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Simple Summary: Pancreatic cystic lesions are diagnosed with an increasing frequency, thus comprising a significant routine condition in clinical practice. In addition to the current approaches, which include surgery and surveillance, endoscopic ultrasound (EUS) provides the potential of an additional therapeutic tool. This review collected the existing literature regarding EUS-guided ablation techniques for pancreatic cystic lesions and assessed its efficacy and safety. The cumulative effect in treating pancreatic cysts was 44% (95%CI: 31–57), with the highest rate achieved when a combination of ethanol and paclitaxel was injected into the cysts (70%; 95%CI: 64–76). Considering safety, most adverse events were mild and occurred after ethanol injection. EUS-guided pancreatic cyst ablation seems to be an acceptable and safe procedure, with promising results in appropriately selected patients. Background: Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients' lives and medical resources. Endoscopic ultrasound (EUS) ablation techniques have been utilized to treat focal pancreatic lesions. This systematic review with meta-analysis aims to assess the efficacy of EUS ablation on PCL in terms of complete or partial response and safety. Methods: A systematic search in Medline, Cochrane and Scopus databases was performed in April 2023 for studies assessing the performance of the various EUS ablation techniques. The primary outcome was complete cyst resolution, defined as cyst disappearance in follow-up imaging. Secondary outcomes included partial resolution (reduction in PCL size), and adverse events rate. A subgroup analysis was planned to evaluate the impact of the available ablation techniques (ethanol, ethanol/paclitaxel, radiofrequency ablation (RFA), and lauromacrogol) on the results. Meta-analyses using a random effects model were conducted and the results were reported as percentages with 95% confidence intervals (95%CI). Results: Fifteen studies (840 patients) were eligible for analysis. Complete cyst resolution after EUS ablation was achieved in 44% of cases (95%CI: 31–57; 352/767; I2 = 93.7%), and the respective partial response rate was 30% (95%CI: 20–39; 206/767; I2 = 86.1%). Adverse events were recorded in 14% (95%CI: 8–20; 164/840; I2 = 87.2%) of cases, rated as mild in 10% (95%CI: 5–15; 128/840; I2 = 86.7%), and severe in 4% (95%CI: 3–5; 36/840; I2 = 0%). The subgroup analysis for the primary outcome revealed rates of 70% (95%CI: 64–76; I2 = 42.3%) for ethanol/paclitaxel, 44% (95%CI: 33–54; I2= 0%) for lauromacrogol, 32% (95%CI: 27–36; I2 = 88.4%) for ethanol, and 13% (95%CI: 4–22; I2 = 95.8%) for RFA. Considering adverse events, the ethanol-based subgroup rated the highest percentage (16%; 95%CI: 13–20; I2 = 91.0%). Conclusion: EUS ablation of pancreatic cysts provides acceptable rates of complete resolution and a low incidence of severe adverse events, with chemoablative agents yielding higher performance rates. [ABSTRACT FROM AUTHOR]

Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further diagnosis and interventional therapy of focal liver lesions that are difficult to visualize using conventional B-mode ultrasound. Clinical studies on EUS guided image fusion, to date, are limited. EUS–CT image fusion allowed for easier navigation and profiling of the target tumor and/or surrounding anatomical structure. Image fusion techniques encompassing multiple imaging modalities appear to be feasible and have been observed to increase visualization accuracy during interventional and diagnostic applications. [ABSTRACT FROM AUTHOR]

