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Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. It has malignant potential, making it vital to establish the correct diagnosis, assess its malignant risk and follow a management strategy to prevent development of invasive carcinoma of the pancreas., Objective: This review focuses on the epidemiology, natural history, risk factors, diagnosis and management of IPMN of the pancreas, and will provide practical points for general practitioners., Discussion: IPMN of the pancreas can transform into invasive pancreatic carcinoma at a low rate of approximately 2%/year. Upon diagnosis of IPMN, it is risk stratified based on the presence of worrisome or high-risk stigmata, which guides further management. Management needs to be individualised based on IPMN and patient factors due to limitations with the current diagnostic tools.

Pancreatic cystic lesions represent a challenging heterogeneous entity with a potential risk of malignant transformation. The diagnostics include in particular medical history taking with collection of relevant clinical information and high-resolution imaging, preferably using magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) and/or endoscopic ultrasonography. A differentiation between different cystic entities and identification of risk factors are crucial for making appropriate treatment decisions. Only a small proportion of pancreatic cystic neoplasms require surgery. Pancreatic cystic lesions with a relevant risk of malignancy, such as main duct intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), solid pseudopapillary neoplasms (SPN) and general cystic pancreatic lesions with risk factors regardless of the entity, should be resected, whereas an individualized approach is required for branch duct IPMN and serous cystic neoplasms (SCN) and dysontogenetic cysts require no treatment. Parenchyma-sparing and minimally invasive resection techniques should be preferred whenever possible for resecting pancreatic cystic tumors. Approximately 10% of patients develop recurrences over time., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Despite the presence of various guidelines, diagnosing malignant intraductal papillary mucinous neoplasm (IPMN) continues to pose challenges. Furthermore, although endoscopic ultrasonography (EUS) offers high-resolution images, it has not yet recognized as the primary tool for malignancy diagnosis. The study objective was to develop a simplified and user-friendly scoring system to improve the diagnostic accuracy of malignant IPMNs. Additionally, the utility of EUS and its effect on diagnostic accuracy were assessed. We retrospectively collected the clinical data on 160 cases of resected IPMN at Tokyo Medical and Dental University Hospital from January 2008 to December 2022. We examined clinical features, computed tomography (CT) and magnetic resonance imaging (MRI) findings, and EUS results if available. We then calculated the odds ratio of malignancy for these factors and developed an IPMN malignancy prediction (IMAP) scoring system. There were 89 (55.6%) cases of benign IPMNs and 71 (44.4%) of malignant IPMNs. Eight clinical and imaging findings, including age, diabetes mellitus status, jaundice, CA19-9 level, enhancing mural nodules ≥5mm, thickened wall, and main duct dilatation, were significantly associated with malignancy. The IMAP score was calculated by assigning 0 to 2 points to these factors based on the odds ratio. The area under the receiver operating characteristic curve for the IMAP score was 0.78 [95% confidence interval (CI): 0.71-0.85] based on CT/MRI alone and improved to 0.81 (95% CI: 0.74-0.87) when EUS was added. When the total exceeds 5 points, the positive predictive value becomes 100% (95% CI: 95.9-100). In conclusion, the IMAP scoring system has demonstrated promise as a clinically useful tool, offering both simplicity and sufficient accuracy. It holds potential as an important decision criterion for determining the treatment approach for IPMN. Additionally, EUS contributes to enhancing the diagnostic accuracy of the IMAP scoring system, thereby enabling more precise decision-making., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kobayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Reports of pancreatic neuroendocrine neoplasm (P-NEN) concomitant with intraductal papillary mucinous neoplasm (IPMN) are gradually increasing. However, many of these cases were diagnosed in the resected specimen incidentally. We herein report a case of minimal P-NEN concomitant with branch-duct IPMN that was successfully diagnosed preoperatively by contrast-enhanced endoscopic ultrasonography (EUS) and an EUS-guided fine-needle biopsy. These findings suggest that P-NEN as well as pancreatic ductal adenocarcinoma should be considered as concurrent tumors developing in patients with IPMNs. EUS is an essential modality when evaluating IPMN for detecting small lesions concomitant with IPMN.

