Search Results (97)

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article

Background/Objectives: Accurate determination of malignancy in pancreatic masses through endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is crucial for appropriate clinical management and prognostic assessment. However, the diagnostic sensitivity of conventional cytology using Papanicolaou (Pap) staining remains limited, often leading to inconclusive results. In this study, we investigated the diagnostic utility of methionyl-tRNA synthetase 1 (MARS1) through immunohistochemical (IHC) and immunofluorescence (IF) staining as a potential biomarker for pancreatic cancer. IHC analysis was conducted on resected tissue samples from 10 patients, including both pancreatic ductal adenocarcinoma and corresponding non-neoplastic pancreatic tissue. Additionally, cytologic samples were obtained from 198 patients with pancreatic masses who underwent EUS-FNA for diagnostic evaluation. Pap staining and MARS1 IF staining were performed on liquid-based cytology slides derived from EUS-FNA specimens. Results: MARS1 was detected by IHC staining in the 10 surgical specimens diagnosed with pancreatic adenocarcinomas. After Pap staining, 37 patients were excluded because of unsuitable specimens, leaving 161 patients who underwent both Pap and MARS1 IF staining. EUS-FNA specimens from the 151 patients with pancreatic ductal adenocarcinoma were classified by Pap staining as atypia (n = 36), suspicious for malignancy (n = 55), or malignancy (n = 60). MARS1 IF staining was positive in 147 of these patients and negative in 4. MARS1 IF staining distinguished pancreatic cancer in specimens with atypia on Pap staining. The sensitivity for detecting pancreatic cancer was significantly higher for MARS1 IF staining than for conventional Pap staining (97.4% vs. 79.1%, p < 0.0001). Conclusions: The high sensitivity of MARS1 IF staining improved malignancy detection in pancreatic masses. Further prospective studies are required to validate our findings. Full article

Endoscopic ultrasound (EUS) is a helpful tool for the study of the mediastinum, a challenging region for both transesophageal and endobronchial (EBUS) endosonography. This area is divided into sections and contains numerous lymph nodes essential for the staging and diagnosis of conditions like lung cancer, sarcoidosis, and infections. EUS allows for detailed examination of the mediastinal region, identifying various kinds of abnormalities, whether they are benign cysts or malignant tumors. The aim of this narrative review is to provide a clear overview of how EUS contributes to mediastinal diagnostics and to offer practical insights for clinicians. A comprehensive, non-systematic search of PubMed was conducted by the authors to identify relevant studies. EUS methods, such as elastography and contrast-enhanced imaging, have improved diagnosis by analyzing tissue stiffness and blood flow, and they help endosonographers distinguish between different conditions. EUS-guided tissue sampling techniques, like fine needle aspiration and biopsy, are crucial for detecting cancer and examining lymph nodes in a minimally invasive way. By combining EUS with endobronchial ultrasound, operators can achieve more accurate results, especially in cancer staging and treatment planning. Overall, this approach is a key tool in treating thoracic and mediastinal conditions. Full article

Background: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor with malignant potential. Its diagnosis has grown alongside increased use of abdominal imaging. SPN is suspected after classical findings in abdominal imaging studies; however, endoscopic ultrasound-guided (EUS) fine needle aspiration can support preoperative diagnosis. The treatment of choice is still surgical intervention, with an intent to reach curative resection. The prognosis is excellent. Recently, emerging data on EUS-guided radiofrequency ablation (RFA) suggest changing the choice of treatment for small SPN. Methods: We provide a comprehensive overview on pancreatic SPN with a focus on treatment, adverse events, recurrence rate, and outcomes. In addition, we provide a literature summary and pool data analysis. Results: Overall, 70 papers including 6651 patients were identified. The mean SPN size was 5.8 cm, metastasis rate was 1.9%, and recurrence rate was 3%. Moreover, the mortality rate was low at 0.2%, although high postoperative adverse events were reported (32.4%). Small SPN (<2 cm) was present in 4.1% of the studies. Two studies reported EUS-RFA for small SPN <2 cm, without recurrence at a median follow-up of 18.5 months. Conclusions: SPN still necessitates surgical intervention given its malignant potential. However, EUS-RFA can represent a promising and safe therapeutic option for SPN < 2 cm. Full article

