Pancreatic Lesions Research Articles

Abstract C059: Regulatory Elements of Pancreas Development License the Initiation of Pancreatic Ductal Adenocarcinoma

Abstract Mutations in DNA are a known cause of cancer. However, they become oncogenic only under specific cellular conditions and within certain tissue contexts. Tissue injury often leads to the aberrant activation of developmental pathways, eroding markers of cellular differentiation and giving rise to transient cellular states. These states resemble developmental progenitors, characterized by higher transcriptional plasticity. Oncogenes, particularly KRAS, co-opt cellular plasticity by acting on tissue-specific enhancers, preventing the resolution of acinar plasticity and maintaining the pancreas in a pro-inflammatory phase that progresses to cancer1,2. However, the specific role of tissue-specific enhancers in pancreas regeneration and cancer initiation remains unexplored, and strategies to target these regenerative processes are yet to be developed. Our laboratory investigates non-mutational mechanisms of cancer, with a special interest in the intersection of developmental biology and cancer, aiming to elucidate the processes of cellular plasticity and cancer initiation. Recent studies have shown that acinar cells possess remarkable cellular plasticity, giving rise to a diverse population of cellular states in pancreas regeneration and cancer contexts3-5. We have discovered that the transcription factor Sox4 is necessary for the specification of tuft cells and gastric metaplasia found in chronic pancreatitis and in pancreatic intraepithelial lesions (PanINs). Moreover, we have shown that cellular plasticity has a non-cell autonomous protective effect; losing Sox4 and cellular heterogeneity in PanINs results in a fibrotic and immunosuppressive tumor microenvironment and disease progression. Our results demonstrated that targeting cellular plasticity accelerates or prevents cancer initiation through autonomous and non-autonomous cellular processes6. In this study, we leverage a comprehensive resource of ncRNAs transcribed from enhancer elements of pancreas development, together with their inferred target genes and correlations with clinical outcomes. We focused on an ncRNA associated with the risk of pancreatic cancer. To study its function, we developed two novel mouse strains for tissue-specific deletion, enabling precise manipulation and study of its role in the pancreas and other tissues. Our phenotypic analysis demonstrates that the ncRNA is activated following tissue injury and is essential for developing PanINs. Moreover, we show that it regulates cell-cell communication after tissue injury. This mechanism operates independently of cellular plasticity but significantly creates a pro-inflammatory environment that favors cancer development. Our results demonstrate that enhancer elements are actionable targets to regulate cell fate decisions in regeneration and cancer. Additionally, KRAS-induced cancer initiation depends on developmental regulatory elements, opening the window to develop prophylactic interventions to delay tumor onset. Citation Format: Luis Arnes. Regulatory Elements of Pancreas Development License the Initiation of Pancreatic Ductal Adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C059.

Abstract PR-18: RNF43 Loss Induces an IRE1-dependent Metabolic Reprogramming in Pancreatic Cystic Neoplasms