Background: The prevalence of malignancy in patients with small solid pancreatic lesions is low; however, early diagnosis is crucial for successful treatment of these cases. Therefore, a method to reliably distinguish between benign and malignant small solid pancreatic lesions would be highly desirable. We investigated the role of endoscopic ultrasound (EUS) elastography in this setting.Methods: Patients with solid pancreatic lesions ≤ 15 mm in size and a definite diagnosis were included. Lesion stiffness relative to the surrounding pancreatic parenchyma, as qualitatively assessed and documented at the time of EUS elastography, was retrospectively compared with the final diagnosis obtained by fine-needle aspiration/biopsy or surgical resection.Results: 218 patients were analyzed. The average size of the lesions was 11 ± 3 mm; 23 % were ductal adenocarcinoma, 52 % neuroendocrine tumors, 8 % metastases, and 17 % other entities; 66 % of the lesions were benign. On elastography, 50 % of lesions were stiffer than the surrounding pancreatic parenchyma (stiff lesions) and 50 % were less stiff or of similar stiffness (soft lesions). High stiffness of the lesion had a sensitivity of 84 % (95 % confidence interval 73 % - 91 %), specificity of 67 % (58 % - 74 %), positive predictive value (PPV) of 56 % (50 % - 62 %), and negative predictive value (NPV) of 89 % (83 % - 93 %) for the diagnosis of malignancy. For the diagnosis of pancreatic ductal adenocarcinoma, the sensitivity, specificity, PPV, and NPV were 96 % (87 % - 100 %), 64 % (56 % - 71 %), 45 % (40 % - 50 %), and 98 % (93 % - 100 %), respectively.Conclusions: In patients with small solid pancreatic lesions, EUS elastography can rule out malignancy with a high level of certainty if the lesion appears soft. A stiff lesion can be either benign or malignant. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS) has emerged as an excellent tool for imaging the gastrointestinal tract, as well as surrounding structures. EUS-guided fine-needle aspiration (EUS-FNA) has become the standard of care for the tissue sampling of a variety of masses and lymph nodes within and around the gut, providing further diagnostic and staging information. Confocal laser endomicroscopy (CLE) is a novel endoscopic method that enables imaging at a subcellular level of resolution during endoscopy, allowing up to 1000-fold magnification of tissue and providing an optical biopsy. A new procedure that has been developed in the past few years is needle-based confocal laser endomicroscopy (nCLE), which involves a mini-CLE probe that can be passed through a 19-gauge needle during EUS-FNA. This enables the real-time visualization of tissue at a microscopic level, with the potential to further improve the diagnostic accuracy of EUS-FNA. The device has been studied in animals as well as in humans, and the results so far have been promising. Recently, this method has also been used for the visualization of regulatory proteins and receptors in the pancreas, setting a cornerstone for nCLE in molecular imaging. The aim of this article is to review the role of EUS-guided nCLE in modern endoscopy and its implications in molecular imaging. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the diagnostic value of endoscopic ultrasound (EUS) after neoadjuvant therapy (NT) for gastric cancer restaging by meta-analysis. We conducted a systematic search of studies published on PubMed and Web of Science up to 30th August 2021. Assessing the risk of bias in the included studies was done with the QUADAS-2 tool. We used R and Review Manager 5.4.1 for calculations and statistical analysis. To evaluate the diagnostic value of EUS after NT for gastric cancer restaging, we performed a meta-analysis on six studies, with a total of 283 patients, including true-positive, true-negative, false-positive, and false-negative results for T1-T4, N0. EUS as a diagnostic test for GC patients after chemotherapy has a relatively low DOR for the T2 (3.96) and T4 stages (4.79) and a relatively high partial AUC for the T2 (0.85) and T4 (0.71) stages. Our results reveal that the pooled sensitivity for T stages after chemotherapy is rather low (29–56%), except for the T3 stage (71%). A potential limitation of our study was the small number of included studies, but no significant heterogeneity was found between them. Our meta-analysis concludes that EUS is not recommended or is still under debate for GC restaging after NT. [ABSTRACT FROM AUTHOR]

Background and aims. The role of angiogenesis in progression and metastasis of gastric cancer has been studied over the last years. The aim of our study was to assess the microvessel density and vascular endothelial growth factor (VEGF) expression in correlation with prognosis, survival and the risk for upper gastrointestinal (GI) bleeding as well. Method. We prospectively assessed angiogenesis in 40 patients with gastric carcinoma. Microvessel density was calculated using CD31 and CD34 markers, and VEGF expression was assessed in biopsy samples. The tumor stage was established using imaging methods: CT scan for M and N stage and endoscopic ultrasound for T and N stages. The correlation between pathological markers and tumor stage, survival rate and risk of upper gastrointestinal bleeding was assessed. Results. The study included 40 patients with gastric cancer; among them 8 patients presented with upper GI bleeding. The average microvessel density was 10.21 for CD31 and 11.85 for CD34 in all patients VEGF was positive only in 45% of patients. The microvessel density was higher in patients with advanced TNM stage, and a correlation with the risk of UGIB and survival rate was also found. VEGF expression correlated with TNM stage and with the risk of upper GI bleeding. Conclusions. Microvessel density (estimated by CD34) was involved in locally advanced disease, while VEGF was correlated with loco-regional extension and distant metastasis in gastric cancer patients. There was a clear correlation between angiogenic parameters, survival rate and the risk of upper GI bleeding. [ABSTRACT FROM AUTHOR]

