Diagnosis Of Intraductal Papillary Mucinous Neoplasm Research Articles

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.

Intraductal papillary mucinous neoplasms of the pancreas: Cytologic-histologic correlation study and evaluation of the cytologic accuracy in identifying high-grade dysplasia/invasive adenocarcinoma.

Intraductal papillary mucinous neoplasms (IPMNs) may be associated with invasive adenocarcinoma, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). We aimed to review the cytologic-histologic correlation of cases with a histologic diagnosis of IPMN. A database search (January 2010-January 2021) was performed for resected IPMNs with preceding endoscopic ultrasound-guided fine-needle aspiration (FNA). Cytology slides were reviewed for the presence of benign, atypical, or malignant cells, and necrosis. Histologically, IPMNs were classified as benign (LGD) or malignant (HGD or adenocarcinoma). There were 41 patients with IPMN; 24 malignant and 17 benign. Sixteen of the 24 malignant IPMNs were accurately classified as malignant on cytology. There were eight false negatives and one false positive. Cytology yielded a sensitivity of 67% and a specificity of 94%. Among the 16 true positives with FNA diagnosis of adenocarcinoma, seven were IPMNs with HGD, and nine had invasive adenocarcinomas on histology. Cellular morphology and absence or presence of necrosis did not help distinguish HGD from adenocarcinoma on cytology (P > 0.5). Sampling errors and interpretative errors resulted in false-negative cases. Cytology yielded diagnoses related to IPMN in 73% of cases (30/41) and lack of identification of mucinous cells/mucinous background resulted in interpretative errors (9). This study shows that there is a good correlation between cytopathology and surgical pathology diagnoses of IPMNs and that cytology is mostly able to recognize IPMN with HGD/adenocarcinoma. However, heterogeneity in areas of IPMN with HGD/adenocarcinoma may result in sampling errors yielding false-negative cases. Mucinous cells/background should raise the suspicion of IPMN on cytology, even when no neoplastic epithelium is present for the evaluation of dysplasia.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs)

BackgroundMain-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. MethodsWe performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000–2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. Results33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. ConclusionsPostoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

The Role of Genetic, Metabolic, Inflammatory, and Immunologic Mediators in the Progression of Intraductal Papillary Mucinous Neoplasms to Pancreatic Adenocarcinoma.

Intraductal papillary mucinous neoplasms (IPMN) have the potential to progress to pancreatic ductal adenocarcinoma (PDAC). As with any progression to malignancy, there are a variety of genetic and metabolic changes, as well as other disruptions to the cellular microenvironment including immune alterations and inflammation, that can contribute to tumorigenesis. Previous studies further characterized these alterations, revealing changes in lipid and glucose metabolism, and signaling pathways that mediate the progression of IPMN to PDAC. With the increased diagnosis of IPMNs and pancreatic cysts on imaging, the opportunity to attenuate risk with the removal of high-risk lesions is possible with the understanding of what factors accelerate malignant progression and how they can be clinically utilized to determine the level of dysplasia and stratify the risk of progression. Here, we reviewed the genetic, metabolic, inflammatory, and immunologic pathways regulating the progression of IPMN to PDAC.

The role of pancreatoscopy in the diagnostic work-up of intraductal papillary mucinous neoplasms: a systematic review and meta-analysis.

Confirming the diagnosis, invasiveness, and disease extent of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is challenging. The aim of this study was to summarize the literature on the efficacy and safety of peroral pancreatoscopy (POP) in the diagnosis of IPMN, including the impact of pre- and intraoperative POP on the management of IPMN. The EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar databases were systematically searched for articles. Eligible articles investigated cohorts of patients who underwent POP for (suspected) IPMN. 25 articles were identified and included in this review; with 22 of these reporting on the diagnostic yield of POP in IPMN and 11 reporting on the effect of pre- or intraoperative POP on clinical decision-making. Cannulation and observation rates, and overall diagnostic accuracy were high across all studies. Frequently reported visual characteristics of IPMN were intraductal fish-egg-like lesions, hypervascularity, and granular mucosa. Overall, the adverse event rate was 12 %, primarily consisting of post-endoscopic retrograde cholangiopancreatography pancreatitis, with a pooled rate of 10 %, mostly of mild severity. Regarding the impact of POP on clinical decision-making, POP findings altered the surgical approach in 13 %-62 % of patients. POP is technically successful in the vast majority of patients with (suspected) IPMN, has a consistently high diagnostic accuracy, but an adverse event rate of 12 %. Data on intraoperative pancreatoscopy are scarce, but small studies suggest its use can alter surgical management. Future studies are needed to better define the role of POP in the diagnostic work-up of IPMN.