The intricate airway anatomy and poorly understood etiology of pediatric conditions render the diagnosis of mediastinal disorders particularly challenging. Traditional diagnostic methods, such as mediastinoscopy and thoracotomy, carry high risks and are often impractical in children. Endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) enables a minimally invasive, esophageal route to mediastinal lesions, providing a diagnostic approach that is new to pediatrics compared with conventional techniques. We review the technical characteristics, clinical benefits, and prospective role of EUS-B-FNA in pediatric diagnostic investigation. We also review the clinical applications of EUS-B-FNA to date and aim to promote its use as a novel adjunct for the evaluation of complex mediastinal pathology in pediatric medicine. Full article

Pancreatic cancer is a highly malignant digestive system tumor characterized by covert onset and rapid progression, with a 5-year survival rate of less than 10%. Most patients have already reached an advanced or metastatic stage at the time of diagnosis. Therefore, it is particularly important to study the occurrence, development, and drug resistance mechanisms of pancreatic cancer. In recent years, the development of 3D tumor cell culture technology has provided new avenues for pancreatic cancer research. Patient-derived organoids (PDOs) are micro-organ structures that are obtained directly from the patient’s body and rapidly expand in vitro. PDOs have the ability to self-renew and self-organize and retain the genetic heterogeneity and molecular characteristics of the original tumor. However, the use of organoids is limited because most patients with pancreatic ductal adenocarcinoma (PDAC) are inoperable. Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) is an important method for obtaining tissue samples from non-surgical pancreatic cancer patients. This article reviews the factors that affect the formation of pancreatic cancer organoids using EUS-FNA/FNB. High-quality samples, sterile operations, and optimized culture media are key to successfully generating organoids. Additionally, individual patient differences and disease stages can impact the formation of organoids. Pancreatic cancer organoids constructed using EUS-FNA/FNB have significant potential, suggesting new approaches for research and treatment. Full article

Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration. Full article

Pancreatic cystic lesions (PCLs) represent a spectrum of non-neoplasms and neoplasms with varying malignant potential, posing significant challenges in diagnosis and management. While some PCLs are precursors to pancreatic cancer, others remain benign, necessitating accurate differentiation for optimal patient care. Conventional approaches to PCL management rely heavily on radiographic imaging, and endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA), coupled with clinical and biochemical data. However, the observer-dependent nature of image interpretation and the complex morphology of PCLs can lead to diagnostic uncertainty and variability in patient management strategies. This review critically evaluates current PCL diagnosis and surveillance practices, showing features of the different lesions and highlighting the potential limitations of conventional methods. We then explore the potential of artificial intelligence (AI) to transform PCL management. AI-driven strategies, including deep learning algorithms for automated pancreas and lesion segmentation, and radiomics for analyzing heterogeneity, can improve diagnostic accuracy and risk stratification. These advanced techniques can provide more objective and reproducible assessments, aiding clinicians in decision-making regarding follow-up intervals and surgical interventions. Early results suggest that AI-driven methods can significantly improve patient outcomes by enabling earlier detection of high-risk lesions and reducing unnecessary procedures for benign cysts. Finally, this review emphasizes that AI-driven approaches could potentially reshape the landscape of PCL management, ultimately leading to improved pancreatic cancer prevention. Full article

Background: Pancreatic cystic lesions (PCLs) are frequently detected incidentally and vary from benign to malignant. Accurate differentiation between mucinous (M-PCLs) and non-mucinous PCLs (NM-PCLs) is essential for appropriate management. This study aims to validate the accuracy of on-site glucose measurement using a glucometer with a cut-off of 50 mg/dL for distinguishing M-PCLs from NM-PCLs. Methods: In this prospective multicenter study, conducted at three European academic hospitals, patients who underwent endoscopic ultrasound-guided fine-needle aspiration for PCLs between 2019 and 2020 were included. On-site glucose measurement was performed using a conventional glucometer. Data on demographics, clinical features, EUS findings, and histopathology were collected. Results: Fifty patients were enrolled, with 37 having glucose levels < 50 mg/dL and 13 ≥ 50 mg/dL. M-PCLs were more common in the <50 mg/dL group (81%) compared to the ≥50 mg/dL group (23%, p < 0.001). The median CEA was higher in the <50 mg/dL group (146 ng/mL) than in the ≥50 mg/dL group (3 ng/mL, p = 0.047). On-site glucose testing < 50 mg/dl demonstrated a sensitivity of 93.2%, a specificity of 76.5%, and an accuracy of 89% for detecting M-PCLs with an AUC of 0.74 and an OR of 14.29 (p < 0.001). In comparison, CEA > 192 ng/mL had a sensitivity of 55.6%, a specificity of 87.5%, and an accuracy of 75.8% for M-PCLs, with an AUC of 0.65 and an OR of 4.44. Conclusions: On-site glucose measurement using a glucometer with a cut-off of <50 mg/dL is a highly accurate, rapid, and cost-effective method for differentiating M-PCLs from NM-PCLs. Our results validate the glucose cut-off in a multicentric prospective cohort supporting its integration into standard diagnostic protocols for PCLs. Full article

