Intraductal Papillary Neoplasm Research Articles

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 biliary-type 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 rare case report ofIntracholecystic papillary-tubular neoplasm of the gall bladder

The understanding of Intracholecystic Papillary Neoplasm (ICPN) in the gallbladder is a recent development, hypothesized to have similarities in clinical and pathological traits with Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas and Intraductal Papillary Neoplasm of the Bile Duct (IPNB). In this report, we present an uncommon instance of Intracholecystic Papillary-Tubular Neoplasms in a 38-year-old male. Although Intracholecystic Papillary Neoplasm (ICPN) is uncommon in the gallbladder lining, it typically presents a more favorable prognosis in contrast to gallbladder adenocarcinoma. Nonetheless, it still possesses the potential for metastatic spread to other organs. Our discussion delves into this patient’s case within the context of current literature on ICPN, while also delineating future avenues for enhancing clinical comprehension. Moreover, we emphasize the importance of implementing screening protocols, taking into account identified risk factors, to elucidate the natural course of the disease and deter its progression into invasive gallbladder carcinoma.

Identification of RNF213 as a potential suppressor of local invasion in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a lethal cancer with poor survival especially when it spreads. The histopathology of its rare intraductal papillary neoplasm of the bile duct type (IPNB) characteristically shows cancer cells originating within the confined bile duct space. These cells eventually invade and infiltrate the nearby liver tissues, making it a good model to study the mechanism of local invasion, which is the earliest step of metastasis. To discover potential suppressor genes of local invasion in ICC, we analyzed the somatic mutation profiles and performed clonal evolution analyses of the 11 pairs of macrodissected IPNB tissues with local invasion (LI-IPNB) and IPNB tissues without local invasion from the same patients. We identified a protein-truncating variant (PTV) in an E3 ubiquitin ligase, RNF213 (c.6967C>T; p.Gln2323X; chr17: 78,319,102 [hg19], exon 29), as the most common PTV event in LI-IPNB samples (4/11 patients). Knockdown of RNF213 in HuCCT1 and YSCCC cells showed increased migration and invasion, and reduced vasculogenic mimicry, but maintained normal proliferation. Transcriptomic analysis of the RNF213-knockdown versus control cells was then performed in the HuCCT1, YSCCC, and KKU-100 cells. Gene Ontology (GO) enrichment analysis of the common differentially expressed genes revealed significantly altered cytokine and oxidoreductase-oxidizing metal ions activities, as confirmed by western blotting. Gene Set Enrichment Analysis (GSEA) identified the most enriched pathways being oxidative phosphorylation, fatty acid metabolism, reactive oxygen species, adipogenesis, and angiogenesis. In sum, loss of function of RNF213 is a common genetic alteration in LI-IPNB tissues. RNF213 knockdown leads to increased migration and invasion of ICC cells, potentially through malfunctions of the pathways related inflammation, and energy metabolisms.

No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging: A case report.

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

A Case of High-Dose-Rate Brachytherapy Under Endoscopic Retrograde Cholangiopancreatography (ERCP) for Intraductal Papillary Neoplasm of the Bile Duct

A Case of High-Dose-Rate Brachytherapy Under Endoscopic Retrograde Cholangiopancreatography (ERCP) for Intraductal Papillary Neoplasm of the Bile Duct

Cross-Sectional Imaging Characteristics of Pancreatic Intraductal Oncocytic Papillary Neoplasms.

Pancreatic intraductal oncocytic papillary neoplasms (IOPN) are rare precursors to pancreatic ductal adenocarcinoma. We report cross-sectional computed tomography and magnetic resonance imaging (where available) findings of pancreatic IOPNs. Consecutive cases of pancreatic IOPNs identified on pathology between 2008 and 2020 at University of Pittsburgh and Johns Hopkins University were included in the study. Cross-sectional imaging of all patients was reviewed by two subspecialty trained abdominal radiologists. Patient demographics, cross-sectional imaging appearances and growth characteristics were evaluated. In this dual-center study, 14 patients with IOPNs were included. Median age was 64 years, and 64% were male. The median size of the lesions was 5.4 cm (range, 1.4-12.3 cm). All patients had either an enhancing mural nodule (93% of patients) and/or thick internal septations (29%). Thin/imperceptible outer wall was seen in 93%. Main duct was involved in 64% of the cases. Only 14% of the cases did not demonstrate abutment of the main duct. Histologic evaluation of surgical specimen showed high-grade dysplasia without invasive carcinoma in 57% and invasive carcinoma in 43% of cases. Lesions with invasive carcinoma were larger (7.1 cm vs 4.3 cm, P = 0.05) and tended to have larger mural nodule (3.7 cm vs 1.8 cm) compared with those without invasive carcinoma. Pancreatic IOPNs are rare cystic premalignant lesions, which among resected cases, are predominantly seen in middle aged men, are often large, have enhancing mural nodules and frequently harbor invasive carcinoma.

