Current role of endoscopic ultrasound in the diagnosis and management of pancreatic cancer

Endoscopic ultrasound (EUS) has emerged as an invaluable tool for the diagnosis, staging and treatment of pancreatic ductal adenocarcinoma (PDAC). EUS is currently the most sensitive imaging tool for the detection of solid pancreatic tumors. Conventional EUS has evolved, and new imaging techniques, such as contrast-enhanced harmonics and elastography, have been developed to improve diagnostic accuracy during the evaluation of focal pancreatic lesions. More recently, evaluation with artificial intelligence has shown promising results to overcome operator-related flaws during EUS imaging evaluation. Currently, an appropriate diagnosis is based on a proper histological assessment, and EUS-guided tissue acquisition is the standard procedure for pancreatic sampling. Newly developed cutting needles with core tissue procurement provide the possibility of molecular evaluation for personalized oncological treatment. Interventional EUS has modified the therapeutic approach, primarily for advanced pancreatic cancer. EUS-guided fiducial placement for local targeted radiotherapy treatment or EUS-guided radiofrequency ablation has been developed for local treatment, especially for patients with pancreatic cancer not suitable for surgical resection. Additionally, EUS-guided therapeutic procedures, such as celiac plexus neurolysis for pain control and EUS-guided biliary drainage for biliary obstruction, have dramatically improved in recent years toward a more effective and less invasive procedure to palliate complications related to PDAC. All the current benefits of EUS in the diagnosis and management of PDAC will be thoroughly discussed.     

Technology insight: Current status of endoscopic ultrasonography

Endoscopic ultrasound (EUS) has become the most accurate imaging modality for locoregional cancer staging of the gastrointestinal tract. Fine-needle aspiration (FNA) has added a new level of accuracy for EUS in nodal staging, with reported numbers in the 90% range for luminal and pancreaticobiliary disease. In addition, new non-gastrointestinal applications are being evaluated, such as the role of EUS-FNA for the staging of non-small-cell lung cancer and exploration of the posterior mediastinum. Furthermore, the same techniques that make safe tissue sampling possible are being explored for their use as interventional applications, such as EUS-guided celiac plexus neurolysis, fine-needle injection, EUS-guided pseudocyst drainage, and EUS-guided cholangiography and pancreatography. This review describes the current clinical status of EUS in gastrointestinal oncology, as well as future and novel indications and therapeutic strategies for this technology.     

Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases

Endoscopic ultrasonography(EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors. In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration. The development of EUS-guided drainage of the biliopancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures. Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described. Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro-intestinal, bilio-pancreatic and lymph node lesions. In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations.     

Percutaneous ultrasound and endoscopic ultrasound-guided biopsy of solid pancreatic lesions: An analysis of 1074 lesions

Backgrounds: Percutaneous ultrasound (US) and endoscopic ultrasound (EUS)-guided pancreatic biopsies are widely accepted in the diagnosis of pancreatic diseases. Studies comparing the diagnostic performance of US- and EUS-guided pancreatic biopsies are lacking. This study aimed to evaluate and compare the diagnostic yields of US- and EUS-guided pancreatic biopsies and identify the risk factors for inconclusive biopsies. Methods: Of the 1074 solid pancreatic lesions diagnosed from January 2017 to February 2021 in our center, 275 underwent EUS-guided fine needle aspiration (EUS-FNA), and 799 underwent US-guided core needle biopsy (US-CNB/FNA). The outcomes were inconclusive pathological biopsy, diagnostic accuracy and the need for repeat biopsy. All of the included factors and diagnostic performances of both US-CNB/FNA and EUS-FNA were compared, and the independent predictors for the study outcomes were identified. Results: The diagnostic accuracy was 89.8% for EUS-FNA and 95.2% for US-CNB/FNA ( P = 0.001). Biopsy under EUS guidance [odds ratio (OR) = 1.808, 95% confidence interval (CI): 1.083-3.019; P = 0.024], lesion size < 2 cm (OR = 2.069, 95% CI: 1.145-3.737; P = 0.016), hypoechoic appearance (OR = 0.274, 95% CI: 0.097-0.775; P = 0.015) and non-pancreatic ductal adenocarcinoma carcinoma (PDAC) diagnosis (OR = 2.637, 95% CI: 1.563-4.449; P < 0.001) were identified as factors associated with inconclusive pathological biopsy. Hypoechoic appearance (OR = 0.236, 95% CI: 0.064-0.869; P = 0.030), lesions in the uncinate process of the pancreas (OR = 3.506, 95% CI: 1.831-6.713; P < 0.001) and non-PDAC diagnosis (OR = 2.622, 95% CI: 1.278-5.377; P = 0.009) were independent predictors for repeat biopsy. Biopsy under EUS guidance (OR = 2.024, 95% CI: 1.195-3.429; P = 0.009), lesions in the uncinate process of the pancreas (OR = 1.776, 95% CI: 1.014-3.108; P = 0.044) and hypoechoic appearance (OR = 0.127, 95% CI: 0.047-0.347; P < 0.001) were associated with diagnostic accuracy. Conclusions: Both percutaneous US- and EUS-guided biopsies of solid pancreatic lesions are safe and effective; though the diagnostic accuracy of EUS-FNA is inferior to US-CNB/FNA. A tailored pancreatic biopsy should be considered a part of the management algorithm for the diagnosis of solid pancreatic disease.     