Acinar cystic transformation (ACT) of the pancreas is a rare non-neoplastic cystic lesion. It is difficult to distinguish from more concerning pathology, particularly a side-branch duct intraductal papillary mucinous neoplasm (IPMN). All reported cases of ACT have been clinically benign with no evidence of recurrence or malignant transformation. The Fukuoka guidelines is a classification system designed to help guide the management of IPMNs and mucinous cystic neoplasms. We report a case of ACT that was preoperatively diagnosed as a suspected side-branch IPMN. Through the application of current guidelines, the patient underwent a Whipple's procedure. We highlight the difficulties in obtaining an accurate preoperative diagnosis in cases of ACT and the current radiological and cytological methods available to clinicians., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This article constitutes a review of the existing literature on the potential correlation between autosomal dominant polycystic kidney disease (ADPKD) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Additionally, it presents a clinical case where familiarity for both pathologies was observed, derived from the direct experience of our clinic, reinforcing the hypothesis of a possible common pathogenetic pathway. The review focuses on the potential genetic correlation between these two pathologies within the realm of ciliopathies, emphasizing the importance of targeted screening and monitoring strategies to detect pancreatic complications early in patients with ADPKD. Furthermore, it highlights the complexity in the clinical management of these rare conditions and underscores the importance of early diagnosis in optimizing clinical outcomes., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs)., Methods: The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed., Results: A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management., Conclusions: This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases., (Copyright © 2023. Published by Elsevier B.V.)

The current WHO classification of digestive system tumours (2019) has presented the concept of diagnostics of intraductal and cystic neoplasms of the pancreas mostly based on integrated molecular data and evaluations of their malignant potential. Intraductal pancreatic neoplasms with ductal phenotype include microscopic precursor lesions of pancreatic ductal adenocarcinoma - the pancreatic intraepithelial neoplasia and macroscopic precursor lesions of pancreatic cancer, where intraductal papillary mucinous neoplasm represents the most common neoplasm of the pancreas with cystic appearance. Both intraductal oncocytic papillary neoplasm and intraductal tubulopapillary neoplasm are now classified as separate entities associated with less aggressive subtypes of pancreatic carcinoma and better prognosis. Clinical significance of microscopic pancreatic intraepithelial neoplasias is limited, in contrast to other intraductal neoplasms, which are presented as cystic and/or solid tumours by imaging methods with important consequences for further treatment and indication of surgical therapy (resection versus "watch and wait" strategies). Neoplasms of nonductal origin, such as acinar cell carcinomas and neuroendocrine neoplasms, can uncommonly display an intraductal growth and their correct classification has a great clinical importance. Moreover, differential diagnostics of cystic pancreatic lesions include not only cystic and pseudocystically transformed neoplasms, but also a large spectrum of reactive, inflammatory and dysontogenetic cystic lesions.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of the most well-established precursors of pancreatic cancer. Its progression to acquire invasiveness is a complex process, based on the accumulation of morphological and genetic alterations. Recent advances in DNA sequencing also showed that co-occurring IPMNs and pancreatic cancers could be totally independent, further complicating our understanding of this complex scenario. The distinction between IPMN and related pancreatic cancer vs IPMN and co-occurring-but not related-pancreatic cancer is a challenging task in routine diagnostic activity, but may have important implications for precision oncology. Of note, recent multiregional sequencing-based studies focused not only on IPMN multi-step tumourigenesis, but also on the divergent intratumoural heterogeneity of this neoplasm. Globally considered, there are three different situations in which co-occurring IPMNs and invasive carcinomas can be found in the same pancreata, indicated with different terminologies: (1) IPMN-associated carcinoma: this definition indicates a carcinoma arising from an IPMN and can be also defined as IPMN-derived carcinoma, sequential or likely related; (2) independent IPMN and invasive carcinoma: the two lesions are not related, and this situation is defined as concomitant, de novo or likely independent; (3) branch-off pathway, where an invasive carcinoma and an adjacent IPMN develop divergently in a forked fashion from a common ancestral clone. In this review, we aim at clarifying the most important nomenclature/definitions of these different situations, also providing an overview of the molecular state-of-the-art and of the clinical implications of this complex landscape., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

A clinical case of a 71-year-old patient with intraductal papillary mucinous neoplasia (IPMN) is presented. The diagnosis was established using endoscopic retrograde cholangiopancreatography, magnetic resonance imaging, computed tomography. Asymptomatic course, absence of pain syndrome, obstruction, exocrine and endocrine pancreatic failure, relatively satisfactory general health, but the presence of structural changes: an increase cyst in the head of the pancreas measuring 27×23 mm, expansion of the main pancreatic duct up to 13 mm raised doubts about the choice of treatment tactics, the need for surgical intervention. To exclude the risk of malignancy and the choice of treatment tactics, a fine-needle aspiration biopsy was performed, a cytological examination of the material, an expert opinion determined the scope of the surgical intervention. IPMN is a rather rare tumor of the pancreas. For a long time, IPMN flow "under the guise" of chronic pancreatitis. Depending on the type of degree of dysplasia and invasiveness of IPMN, the tactics of treatment and the volume of surgical intervention are determined. High-tech methods provide high information content in the diagnosis of IPMN. But only a morphological study allows you to determine the tactics of treatment.