Tridimensional endoscopic ultrasound (3D-EUS) offers a better understanding of the spatial relations of examined lesions and allowing future assessment of the captured volume. 3D-EUS has been used with both radial and linear transducers, especially in an attempt to improve staging of esophageal, gastric, pancreatic or rectal tumors. The aim of this clinical imaging article was to show the capabilities and perspectives of linear 3D ultrasound, including contrastenhanced 3D-EUS. The 3D reconstruction images were acquired with a freehand technique through rotation (torque) of the EUS scope along its long axis. 3D acquisition of contrast-enhanced EUS images was also used. Esophageal, gastric and mediastinal tumors are easily visualized by 3DEUS reconstructions and also, 3D-EUS facilitates anatomical interpretation of the images in the pancreatobiliary area. In conclusion, the advantages of 3D reconstructions in EUS are clear and multiple, especially in the assessment of the location of tumors and their relationships with neighboring organs and blood vessels. [ABSTRACT FROM AUTHOR]

Gastric cancer preoperative staging is of outmost importance to assure proper management of the disease. Providing a relevant clinical stage relies on different imaging methods such as computed tomography (CT) or endoscopic ultrasound (EUS). We aimed to perform a network meta-analysis for gastric cancer clinical stage diagnostic tests, thus comparing the diagnostic accuracy of EUS vs. multidetector CT (MDCT) and EUS vs. EUS + MDCT. We plotted study estimates of pooled sensitivity and specificity on forest plots and summary receiver operating characteristic space to explore between-study variation in the performance of EUS, MDCT and EUS + MDCT for T1–T4, N0–N3, M0–M1 when data were available. Exploratory analyses were undertaken in RevMan 5. We included twelve studies with 2047 patients. Our results suggest that EUS was superior to MDCT in preoperative T1 and N staging. MDCT is more specific for the M stage but no significant difference in sensitivity was obtained. When comparing EUS vs. EUS + MDCT for T1 both sensitivity and specificity were not relevant. No significant differences were observed in T2–T4 stages. Even though EUS helped differentiate between the presence of invaded nodules, N stages should be carefully assessed by both methods since there is not sufficient data. [ABSTRACT FROM AUTHOR]

Ex-vivo freshly surgical removed pancreatic ductal adenocarcinoma (PDAC) specimens were assessed using pCLE and then processed for paraffin embeding and histopathological diagnostic in an endeavour to find putative image analysis algorithms that might recognise adenocarcinoma. Methods: Twelve patients diagnosed with PDAC on endoscopic ultrasound and FNA confirmation underwent surgery. Removed samples were sprayed with acriflavine as contrast agent, underwent pCLE with an experimental probe and compared with previous recordings of normal pancreatic tissue. Subsequently, all samples were subjected to cross-sectional histopathology, including surgical resection margins for controls. pCLE records, as well as corespondant cytokeratin-targeted immunohistochemistry images were processed using the same morphological classifiers in the Image ProPlus AMS image analysis software. Specific morphometric classifiers were automatically generated on all images: Area, Hole Area (HA), Perimeter, Roundness, Integrated Optical Density (IOD), Fractal Dimension (FD), Ferret max (Fmax), Ferret mean (Fmean), Heterogeneity and Clumpiness. Results: After histopathological confirmation of adenocarcinoma areas, we have found that the same morphological classifiers could clearly differentiate between tumor and non-tumor areas on both pathology and correspondand pCLE (area, roundness, IOD, ferret and heterogeneity (p < 0.001), perimeter and hole area (p < 0.05). Conclusions: This pilot study proves that classical morphometrical classifiers can clearly differentiate adenocarcimoma on pCLE data, and the implementation in a live image-analysis algorithm might help in improving the specificity of pCLE in vivo diagnostic. [ABSTRACT FROM AUTHOR]