Biliary Duct Dilatation: AJR Expert Panel Narrative Review.

Biliary duct dilatation is a common incidental finding in practice, but it is unlikely to indicate biliary obstruction in the absence of clinical symptoms or elevated levels on liver function tests (LFTs). However, the clinical presentation may be nonspecific, and LFTs may either be unavailable or difficult to interpret. The goal of this AJR Expert Panel Narrative Review is to highlight a series of topics fundamental to the management of biliary duct dilatation, providing consensus recommendations in a question-and-answer format. We start by covering a basic approach to interpreting LFT results, the strengths and weaknesses of the biliary imaging modalities, and how and where to measure the extrahepatic bile duct. Next, we define the criteria for biliary duct dilatation, including patients with prior cholecystectomy and advanced age, and discuss when and whether biliary duct dilatation can be attributed to papillary stenosis or sphincter of Oddi dysfunction. Subsequently, we discuss two conditions in which the duct is pathologically dilated but not obstructed: congenital cystic dilatation (i.e., choledochal cyst) and intraductal papillary neoplasm of the bile duct. Finally, we provide guidance regarding when to recommend obtaining additional imaging or testing, such as endoscopic ultrasound or ERCP, and include a discussion of future directions in biliary imaging.

Intraductal Papillary Neoplasm of the Bile Duct Treated with Argon Plasma Coagulation via Endoscopic Ultrasound-guided Choledochoduodenostomy.

A 93-year-old man presented to our hospital with a fever, abdominal pain, and jaundice. Computed tomography revealed bilateral bile duct dilation, cystic lesions with bile duct communication, and intraluminal solid nodules arising from the bile duct wall. The patient was diagnosed with intraductal papillary neoplasm of the bile duct. Surgery was not performed, considering the patient's age. It was impossible to control cholangitis using conventional endoscopic therapy. We therefore created an access route to the bile duct using endoscopic ultrasound-guided choledochoduodenostomy and inserted a lumen-apposed metal stent. Thereafter, we performed argon plasma coagulation of the tumor in the bile duct, which successfully prevented cholangitis recurrence.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts

AimsTo clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma.MethodsImmunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18...

O77: Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcinomas arising from Intraductal papillary mucinous neoplasms (IPMN): adjuvant chemotherapy, patterns of recurrence and survival

Abstract Introduction Invasive intraductal oncocytic papillary neoplasms (IOPNs) are extremely rare and are increasingly being recognised as their own entity, distinct from intraductal papilliary mucinous neoplasism subtypes (IPMN). Their clinicopathologic behaviour, recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown compared to adenocarcinomas arising from IPMN but were investigated in the present study. Methods Patients undergoing pancreatic resection between 2010-2020 for invasive IOPNs and adenocarcinoma arising from IPMNs were identified retrospectively from 18 academic pancreatic centers worldwide. Survival analyses were conducted to compare outcome measures between IOPNs and IPMN precursor epithelial subtypes and invasive components. Results Of the 459 patients with invasive IOPN/IPMNs, 20 patients had an invasive IOPN (median age,69; male,n=11), the majority of which were in the pancreatic head (75%) and underwent either a Whipples procedure (40%) or PPPD (35%). After a median follow-up of 6 years, 45% of invasive IOPNs developed recurrence (1-year,30.0%; 5-year,69.2%) and 40% survived follow-up (2-year survival 55.0%, 5-year survival, 30.8%). Recurrence rates and survival of invasive IOPNs were higher than colloid IPMNs (n=64) (p=0.031 and p=0.007) and comparable with ductal IPMNs (n=331) as well as gastric (n=54) and pancreatobiliary (n=111) IPMN subtypes. Invasive IOPN had significantly lower cancer-specific survival compared to colloid carcinomas (p<0.001). Adjuvant chemotherapy did not improve rates of recurrence in invasive IOPN and IPMN subtypes (p>0.05). Conclusions Invasive IOPNs are more aggressive than previously suspected and should be regarded as their own entity. Adjuvant chemotherapy does not reduce rates of recurrence regardless of neoplasm type.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Endoscopic treatment of a hepatic abscess arising from a biliary stricture due to intraductal papillary neoplasm of the bile duct.

