPMN),branch duct-IPMN(BD-IPMN),and mixed type-IPMN.In this review,diagnostics,including clinical presentation and radiological investigations,were described.Magnetic resonance imaging is the most useful for most IPMNs.Management depends on the type and radiological features of IPMNs.Surgery is recommended for MD-IPMN.For BD-IPMN,management involves surgery or surveillance depending on the tumor size,cyst growth rate,solid components,main duct dilatation,high-grade dysplasia in cytology,the presence of symptoms(jaundice,new-onset diabetes,pancreatitis),and CA 19.9 serum level.The patient’s age and comorbidities should also be taken into consideration.Currently,there are different guidelines regarding the diagnosis and management of IPMNs.In this review,the following guidelines were presented:Sendai International Association of Pancreatology guidelines(2006),American Gastroenterological Association guidelines,revised international consensus Fukuoka guidelines(2012),revised international consensus Fukuoka guidelines(2017),and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas(2018).The Verona Evidence-Based Meeting 2020 was also presented and discussed.

Intraductal papillary mucinous neoplasm originating from a jejunal heterotopic pancreas:A case report

BACKGROUND Intraductal papillary mucinous neoplasm(IPMN)is a rare pancreatic tumor and has the potential to become malignant.Surgery is the most effective treatment at present,but there is no consensus on the site of resection.Heterotopic pancreas occurs in the gastrointestinal tract,especially the stomach and duodenum but is asymptomatic and rare.We report a case of ectopic pancreas with IPMN located in the jejunum.CASE SUMMARY A 56-year-old male patient suffered from severe pain,nausea and vomiting due to a traffic accident and sought emergency treatment at our hospital.Contrast-enhanced computed tomography of the whole abdomen suggested splenic congestion,which was considered to be splenic rupture.Emergency laparotomy was performed,and the ruptured spleen was removed during the operation.Unexpectedly,a cauliflower-like mass of about 2.5 cm×2.5 cm in size was incidentally found about 80 cm from the ligament of Treitz during the operation.A partial small bowel resection was performed,and postoperative pathology confirmed the small bowel mass as heterotopic pancreas with low-grade IPMN.CONCLUSION Ectopic pancreas occurs in the jejunum and is pathologically confirmed as IPMN after surgical resection.

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.

Blood group type antigens in pancreatic intraductal papillary mucinous neoplasms

BACKGROUND: There are few data on blood group(BG) types and types of pancreatic cancers. The aims of this study were to study BG types and BG-antigens in pancreatic intraductal papillary mucinous neoplasms(IPMNs). METHODS: BG type and tumor BG-antigen(glycoprotein) expression(studied by immunohistochemistry on tissue microarrays) were analyzed with regard to characteristics of 101 surgically resected pancreatic IPMNs. RESULTS: Non-O BG type predicted invasive carcinoma independently from high serum CA19-9 and male gender. BG type A was observed more frequently in women than in men. Chronic pancreatitis was more frequently seen in patients with BG type B or AB. Aberrant tumor expression(with regard to BG type) of loss of A antigen expression type occurred in 15.0% of IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm BG-antigen expression was not related to dysplasia grade or invasion. CONCLUSION: The results of the study suggest that in pancreatic IPMN, non-O BG type predicted invasive carcinoma, whereas for intratumor BG-antigen expression no specific patterns were detected with regard to the progression of glandular epithelial dysplasia or invasion.

Predictive factors associated with malignancy of intraductal papillary mucinous pancreatic neoplasms

AIM:To identify preoperative predictive factors associated with malignancy of intraductal papillary mucinous neoplasms(IPMNs) of the pancreas.METHODS:Between April 1995 and April 2010,129 patients underwent surgical resection for IPMNs at our institute and had confirmed pathologic diagnoses.The medical records were retrospectively reviewed and immunohistochemical staining for mucin(MUC) in pancreatic tissues was performed.RESULTS:Univariate analysis showed that the following five variables were closely associated with malignant IPMNs preoperatively:absence of extrapancreatic malignancy;symptoms;tumor size > 4 cm;main pancreaticduct(MPD) size > 7 mm;and lymph node enlargement on preoperative computed tomography(CT).Multivariate analysis revealed that the following two factors were significantly associated with malignant IPMNs preoperatively:MPD size > 7 mm [odds ratio(OR) = 2.50];and lymph node enlargement on preoperative CT(OR = 3.57).No significant differences in the expression of MUC1,MUC2 and MUC5AC were observed between benign and malignant IPMNs.CONCLUSION:MPD size > 7 mm and preoperative lymph node enlargement on CT are useful predictive factors associated with malignancy of IPMNs.

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Pancreatic cancer has a high mortality rate with minimal proven interventions.Intraductal Papillary Mucinous Neoplasms(IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies,successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia(high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include-through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms

BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different methods.On the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over time.AIM To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics.METHODS Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed.The diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were measured.The development of worrisome features was evaluated.RESULTS We evaluated exams of 98 patients across a 40.5-mo median follow-up time.Ten patients developed worrisome features.Cysts at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical significance.Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs.Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.

Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis:A case report

BACKGROUND There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm(IPMN),who are surgically intolerant and require less invasive treatment options,which are limited.In the present study,we report a case of IPMN presenting with acute recurrent pancreatitis(ARP),in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume.CASE SUMMARY An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst.Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas,with dilated pancreatic ducts and mural nodules.The patient was diagnosed with mixed-type IPMN,and five years later,he developed ARP.Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks.Surgery was considered clinically inappropriate because of his old age and comorbidities.He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy.An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation.Fourteen months later,he remains symptom-free from ARP.CONCLUSION This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

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.

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs:A case report

BACKGROUND Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct(IPNB),distant metastasis remains unexplained especially in cases of carcinoma in situ.In the present study,we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain.CASE SUMMARY A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma.Laboratory tests on admission reported a mild elevation of alkaline phosphatase,γ-glutamyl transpeptidase,and total bilirubin in serum.Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct(CBD)extending to the left hepatic duct.Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern.Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis.Therefore,a diagnosis of IPNB cT1N0M0 was established.Left hepatectomy with bile duct reconstruction was performed.Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement.The patient was monitored carefully by regular examinations.However,at 32 mo after the operation,a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level.Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated.In addition to histopathological results,a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer.CONCLUSION This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.