Abstract Background: RNF43 is frequently mutated in intraductal papillary mucinous neoplasms (IPMNs), which are cystic precursor lesions of pancreatic ductal adenocarcinoma (PDAC). RNF43 encodes for an E3 ubiquitin ligase and was initially identified as a negative regulator of Wnt signaling in colorectal cancer. Clinical trials targeting ligand dependent Wnt signaling in RNF43-mutated cancers have failed to demonstrate any efficacy, suggesting other mechanisms may be involved. Methods: To elucidate the role of RNF43 in an organ specific context, we generated a genetically engineered mouse model with pancreas-specific loss of Rnf43 and co-expression of mutant Kras (referred to as Kras;Rnf43 mice). The Kras;Rnf43 mice develop pancreatic cystic lesions resembling human IPMNs, a subset of which progressive to invasive cancers. We generated derivative cell lines from the IPMN-associated cancers, referred to as Kras;Rnf43 lines. Single-cell RNA sequencing (scRNA-seq) was performed to compare murine PDAC arising in Kras;Rnf43 mice with that of the Kras;p53 (“KPC”) mice. To determine if observed perturbations were dependent on Rnf43, we also created isogenic Kras;Rnf43 cell lines with re-expression of full-length Rnf43 (Kras;Rnf43-RNF43OE). Results: Kras;Rnf43 tumors showed upregulation of several mitochondrial transcripts (Mt-Atp8, Atp5o.1, and Atp6v0c), as well as mitochondrial biogenesis markers (PPARGC1A and NFE2L2), compared to KPC mice. Concurrently, the oxidative phosphorylation (OXPHOS) pathway was enriched on proteomics analyses of Kras;Rnf43 cells, relative to isogenic cell lines with RNF43 restitution. Seahorse metabolic flux analyzer revealed enhanced mitochondrial OXPHOS activity in Kras;Rnf43 cell lines, along with increased mitophagy. Kras;Rnf43 cells harbored gene signatures indicative of endoplasmic reticulum (ER) stress compared to KPC lines. Endoplasmic reticulum-mitochondria contact sites (ERMCS) regulate ER stress and mitochondrial dynamics. Notably, Kras;Rnf43 cells had significantly increased ERMCS compared to KPC cells, and these were attenuated upon RNF43 re-expression. We further identified the ER stress sensor inositol-requiring protein 1 (IRE1) was markedly elevated in Kras;Rnf43 cells compared to KPC cells, and decreased upon RNF43 re-expression. Furthermore, IRE1 localized at the mitochondrial-associated membrane (MAM) and enhanced ERMCS formation via a non-canonical scaffolding function. Deletion of IRE1 by CRISPR/Cas9 editing in Kras;Rnf43 cells inhibited OXPHOS and significantly impaired cell viability. Conclusion: Our data suggests that bi-allelic loss of RNF43 caused increased mitochondrial function and OXPHOS dependency. This is largely attributed to upregulated level of IRE1, which localizes at MAM to promote ERMCS formation and OXPHOS in Kras;Rnf43 cells. IRE1-dependent reprogramming of mitochondrial bioenergetics serves as a cell survival mechanism. Therefore, targeting OXPHOS or the noncanonical function of IRE1 could be a potential strategy to inhibit the progression of RNF43-mutated IPMNs to PDAC. Citation Format: Akiko Sagara, Xiangdong Lv, Brandon Chen, Yuki Makino, Shui Ping So, Sonja M Woermann, Costas A Lyssiotis, Yatrik M Shah, Bidyut Ghosh, Xi Chen, Johannes F Fahrmann, Anirban Maitra. RNF43 Loss Induces an IRE1-dependent Metabolic Reprogramming in Pancreatic Cystic Neoplasms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-18.

Abstract B025: Surveillance outcome in individuals at high risk of pancreatic cancer

Abstract INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRIs) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs. METHODS: from January 2015 up to date, a total of 340 HRIs from 291 families visited our pancreatic cancer high-risk clinic. Surveillance included annual clinic visits, EUS/MRI imaging, genetic and laboratory blood testing. Participants completed a questionnaire that included personal and familial medical history, dietary habits, daily activities with emphasis on smoking habits, alcohol use, and physical activity. RESULTS: Our cohort was divided into 3 groups: familial pancreatic cancer that include individuals with family history of 2 or more first degree family (FDR) with PDAC (FPC; 96 individuals), familial non-FPC, families with at least 2 biological relatives with PDAC and not meeting FPC criteria, (119 individuals), and hereditary pancreatic cancer (PC), individuals with PGV in a PC susceptibility gene and a family member with PDAC carrying the same PGV (124 individuals). The cohort average age at first visit was 54 years with 44% male and 56% female ratio. Seventy percent of the cohort was of Jewish Ashkenazi decent. Genetic testing was performed in several steps, first BRCA1/2 founder mutations was performed in all individuals followed by genetic panels and whole exome sequencing (WES). PGVs were detected in 36.4% of all families. There was no significant difference in the genetic finding between the FPC and non-FPC groups (11% and 9.6% respectively). Of the study cohort 35% were screened by EUS and 8% by MRI/MRCP. Pancreatic lesions detected included 11 cases of new PDAC (3.2%), 69 cystic lesions (20.3%), 43 cases early chronic pancreatitis (12.6%) and 11 cases of main pancreatic duct dilation (3.2%). To better understand the risk of PDAC development in HRIs we recently added a novel cell-free chromatin blood test for early cancer detection (in collaboration with SENSEERA, Israel) and compared it to EUS imaging results. The test provides multidimensional epigenetic information that sheds light on the identity and the transcriptional state of the cells that are dying in the body of the patient. Our preliminary results show nice separation between the healthy control and PC groups. PC HRIs show slight increase in score compared to the general population while individuals with worrisome features show substantial increase compared to HRIs with no EUS findings. DISCUSSION: Surveillance seems effective for detection of early-stage PDAC and precursor lesions. However, screening strategy can be improved by adding newer modalities like chromatin-based tests that might help to further define the risk of cancer development in HRIs. Citation Format: Merav Ben Yehoyada, Erez Scapa, Oren Shibolet, Guy Rosner. Surveillance outcome in individuals at high risk of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B025.