Possibilities of interventional endoscopic ultrasound

Since endoscopic ultrasound (EUS) was developed in the 1990s, EUS has become widely accepted as an imaging tool. EUS is categorized into radial and linear in design. Radial endoscopes provide cross-sectional imaging of the mediastinum, gastrointestinal tract, liver, spleen, kidney, adrenal gland, and pancreas, which has highly accuracy in the T and N staging of esophageal, lung, gastric, rectal, and pancreatic cancer. Tumor staging is common indication of radial-EUS, and EUSstaging is predictive of surgical resectability. In contrast, linear array endoscope uses a side-viewing probe and has advantages in the ability to perform EUSguides fine needle aspiration (EUS-FNA), which has been established for cytologic diagnosis. For example, EUS-FNA arrows accurate nodal staging of esophageal cancer before surgery, which provides more accurate assessment of nodes than radial-EUS imaging alone. EUS-FNA has been also commonly used for diagnose of pancreatic diseases because of the highly accuracy than US or computed tomography. EUS and EUS-FNA has been used not only for TNM staging and cytologic diagnosis of pancreatic cancer, but also for evaluation of chronic pancreatitis, pancreatic cystic lesions, and other pancreatic masses. More recently, EUS-FNA has developed into EUS-guided fine needle injection including EUS-guided celiac plexus neurolysis, celiac plexus block, and other "interventional EUS" procedures. In this review, we have summarized the new possibilities offered by "interventional EUS".     

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study

BACKGROUNDCurrently, there is insufficient data about the accuracy in the diagnosing of pancreatic cystic lesions (PCLs), especially with novel endoscopic techniques such as with direct intracystic micro-forceps biopsy (mFB) and needle-based confocal laser-endomicroscopy (nCLE).AIMTo compare the accuracy of endoscopic ultrasound (EUS) and associated techniques for the detection of potentially malignant PCLs: EUS-guided fine needle aspiration (EUS-FNA), contrast-enhanced EUS (CE-EUS), EUS-guided fiberoptic probe cystoscopy (cystoscopy), mFB, and nCLE.METHODSThis was a single-center, retrospective study. We identified patients who had undergone EUS, with or without additional diagnostic techniques, and had been diagnosed with PCLs. We determined agreement among malignancy after 24-mo follow-up findings with detection of potentially malignant PCLs via the EUS-guided techniques and/or EUS-guided biopsy when available (EUS malignancy detection). RESULTSA total of 129 patients were included, with EUS performed alone in 47/129. In 82/129 patients, EUS procedures were performed with additional EUS-FNA (21/82), CE-EUS (20/82), cystoscopy (27/82), mFB (36/82), nCLE (44/82). Agreement between EUS malignancy detection and the 24-mo follow-up findings was higher when associated with additional diagnostic techniques than EUS alone [62/82 (75.6%) vs 8/47 (17%); OR 4.35, 95%CI: 2.70-7.37; P < 0.001]. The highest malignancy detection accuracy was reached when nCLE and direct intracystic mFB were both performed, with a sensitivity, specificity, positive predictive value, negative predictive value and observed agreement of 100%, 89.4%, 77.8%, 100% and 92.3%, respectively (P < 0.001 compared with EUS-alone). CONCLUSIONThe combined use of EUS-guided mFB and nCLE improves detection of potentially malignant PCLs compared with EUS-alone, EUS-FNA, CE-EUS or cystoscopy.     