Background: An intraductal papillary mucinous neoplasm (IPMN) is a pancreatic tumor with malignant potential. Although we anticipate a sensitive method to diagnose the malignant conversion of IPMN, an effective strategy has not yet been established. The combination of probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning provides a promising solution for this purpose., Methods: We prospectively analyzed 42 serum samples obtained from IPMN patients who underwent pancreatic resection between 2020 and 2021. Based on the postoperative pathological diagnosis, patients were classified into two groups: IPMN-low grade dysplasia (n = 17) and advanced-IPMN (n = 25). Serum samples were analyzed by PESI-MS, and the obtained mass spectral data were converted into continuous variables. These variables were used to discriminate advanced-IPMN from IPMN-low grade dysplasia by partial least square regression or support vector machine analysis. The areas under receiver operating characteristics curves were obtained to visualize the difference between the two groups., Results: Partial least square regression successfully discriminated the two disease classes. From another standpoint, we selected 130 parameters from the entire dataset by PESI-MS, which were fed into the support vector machine. The diagnostic accuracy was 88.1%, and the area under the receiver operating characteristics curve was 0.924 by this method. Approximately 10 min were required to perform each method., Conclusion: PESI-MS combined with machine learning is an easy-to-use tool with the advantage of rapid on-site analysis. Here, we show the great potential of our system to diagnose the malignant conversion of IPMN, which would be a promising diagnostic tool in clinical settings., (© 2023. The Author(s).)

Background: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroenterological Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN., Methods: Patients who underwent surgery were extracted from a prospective database (January 2006-January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline., Results: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%)., Conclusion: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update., (Copyright © 2023. Published by Elsevier B.V.)

Modern series report a prevalence of pancreatic cysts in the general population of up to 50% in prospective studies. Of these, about half will be pancreatic cystic neoplasms (PCNs) that have varying degrees of malignant potential. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most common PCNs and are known predecessors of pancreatic adenocarcinoma. Critically, they are one of the only radiographically identifiable precursors of pancreatic cancer and thus provide an opportunity for early cancer detection and surgical resection with curative intent. The combination of high prevalence and potential for malignant degeneration underscore the relevance of discussing the best management of IPMNs and improving the existing standard of care. Landmark data on IPMN prevalence, guidelines, surveillance, biomarkers, and immune landscape are highlighted., (© 2023. The Author(s).)

Background: With increasing use and enhanced accuracy of cross-sectional imaging, the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has increased over the last few decades. The extent to which malignant transformation occurs remains unclear, making the management of IPMNs controversial. The aim of this study was to evaluate the progression rate and outcome of follow-up in patients with IPMNs., Methods: A database of all patients diagnosed with IPMN at the Cantonal Hospital HFR Fribourg, Switzerland, between January 2006 and December 2019 with a follow-up of at least 6 months was analyzed retrospectively. Descriptive statistics were performed on patient demographics, IPMN characteristics, and follow-up data., Results: A total of 56 patients were included in this study. Ten patients underwent primary surgery, 46 were enrolled in a surveillance program.21.7% (n = 5) of patients under surveillance presented with worrisome features of IPMN; progression rates were significantly higher in these patients (p = 0.043). Most progression occurred in the early follow-up period. Five patients underwent surgery due to progression, of which 2 presented high-grade dysplasia and 2 malignancy on postoperative histology., Conclusions: The limited predictive value of current guidelines may lead to surgical overtreatment, and the decision to proceed with surgical resection should be made with caution. Further prospective analyses and the development of novel biomarkers are needed to better understand the natural history of IPMN and improve diagnostic precision., (© 2023. The Author(s).)

Background: Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs., Methods: We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy., Results: The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup., Conclusions: Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy., (© 2022. The Author(s).)