Diagnostic yield of endoscopic ultrasound in dilated common bile duct with non-diagnostic cross-sectional imaging

BackgroundBiliary dilatation without obvious etiology on cross sectional imaging warrants further investigation. This study aimed to assess yield of endoscopic ultrasound in providing etiologic diagnosis in such situation.MethodsProspective cohort of consecutive patients with biliary dilatation & non diagnostic computed tomography (CT) and /or magnetic resonance imaging (MRI) underwent endoscopic ultrasound (EUS) with/without fine needle aspiration cytology (FNAC) and were followed clinically, biochemically with/without radiology for up to six months. The findings of EUS were corroborated with histopathology of surgical specimens and endoscopic retrograde cholangiography (ERCP) findings in relevant cases.ResultsMedian age of 121 patients completing follow up was 55 years. 98.2% patients were symptomatic and median common bile duct (CBD) diameter was 13 mm. EUS was able to identify lesions attributable for biliary dilatation in (67 out of 121) 55.4% cases with ampullary neoplasm being the commonest (29 out of 67 i.e. 43%). Multivariate logistic regression analysis identified jaundice as the predictor of positive diagnosis on EUS, of finding ampullary lesion and pancreatic lesion on EUS. EUS had sensitivity, specificity, positive predictive value and diagnostic accuracy of 95.65%, 94.23%, 95.65% and 95.04% respectively in providing etiologic diagnosis. Threshold value for baseline bilirubin of 10 mg%, for baseline CA 19.9 of 225 u/L and for largest CBD diameter of 16 mm were determined to have specificity of 98%, 95%, 92.5% respectively of finding a positive diagnosis on EUS.ConclusionEUS provides considerable diagnostic yield with high accuracy in biliary dilatation when cross sectional imaging fails to provide etiologic diagnosis.

Endoscopic ultrasound (EUS) elastography-guided fine-needle aspiration cytology (FNAC) versus conventional EUS FNAC for solid pancreatic lesions: A pilot randomized trial.

Endoscopic ultrasound guided fine-needle aspiration (EUS FNA) is the first-line modality to diagnose suspected solid pancreatic malignant lesions. Elastography-guided FNA has been shown to improve the diagnostic yield of EUS FNA but prospective studies are limited. The aim of the study was to compare diagnostic accuracy, sensitivity and specificity of conventional and elastography-guided EUS FNA in patients with suspected malignant pancreatic solid masses. Patients with suspected malignant solid pancreatic lesions presenting to our institute from July 2021 to January 2023 were recruited and randomized to conventional and elastography-guided EUS FNA using a 22-G EUS FNA needle. Diagnostic accuracy, sensitivity, specificity and positive and negative predictive values were calculated. Total 48 patients were initially screened for inclusion in the study, of which six were excluded and 42 patients underwent randomization. Finally, 20 patients in each group underwent the assigned intervention and were analyzed further. Baseline patient characteristics were similar in conventional FNA and elastography-guided FNA group with median age 52 (range 29-74) years and 51.8 (range 31-72) years, respectively, males being 70% and 75%, respectively. Median size of the lesion was 34mm (range 14-48mm) and 37 (range 18 to 50mm), respectively, for both conventional and elastography arm. The average size of the lesion was 35.7mm. Overall, the diagnosis of adenocarcinoma was made in 65% of cases. In the remaining cases, diagnoses were inflammatory mass, Castleman's disease, solid pseudopapillary epithelial neoplasm (SPEN), diffuse large B-cell lymphoma (DLBCL), pancreatic gastrointestinal stromal tumor (GIST) and metastasis. Conventional EUS FNA had diagnostic accuracy, sensitivity, specificity and positive and negative predictive values of 90%, 87.5%, 100%, 100% and 62.92%, respectively, and elastography-guided EUS FNA had diagnostic accuracy, sensitivity, specificity and positive and negative predictive values of 85%, 100%, 100% and 54.59%, respectively. No severe adverse events were noted. There is no significant difference between conventional and elastography-guided EUS FNA in terms of diagnostic accuracy, sensitivity, specificity and positive and negative predictive values. Both techniques appear safe and effective for characterizing solid pancreatic masses and elastography did not score numerically over the conventional arm.