Endoscopic treatment of a hepatic abscess arising from a biliary stricture due to intraductal papillary neoplasm of the bile duct.

Neoplastic Progression in Macroscopic Precursor Lesions of the Pancreas.

Macroscopic precursor lesions of the pancreas represent a complex clinical management problem. Molecular characterization of pancreatic cysts has helped to confirm and refine clinical and pathologic classifications of these lesions, inform our understanding of tumorigenesis in the pancreas, and provide opportunities for preoperative diagnosis. To review the pathologic classification of macroscopic cystic lesions of the pancreas: intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), intraductal oncocytic papillary neoplasms (IOPNs), and intraductal tubulopapillary neoplasms (ITPNs), and to describe our current state of understanding of their molecular underpinnings, relationship to invasive carcinomas, and implications for diagnosis and prognostication. We assessed the current primary literature and current World Health Organization Classification of Digestive System Tumours. Macroscopic cystic lesions of the pancreas are morphologically and molecularly diverse. IPMNs and MCNs share mucinous cytoplasm with papillae. MCNs are defined by ovarian-type stroma. IOPNs have granular eosinophilic cytoplasm, prominent nucleoli, and complex, arborizing papillae. ITPNs demonstrate complex, back-to-back tubules and anastomosing papillae and lack prominent intracellular mucin. IPMNs and MCNs are characterized by driver mutations in KRAS/GNAS (IPMNs) and KRAS (MCNs), with later driver events in RNF43, CDKN2A, SMAD4, and TP53. In contrast, IOPNs and ITPNs have recurrent rearrangements in PRKACA/PRKACB and MAPK-associated genes, respectively. The recurrent alterations described in cysts provide an opportunity for diagnosis using aspirated cyst fluid. Molecular characterization of IPMNs shows a striking spatial and mutational heterogeneity, challenging traditional models of neoplastic development and creating challenges to interpretation of cyst fluid sequencing results.

Utilization of texture features of volumetric ADC maps in differentiating between serous cystadenoma and intraductal papillary neoplasms.

The rising incidence of incidental detection of pancreatic cystic neoplasms has compelled radiologists to determine new diagnostic methods for the differentiation of various kinds of lesions. We aim to demonstrate the utility of texture features extracted from ADC maps in differentiating intraductal papillary mucinous neoplasms (IPMN) from serous cystadenomas (SCA). This retrospective study was performed on 136 patients (IPMN = 87, SCA = 49) split into testing and training datasets. A total of 851 radiomics features were extracted from volumetric contours drawn by an expert radiologist on ADC maps of the lesions. LASSO regression analysis was used to determine the most predictive set of features and a radiomics score was developed based on their respective coefficients. A hyper-optimized support vector machine was then utilized to classify the lesions based on their radiomics score. A total of four Wavelet features (LHL/GLCM/LCM2, HLL/GLCM/LCM2, /LLL/First Order/90percent, /LLL/GLCM/MCC) were selected from all of the features to be included in our classifier. The classifier was optimized by altering hyperparameters and the trained model was applied to the validation dataset. The model achieved a sensitivity of 92.8, specificity of 90%, and an AUC of 0.97 in the training data set, and a sensitivity of 83.3%, specificity of 66.7%, and AUC of 0.90 in the testing dataset. A support vector machine model trained and validated on volumetric texture features extracted from ADC maps showed the possible beneficence of these features in differentiating IPMNs from SCAs. These results are in line with previous regarding the role of ADC maps in classifying cystic lesions and offers new evidence regarding the role of texture features in differentiation of potentially neoplastic and benign lesions.

Non-invasive intraductal oncocytic papillary neoplasm forming a protruding lesion toward the duodenum from the accessory papilla: a case report

BackgroundIntraductal oncocytic papillary neoplasm (IOPN), previously classified as a subtype of intraductal papillary mucinous neoplasm (IPMN), has been described as an independent disease by the WHO since 2019. IOPN is a rare tumor, with few reported cases. Herein, we report a case of resected non-invasive IOPN that formed a lesion protruding toward the duodenum from the accessory papilla.Case presentationAn 80-year-old woman was referred to our hospital because of a giant mass in the pancreatic head detected on abdominal contrast-enhanced computed tomography (CT) performed for a close examination of a mass in the right breast. CT revealed a 90-mm-sized tumor with a mixture of solid and cystic components, with contrast enhancement in the pancreatic head, and a dilated main pancreatic duct. Esophagogastroduodenoscopy revealed a semi-circumferential papillary tumor protruding toward the duodenal lumen, which did not protrude from the papilla of Vater. Transpapillary biopsy led to a preoperative diagnosis of IPMN with an associated invasive carcinoma. As there were no distant metastasis, open subtotal stomach-preserving pancreaticoduodenectomy was performed. Analysis of the surgical specimen and histopathological examination revealed that the tumor was an IOPN that protruded toward the duodenal mucosa from the accessory papilla while replacing the duodenal mucosa with no obvious stromal invasion.ConclusionIOPN is a rare and poorly recognized tumor with few reported cases. There have been no reports describing IOPN forming a protruding lesion toward the duodenum from the accessory papilla. Therefore, further accumulation of cases such as this one is important to advance the study of IOPN.