Aim: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. Material and methods: Thirty patients with PDAC or pNET who underwent CEH-EUS and EUS-guided fine needle aspiration (EUS-FNA) were included. Quantitative analysis of tumor vascularity was performed using time-intensity curve (TIC) analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software (VueBox). Cox proportional hazards models were used to determine associations with survival outcome. Results: Median overall survival (OS) for PDAC patients was 9.61 months (95% CI: 0.1-38.7) while the median OS for pNET patients was 15.81 months (95% CI: 5.8-24.75. In a multivariate model for OS, a lower peak enhancement (HR=1.76, p=0.02) and a lower wash-in area under the curve (HR=1.06, p=0.001) were associated with worse survival outcome for patients with PDAC. Conclusions: CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an intense fibrosis which enhances the growth of tumor cells and drives an epithelialmesenchymal transition. The consequence is the uncontrolled proliferation of cancer cells, including pancreatic cancer stem cells (PCSC), which can enhance the metastatic potential. Objective. The aim of this study is to assess the expression of pancreatic cancer stem cells, on pancreatic endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) specimens. Material and Methods. A total of 21 patients diagnosed with PDAC after EUS-FNB within the Research Center of Gastroenterology and Hepatology of Craiova, were included in the study, and the samples were sent for immunohistochemical assessment. Anti-Human CD 24 (policlonal, Abcam, ab 199140) and EpCAm (Epr 20532-225, Rb monoclonal, Abcam, ab 223582) were used. Results. All cases were positive for CD24 and EpCAM. In NOS ductal adenocarcinomas, CD24 immunomarking was heterogeneous, with variable intensity and a variable number of positive cells within the same case. Well and moderately differentiated adenocarcinomas that formed tubular or papillary structures showed a higher intensity CD24 expression compared to poorly differentiated or undifferentiated adenocarcinomas. EpCam showed a stronger immunolabeling intensity in the analyzed samples. PDAC EpCam expression was of moderate and high intensity and with a heterogeneous appearance in NOS G1 adenocarcinomas, but the intensity of the immunomarking tended to decrease with increasing histological grade. Conclusions. EUS-FNB PCSC immunohistochemistry is feasible. At the subcellular level, the basolateral membranous and cytoplasmic staining of EpCam in PDAC could be correlated with tumor invasion and possibly with the unfavorable evolution of this type of carcinoma, while CD24 frequently presents an apical immunostaining pattern and could suggest the presence of an epithelial-type phenotype of tumor cells, with a lower potential for invasiveness and metastasis. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound tissue acquisition, in the form of fine needle biopsy (EUS-FNB) was designed to provide a proper quantitative sample for determining the histologic architecture and further immunohistochemical staining. This study aimed to investigate the contribution of associating contrast-enhanced ultrasound imaging (CEUS) with EUS-FNB for differentiating solid pancreatic lesions without on-site cytopathology. Patients from our institutional database who underwent CE-FNB-EUS for the evaluation of a solid pancreatic lesion were retrieved. Micro vascularization of the tumor was evaluated over 2 min during CEUS after intravenous injection of 4.8 mL SonoVue and was classified as hypervascular, isovascular or hypovascular during both arterial and venous phase. Final diagnosis was based on histopathology of surgical specimens or EUS-guided tissue acquisition and clinical follow-up. Our retrospective study (2018-2021) enrolled 46 patients with a mean age of 58, female to male ratio 1:2, mass location: 2/3 head, 1/3 body and tail of the pancreas, average mass size 3.5 cm, mean number of needle passes (fanning technique): 2. Final pathology revealed pancreatic ductal adenocarcinoma-PDAC (26), mass-forming pancreatitis-MFP (10), pancreatic neuroendocrine tumors-pNETs (4), undifferentiated carcinoma (3), mucinous carcinoma (1), pancreatic metastasis (1). Hypo-enhancement was noted in 67% of the patient, and the final diagnosis was malignancy in all those cases. Regarding the enhancement patterns: hypovascularity in both arterial and venous phase was associated to PDAC, hypervascularity or isovascularity in both phases were associated to either MFP or NETs, while the carcinomas were hypervascular. A heterogeneous appearance with non-enhancing areas was noted in a small percentage of the hypo-enhancing lesions and it might suggest necrosis. The overall diagnostic accuracy was 91%. CE-EUS allows detailed visualization of the dynamic enhancement patterns hence it helps to identify the target of EUS-FNB among different pathological areas of the lesions. CE-FNB-EUS can be used for the differential diagnosis and adequate sampling of solid pancreatic lesions without on-site cytopathology. [ABSTRACT FROM AUTHOR]