Background: Different surveillance strategies for patients with low-risk branch-duct (BD) intraductal papillary neoplasm (IPMN) have been described. The aim of this study was to describe the natural history of low-risk BD-IPMN, and to identify risk factors for the development of worrisome features (WF)/high-risk stigmata (HRS) and of pancreatic malignancies., Methods: This was a multicentre retrospective study of patients with BD-IPMN who were under active surveillance between January 2006 and December 2015. Patients were eligible if they had a low-risk lesion and had a minimum follow-up of 24 months. Outcomes were development of WF/HRS or cytologically/histologically confirmed malignant IPMN., Results: Of 837 patients included, 168 (20 per cent) developed WF/HRS. At the end of the observation time, 132 patients (79 per cent) with WF/HRS were still under surveillance without progression to pancreatic cancer. Factors associated with the development of WF or HRS in multivariable analysis included localized nodules (versus diffuse: hazard ratio (HR) 0.43, 95 per cent c.i. 0.26 to 0.68), cyst size 15-19 mm (versus less than 15 mm: HR 1.88, 1.23 to 2.87) or at least 20 mm (versus less than 15 mm: HR 3.25, 2.30 to 4.60), main pancreatic duct size over 3 mm (versus 3 mm or less: HR 2.17, 1.41 to 3.34), and symptoms at diagnosis (versus no symptoms: HR 2.29, 1.52 to 3.45). Surveillance in an endoscopy-oriented centre was also associated with increased detection of WF or HRS (versus radiology-oriented: HR 2.46, 1.74 to 3.47)., Conclusion: Conservative management of patients with low-risk BD-IPMN is safe and feasible., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: The international consensus guidelines for intraductal papillary mucinous neoplasm of the pancreas (IPMN) presented clinical features as indications for surgery. Whereas surveillance for recurrence, including de novo lesions, is essential, optimal surveillance protocols have not been established., Aim and Methods: This study aimed to assess the clinical features of recurrence at the remnant pancreas (Rem-Panc) and extra-pancreas (Ex-Panc) after surgery for IPMN. Ninety-one patients of IPMN that underwent detailed preoperative assessment and pancreatectomy were retrospectively analyzed, focusing especially on the type of recurrence., Results: The IPMNs were finally diagnosed as low-grade dysplasia (LDA, n = 42), high-grade dysplasia (HAD, n = 19), and invasive carcinoma (IPMC, n = 30). Recurrence was observed in 26 patients (29%), of which recurrence was seen at Rem-Panc in 19 patients (21%) and Ex-Panc in 7 patients (8%). The frequency of Rem-Panc recurrence was 10% in LDA, 21% in HDA, and 37% in IPMC. On the other hand, Ex-Panc recurrence was observed only in IPMC (23%). Ex-Panc recurrence showed shorter median recurrence-free survival (RFS) and overall survival (OS) than Rem-Panc recurrence (median RFS 8 months vs. 35 months, p < 0.001; median OS 25 months vs. 72 months, p < 0.001). Regarding treatment for Rem-Panc recurrence, repeat pancreatectomy resulted in better OS than no repeat pancreatectomy (MST 36 months vs. 15.5 months, p = 0.033). On multivariate analysis, main duct stenosis or disruption as a preoperative feature (hazard ratio [HR] 10.6, p = 0.002) and positive surgical margin (HR 4.4, p = 0.018) were identified as risk factors for Rem-Panc recurrence., Conclusions: The risk factors for Rem-Panc and Ex-Panc recurrence differ. Therefore, optimal surveillance on these features is desirable to ensure that repeat pancreatectomy for Rem-Panc recurrence can be an appropriate surgical intervention., (© 2022. The Author(s).)