The malignant potential of pancreatic intraductal papillary mucinous neoplasm is reflected in expression levels of fucosylated glycans in α1 -acid glycoprotein.

Pancreatic intraductal papillary mucinous neoplasm (IPMN) involves multiple histopathological stages from benign to malignant lesions. Further, a biomarker to diagnose the malignant IPMN (IPMC) is clinically relevant. Recently, we found that serum fucosylated α1 -acid glycoprotein (fAGP) level markedly elevated along with disease progression in large cohorts of patients with various cancers. The fAGP level was retrospectively analyzed in preoperative sera from 109 patients with IPMN, and the clinical relevance of fAGP was compared with currently available predictors as standard. The fAGP level in IPMC was found to be significantly higher than in benign IPMN (P=.0012). At a cutoff value of 27.04 U/μg, its sensitivity, specificity, and accuracy for IPMC were determined to be 83.61%, 65.96%, and 75.93%, respectively. Multivariate analyses revealed that the fAGP level was the only independent risk factor for predicting IPMC. Additionally, a combination of the fAGP level and 18 F-fluorodeoxyglucose uptake on the PET/CT imaging in the lesions seemed to offer the best diagnosis of IPMN. Accordingly, 27 of the 28 patients who were positive in both tests had IPMC, while patients who are negative had benign IPMN. The fAGP level appeared to be a relevant biomarker for malignant potential of IPMN.

Increased prevalence of colorectal neoplasia in patients with intraductal papillary mucinous neoplasms.

Background:The association between intraductal papillary mucinous neoplasms (IPMNs) and colorectal cancer (CRC) and polyps is controversial.Objectives:To compare the prevalence of CRC and colorectal polyps among patients with IPMN and matched average risk individuals.Methods:A match cross-sectional historical study comparing colonoscopy findings of 310 patients with IPMN cysts who underwent at least one colonoscopy examination from 2004 through 2019, with 310 age- and gender-matched average risk participants who underwent a screening colonoscopy. CRC and polyps were assessed in both groups. The prevalence and odds ratio were calculated.Results:CRC was diagnosed in 16 of 310 patients with IPMN (5.2%), and at least one polyp was detected in 96 patients (31%). The prevalence of CRC was greater among patients with IPMN than in matched individuals [5.2% versus 1.3%, p = 0.012, prevalence odds ratio (POR) 4, confidence interval (CI) 1.29–16.44]. The overall prevalence of polyps was not higher among patients with IPMN than in matched individuals (31% versus 26.8%, p = 0.291, POR 1.22, CI 0.85–1.76). However, the prevalence of colorectal adenomas with high-grade dysplasia was higher in patients with IPMN than in matched individuals (4.2% versus 1%, p = 0.02, POR 4.33, CI, 1.19–23.7). The prevalence of large polyps (i.e. more than 20 mm in size) was also greater in patients with IPMN than in matched individuals (6.1% versus 1.9%, p = 0.011, POR 3.6, CI, 1.29–12.40).Conclusion:Patients with IPMN have a significantly higher prevalence of CRC and advanced polyps than the average risk population. In view of our findings, we suggest that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken.