Results of Molecular Testing in Pancreatic Cystic Lesions: Experience from a Tertiary Care Center

Results of Molecular Testing in Pancreatic Cystic Lesions: Experience from a Tertiary Care Center

Quality of Pancreatic Cyst Clinical Practice Guidelines.

There are various published clinical practice guidelines (CPGs) for the management of pancreatic cystic lesions. However, the quality of these guidelines has not been systematically appraised. This study aimed to evaluate the quality of CPGs published in the last 5 years for the management of pancreatic cysts. A systematic search of the PubMed database for eligible CPGs published between January 1, 2016 and November 17, 2021, using a sensitive filter. The quality of the CPGs was independently evaluated using the Appraisal of Guidelines for Research & Evaluation II instrument, with domain scores considered sufficient quality if >60% and good quality if >80%. The search yielded 4 eligible CPGs out of 426 citations. The scores varied for different domains for each CPG, with the overall median score being 79% for scope and purpose, 26% for stakeholder involvement, 51% for rigor of development, 69% for clarity of presentation, 14% for applicability, and 75% for editorial independence. The study revealed that the quality of the CPGs for pancreatic cyst management in adults remains moderate at best. Patient representatives were not involved in any of the CPG development process. There is a significant scope for improvement in methodological rigor and clarity of presentation.

Increased needle passes for comparable diagnostic yield in endoscopic ultrasound-guided tissue acquisition for pancreatic stiff lesions measured by elastography

Background/objectivesPancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. MethodsPatients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. ResultsA total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). ConclusionsThe higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.

Endoscopic Ultrasound–Guided Fine Needle Asperation and Core Biopsy in Sampling Pancreatic Lesions

Endoscopic Ultrasound–Guided Fine Needle Asperation and Core Biopsy in Sampling Pancreatic Lesions

Multicenter, randomized controlled trial of EUS-guided fine-needle biopsy using a fork-tip needle with macroscopic or rapid on-site evaluation for pancreatic lesions (H2O trial)

ABSTRACT Background and Objectives According to previous reports, EUS–fine-needle biopsy (FNB) with or without rapid on-site evaluation (ROSE) showed the nonsuperiority of EUS-FNB + ROSE over EUS-FNB. However, previous studies included various kinds of FNB needle. This might be a critical limitation due to heterogeneity. Therefore, the aim of the present multicenter, randomized controlled trial was to compare the diagnostic accuracy of the fork-tip needle with or without ROSE for pancreatic lesions. Methods In the ROSE group, if an adequate sample was obtained to diagnose by on-site evaluation, EUS-FNB was stopped. If cytological results were insufficient or indeterminate, EUS-FNB was repeated. In the macroscopic on-site evaluation (MOSE) group, if a 4-mm length of visible core tissue was obtained, EUS-FNB was finished. If visible core tissue was not obtained or was less than 4 mm in length, a second puncture was attempted. Results One hundred seventy-one patients were randomized, 85 to the ROSE group and 86 to the MOSE group. In the MOSE group, diagnostic sensitivity and accuracy were 94.4% and 91.8%, respectively, for visible core tissue and 80.6% and 70.0%, respectively, for red tissue. Finally, overall diagnostic sensitivity and accuracy were 97.1% and 95.3%, respectively, in the ROSE group and 95.8% and 95.3%, respectively, in the MOSE group. Although there were no significant differences regarding adverse events between groups, the mean number of punctures was significantly lower in the MOSE group than in the ROSE group (1.47 vs. 1.20, P = 0.0171). Conclusions EUS-FNB using a fork-tip needle for pancreatic lesions has high diagnostic yield even without ROSE.

Differential Diagnosis of Pancreatic Cancer and its Mimicking Lesions.

Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.

