Search Results (105)

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75–80% of all renal carcinomas, and is often diagnosed incidentally on abdominal imaging, such as abdominal ultrasound or CT scan. Among other types of renal cancer, ccRCC is recognized to be highly aggressive due to its metastatic potential, which leads to a poor prognosis and an increased mortality rate. The most common sites of ccRCC metastasis are the lung, lymph nodes, bone, liver, and adrenal glands. Clear cell RCC is the most frequent primary tumor associated with secondary pancreatic involvement, while overall, pancreatic metastases represent only 2–5% of all malignant pancreatic lesions. These metastases often occur many years after nephrectomy and may present as solitary or oligometastatic disease, frequently displaying a paradoxically favorable prognosis compared with other metastatic sites. The present narrative review we conducted emerged from presentations of ccRCC with pancreatic distant metastases, potentially labeled as primary pancreatic tumors on imaging studies, mimicking pancreatic neuroendocrine tumors due to the hypervascular nature of ccRCC. Four patients were investigated in our clinic for suspicious pancreatic lesions identified on CT imaging, involving both the head and body of the pancreas. The definitive diagnosis was established by performing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) and histopathological analysis of the collected tissue samples. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has emerged as a pivotal tool for obtaining tissue diagnosis, particularly when cross-sectional imaging is inconclusive. Through a synthesis of clinical data and literature, this article underscores the essential diagnostic role of EUS-guided tissue acquisition and its impact on therapeutic decision-making. Full article

Background: Pancreatic cancer (PC) has a very poor 5-year survival and prognosis. Even when CT or MRI shows no metastasis, staging laparoscopy(SL) still detects tiny peritoneal deposits in 20–30% of patients, making them ineligible for surgery. SL is invasive, requiring general anesthesia and substantial resources. Endoscopic ultrasound (EUS) allows the observation of the bile ducts, pancreas, and abdominal cavity, and EUS-guided fine-needle aspiration (EUS-FNA) is essential for pathological diagnosis. Reports on using EUS to perform peritoneal lavage cytology are currently not available. We hypothesized that combining EUS-FNA with peritoneal lavage (EUS-lavage technique; EUS-LT) could enhance staging accuracy and avoid unnecessary surgical procedures. Methods: Ten in vivo porcine models underwent EUS-LT. Using a 19G FNA needle, 800 mL saline was instilled into the intraperitoneal cavity and then recovered. Two refinements were introduced sequentially: an ENBD catheter with additional side holes and, subsequently, a side-hole introducer (EndoSheather) that eliminated balloon dilation. The primary endpoint was procedural success. Secondary endpoints included safety, complications, recovered volume, duration of endoscopic procedure, and time required to instill 800 mL. Nonparametric tests compared outcomes across iterations. Results: Ten-model porcine in vivo model series were included, and all procedures were successful. No device malfunctions or unanticipated technical failures; one minor mucosal injury during saline injection resolved after re-puncture. The average procedure time was 31.1 min. Stepwise refinements shortened procedure and infusion times and increased recovered volume. Recovered volume approached the instilled amount in later cases, indicating efficient performance. Conclusions: In this ten-model in vivo series, EUS-LT demonstrated technical feasibility and short-term safety. Full article

Objectives: Pancreatic cystic lesions (PCLs) are increasingly detected due to the widespread use of imaging techniques. The identification of pancreatic mucinous cysts is especially important since these carry a risk of malignant transformation and require follow-up or surgical resection. The aim of this study was to determine the diagnostic yield of the molecular analysis of K-RAS (Kirsten RAt Sarcoma virus) and GNAS (Guanine Nucleotide-binding protein, Alpha Stimulating protein activity) gene mutations in pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). Methods: In this prospective trial, we assessed the sensitivity, specificity, and positive and negative predictive values of K-RAS and GNAS mutation analysis in differentiating mucinous versus non-mucinous cysts and the subsequent impact on decision-making in daily clinical practice. The reference standard used comprised the combination of morphology on cross-sectional imaging and EUS, string sign, cyst fluid cytology, intracystic carcinoembryonic antigen (CEA), and glucose levels, with subsequent correlation of surgical pathology in resected cases. Fluid samples of 47 cysts obtained by EUS-FNA over a 39-month period were analyzed. Mutation analysis of KRAS (exon 2) was performed in all cases, and additionally, GNAS (exon 8) in 28 cases using Sanger sequencing. Results: 33 out of 47 PCLs were classified as mucinous cysts and 14 as non-mucinous cysts defined using conventional standards, including morphological characteristics, string-sign, cytology, cyst fluid testing, and histology in resected cases. Of these 33 mucinous cysts, KRAS mutation was detected in 14 samples. A further 23 mucinous lesions were additionally tested for GNAS mutation, which was detected in 10 of the 23 cysts. A 42.4% sensitivity for KRAS and 43.5% for GNAS mutation analysis was calculated, with a specificity of 92.9% and 100%, respectively, for detecting mucinous lesions. The clinical management was altered through the genetic testing results in one single case. Conclusions: In this cohort, K-RAS and GNAS mutational analysis in cyst fluid did not improve the detection of mucinous pancreatic cysts significantly after conventional testing. However, the method may be useful due to its high specificity in uncertain cases. Full article