The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management., Aim: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN., Methods: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated., Results: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN., Conclusions: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features., Competing Interests: Declaration of Competing Interest No author has conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To propose a noninvasive diagnostic approach, which allows reliable distinction between low- and high-risk pancreatic intraductal papillary mucinous neoplasms (IPMNs)., Background: IPMNs are identifiable precursor lesions of pancreatic cancer, of which surgical resection is warranted prior to the development of invasive carcinoma, but low-grade IPMNs should not be unnecessarily resected. However, diagnostic tools that preoperatively enable accurate risk stratification of IPMNs are missing., Methods: This single-center, retrospective cohort study included 56 patients who underwent surgical resection for IPMN including 18 low-risk (low-grade) and 38 high-risk (high-grade/invasive carcinoma) IPMNs, from whom clinical features and serum samples were prospectively obtained. An antibody microarray platform was used to analyze the serum proteome. Based on serum markers and selected clinical characteristics support vector machine models were constructed to predict the risk of IPMN malignancy., Results: A serum protein signature discriminating low- and high-risk IPMN patients was identified. Combinations of established clinical features and the newly identified serum biomarkers correctly distinguished low- and high-risk IPMNs in 93% on 1000-fold cross-validation., Conclusions: This study highlights the synergistic predictive value of combining a novel serum protein signature with conventional clinical characteristics to risk-stratify IPMN patients. If these findings are supported by larger validation studies, they might enable more rational decision-making in clinical management of IPMN patients in conjunction with clinical guidelines., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Recently, the term mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) has been proposed as an umbrella definition covering different possible combinations of mixed neuroendocrine-exocrine neoplasms. Among these, the adenoma plus neuroendocrine tumor (NET) combination is among the rarest and not formally recognized by the 2019 WHO Classification. In this setting, the debate between either collision tumors or true mixed neoplasms is still unsolved. In this report, a pancreatic intraductal papillary mucinous neoplasm (IPMN) plus a NET is described, and the molecular investigations showed the presence in both populations of the same KRAS, GNAS, and CDKN2A mutations and the amplification of the CCND1 gene. These data prove clonality and support a common origin of both components, therefore confirming the true mixed nature. For this reason, mixed neuroendocrine-exocrine neoplasms, in which the exocrine component is represented by a glandular precursor lesion (adenoma/IPMN) only, should be included into the MiNEN family.

Objective: To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN). Methods: A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤ a cyst diameter ≥40 mm,⑤ b cyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 μg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results: Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly ( P <0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail, OR =3.284,95% CI :1.268-8.503, P =0.014),thickened/enhancement cyst wall (with vs. without, OR =2.713,95% CI :1.177-6.252, P =0.019),CA19-9(≥37 U/L vs. <37 U/L, OR =5.086,95% CI :2.05-12.62, P <0.01) and NLR(≥2 vs. <2, OR =2.380,95% CI :1.043-5.434, P =0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤ b ⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤ a ⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤ b ⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions: Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.

Introduction: Determining the risk of malignancy in a pancreatic cyst (PC) is a clinical and diagnostic challenge. Monoclonal antibody (mAb) Das-1 test was shown to have high sensitivity, specificity, and accuracy in detecting high-risk (HR) cysts. Das-1 mAb test detects HR mucinous cysts with high-grade dysplasia (HGD), invasive carcinoma, and/or intestinal-type epithelium. Correlation of mAb Das-1 testing of PC fluids with cytomorphologic findings has not been evaluated., Materials and Methods: We correlated cytology with mAb Das-1 test results and resection histology in 26 PCs. There were 18 intraductal papillary mucinous neoplasms (IPMN), 1 intraductal oncocytic papillary neoplasm (IOPN), 4 mucinous cystic neoplasms (MCN), 2 serous cystadenomas, and 1 cystic pancreatic neuroendocrine tumor (PanNET). HR cysts included cysts with high-grade atypia on cytology or HGD on histology, invasive carcinoma, IOPNs, and cystic PanNETs. Intestinal type IPMNs were also HR cysts on histology., Results: In 17 cases (65.38%), cytology and mAb Das-1 test correlated with histology. There were 2 (7.69%) mAb Das-1 test negative HR PCs diagnosed by cytology. Five (19.23%) mAb Das-1 test positive HR PCs had mucin only or cells with low-grade dysplasia on cytology. Two mAb Das-1 test positive HR PCs had nondiagnostic cytology. HR IOPN and cystic PanNET were not detected by mAb Das-1 test., Conclusion: The mAb Das-1 is a sensitive and specific biomarker for detecting HR mucinous PCs. Adding cytology to mAb Das-1 testing improves the sensitivity for the detection of nonmucinous HR PC. Together, cytology with mAb Das-1 testing is more accurate than either one alone., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI., Methods: Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts., Results: 356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria., Conclusions: In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI., Competing Interests: Declaration of competing interest Dr. Hruban has the right to receive royalty payments from Thrive Earlier Detection for the GNAS invention through a relationship managed by Johns Hopkins University. All other authors disclose no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background and Aims: Advances in cross-sectional imaging have resulted in increased detection of intraductal papillary mucinous neoplasms (IPMNs), and their management remains controversial. At present, there is no reliable noninvasive method to distinguish between indolent and high risk IPMNs. We performed extracellular vesicle (EV) analysis to identify markers of malignancy in an attempt to better stratify these lesions., Methods: Using a novel ultrasensitive digital extracellular vesicle screening technique (DEST), we measured putative biomarkers of malignancy (MUC1, MUC2, MUC4, MUC5AC, MUC6, Das-1, STMN1, TSP1, TSP2, EGFR, EpCAM, GPC1, WNT-2, EphA2, S100A4, PSCA, MUC13, ZEB1, PLEC1, HOOK1, PTPN6, and FBN1) in EV from patient-derived cell lines and then on circulating EV obtained from peripheral blood drawn from patients with IPMNs. We enrolled a total of 133 patients in two separate cohorts: a clinical discovery cohort (n = 86) and a validation cohort (n = 47)., Results: From 16 validated EV proteins in plasma samples collected from the discovery cohort, only MUC5AC showed significantly higher levels in high-grade lesions. Of the 11 patients with invasive IPMN (inv/HG), 9 had high MUC5AC expression in plasma EV of the 11 patients with high-grade dysplasia alone, only 1 had high MUC5AC expression (sensitivity of 82%, specificity of 100%). These findings were corroborated in a separate validation cohort. The addition of MUC5AC as a biomarker to imaging and high-riskstigmata allowed detection of all cases requiring surgery, whereas imaging and high-risk stigmata alone would have missed 5 of 14 cases (36%)., Conclusions: MUC5AC in circulating EV can predict the presence of invasive carcinoma within IPMN. This approach has the potential to improve the management and follow-up of patients with IPMN including avoiding unnecessary surgery., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pancreatic cystic neoplasms are increasingly detected in the general population. Although most of these lesions are benign, some are (pre)malignant and require follow-up or even surgical intervention. Three cases are presented and used to discuss the clinical implications of the renewed European Guideline on pancreatic cystic neoplasms in which relative and absolute indications for resection are proposed. In the first case, a pancreatic cystic lesion was found on abdominal ultrasound in a 77-year old female patient. After endoscopic ultrasound was performed, a serous cystic neoplasm was diagnosed without need for surveillance. In a 57-year old male, an abdominal MRI was performed to further assess an incidentally found pancreatic cystic lesion. Based on the MRI, a side-branch intraductal papillary mucinous neoplasm (SB-IPMN) was diagnosed and yearly surveillance was initiated. A 61-year old male underwent a laparoscopic distal pancreatectomy because of a mixed-type IPMN (MT-IPMN). The pathological results showed an IPMN with high-grade dysplasia.

