Efficacy of diagnosing intraductal papillary mucinous neoplasm with mural nodules by contrast-enhanced endoscopic ultrasound using time-intensity curve analysis with a new support program: A multicenter retrospective study (with video).

Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time - intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time - intensity curve parameters and tumor microvessel density. Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time - intensity curve analysis were evaluated retrospectively. Time - intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time - intensity curve parameters was evaluated. The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (P = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (r = 0.803, P < 0.001). CH-EUS with time - intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 (P = .001), prognostic nutritional index (PNI) < 45 (P = .016), CA 19-9 > 37 U/mL (P = .039), and cystic diameter ⩾ 30 mm (P = .010), and mural nodule (P = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1

Efficacy of contrast-enhanced EUS for lymphadenopathy: a prospective multicenter pilot study (with videos)

Mo1403 Preoperative Endoscopic Tissue Sampling of Intraductal Papillary Mucinous Neoplasms (IPMNs) With Mural Nodules (MNs)

The purpose of this study was to conduct an intraoperative evaluation of focal liver lesions using time intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) to better assess liver tumor margins.This study included 28 patients (21 men 75%, 7 women 25%) with malignant liver lesions (cholangiocellular carcinoma (CCC), n = 9; hepatocellular carcinoma (HCC), n = 6; hepatic metastases (HepMET), n = 13). A B-mode scan, color-coded Doppler sonography, and CEUS were performed intraoperatively to analyze the focal lesions. The generated parametric images were based on continuous cine loops, acquired with a multifrequency T-probe (6-9 MHz), from the early arterial phase (0-15 seconds) to the portal venous phase (1 minute), generated by integrated perfusion software. Analyses of the CEUS loops were performed using TICs with respect to time-to-peak (TTP) and area under the curve (AUC). Perfusion analysis was performed in the center and periphery of the tumor as well as in healthy liver tissue. All tumor lesions were evaluated histopathologically to verify the diagnosis.Sufficient image quality was achieved in all cases using CEUS for TIC analysis. A comparison of all groups showed a clear difference compared with the center, margin, and healthy liver tissue in the measured parameters of TTP and AUC (p = 0.035 and p = 0.045, respectively). In detail, differences were observed in the CCC group (TTP: p = 0.025) and in the HepMET group (TTP: p = 0.009), particularly in the peripheral areas (strong arterial flooding with a rapid increase in the flooding curve), with equally clear tumor edge representation compared with healthy liver tissue, as shown by the AUC analysis (CCC AUC: p = 0.032 and HepMET AUC: p = 0.029). In patients with HCC, the perfusion pattern (starting from the center) showed the center to be more clearly distinguishable from the edge with significant TTP and AUC (p = 0.035 and p = 0.038).Intraoperative TIC analysis of malignant liver tumors is an important diagnostic tool for better highlighting liver tumor margins during surgery. · CEUS with dynamic vascularization. Analysis of liver malignancies and tumor margins. Intraoperative time intensity curve analysis.. · Dropco I, Kaiser U, Jung F et al. Intraoperative contrast-enhanced ultrasound (CEUS) with time intensity curve (TIC) analysis for better assessment of liver tumor margins. Rofo 2025; DOI 10.1055/a-2600-7229.

BackgroundThe degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. MethodsThis is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. ResultsOut of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0–252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. ConclusionOverall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

Surgical indication for intraductal papillary mucinous neoplasm without mural nodule ≥5 mm