Combined Type IPMN: Radiographic versus Endoscopic Diagnosis

Introduction: Main duct and combined type pancreatic intraductal papillary mucinous neoplasm (IPMN) are associated with significant rates of high-risk pathology. The diagnosis is suggested radiographically, but endoscopic interventions are generally performed for confirmation. The goal of this study was to evaluate whether these interventions change management and increase accuracy in patients thought to have combined type IPMN based upon imaging alone. Methods: Patients thought to have main duct or combined type IPMN based on imaging were evaluated retrospectively. The outcome of endoscopic interventions performed on these patients was reviewed. Final pathology was available for patients who underwent resection. Results: 142 patients were felt to have main duct IPMN radiographically. 89 of those patients underwent EUS and 49 of these patients ultimately underwent resection. Final pathology showed main duct IPMN in 39 patients. 55 patients were felt to have combined type IPMN radiographically. 39 of these patients underwent EUS. 21/39 patients had an elevated CEA. 18/39 patients were felt to have combined type IPMN by endoscopic appearance. 24/55 patients ultimately underwent resection. Final pathology showed combined type (or main duct) IPMN in 23 patients with four harboring adenocarcinoma. Of the 24 patients that underwent resection, 11 had an elevated CEA and 12 were felt to have combined type IPMN by endoscopic appearance. Conclusions: Diagnosis of combined type IPMN on high-quality imaging is highly predictive of final pathology. Endoscopic interventions subject patients to additional procedural complications but often add little and may not improve accuracy.Tabled 1Main Duct IPMNRadiographic Diagnosis of Main Duct IPMN142EUS Diagnosis of Main Duct IPMN57/89Number Resected49Final Pathology Main Duct IPMN39/49 (80%) Malignancy6/49 (12%)Combined Type (Mixed-Type) IPMNRadiographic Diagnosis of Combined Type IPMN55EUS Diagnosis of Combined Type IPMN18/39Number Resected24Final Pathology Combined Type or Main Duct IPMN23/24 (96%) Malignancy4/24 (16%) Open table in a new tab Table: IPMN Diagnosis by Different Diagnostic Modalities.

Indicators of Malignancy and Invasive Cancer in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Introduction: There are still many debates on the indication of surgical resection of IPMN. This study aims to validate malignant features detected in preoperative diagnosis of IPMN and establish selection criteria for appropriate surgical management. Method: Forty-eight IPMN patients who underwent surgical resection from January 2005 to December 2020 were enrolled. We assessed the correlation of factors with malignancy and searched for risk factors for invasive cancer. Results: Patients' characteristics; primary site (head/body and tail=28/20), type of IPMN (main pancreatic duct (MPD) type/ branched pancreatic duct (BD) type/ mixed type=9/20/19), malignancy (IPMA/high grade dysplasia/IPMC=17/11/10), jaundice (yes/no=1/47), diameter of main pancreatic duct >10mm (yes/no=17/31), enhanced nodule (yes/no=16/32), median cyst diameter >=30 mm (yes/no=20/28), thickened or contrast-enhanced septum (yes/no=19/29). Multivariate analysis showed the MPD diameter, enhanced nodule, and cyst size were indicators of malignancy. The malignancy rates of patients with two or more, one, and none of these factors were 100%/47%/24%, respectively. Multivariate analysis showed enhanced nodule and number of lesions (single or multiple) were indicators of invasive cancer. The invasive cancer rates of patients with two, one, and none of these factors were 80%/37%/7%, respectively. Conclusion: It was re-verified that the HRS factor and WF factors help indicate the presence of malignancy and invasiveness. Combinations of these findings will lead to more accurate predictions for malignancy and invasive cancer. Less invasive surgical procedures (limited lymphatic dissection, organ preservation) might be considered in patients with only a few HRS or WF factors.

Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis

Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs). Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P< .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I2= 86.74%), 91% (95% CI, 72-98; I2= 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P< .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P< .001). Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.

Intraductal papillary mucinous neoplasm of the pancreas: A 10-year experience at a single center

Background: The incidence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the past years along with the development of diagnostic imaging tests. Objective: The aim of this study is to describe our experience on long-term management of patients with IPMNs in a reference center. Material and methods: We conducted a retrospective and descriptive analysis of patients with pancreatic neoplasms followed-up at the Department of General Surgery and Hepato-Biliary Surgery, Hospital Universitario Fundación Favaloro, between January 2010 and December 2019. The patients were classified into 2 groups: group A (diagnosis of IPMN made in the outpatient clinic), and group B (diagnosis of IPMN in the pathological examination). Results: Eighty-six patients were analyzed: 79 (90%) in group A and 7 in group B. In group A, a watchful waiting with monitoring (AM) was decided in 57 cases (66%). Of the remaining 22 patients, 18 (29%) patients underwent surgery (AS) and 4 are waiting for surgery. Survival at 5 years was 89% in group AM, 86% in group AS and 43% in group B (Breslow 0.001, log-rank test 0,001 vs. group A). Conclusion: The diagnosis and management of IPMNs is currently standardized. Surgery is indicated in MD-IPMN and mixed type IPMN. Patients with BD-IPMN type should be monitored due to the risk of malignant transformation. When surgery is indicated, long-term survival should be similar to that of the surveillance group.