Cystic tumors of the pancreas are uncommon entities. Synchronic occurrence of intraductal papillary mucinous neoplasm (IPMN) and other pancreatic tumors is extremely rare. Two patients with this diagnosis are reported in the manuscript. Cystic tumors of the pancreas can rarely occur in various combinations while malignancy potential of each neoplasm may be different. Surgery depends on localization and type of each tumor and must be determined individually.

Background: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN)., Methods: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR., Results: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance., Conclusions: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

A 45-year-old woman was referred from Department of Dermatology to Surgery outpatient department with pruritus since 6 months and an episode of jaundice that lasted for 15 days about 6 months ago. She was referred with a contrast-enhanced MRI finding that showed a small lesion in the lower end of common bile duct. Endoscopy-guided biopsy was performed twice at our hospital, the second revealed low grade dysplasia. Consequently, she underwent pancreaticoduodenectomy. Intraoperatively, there were both vascular and biliary anatomical variations that were missed on preoperative images. On histopathological examination, it turned out to be a mixed variety of intraductal papillary neoplasm of bile duct (IPNB). As all findings were rare in one, hence, we present this case of IPNB that presented to us with variable clinical, radiological, surgical and pathological findings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study the clinical features, diagnosis, surgery treatment and prognosis of intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B). Methods: The data of 16 patients with IPMN-B admitted to The First Hospital of Jilin University and Xi'an Third Hospital from January 2014 to January 2018 were retrospectively analyzed. Kaplan-Meier method was used to conduct the survival analysis. These patients included 10 males and 6 females, the median age was 57 years. Results: Clinical manifestations were mainly jaundice (11 cases), upper abdominal pain (12 cases) and hyperpyretic chills (4 cases), combined with bile duct stones (14 cases) and hepatic lobe atrophy (2 cases). The average size of the tumor was (2.6±0.7) cm. All of 16 cases were diagnosed as IPMN-B, including 5 cases of invasive carcinoma (4 cases were perineural invasion) without vascular invasion and 6 cases of non-invasion carcinoma. The pathological type included 8 cases of pancreaticobiliary duct type, 5 cases of gastric type, 2 cases of intestinal type and 1 case of eosinophils type. Laboratory tests showed abnormal liver function (12 cases), increased direct bilirubin (9 cases), increased carbohydrate antigen199 (CA199, 8 cases) and carcinoembryonic antigen (CEA, 4 cases). The enhanced CT detection showed 9 cases of intrabile duct mass and 14 cases of bile duct dilatation. Surgical resection is the main treatment method, including 2 cases of partial resection of liver, 12 cases of bile duct mass resection combined with choledochojejunostomy and 2 cases of pancreatoduodenectomy, all of whom achieved R0 resection. Fifteen patients were followed up and 4 died during the period. The median postoperative progression free survival was 31 months (95% CI: 33-47 months), and the recurrence rate at 1 year, 2-years and 3-years were 6.7%, 40.0% and 73.3%, respectively. The median overall survival was 35 months (95% CI: 23-47 months), and the 1 year, 2-years, and 3-years cumulative survival rates were 100%, 80.0%, and 53.3%, respectively. Conclusions: IPMN-B is a rare tumor of biliary tract system, which is difficult to be diagnosed early. The main treatment is surgical resection, which can achieve a good prognosis.