The accurate classification of pancreatic cystic lesions remains clinically challenging due to overlapping imaging features and variable malignant potential. Mucinous cystic neoplasms, in particular, require early identification given their premalignant nature. RNA profiling presents a promising alternative to current diagnostic limitations—a molecular lens sharpened by AI-driven pattern recognition. This study aimed to evaluate the diagnostic potential of RNA signatures for differentiating pancreatic cyst subtypes and to clarify their roles in their pathophysiology. The study included 31 patients with pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration. RNA was extracted from cyst fluid, tissue, and peripheral blood. Expression of 17 target genes was analyzed using qPCR. Gene expression patterns were compared across mucinous cystic neoplasms, serous cystic neoplasms, pseudocysts, adenocarcinoma, and chronic pancreatitis cohorts. Diagnostic accuracy was evaluated via ROC analysis. Mucinous cysts exhibited significant overexpression of MUC1, ITGA2, ELOVL6, and MUC5AC genes compared to serous cysts and pseudocysts. PKM gene expression correlated with increasing malignant potential. In blood plasma, only MUC1, MUC4, and PYGL were elevated in adenocarcinoma compared to mucinous neoplasms. We identified a distinct RNA signature that can distinguish mucinous cystic neoplasms from benign cystic lesions (serous cysts and pseudocysts), which could be useful for guiding patient management and improving clinical outcomes. Validation in broader cohorts is essential for clinical implementation. Full article

Background/Objectives: There is limited evidence on imaging characteristics and pathological grading of small pancreatic neuroendocrine tumors (PNENs). This study aimed to compare imaging features and histopathological diagnoses of PNENs based on tumor size. Methods: Patients with PNEN who underwent pathological diagnosis at Hiroshima University Hospital were retrospectively reviewed. Detection rates, imaging findings, and diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) were analyzed according to tumor size. Results: Among 107 patients with PNEN, 42 had tumors ≤10 mm, and 65 had tumors >10 mm. The detection rate for lesions ≤10 mm was 92.3% according to EUS and 83.3% according to contrast-enhanced CT, showing the superior sensitivity of EUS. Typical imaging features—well-defined margins, homogeneous internal structure, and early enhancement—were significantly more frequent in tumors ≤10 mm (p < 0.001). There were no significant differences in imaging findings between G1 and G2 tumors ≤10 mm. The diagnostic sensitivity of EUS-FNA was 91.2% for tumors ≤10 mm and 86.3% for tumors >10 mm, with no significant difference. However, the concordance rate between EUS-FNA and surgical histology for tumor grading was significantly higher in the ≤10 mm group (87.5% vs. 56.3%, p = 0.012). Discussion: In small PNENs (≤10 mm), imaging features are often typical but do not reliably determine tumor grade. In our cohort, EUS-FNA showed high diagnostic accuracy and provided essential pathological information to guide management, including the choice between surveillance and surgery. Full article

Background and Aims: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) or biopsy (FNB) is the standard method for diagnosing abdominal masses, but sample inadequacy and diagnostic accuracy remain challenges. Conventional smear (CS) and liquid-based cytology (LBC) are standard processing methods, yet their comparative effectiveness and potential combined benefit remain unclear. We performed a systematic review and meta-analysis to evaluate and compare the diagnostic performance and adequacy of CS, LBC, and their combination. Methods: A systematic search was conducted in Medline, Embase, and CENTRAL on 17 November 2024. Studies comparing CS, LBC, or their combination following EUS-FNA/FNB for abdominal masses were included. Diagnostic parameters, including sensitivity, specificity, accuracy, and inadequacy rates, were extracted and analyzed. Methodological quality was assessed using QUADAS-2. Results: 16 studies (2128 patients) were included. Sensitivity for pancreatic masses was 71.4% (CI: 62.9–78.7) for CS, 74.7% (CI: 64.3–82.8) for LBC, and 86.2% (CI: 82.4–89.3) for combined methods (p = 0.001). For all abdominal masses, sensitivity was 76.3% (CI: 67.9–83.0) for CS, 73.6% (CI: 65.6–80.2) for LBC, and 88.0% (CI: 84.0–91.2) for combined methods (p ≤ 0.006). Specificity was nearly 100%. Inadequacy rates were lowest for combined methods (1.5%, CI: 0–36.2), when compared to LBC (7.7%, CI: 2.7–20.4) and CS (4.4%, CI: 2.4–7.9). Moderate bias risk was noted, primarily due to incorporation bias. Domain 3 (reference standard) of QUADAS was uniformly moderate-risk across studies. Conclusions: Combining CS and LBC methods improves diagnostic sensitivity and reduces sample inadequacy after EUS-guided tissue acquisition for abdominal masses, particularly pancreatic lesions. Clinical guidelines should consider recommending the combined approach to enhance diagnostic yield and clinical outcomes. Full article