Endoscopic ultrasound (EUS)-guided tissue sampling includes the techniques of fine needle aspiration (FNA) and fine needle biopsy (FNB), and both procedures have revolutionized specimen collection from the gastrointestinal tract, especially from remote/inaccessible organs. EUS-FNB has replaced FNA as the procedure of choice for tissue acquisition in solid pancreatic lesions (SPLs) across various society guidelines. FNB specimens provide a larger histological tissue core (preserving tissue architecture) with fewer needle passes, and this is extremely relevant in today’s era of precision and personalized molecular medicine. Innovations in needle tip design are constantly under development to maximize diagnostic accuracy by enhancing histological sampling capabilities. But, apart from the basic framework of the needle, various other factors play a role that influence diagnostic outcomes, namely, sampling techniques (fanning, aspiration or suction, and number of passes), collection methods, on-site evaluation (rapid, macroscopic, or visual), and specimen processing. The choice taken depends strongly on the endoscopist’s preference, available resources at the disposal, and procedure objectives. Hence, in this review, we explicate in detail the concepts and available literature at our disposal on the topic of EUS-guided pancreatic tissue sampling to best guide any practicing gastroenterologist/endoscopist in a not-to-ideal set-up, which EUS-guided tissue acquisition technique is the “best” for their case to augment their diagnostic outcomes. Full article

Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging, with a high rate of diagnostic error. We present a case of a peripancreatic mass identified by radiology as a gastrointestinal stromal tumor. Endoscopic ultrasound-guided fine-needle aspiration (FNA) of the mass showed a moderately cellular tumor composed of small-to-medium-sized neoplastic cells with round-to-oval nuclei arranged singly and in loose clusters. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin) and negative for CD117. A diagnosis of neoplasm with a neuroendocrine tumor (NET) was made based on FNA cytology. The subsequent surgical resection of the tumor revealed peripancreatic paraganglioma with immunohistochemistry positive for synaptophysin, chromogranin, and S100. The latter delineated the sustentacular cells. Although paraganglioma is a well-recognized tumor, a detailed comparison of peripancreatic paraganglioma versus pancreatic/gastrointestinal NET is still lacking. Full article

Recently, endoscopic ultrasound-guided tissue acquisition (EUS-TA) has been widely used to diagnose pancreatic ductal adenocarcinoma (PDAC). The histological examination of core tissues acquired using novel biopsy needles is the primary diagnostic approach for patients with PDAC. However, in patients with early-stage PDAC, such as Stages 0 and I, EUS-TA can be challenging, and its diagnostic accuracy may be limited. This presents a clinical dilemma: The earlier that clinicians attempt to accurately diagnose PDAC, the more difficult it becomes to do so using EUS-TA. Liquid-based cytology (LBC) is a technique for preparing pathological specimens from liquefied cytology specimens by placing the collected material in a special fixative preservative fluid. LBC offers advantages, such as specimen optimization with reduced blood interference, a high cell-collection rate, and the simplicity of the procedure in the endoscopy room. The use of LBC may improve diagnostic accuracy, particularly for early-stage PDAC. Therefore, we emphasize that cytology remains a valuable tool for the endoscopic diagnosis of PDAC. In this review, we discuss the role of LBC in the endoscopic diagnosis of PDAC. Full article

