International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.

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.

Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review.

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.

The combination of EyeMax direct visualization system, EUS and ERCP for the precise treatment of intraductal papillary mucinous neoplasm / La combinación de EyeMax sistema de visualización directa, EUS y CPRE para la precisión tratamiento de intraductal neoplasia papilar mucinosa

Intraductal papillary mucinous neoplasm (IPMN) accounted for 5.0%~7.5% of pancreatic tumors and 21%~33% of cystic tumors. It usually occurs in people aged 60 to 70. The main treatment is surgical excision. The operation method is different according to the location of lesion, so we try our best to achieve accurate treatment. Here, we provide endoscopic ultrasonography combined with ERCP and eyeMax three endoscopic systems, so as to achieve accurate treatment of IPMN, which is recommended to the majority of endoscopists.(AU)

[Diagnostics and treatment of intraductal papillary mucinous pancreas neoplasm].

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.

Co-occurring IPMN and pancreatic cancer: the same or different? An overview from histology to molecular pathology.

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.

Diagnostic accuracy of the AGA, IAP, and European guidelines for detecting advanced neoplasia in intraductal papillary mucinous neoplasm/neoplasia.

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.

The Landmark Series: Intraductal Papillary Mucinous Neoplasms of the Pancreas-From Prevalence to Early Cancer Detection.

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.

New Diagnostic Modality Combining Mass Spectrometry and Machine Learning for the Discrimination of Malignant Intraductal Papillary Mucinous Neoplasms.

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.

Limitations and prospects in the management of IPMN: a retrospective, single-center observational study.

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.

Blood-Based Diagnosis and Risk Stratification of Patients with Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN).

PURPOSE: Intraductal papillary mucinous neoplasm (IPMN) is a precursor of pancreatic ductal adenocarcinoma. Low-grade dysplasia has a relatively good prognosis, whereas high-grade dysplasia and IPMN invasive carcinoma require surgical intervention. However, diagnostic distinction is difficult. We aimed to identify biomarkers in peripheral blood for accurate discrimination. EXPERIMENTAL DESIGN: Sera were obtained from 302 patients with IPMNs and 88 healthy donors. For protein biomarkers, serum samples were analyzed on microarrays made of 2,977 antibodies. A support vector machine (SVM) algorithm was applied to define classifiers, which were validated on a separate sample set. For microRNA biomarkers, a PCR-based screen was performed for discovery. Biomarker candidates confirmed by quantitative PCR were used to train SVM classifiers, followed by validation in a different sample set. Finally, a combined SVM classifier was established entirely independent of the earlier analyses, again using different samples for training and validation. RESULTS: Panels of 26 proteins or seven microRNAs could distinguish high- and low-risk IPMN with an AUC value of 95% and 94%, respectively. Upon combination, a panel of five proteins and three miRNAs yielded an AUC of 97%. These values were much better than those obtained in the same patient cohort by using the guideline criteria for discrimination. In addition, accurate discrimination was achieved between other patient subgroups. CONCLUSIONS: Protein and microRNA biomarkers in blood allow precise diagnosis and risk stratification of IPMN cases, which should improve patient management and thus the prognosis of IPMN patients. See related commentary by Löhr and Pantel, p. 1387.

Carbohydrate antigen 125 supplements carbohydrate antigen 19-9 for the prediction of invasive intraductal papillary mucinous neoplasms of the pancreas.

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.

Optimal surveillance of intraductal papillary mucinous neoplasms of the pancreas focusing on remnant pancreas recurrence after surgical resection.

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.

Identification of patients with branch-duct intraductal papillary mucinous neoplasm and very low risk of cancer: multicentre study.

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.

Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.

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.

A case of intraductal tubulopapillary neoplasm of the pancreas originating from the branch duct: cast in the mold sign.

A 59-year-old man with jaundice and lower common bile duct stenosis was referred to our institution for diagnosis and treatment. Computed tomography and magnetic resonance imaging showed a well-circumscribed smoothly marginated solid mass lesion in the pancreatic head. He underwent pyloric preserving pancreatoduodenectomy. Histopathological specimen revealed that the mass was located in the dilated branch duct of the pancreatic head, and an intraductal tubulopapillary neoplasm originating from the branch pancreatic duct was diagnosed. On magnetic resonance cholangiopancreatography, the mass within the dilated duct branch in the pancreatic head was similar to a "cast in the mold" image, which we retrospectively deemed, might be reflecting the nature of this tumor.

A tug-of-war in intraductal papillary mucinous neoplasms management: Comparison between 2017 International and 2018 European guidelines.

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.

[Diagnostic efficacy for predicting intraductal papillary mucinous neoplasms of the pancreas with high grade dysplasia or invasive carcinoma based on the surgery indications in different guidelines].

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,⑤acyst diameter ≥40 mm,⑤bcyst 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(①②③④⑤b⑥⑦⑧⑨) 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(①②③④⑤a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤b⑥⑧⑨) 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.