Intraductal papillary mucinous neoplasms (IPMNs)have a wide pathologic spectrum and it is difficult to differentiate malignant from benign tumors. The aim of this study was to identify predictors of malignancy using contrast-enhanced endoscopic ultrasound (CE-EUS). In our institute, main duct type and mixed type IPMNs, branch duct type IPMNs with mural nodules, and IPMNs with coexistent invasive ductal cancer were indications for surgery. Eighty-seven IPMNs (14 main duct, 25 mixed, and 48 branch duct type) were resected and CE-EUS findings were compared with pathologic findings. Twelve clinicopathological variables and CE-EUS morphologic findings were assessed.Mural nodules defined as blood flow supplied protrusions were classified into 4 types: type I: low papillary nodule, type II: polypoid nodule, type III:papillary nodule, and type IV: invasive nodule. Forty-two, 26, 16, and 3 were pathologically diagnosed as adenoma,noninvasive carcinoma, invasive IPMNs, and coexistent invasive ductal cancer, respectively. Multivariable logistic regression analysis showed that types III/IV mural nodule (odds ratio = 10.8; 95% confidential intervals = 2.75-56.1) and symptomatic IPMNs (odds ratio = 4.31; 95% confidential intervals = 1.37-14.7) were significant for malignancy. For mural nodule diameter, invasive IPMNs were significantly larger, but types III and IV mural nodules were more frequently associated with malignancy, particularly invasive cancer, at 88.9% and 91.7%, respectively. The diagnosis of IPMNs with types III or IV mural nodule as malignant resulted in a sensitivity of 60%, specificity of 92.9%, and accuracy of 75.9%. In conclusion, new morphologic criteria were useful to identify the malignant potentials of IPMNs.

Endoscopic ultrasonographic findings predict the risk of carcinoma in branch duct intraductal papillary mucinous neoplasms of the pancreas

Mural nodule of 10mm or larger as predictor of malignancy for intraductal papillary mucinous neoplasm of the pancreas: Pathological and radiological evaluations.

Pancreatic cancer is associated with poor clinical outcomes primarily due to the advanced stage at the time of diagnosis. Endoscopic harmonic ultrasound imaging (HI) is being used to characterize pancreatic masses. Alternatively, transabdominal subharmonic imaging (SHI) may limit invasiveness and better suppress nonlinear tissue echoes. In both approaches, time-intensity curve (TIC) analysis can be performed to quantify blood flow dynamics. The purpose of this study was to compare TICs from both HI and SHI ultrasound of pancreatic masses. Patients underwent both endoscopic HI and SHI prior to an endoscopic biopsy of a pancreatic mass. SHI (transmitting/receiving at 2.5/1.25 MHz) was performed on a modified Logiq 9 system with a 4C probe (GE Healthcare, Milwaukee, WI), while endoscopic HI ultrasound (transmitting/receiving at 4.7/9.4 MHz) was performed with a radial endoscope (GF-UTC180; Olympus, Tokyo, Japan) and a ProSound SSD α-10 scanner (Hitachi-Aloka, Tokyo, Japan). TIC analysis was performed on a pixel by pixel basis to generate parametric images of peak intensity, time to peak, perfusion, and area under the curve and compared by modality to pathology. To date, TIC processing has been completed on 10 cases that were not compromised by excessive motion. No significant differences were observed between imaging modes for time to peak, perfusion, or area under the curve (p>0.11), while peak intensity was different (p=0.01) most likely due to scanner-specific properties such as transmit power, etc. When grouped by pathology (adenocarcinoma vs. other masses), neither modality showed significant differences in any TIC parameter, with peak intensity being the closest to demonstrating differences (p= 0.06). While the feasibility of parametric imaging of pancreatic masses has been demonstrated, future efforts with increased sample size and motion correction are likely needed to better elucidate any differences in blood flow TIC parameters between benign and malignant pancreatic lesions.

Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses (with videos)