Background/Objectives: Although the overall survival prognosis of patients in advanced stages of pancreatic ductal adenocarcinoma (PDAC) is poor, typically ranging from days to months from diagnosis, there are rare cases of patients remaining in therapy for longer periods of time. Early estimations of survival prognosis would allow rational decisions on complex therapy interventions, including radical surgery and robust systemic therapy regimens. Understandably, there is great interest in finding prognostic markers that can be used for patient stratification. We determined the role of various KRAS mutations in the prognosis of PDAC patients using biopsy samples and circulating tumor DNA. Methods: A total of 118 patients with PDAC, clinically confirmed by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNB), were included in the study. DNA was extracted from cytological slides following a standard cytology evaluation to ensure adequacy (viability and quantity) and to mark the tumor cell fraction. Circulating tumor DNA (ctDNA) was extracted from plasma samples of 45 patients in stage IV of the disease. KRAS mutations in exons 12 and 13 were detected by denaturing capillary electrophoresis (DCE), revealing a minute presence of mutation-specific heteroduplexes. Kaplan–Meier survival curves were calculated for individual KRAS mutation types. Results:KRAS mutations were detected in 90% of tissue (106/118) and 44% of plasma (20/45) samples. All mutations were localized at exon 2, codon 12, with G12D (GGT > GAT) being the most frequent at 44% (47/106) and 65% (13/20), followed by other types including G12V (GGT > GTT) at 31% (33/106) and 10% (2/20), G12R (GGT > CGT) at 17% (18/106) and 10% (2/20), G12C (GGT/TGT) at 5% (5/106) and 0% (0/20) and G12S (GGT/AGT) at 1% (1/106) and 5% (1/20) in tissue and plasma samples, respectively. Two patients had two mutations simultaneously (G12V + G12S and G12D + G12S) in both types of samples (2%, 2/106 and 10%, 2/20 in tissue and plasma samples, respectively). The median survival of patients with the G12D mutation in tissues was less than half that of other patients (median survival 101 days, 95% CI: 80–600 vs. 228 days, 95% CI: 184–602), with a statistically significant overall difference in survival (p = 0.0080, log-rank test), and furthermore it was less than that of all combined patients with other mutation types (101 days, 95% CI: 80–600 vs. 210 days, 95% CI: 161–602, p = 0.0166). For plasma samples, the survival of patients with this mutation was six times shorter than that of patients without the G12D mutation (27 days, 95% CI: 8–334 vs. 161 days, 95% CI: 107–536, p = 0.0200). In contrast, patients with detected KRAS G12R in the tissue survived nearly twice as long as other patients in the aggregate (286 days, 95% CI: 70–602 vs. 162 days, 95% CI: 122–600, p = 0.0374) or patients with other KRAS mutations (286 days, 95% CI: 70–602 vs. 137 days, 95% CI: 107–600, p = 0.0257). Conclusions: Differentiation of specific KRAS mutations in EUS-FNB and ctDNA (above all, the crucial G12D and G12R) is feasible in routine management of PDAC patients and imperative for assessment of prognosis. Full article

Pancreatic cancer has one of the worst prognoses among all malignancies and few available treatment options. Patient-derived xenografts can be used to develop personalized therapy for pancreatic cancer. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) may provide a powerful alternative to surgery for obtaining sufficient tissue for the establishment of patient-derived xenografts. In this study, EUS-FNA samples were obtained for 30 patients referred to the Ottawa Hospital, Ottawa, Ontario, Canada. These samples were used for xenotransplantation in NOD-SCID mice and for genetic analyses. The gene expression of pancreatic-cancer-relevant genes in xenograft tumors was examined by immunohistochemistry. Targeted sequencing of both the patient-derived tumors and xenograft tumors was performed. The xenografts’ susceptibility to oncolytic virus infection was studied by infecting xenograft-derived cells with VSV∆51-GFP. The xenograft take rate was found to be 75.9% for passage 1 and 100% for passage 2. Eighty percent of patient tumor samples were successfully sequenced to a high depth for 42 cancer genes. Xenograft histological characteristics and marker expression were maintained between passages. All tested xenograft samples were susceptible to oncoviral infection. We found that EUS-FNA is an accessible, minimally invasive technique that can be used to acquire adequate pancreatic cancer tissue for the generation of patient-derived xenografts and for genetic sequencing. Full article

Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events. Full article