Jehlová konfokální laserová endomikroskopie v diferenciální diagnostice cystických lézí pankreatu

Summary: Background: Pancreatic cystic lesions are relatively common findings, and their prevalence continues to rise, which is also related to the expansion of imaging methods. Up to 15% of pancreatic cancers arise from mucinous cystic tumours of the pancreas, primarily from intraductal papillary mucinous neoplasia (IPMN). Needle-based confocal laser endomicroscopy (nCLE) represents an advanced diagnostic method with the potential to improve the accuracy of diagnosing focal pancreatic lesions. Aim: The aim of the work is to provide a recent overview of the position of nCLE in the diagnosis of pancreatic cystic lesions and some of our own experiences. The nCLE method is based on so-called real-time optical biopsy, which brings better diagnostic results compared to traditional methods such as CT, MRI/MRCP, and EUS, as confirmed by the authors‘ own data. Although nCLE offers certain advantages, its wider use in clinical practice is limited by the high costs of equipment, technical difficulties during examination, and the need for thorough training of endoscopists. The integration of all diagnostic procedures (EUS, cytology, nCLE, and next-generation sequencing) into artificial intelligence algorithms could minimize the disadvantages of individual methods and increase the overall efficiency of diagnosing pancreatic cystic lesions. Conclusion: nCLE represents an innovative method for diagnosing pancreatic cystic lesions, which, in combination with other procedures (microforceps biopsy, next-generation sequencing, assessment of nCLE findings, and overall malignancy risk using artificial intelligence), can further enhance its diagnostic accuracy in this context. Key words: needle-based confocal laser endomicroscopy – pancreatic cystic lesion – optical biopsy – endoscopic ultrasound – artificial intelligence

Utility of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in a Paediatric Population: A Single-Centre Experience

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a modern and minimally invasive technique to acquire diagnostic material from within the gastrointestinal tract, as well as from adjacent organs and structures, which can help in the diagnosis and staging of a variety of gastrointestinal malignancies, as well as for non-malignant conditions. Though well described in adults, there is limited literature on the diagnostic utility of EUS-FNA in paediatric patients. The objective of this study was to evaluate the diagnostic accuracy and clinical utility of EUS-FNA in paediatric patients performed at our centre over the last 17 years. Materials and Methods: After obtaining Institutional Review Board approval, 63 cases of paediatric EUS-FNA performed at SKMCH&RC from 2005 to 2022 were retrieved. A 22-gauge EUS-FNA needle was used for obtaining samples with the use of suction (when required). The sample was then smeared onto glass slides, with half being stained with RAPI stain while the rest with the Papanicolaou stain. Demographic details, indication for the procedure, results of rapid on-site adequacy status (ROSE), site of lesion, and cytological diagnosis were reviewed and analysed. Results: Of the 63 patients, 55 (87.3%) had an adequate sample (confirmed on ROSE). Forty-two (66.7%) were male and the mean age was 12.4 years. The most frequent indication of EUS-FNA was a sampling of enlarged lymph nodes (74.6%). The most common sites of nodal aspiration were sub-carinal (33.3%) and celiac lymph nodes (14.3%). EUS-FNA of a pancreatic lesion accounted for an additional 17.5% of cases. Involvement by Hodgkin’s lymphoma was the most common diagnosis (25.4%) followed by granulomatous inflammation (19.1%). Cases of solid pseudo-papillary tumour (4.8%) and recurrent Wilm’s tumour (3.2%) were also diagnosed. No patient suffered complications, and none required hospital admission, post-procedure. The sensitivity, specificity, PPV, and NPV of EUS-FNA were 98.1, 83.3, 96.4, and 90.9%, respectively. Conclusion: EUS-FNA is a safe, well-tolerated, minimally invasive outpatient setting procedure with high sensitivity and significant utility in the diagnosis and staging of disease.

Detective flow imaging versus contrast-enhanced EUS in solid pancreatic lesions.

Detective flow imaging EUS (DFI-EUS) is a new technology that detects fine vessels and low-flow velocity without contrast agents, used in real time during EUS, with a better resolution compared to usual technologies such as color Doppler and eFLOW. The aim of this study was to compare DFI-EUS with contrast-enhanced EUS (CE-EUS) for the evaluation of vascularization in solid pancreatic lesions. We included patients who had a pancreatic mass visualized by EUS, with recorded images of their assessment in DFI-EUS and CE-EUS techniques and a histological diagnosis confirmed malignant tumors or a minimum of 1-year follow-up for benign lesions. Of the 107 patients included in this retrospective single-center study, the histological diagnosis revealed 69 cases (64.5%) of pancreatic adenocarcinoma, 18 cases (16.8%) of neuroendocrine tumors (NETs), and 10 cases (9.3%) of metastases from nonpancreatic cancers. A smaller proportion (9.4%) exhibited other lesions. As a result, the incidence of intralesional microvascularization was 43.9% with DFI-EUS and 48.6% with CE-EUS, indicating a positive correlation between the 2 techniques (P = 0.0001). Compared to CE-EUS, DFI-EUS exhibited sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 88.5%, 98.2%, 97.9%, and 90%, respectively, for the detection of intralesional vessels. The novel technique DFI-EUS demonstrates a remarkable correlation with CE-EUS, exhibiting high sensitivity and specificity for the assessment of microvascularization in solid pancreatic lesions. This method eliminates the need for a contrast agent, thus carrying no risk of adverse effects.