Objectives: 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., Methods: 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., Results: 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., Conclusions: A multidisciplinary approach including combined use of cytology and ancillary testing is helpful in establishing a diagnosis of MCL and identifying associated malignancy., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To clarify the usefulness of cancer-related inflammation, hypermetabolism, and subsequent host malnutrition biomarkers for predicting the histological grades of intraductal papillary mucinous neoplasms of the pancreas (IPMNs)., Methods: The systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and maximum standardized uptake value (SUVmax) on fluorodeoxyglucose-positron emission tomography were compared across 171 resected IPMN cases of different histological grades. The diagnostic performance of each marker and of their combinations for predicting IPMN with high-grade dysplasia (HGD)/associated invasive carcinoma (INV) was also tested., Results: Of the 171 IPMNs, the IPMN cases with HGD showed significantly higher values of SII (median 406 vs. 340; P = 0.041) and SUVmax (median 2.5 vs. 2.0; P = 0.001) than those with low-grade dysplasia (LGD). On a multivariate analysis, the SII and SUVmax were both independent markers for predicting HGD/INV. A combination analysis including the tumor- and host-derived markers in combination with imaging findings showed an improved diagnostic performance (area under the curve 0.824; sensitivity 75.9%; specificity 80.0%)., Conclusions: The combination of multiple markers of host-derived inflammation and tumor-derived focal hypermetabolism can serve as a predictor for the presence of HGD/INV.

Background: The accuracy and costs of current diagnostic methods in the differential diagnosis of pancreatic cystic lesions still has ample room for improvement., Aims: The aim of the study was to confirm the diagnostic yield of intracystic glucose in the diagnosis of pancreatic cyst subtypes., Methods: We prospectively recruited all patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration of pancreatic cyst at our Institution., Results: Fifty-six patients were included in the study. We found that intracystic glucose concentration < 50 mg/dL was significantly more sensitive than a concentration of Carcinoembryonic Antigen > 192 ng/mL (93.6% vs 54.8%; p = 0.003) for the diagnosis of mucinous cysts. In terms of specificity, the two markers were not different (96% vs 100%; p = 1). Regarding the diagnosis of non-mucinous cysts, intracystic glucose concentration ≥ 50 mg/mL showed higher sensitivity than Carcinoembryonic Antigen level < 5 ng/mL (96% vs 72%) although a statistical significance could not be reached (p = 0.07). The two markers were not statistically different in terms of specificity (93.6% vs 87.1%; p = 0.62)., Conclusion: Given its diagnostic performance and ease of measurement, intracystic glucose may replace Carcinoembryonic Antigen in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts., Competing Interests: Declaration of Competing Interest Claudio De Angelis is consultant for Boston Scientific., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described., Aims: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis., Materials and Methods: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological., Results: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis., Conclusion: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