Comparison of Preoperative Evaluation with the Pathological Report in Intraductal Papillary Mucinous Neoplasms: A Single-Center Experience.

The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy.

Intraductal papillary mucinous neoplasms (IPMN): long term management and results at single HPB center

Introduction: IPMN origins within the cells of the pancreatic duct. Accepted as lesions that can progress to pancreatic cancer, TC, MRI and EUS should be used to identify risk factors to decide whether the patient should benefit from a surgical approach. Methods: Retrospective analysis of patients diagnosed of IPMN between 2015 and 2019. Variables analyzed include demographics, symptoms, images, surgical indication, type of lesion, presence of malignant disease and survival. The statistical studies performed will be described in each of the results reports and were performed using SPSS version 17. Results: 58 patients were diagnosed with IPMN: 48 were found pre-operatively (Group 1) while 10 post-resection (Group 2, 9.7%). G1: 73% were fem., 71% asymptomatic, 23 (48%) multifocal, 13 (27%) located the head of the pancreas, 8 (17%) in the body and 4 (8%) in the tail. Table 1 summarizes the analyzed. The average time to surgery was 22.4 +/- 29.4 months. In G2: 6 were associated to invasive AdenoCa, 2 to an Ampuloma, 1 to a NET and 1 in a pancreas divisum. Long term survival: 100% for G1 at 10 years, while in G2 is 100% and 86% at 1 and 10 years respectively. Recurrence rate: 22%. Conclusions: Those results highlight the value of following stablished guidelines in order to be successful with a conservative approach when an IPMN is diagnosed. In patients with IPMN I or III, surgery is recommended. Newly diagnosed IPMN II should be strictly followed due to an increased risk of malignancy.Tabled 1[Patients that underwent surgery with preo-operative diagnosis of IPMN.]Preo-operative DiagnosisGenderAgeSurgery or Follow upSurgical indicationPathology reportSurvival (month)AliveRecurrencyPatients with indication of surgeryIPMN IIPMN IIPMN IIPMN IIPMN IMFMFF8869723660Distal PancreatectomyCephalic duodenopancreatectomyDistal PancreatectomyDistal PancreatectomyPending SurgeryType of IPMNType of IPMNType of IPMNType of IPMNHigh CA19.9 in EUS. Size >4cmIPMN I with LGDIPMN I with MGDMixed type IPMN with LGDMicrocystic Serous Cystadenoma-2229271424YesYesYesYesYesNoNoYesNo-Patients with indication of surgeryIPMN IIIPMN IIIPMN IIIPMN IIFFMF74737166Cephalic duodenopancreatectomyCephalic duodenopancreatectomyDistal PancreatectomyPending SurgeryMural tumor with contrast enhacementMural tumor with contrast enhacementMural nodule >5mmSize >4cm. Atrofic pancreasIPMN I with MGDIPMN IIIPMN II with MGD-38108871YesYesYesYesNoYesNo-Patients with indication of surgeryIPMN IIIIPMN IIIIPMN IIIFFM706871Total DuodenopancreatectomyTotal DuodenopancreatectomyPending SurgeryHigh CEA in EUSGrowth >5mm/2 yearsDilatated WirsungMixed type IPMN with LGDMixed type IPMN with HGD-58453YesYesYesNoNo-Follow upIPMN IN=1F63Follow up--72Yes-Follow upIPMN IIN=30M=7F= 2363+/-13Follow up--12+/-13All-Follow upIPMN IIIN=5F=4M=160+/-14Follow up--20+/-8All- Open table in a new tab