Intraductal papillary mucinous neoplasms (IPMN) are precancerous cysts representing the only radiographically identifiable precursor to pancreatic ductal adenocarcinoma (PDAC). Successful interception of PDAC requires identifying high-risk disease, which accounts for approximately 15-20% of IPMN. Currently, this is only achieved by detecting high-grade dysplasia (HGD) in the epithelial lining of the cyst, which is challenging due to the heterogeneity of the disease. Minute foci of HGD can reside adjacent to abundant low-grade dysplasia (LGD), making it nearly impossible to detect HGD without histopathological review of a surgically resected lesion. Additionally, IPMN-associated PDAC is often detected only after surgical removal. The heterogeneity of these lesions has hindered efforts to accurately profile pure HGD or invasive regions, leading to unsuccessful attempts to identify diagnostic biomarkers. The predominant pathology in many IPMN lesions is LGD. Therefore, we hypothesized that if there are differences between the low-grade regions of low-risk, high-risk, and invasive IPMN, we could identify a diagnostic biomarker without the need to detect HGD or PDAC specifically. While single-cell RNA-sequencing (scRNA-seq) presents an attractive approach for characterizing IPMNs, it has been limited by the inability to sequence IPMN samples with confirmed pathology. Recently, 10X Genomics introduced a scRNA-seq method for formalin-fixed, paraffin-embedded (FFPE) tissues, mitigating the challenge of sequencing these highly heterogeneous samples prior to histological annotation. We employed this scRNA-seq assay on 13 FFPE tissue blocks confirmed to harbor LGD epithelium only. These blocks were derived from five patients with only LGD within the entire specimen (low-risk), five patients who had focal HGD detected in other blocks from the same specimen (high-risk), and four patients who had invasive cancer detected in other blocks. We also included two samples containing LGD, HGD, and PDAC within the same specimen for comparative analysis. Overall, we profiled 90,950 cells, the largest known IPMN single-cell sequencing effort to date. We identified a cell population indicative of acinar-to-ductal metaplasia (ADM) in low-risk samples that disappeared through disease progression. Moreover, we discovered that populations of immune cells differed between the low-grade lesions of low-risk, high-risk, and invasive IPMN. For instance, low-risk samples had the highest proportion of effector memory CD8+ T cells, high-risk samples had the highest proportion of pro-inflammatory macrophages, and invasive samples had the highest proportion of B cells. Furthermore, we analyzed inferred cell–cell interactions and identified differences in signaling strength between distinct ductal, stromal, and immune cell populations across these sample groups. These results demonstrate the first instance of resolving and comparing the microenvironment surrounding LGD lesions in low-risk, high-risk, and invasive IPMN. Citation Format: Ashley A. Fletcher, Erika J. Crosby, Daniel P. Nussbaum, Margaret O'Connor, Elishama N. Kanu, Peter J. Allen. scRNA-seq from FFPE tissue resolves the tumor microenvironment of intraductal papillary mucinous neoplasms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B074.

Guidelines on Pancreatic Cystic Neoplasms: Major Inconsistencies With Available Evidence and Clinical Practice— Results From an International Survey

Background/Objectives: Detective flow imaging (DFI) endoscopic ultrasonography (EUS) can identify the microvascular flow imaging of a mural nodule (MN) in an intraductal papillary mucinous neoplasm (IPMN) without the use of contrast agents. This retrospective study evaluated the diagnostic accuracy of DFI-EUS and its ability to evaluate the blood flow of MNs in IPMNs. Methods: Between April 2021 and September 2023, 68 patients with MNs in IPMNs observed on EUS images were retrospectively analyzed. Both DFI-EUS and contrast-enhanced EUS (CE-EUS) were performed during the same session. Three expert endosonographers blinded to the patients' clinical data assessed the MN images obtained with CE-EUS and DFI-EUS. First, DFI-EUS images were evaluated using a predefined scoring system; thereafter, CE-EUS images were evaluated. The diagnostic capability of DFI-EUS to detect MN blood flow was assessed with CE-EUS as the gold standard. Secondary outcomes included inter-reader agreement, the correlation between MN size and detection rates, and the association between DFI blood flow signal patterns and malignancy of MNs in surgically resected cases. Results: CE-EUS showed a contrast effect in the MN in 24 cases. Among these, DFI-EUS detected blood flow signals in 20 cases; false-positive results were not observed. DFI-EUS demonstrated a sensitivity of 83%, specificity of 100%, and accuracy of 93% for detecting MN blood flow. Inter-reader agreement was substantial (kappa values, 0.6-0.8). The subgroup analysis revealed that all MNs ≥ 10 mm had detectable blood flow on DFI-EUS, whereas MNs < 10 mm had reduced detection rates (75%; 12/16 cases). No significant correlation between the DFI blood flow signal patterns and MN malignancy of resected cases was observed. Conclusions: DFI-EUS demonstrated high diagnostic accuracy for detecting MN blood flow. Because of its simplicity and cost-effectiveness, DFI-EUS could be an alternative to CE-EUS for patients with MNs inside IPMNs.