Aims: Pancreatic cancer and hepatocellular carcinoma are two of the most aggressive types of cancer with limited therapeutic options in stages of advanced disease. Our objective is to assess the safety and feasibility of injecting iron oxide nanoparticles (IONs) via endoscopic ultrasound (EUS)-guidance, both systemically and locally in the liver and pancreas in order to study new potential therapies for liver and pancreatic tumors.Material and Methods: Six domestic pigs were used for our study design, and divided into three groups: two were injected in the portal vein, and other four were subjected to local exposure of IONs in the liver and pancreas, two each. The pigs were on a 7 days follow-up and necropsy was performed with their organs harvested. A 3T MRI scan was also performed.Results: All animals underwent an endoscopic ultrasound fine needle injection (EUS-FNI) procedure without any complications. EUS-FNI procedure had an average time of 5 minutes and 21 seconds and consisted of 2 ml of ION injection. No perforations and no risk of potential bleeding were recorded. Macroscopic changes were observed only after pancreatic EUS-FNI. A significant amount of IONs was observed in the liver after local injection and after vascular EUS-FNI. The imaging results were confirmed by pathological examination with most of the IONs accumulated in Ito-like cells, Kupfer cells, and sinusoids.Conclusions: IONs have been widely studied for both diagnostic and therapeutic purposes. Their injection through EUS-guidance may develop new diagnosis strategies as well as curative or palliative therapies in pancreatic and liver tumors. [ABSTRACT FROM AUTHOR]

Midgut carcinoid tumors are rare neuroendocrine tumors that can spread to the intestinal mesentery. Although the mesenteric tumor is usually the first finding due to abdominal discomfort, some patients with hepatic metastases might experience symptoms of carcinoid syndrome. We present the case of a 74 year old male with weight loss, diffuse abdominal pain, facial flushing and diarrhea for about 2 months who was diagnosed with an ill-defined mesenteric mass andhepatic, pulmonary and lymph node metastatic lesions. To better characterize the hepatic lesions, contrast-enhanced ultrasonography (CEUS) was performed. It revealed hypervascular lesions in the arterial phase and complete washout during the portal phase, suggestive for liver metastases. Surprisingly, a reflux of contrast into the inferior vena cava was also noticed in the arterial phase. This can be an uncommon finding on contrast-enhanced ultrasound (CEUS) or computed tomography (CECT) that may indicate right-sided heart disease or high flow contrast injection rates. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the diagnosis of peripancreaticlymph node and liver metastases of neuroendocrine tumor. This case report illustrates the role of ultrasound imaging for the diagnosis of rare tumors such as carcinoid tumors and also a peculiar finding on liver CEUS. [ABSTRACT FROM AUTHOR]

Angiogenesis is a critical process for tumor growth and metastasis, it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy. However, gastric cancer (GC) studies are rather scarce. CHI-EUS was proposed in this study as a useful method to assess GC vascularization patterns. Patients initially diagnosed with GC, only adenocarcinoma type, who subsequently performed CHI-EUS examinations before any treatment decision, were included in this study. Dedicated software named Vuebox (Bracco Imaging S.p.A., Milan, Italy) was used to quantitatively evaluate angiogenesis in the chosen regions of interest (ROI). As a result, this software generated automatically parameters derived from time-intensity curve (TIC) like peak enhancement (PE), rise time (RT), time to peak (TTP), wash in perfusion index (WiPI), ROI area, and others were compared to immunohistopathological data. CD105 and CD31 immunostaining was performed to calculate the vascular diameter (vd) and the microvascular density (MVD). The final results were compared with CHI-EUS parameters. A total of eighty CHI-EUS video sequences were assessed. Multiple high statistical correlations (p<0.05) were highlighted between TIC analysis parameters, MVD, and vd CD31. Also, strong correlations were found between tumor grade and CHI-EUS parameters, p<0.005. Differences in TIC parameters and immunohistochemical markers between the group of patients without (M0) versus the group with (M1) metastasis were noted. Our study demonstrated that GC angiogenesis assessed by CHI-EUS was a feasible method and may be considered for future studies based on TIC analysis. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound has been recently established as a routine diagnostic and staging procedure in lung cancer patients, mainly because of the possibility of tissue sampling. Transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) represents a method which not only allows the visualization of the upper gastrointestinal tract, but also offers good visualisation of the posterior and inferior mediastinum. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) permits the assessment of the tumors in the anterior mediastinum. Based on previously published literature, it is obvious that this minimally invasive procedure now offers the possibility of tissue diagnosis in mediastinal masses including primary tumours or secondary lesions from both benign and malignant diseases. [ABSTRACT FROM AUTHOR]