Magnetic resonance (MR) for mural nodule detection studying Intraductal papillary mucinous neoplasms (IPMN) of pancreas: Imaging-pathologic correlation

PurposeMagnetic Resonance (MR) is recommended to diagnose Intraductal Papillary Mucinous Neoplasms (IPMN) and in the follow-up of borderline lesions. The purpose of this work is to evaluate the diagnostic accuracy of dynamic MR with Diffusion Weighted Imaging (DWI) in the identification of mural nodules of pancreatic IPMN by using pathological analysis as gold standard. Materials and methodsNinety-one preoperative MR with histopathological diagnosis of IPMN were reviewed by two radiologists. Presence, number and size of mural nodule, signal intensity of the nodule on T1-weighted imaging (T1-WI) after contrast medium administration and on DWI. Inter-observer agreement was evaluated. ResultsSignificant correlation (p < 0.0001) were found for presence of nodules > 5 mm on MR and pathological specimen, size and number of mural nodules evaluated on pathological review and degree of dysplasia, size and number of mural nodules evaluated on MR and tumoral dysplasia, presence of nodule > 5 mm with enhancement after contrast medium administration and hyperintensity on DWI and degree of dysplasia. Interobserver agreement was moderate for the presence of mural nodule (K = 0.56), for the presence of high signal intensity on DWI (K = 0.57) and enhancement of mural nodule (K = 0.58). Apparent Diffusion Coefficient (ADC) map histogram analysis showed a correlation between Entropy of the entire cystic lesion and the degree of dysplasia (p < 0.034). ConclusionsMR with dynamic and DWI sequences was an accurate method for the identification of ≥ 5 mm solid nodules of the IPMNs and correlate with the lesion malignancy. Entropy, calculated from the histogram analysis of the IPMN ADC map, correlated with the lesion dysplasia.

Abstract 4162: The identification of biomarker for the early diagnosis of IPMN associated PDAC based on serum protein profiling

Abstract Background: Most of pancreatic cancer patients are diagnosed at late stage due to the inability of early diagnosis for pancreatic ductal adenocarcinoma (PDAC), finally leading to a very high mortality. Therefore the identification of effective biomarkers for the early diagnosis of PDAC has a critical significance for improving the outcome of PDAC patients at early stage. Up to 15% of PDACs are thought to come from Mucinous pancreatic cysts, most of which belong to intraductal papillary mucinous neoplasm (IPMN). Consequently, screening and detecting high-risk IPMN patients at early stage by potential biomarkers can help a lot to prevent these patients from developing into invasive PDAC at late stage. Methods: We collected 38 normal serum sample as control and 243 IPMN serum samples with different progression stages including 83 adenomas, 73 borderlines, 40 carcinoma in situs and 47 invasive carcinomas. Then we performed antibody microarray experiment on all serum samples and implemented data analysis on serum protein profiling by R programming. After that, we divided the protein expression data into discovery set and validation set. With data pre-progressing, quality control, differential expression analysis and feature selection, we screened some protein panels for the construction of diagnostic model including logistic regression (LR) model and support vector machine (SVM) model based on discovery set. Finally, we further confirmed the diagnostic performance of these protein panels on IPMN associated PDAC based on validation set. Results: By data analysis, we finally constructed a stepwise diagnostic model of IPMN associated PDAC based on 11 protein panels with high sensitivity and specificity. For example, protein panel 1 containing 2 proteins can separate the normal and IPMN at all stages with sensitivity of 0.988 and specificity of 0.946 by SVM model; protein panel 2 containing 15 proteins can separate invasive carcinoma and non invasive carcinoma (adenoma, borderline and carcinoma in situ) with AUC of 0.99 by LR model; protein panel 3 containing 16 proteins can specifically separate invasive carcinoma from the normal with AUC of 0.978 by SVM model; protein panel 4 containing 8 proteins can specifically separate serum samples at early stages (adenoma and borderline) from the normal with AUC of 0.969 by SVM model, which is useful for the early diagnosis of IPMN associated PDAC; protein panel 5 containing 7 proteins can specifically separate serum samples at early-middle stage (adenoma, borderline and carcinoma in situ) from the normal with AUC of 0.987 by SVM model. In summary, this comprehensive diagnostic model can effectively accomplish IPMN serum samples classification for different tumor stages with high accuracy. Further validation on these protein panels with more IPMN serum samples by ELISA is in progress. Citation Format: Chaoyang Zhang, Mohamed Alhamdani, Andrea Bauer, Li Peng, Jörg Hoheisel. The identification of biomarker for the early diagnosis of IPMN associated PDAC based on serum protein profiling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4162.