How should the liver be approached in patients with severe abdominal wall varices?

AbstractAlthough liver resection in patients with abdominal wall varices (AWV) is rare, we should have a special surgical strategy for the liver in such cases. We report our experience of approaching the liver in a patient with severe AWV. The patient was a 77‐year‐old man who had undergone inferior vena cava (IVC) filter placement for a pulmonary embolism 10 years prior. Severe AWV due to complete IVC obstruction appeared 3 years ago. The patient was diagnosed with intraductal papillary neoplasm of the bile duct and referred to our hospital. Although it was difficult to see the small AWV, it was necessary to avoid bleeding due to AWV injury. The ports were inserted while confirming the AWV with indocyanine green (ICG) imaging, and laparoscopic left hepatectomy was performed. Our approach to the liver using abdominal wall ICG imaging might be a standard strategy to avoid severe AWV injury.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan

BackgroundIntraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. MethodsA multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. ResultsA total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DiscussionDespite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Clinicopathological Features of 12 Cases of Intraductal Papillary Neoplasm of the Bile Duct: A Case Series

Clinicopathological Features of 12 Cases of Intraductal Papillary Neoplasm of the Bile Duct: A Case Series

Surveillance Outcome and Genetic Findings in Individuals at High Risk of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRIs) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs. A total of 239 HRIs from 202 families were tested genetically and underwent prospective pancreatic surveillance for 6 years. The cohort was divided into 3 groups: familial pancreatic cancer (FPC; 70 individuals, 54 families), familial non-FPC (81 individuals, 73 families), and hereditary pancreatic cancer (PC) (88 individuals, 75 families). PGVs were detected in 37.6% of all families, including 11.1% of FPC families and 9.6% of familial non-FPC families. The hereditary PC group had earlier onset of PDAC compared with the other 2 groups. BRCA2 PGV carriers showed earlier onset of PDAC and pancreatic cysts. Of the 239 HRIs, PDAC was detected in 11 individuals (4.6%), with 73% diagnosed at an early stage; 4 (1.67%) had pancreatic neuroendocrine tumor; 6 (2.5%) had main-duct intraductal papillary neoplasm (IPMN); and 41 (17.15%) had side-branch IPMN. Seventeen individuals were referred to surgery, and 12 were alive at the end of the study. The percentage of PDAC was similar in the 3 groups studied. The hereditary PC group, and particularly BRCA2 PGV carriers, had an earlier age of PDAC onset. PGVs were detected in a significant percentage of HRIs with PC. Surveillance seems effective for detection of early-stage PDAC and precursor lesions.

Focal Intrahepatic Duct Dilatation (FIDD): a Finding That Mandates Further Evaluation That May Amount to Liver Resection

AbstractThe increasing use of imaging has led to incidental findings in the liver. The Western experience of managing focal intrahepatic duct dilatation (FIDD) is not well recorded. We present our experience based on a large prospectively maintained database at a tertiary hepatobiliary surgical unit. We identified patients with liver resection for focal incidental duct dilatation from January 2003 to December 2019 from the liver unit database. We recorded the demographics, symptomatology, blood test results, imaging, type of liver resection, morbidity, mortality and histology of resected specimens. Nine patients had focal intrahepatic duct dilatation among 994 liver resections performed (0.9%). Six patients were asymptomatic, 2 upper abdominal pain and 1 recurrent gram-negative sepsis. Liver function tests were normal in all patients. Two patients had cholangiocarcinoma (CCA), 4 intrahepatic stones, 1 intraductal papillary neoplasm of bile duct (IPN-B) and 2 benign strictures. Focal incidental duct dilatation is rare in the Western population. Most patients are asymptomatic with an incidental finding of intrahepatic duct dilatation on cross-sectional imaging. Differentiating benign and malignant pathology is difficult warranting liver resection, in fit patients, to resolve the diagnosis. Liver resection is safe and can be potentially curative in patients with a neoplasm, which can occur in 30% of patients with focal intrahepatic duct dilatation.