This article outlines the principles behind the management of pancreatic cystic lesions. We outline what the general surgeon needs to know in managing and triaging these patients. It is our feeling that the general surgeon is often the first line of evaluation of these complex patients and a working knowledge of the different types of cysts is critical to safe care of the patient., Competing Interests: Disclosure No conflicts of interest; no disclaimers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Pancreatic cancer (PC) is a leading cause of cancer related mortality worldwide, with poor survival due to late diagnosis. Currently, biomarkers have limited use in early diagnosis of PC. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) has been implicated as a potential serum biomarker in PC and other malignancies., Aim: To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program., Methods: A feasibility prospective single centre cohort study was performed. Participants recruited for yearly surveillance with endoscopic ultrasound (EUS) had serial fasting blood samples collected before EUS for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings: Normal; pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm; diffuse non-specific abnormalities; and neoplastic tumours. MIC-1/GDF15 serum levels were quantified using ELISA. Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging (MRI) or computed tomography., Results: One hundred twenty participants were prospectively recruited from 2011-2018. Forty-seven participants (39.2%) had an abnormal EUS and five participants (4.2%) were diagnosed with neoplastic tumours, three by EUS (two pancreatic and one liver) and two by MRI/computed tomography (breast cancer, bladder cancer), which were performed for follow up of abnormal EUS. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis [area under curve (AUC) = 0.814, P = 0.023]. Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm (AUC = 0.644) and neoplastic tumours noted on EUS (AUC = 0.793), however this was not significant ( P = 0.188 and 0.081 respectively). Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS ( P = 0.213). Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours (Median = 1039.6, interquartile range = 727.0-1977.7) compared to those diagnosed with a benign lesion (Median = 570.1, interquartile range = 460.7-865.2) on EUS and MRI ( P = 0.012)., Conclusion: In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC. Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15. Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.

Intraductal tubulopapillary neoplasms (ITPNs) of the pancreas and bile duct are contemporary entities. It is unclear on how to best manage patients with this diagnosis because little is known about its progression to cancer. This review provides an update on the current knowledge of ITPN of the pancreas and bile duct with an overview of clinical, radiological, histopathological, and molecular features, as well as the prognosis and management. Embase and Medline databases search were performed to identify studies that evaluated ITPN of the pancreas and bile duct. The infrequent exposure to this variant poses a diagnostic challenge. The diagnosis of ITPN is almost always made postoperatively because there are no characteristics on radiological studies to distinguish it from other cystic neoplasms of the pancreas. As ITPN has a favorable prognosis, it is crucial to establish an accurate diagnosis and differentiate it from other pancreatic and biliary variants. These neoplasms are considered to be precursor lesions to carcinomas, hence, surgery and close clinical surveillance are recommended. Further studies are essential to elucidate the natural history of ITPN, guide best treatment strategy and determine disease recurrence and survival.

Introduction: Most intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery., Methods: Patients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias., Results: Two hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046)., Conclusion: Patients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Intraductal tubulopapillary neoplasm (ITPN) is a premalignant epithelial tumor of the pancreas. We report a case of ITPN detected incidentally during histopathology examination (HPE) from a specimen taken at the time of endosonography in a patient with pancreatitis. A 53-year-old man presented with severe recurrent epigastric pain, associated with episodic nonbilious vomiting, with a weight loss of about 7 Kg since 15 days. He underwent Magnetic resonance cholangiopancreatography which showed an ovoid soft tissue lesion in the Pancreatic duct (PD) reported as possible intraductal neoplasm. Patient underwent Endoscopic Ultrasound, whereby the PD was dilated and a large hypoechoic lesion was noted in the PD (head region) causing upstream dilatation. Lesion did not show any vascularity on Doppler. Fine needle biopsy was sent from the intraductal lesion for histopathology examination (HPE). Patient then underwent an ERCP. After performing a pancreatic sphincterotomy, pancreaticoscopy was done using SPYGLASS DS system which showed a nodular intraluminal lesion in the head region with irregular and abnormal vascularity and papillary fronds. Biopsies were taken from this lesion using SpyBite biopsy forceps. To our surprise this HPE report came out to be ITPN. Patient was then referred for surgery. There is often a difference of opinion in distinguishing and classifying such tumors when compared to the subtypes of mucinous neoplasm. Identification of this neoplasm is often challenging for pathologists as well as radiologists. We present this case since it is infrequent and atypical in routine medical practice.

A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.

A small proportion of intraductal papillary mucinous neoplasms (IPMNs) are accompanied by type 1 autoimmune pancreatitis (AIP); however their clinical courses and image characteristics have not been fully reported. A 65-year-old woman was referred to our hospital for the examination of a pancreatic head cyst that had shown exacerbation for two years. Several images demonstrated a multilocular cyst with a symmetrically thickened, enhanced, cyst wall. Cancerization of IPMN was suspected, and pancreatoduodenectomy was performed. The resected specimens showed a multilocular cyst with solid areas. The solid areas demonstrated pathological findings that corresponded with type 1 AIP. Papillary epithelia suggestive of IPMN was recognized in some parts of the cystic wall.