CD117 Is a Specific Marker of Intraductal Papillary Mucinous Neoplasms (IPMN) of the Pancreas, Oncocytic Subtype.

The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring PRKACA/B fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes (p < 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype; notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytologic Evaluation of Intraductal Papillary Mucinous Neoplasm and Mucinous Cystic Neoplasms of Pancreas.

To evaluate the role of endoscopic ultrasound-guided fine needle aspiration cytology in identifying mucinous cystic lesions (MCLs) in histologically proven cases of intraductal papillary mucinous neoplasm (IPMN) or mucinous cystic neoplasm (MCN) and risk of malignancy associated with each cytologic category based on the Papanicolaou Society of Cytopathology (PSC) guidelines. All resected cases with histologic diagnosis of IPMN or MCN at our institution from January 1, 2004, to August 31, 2019, with associated cytology were included. Available cytology slides of nondiagnostic (ND), negative/benign (BN), and atypical cytology (AC) cases were reviewed and reclassified based on the PSC guidelines. A total of 120 cases were identified, including 57 IPMNs with low-grade or moderate dysplasia (LGD/MD) and high-grade dysplasia (HGD), 34 MCNs with LGD/MD or HGD, and 29 IPMNs with invasive malignancy. After cytology slide review and reclassification, we observed that ND and BN cases were paucicellular and lacked ancillary testing (carcinoembryonic antigen levels or KRAS mutation analysis). The risk-of-malignancy rates were 33% for ND, 11% for BN, 28.5% for AC, 17% for MCL, and 100% for suspicious/positive cytologic diagnosis. A multidisciplinary approach including combined use of cytology and ancillary testing is helpful in establishing a diagnosis of MCL and identifying associated malignancy.

3013 Fish Mouth Ampulla: Classic Main Duct Intraductal Papillary Mucinous Neoplasm

INTRODUCTION: Intraductal Papillary Mucinous Neoplasms (IPMNs) were first identified in 1982 and there have been increasing rates of diagnosis of IPMNs in recent years with the improvement of imaging modalities. Due to the indolent course of IPMNs, many patients may initially remain asymptomatic for many years. IPMNs should be acted on quickly after diagnosis as they can progress to malignancy. We present a case of a patient who presented with symptoms similar to pancreatitis but was found to have a main duct IPMN with the classic fish mouth appearance of the ampulla. CASE DESCRIPTION/METHODS: A 62-year-old male presented to an outside hospital with epigastric abdominal pain and nausea. RUQ Ultrasound revealed normal liver and gallbladder with heterogenous echotexture within an enlarged pancreas. Abdominal CT Scan revealed a low density heterogenous, contrast enhancing, possibly multicystic lesion at the uncinate process and near the pancreatic head measuring 3.6 × 3.6 cm with dilation of the pancreatic duct. MRCP revealed a dilated pancreatic duct at 6 mm and a cystic appearing pancreatic mass involving uncinate process and portion of the right pancreatic head concerning for intraductal papillary mucinous neoplasm. He was transferred to our facility for formal Gastroenterology evaluation. EGD was performed and revealed a markedly dilated ampulla with mucinous discharge, with classic “fish mouth” appearance. The pancreatic duct was diffusely dilated from the tail to ampulla, up to 17 mm in the head/neck. A cystic lesion measuring 41 × 35 mm adjacent to the main pancreatic duct extending to the uncinate was noted. FNA was performed and pathology confirmed the diagnosis of main duct IPMN. He successfully underwent a Whipple procedure. DISCUSSION: This case illustrates the importance of recognizing a classic endoscopic feature of main duct IPMN: the fish mouth ampulla of Vater. There are three types of IPMNs: main duct, side branch and mixed. MD-IPMNs have the most malignant potential of the three and should be acted on promptly with surgical referral for resection. Approximately 65% of MD-IPMNs are malignant, compared to 20% for side branch IPMNs. Due to the indolent course of IPMNs, many patients will remain asymptomatic for many years. Eventually, patients will present with symptoms similar to pancreatitis. Despite the lack of clear consensus for management of pancreatic cystic lesions between multiple guidelines, all agree that MD-IPMNs should be surgically resected due to the high malignant potential.