Background/Objectives: Mass-forming chronic pancreatitis (MFP) and pancreatic ductal adenocarcinoma (PDAC) can present with overlapping radiological, clinical, and serological features in patients with underlying chronic pancreatitis (CP), making differential diagnosis particularly challenging. Current diagnostic tools, including CA19-9 and endoscopic ultrasound (EUS) imaging, often lack the specificity needed to reliably distinguish between these conditions. The objective of this study was to investigate whether the proteomic profiling of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples could provide molecular-level discrimination between MFP and PDAC in patients with CP. Methods: Thirty CP patients with solid pancreatic lesions were prospectively enrolled: 15 with histologically confirmed PDAC and 15 with MFP. Traditional diagnostic parameters, including CA19-9 levels and EUS characteristics, were recorded but found insufficient for differentiation. EUS-FNA samples were analyzed using label-free mass spectrometry. A total of 928 proteins were identified in PDAC samples and 555 in MFP samples. Differential abundance analysis and pathway enrichment were performed. Results: Overall, 88 proteins showed significant differential abundance between PDAC and MFP samples, of which 26 met stringent statistical thresholds. Among these, Carboxylesterase 2 (CES2), Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1), Lumican (LUM), Transmembrane Protein 205 (TMEM205), and NAD(P)H Quinone Dehydrogenase 1 (NQO1) emerged as key discriminatory proteins. Pathway enrichment analysis revealed distinct biological processes between the groups, including mitochondrial fatty acid β-oxidation, Rho GTPase signaling, and platelet degranulation. Conclusions: Proteomic signatures derived from EUS-FNA samples offer a promising molecular approach to distinguish inflammatory pseudotumoral lesions from malignant pancreatic tumors in CP patients. This minimally invasive strategy could enhance diagnostic accuracy where current methods fall short. Further validation in larger, multicenter cohorts is warranted to confirm these findings and evaluate their clinical applicability. Full article

Background: Biliary strictures are diagnosed using endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology and biopsy. However, brush cytology shows a sensitivity of 9–56.1% and a diagnostic accuracy of 43–65.4%, while biopsy demonstrates a sensitivity of 48%. Both methods exhibit high specificity but limited sensitivity. While rapid on-site evaluation (ROSE) is effective in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), its application in ERCP-obtained samples remains underexplored. Methods: This prospective pilot study was conducted at Okayama University Hospital from April 2019 to July 2024. Patients requiring ERCP-guided sampling for bile duct strictures were included. ROSE was applied to brush cytology with up to three additional attempts and to imprint cytology from biopsy samples with up to two attempts. Diagnostic accuracy was assessed based on pathology and clinical course. Results: Among 37 patients (median age: 73 years, add range, and male–female ratio: 27:10), 18 had hilar and 19 had distal bile duct strictures. Brush cytology required one, two, or three attempts in twenty-six, six, and five cases, respectively, whereas biopsy required one or two attempts in thirty-five and two cases, respectively. Among the thirty-seven cases, thirty-five were malignant and two were benign. The B-ROSE group showed a sensitivity, specificity, and accuracy of 71.4%, 100.0%, and 73.0%, respectively, compared to lower accuracy in the conventional group, where single brush cytology attempts yielded a sensitivity of 48.6% and an accuracy of 48.6%, and single biopsy attempts showed a sensitivity of 68.6% and an accuracy of 70.3%. Conclusions: B-ROSE improves diagnostic accuracy, reduces repeat sampling, and minimizes patient burden in ERCP-based diagnosis of bile duct strictures, making it a valuable addition to current diagnostic protocols. Full article

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