The role of CEUS as problem-solving technique when abdominal CT or MRI are inconclusive

PurposeTo evaluate the role of CEUS in the characterization of abdominal lesions compared to CT and MRI and whether it could be “problem-solving” when CT and/or MRI are inconclusive or contraindicated.MethodsA retrospective study was conducted on 39 patients (22 males; mean age: 64 years) with one or more abdominal focal lesions (total: 41; mean diameter: 2.9 cm) who underwent CEUS, had already undergone CT/MRI without a definitive diagnosis or had not undergone them due to contraindications. The frequency, out of the total lesions included, in which CEUS was problem-solving, confirmatory or inconclusive was evaluated.ResultsCEUS proved to be problem-solving for 20/41 (48.8%) lesions, confirmatory for 17/41 (41.5%) lesions and inconclusive for 4/41 (9.7%) lesions. Including problem-solving and confirmatory diagnosis, CEUS correctly identified 24/27 (88.9%) liver lesions, 11/11 (100%) kidney lesions, a gallbladder and a pancreatic lesion, while it did not provide useful information for 4/41 (9.7%) lesions, specifically three liver lesions and a testicular one.ConclusionsCEUS is a promising technique when CT and/or MRI are inconclusive or contraindicated and to increase the radiologist’s diagnostic confidence.

Comments and illustrations of the European Federation of Societies for Ultrasound in Medicine contrast-enhanced ultrasound guidelines: Multiparametric imaging and EUS-guided sampling in rare pancreatic tumors. Benign mesenchymal pancreatic tumors.

The focus of the review is on primary benign mesenchymal pancreatic tumors and their imaging appearance. These tumors are extremely rare. Usually, they are not diagnosed until postoperative histology is available, and so even benign tumors have undergone extensive pancreatic resection. The very limited data on abdominal and EUS findings including contrast-enhanced techniques of these pancreatic lesions are summarized here. Case reports will be presented for some of these rare tumors with application of modern ultrasound and endosonographic techniques.

Effect of deep learning reconstruction on the assessment of pancreatic cystic lesions using computed tomography.

This study aimed to compare the image quality and detection performance of pancreatic cystic lesions between computed tomography (CT) images reconstructed by deep learning reconstruction (DLR) and filtered back projection (FBP). This retrospective study included 54 patients (mean age: 67.7 ± 13.1) who underwent contrast-enhanced CT from May 2023 to August 2023. Among eligible patients, 30 and 24 were positive and negative for pancreatic cystic lesions, respectively. DLR and FBP were used to reconstruct portal venous phase images. Objective image quality analyses calculated quantitative image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) using regions of interest on the abdominal aorta, pancreatic lesion, and pancreatic parenchyma. Three blinded radiologists performed subjective image quality assessment and lesion detection tests. Lesion depiction, normal structure illustration, subjective image noise, and overall image quality were utilized as subjective image quality indicators. DLR significantly reduced quantitative image noise compared with FBP (p < 0.001). SNR and CNR were significantly improved in DLR compared with FBP (p < 0.001). Three radiologists rated significantly higher scores for DLR in all subjective image quality indicators (p ≤ 0.029). Performance of DLR and FBP were comparable in lesion detection, with no statistically significant differences in the area under the receiver operating characteristic curve, sensitivity, specificity and accuracy. DLR reduced image noise and improved image quality with a clearer depiction of pancreatic structures. These improvements may have a positive effect on evaluating pancreatic cystic lesions, which can contribute to appropriate management of these lesions.

The Role of CT-guided Core Needle Biopsy in Pancreatic Tumors: An Initial Evaluation in Modern Oncology.