INN: Inflated Neural Networks for IPMN Diagnosis.

Intraductal papillary mucinous neoplasm (IPMN) is a precursor to pancreatic ductal adenocarcinoma. While over half of patients are diagnosed with pancreatic cancer at a distant stage, patients who are diagnosed early enjoy a much higher 5-year survival rate of 34% compared to 3% in the former; hence, early diagnosis is key. Unique challenges in the medical imaging domain such as extremely limited annotated data sets and typically large 3D volumetric data have made it difficult for deep learning to secure a strong foothold. In this work, we construct two novel "inflated" deep network architectures, InceptINN and DenseINN, for the task of diagnosing IPMN from multisequence (T1 and T2) MRI. These networks inflate their 2D layers to 3D and bootstrap weights from their 2D counterparts (Inceptionv3 and DenseNet121 respectively) trained on ImageNet to the new 3D kernels. We also extend the inflation process by further expanding the pre-trained kernels to handle any number of input modalities and different fusion strategies. This is one of the first studies to train an end-to-end deep network on multisequence MRI for IPMN diagnosis, and shows that our proposed novel inflated network architectures are able to handle the extremely limited training data (139 MRI scans), while providing an absolute improvement of 8.76% in accuracy for diagnosing IPMN over the current state-of-the-art. Code is publicly available at https://github.com/lalonderodney/INN-Inflated-Neural-Nets.

AB100. P074. Novel biomarkers for differential diagnosis of intraductal papillary mucinous neoplasms revealed by profiling microbial composition and translocation markers in liquid biopsies

: Pancreatic ductal adenocarcinoma (PDAC) has a major impact on public health, being the fourth-leading cause of cancer-related death in Western countries with a low overall survival rate and rapid deterioration in quality of life. Intraductal papillary mucinous neoplasms (IPMNs) are neoplastic precursor lesions which are understood to evolve from lesions with low-grade dysplasia to high-grade dysplasia to PDAC. Currently, the accuracy of pre-surgery differential diagnosis of cystic lesions is merely 47–78%. However, only after surgical resection of the pancreas can the type of cystic neoplasms and degree of IPMN dysplasia accurately be determined. The discovery of novel biomarkers that improve timely and accurate diagnosis of IPMN and its grade of dysplasia, and thus assist the determination of health risk, are of great importance for better patient management and to minimize diagnostic errors and unnecessary surgical procedures. We hypothesize that gut microbiota may have a role on pancreatic tumorogenesis and progression, given the strong association of oral pathogens such as P. gingivalis and F. nucleatum with systemic inflammation and intestinal cancers. We aimed to (I) determine whether (oral) bacteria are present in pancreatic cystic lesions, and (II) whether cystic microbiota composition associates with IPMN disease severity. We have established a biobank of pancreatic cyst fluid and peripheral blood from patients with pancreatic cystic lesions (n=90, IPMN and benign neoplasms as control) with post-surgery validated diagnosis. The absolute bacterial 16S rRNA gene copy numbers were determined by TaqMan qPCR and microbial compositional profiling by 16S rRNA gene sequencing is being undertaken. Additionally, we measured the magnitude of microbial translocation (MT) inflammation markers in these samples. We found a statistically significant difference of bacterial 16S gene quantities as well as biomarkers of MT and inflammation between different types of pancreatic cystic lesions, as well as significant correlation with IPMN grade of dysplasia. Our finding that several novel biomarkers from liquid biopsies might be used to differentiate between benign and (pre-)malignant pancreatic cystic lesions is of important clinical relevance in diagnosis and treatment for IPMN-related morbidity and mortality, including PDAC.