Neoadjuvant chemotherapy has recently become the standard of care for borderline resectable pancreatic ductal adenocarcinoma (PDAC), and there have even been numerous reports evaluating its potential benefits in resectable PDAC. However, neoadjuvant therapy first requires a histological or cytological diagnosis. This study aimed to analyze the safety and diagnostic yield of CT-guided core needle biopsy (CNB). A retrospective analysis of patients with pancreatic tumor requiring a CNB during the period 2015 to 2023 were included. Biopsies were performed with an 18-20 G Tru-Core needle using a coaxial system and automatic biopsy gun. Demographics, procedural variables, postoperative outcomes, and histological results were analyzed. A total of 43 pancreatic biopsies were performed in 42 patients. The mean age was 60 years (35 to 81y), and 24 (56%) were males. Tumors were more frequently localized in the head (42%) and body (42%) of the pancreas. The mean size of the pancreatic lesions was 53.77 mm (17 to 181 mm) and the mean number of samples per biopsy was 4 (1 to 12). Most procedures were performed via direct access (81%). No major complications were observed. Histological diagnosis was obtained in 40 (93%) patients, with a sensitivity of 93%, specificity of 100% and an overall accuracy rate of 93%. The probability of performing a molecular diagnostic test increased with the year of biopsy (OR 3.34, 95% CI 1.33-8.40, P=0.01). CNB is an efficient and safe method for obtaining high-quality material. This approach could be essential as molecular profiling continues to improve the diagnosis, prognosis, and treatment of PDAC.

Endoscopic ultrasonography for microvascular imaging without contrast enhancement in the differential diagnosis of pancreatic lesions.

Detective flow imaging endoscopic ultrasonography (DFI-EUS) is a recent imaging modality developed for detecting fine vessels without the need for ultrasound contrast agents. The aim of the present study was to evaluate the utility of DFI-EUS for solid pancreatic lesions and to compare the diagnostic ability for pancreatic cancer (PC) between DFI-EUS, directional power Doppler (eFLOW) EUS, and contrast-enhanced harmonic (CH)-EUS. Patients with a pancreatic lesion who underwent DFI-EUS, eFLOW-EUS, and CH-EUS between March 2019 and November 2023 were retrospectively enrolled. Final diagnoses were confirmed by pathologic examination of EUS-guided tissue acquisition and/or resected specimens. Lesions were categorized into the three patterns of poor, mild, and rich vascularity on DFI-EUS and eFLOW-EUS, and hypo-, iso-, and hypervascular on CH-EUS. PC was defined as a poor pattern on DFI-EUS and eFLOW-EUS, and a hypovascular pattern on CH-EUS. The final diagnoses of 90 examined tumors were PC (n = 57), inflammatory mass (n = 6), autoimmune pancreatitis (n = 13), neuroendocrine tumor (n = 9), and others (n = 5). The sensitivity, specificity, and accuracy for diagnosis of PC were 93%, 82%, and 88%, respectively, on DFI-EUS, 97%, 42%, and 77% on eFLOW-EUS, and 95%, 89%, and 92% on CH-EUS. The accuracy of DFI-EUS was significantly superior to eFLOW-EUS (P = 0.005), but no significant difference was found between DFI-EUS and CH-EUS. DFI-EUS is more sensitive for depicting vasculature than eFLOW-EUS, and has higher diagnostic sensitivity for PC. Evaluation of vascularity on DFI-EUS is useful for the differential diagnosis of pancreatic lesions without the need for intravenous contrast agent.

Diagnostics and Management of Pancreatic Cystic Lesions-New Techniques and Guidelines.

Pancreatic cystic lesions (PCLs) are increasingly diagnosed owing to the wide use of cross-sectional imaging techniques. Accurate identification of PCL categories is critical for determining the indications for surgical intervention or surveillance. The classification and management of PCLs rely on a comprehensive and interdisciplinary evaluation, integrating clinical data, imaging findings, and cyst fluid markers. EUS (endoscopic ultrasound) has become the widely used diagnostic tool for the differentiation of pancreatic cystic lesions, offering detailed evaluation of even small pancreatic lesions with high sensitivity and specificity. Additionally, endoscopic ultrasound-fine-needle aspiration enhances diagnostic capabilities through cytological analysis and the assessment of fluid viscosity, tumor glycoprotein concentration, amylase levels, and molecular scrutiny. These detailed insights play a pivotal role in improving the clinical prognosis and management of pancreatic neoplasms. This review will focus mainly on the latest recommendations for the differentiation, management, and treatment of pancreatic cystic lesions, highlighting their clinical significance.