Therapeutic role of endoscopic ultrasound in pancreaticobiliary disease: A comprehensive review

With the development of technology and accessories,the role of endoscopic ultrasound(EUS) has evolved from diagnostics to therapeutics. In order to characterise the therapeutic role of EUS,we searched Web of Knowledge database and reviewed articles associated with therapeutic EUS. There are two modalities for the therapeutic purpose: drainage and fine-needle injection. EUS-guided drainage is a promising procedure for the treatment of peripancreatic fluid collection and biliary obstruction; EUS-guided fine-needle injections such as celiac plexus neurolysis,for the purpose of pain relief for pancreatic cancer and chronic pancreatitis,has emerged as a promising procedure. The aim of the study was to perform a comprehensive and conscientious review on the techniques,complications and clinical outcomes of those EUS-based procedures.     

Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration diagnosis of pancreatic masses

Endoscopic ultrasound (EUS) has become an essential tool for the study of pancreatic diseases. Specifically, EUS plays a pivotal role evaluating patients with a known or suspected pancreatic mass. In this setting, differential diagnosis remains a clinical challenge. EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) have been proven to be safe and useful tools in this setting. EUS-guided FNA and FNB, by obtaining cytological and/or histological samples, are able to diagnose pancreatic lesions with high sensitivity and specificity. In this context, several methodological features, trying to increase the diagnostic yield of EUS-guided FNA and FNB, have been evaluated. In this review, we focus on the role of rapid on-site evaluation (ROSE). From data reported in the literature, ROSE may increase diagnostic yield of EUS-FNA specimens by 10%-30%, and thus, diagnostic accuracy. However, we should point out that many recent studies have reported adequacy rates of > 90% without ROSE, indicating that, perhaps, at high-volume centers, ROSE may not be indispensable to achieve excellent results. The use of ROSE can be considered important during the learning curve of EUS-FNA, and also in hospital with diagnostic accuracy rates < 90%.     

Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors

Background and aim: Pancreatic neuroendocrine tumors (pNETs) are histologically categorized according to the WHO 2010 classification by their mitotic index or Ki-67 index as G1, G2, or G3. The present study examined the efficacy of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis and grading of pNET. Methods: We retrospectively reviewed 61 pNETs in 51 patients who underwent EUS between January 2007 and June 2014. All lesions were pathologically diagnosed by surgical resection or EUS-FNA. We evaluated the detection rates of EUS for pNET and sensitivity of EUS-FNA, and compared the Ki-67 index between EUS-FNA samples and surgical specimens. EUS findings were compared between G1 and G2/G3 tumors. Results: EUS showed significantly higher sensitivity (96.7%) for identifying pNET than CT (85.2%), MRI (70.2%), and ultrasonography (75.5%). The sensitivity of EUS-FNA for the diagnosis of pNET was 89.2%. The concordance rate of WHO classification between EUS-FNA and surgical specimens was 69.2% (9/13). The concordance rate was relatively high (87.5%, 5/6) in tumors?<20?mm but lower (57.1%; 4/7) in tumors?≥20?mm. Regarding EUS findings, G2/G3 tumors were more likely to be large (>20?mm), heterogeneous, and have main pancreatic duct (MPD) obstruction than G1 tumors. Multivariate analysis showed large diameter and MPD obstruction were significantly associated with G2/G3 tumors. Conclusions: EUS and EUS-FNA are highly sensitive and accurate diagnostic methods for pNET. Characteristic EUS findings such as large tumor size and MPD obstruction are suggestive of G2/G3 tumors and would be helpful for grading pNETs.     

内镜超声及其引导下的细针穿刺活检在胰腺疾病中的诊断价值

目的:探讨内镜超声(EUS)及其引导下的细针穿刺活检(EUS-FNA)在胰腺疾病诊断中的价值.方法:回顾性分析2008-03/2010-03经EUS检查的62例胰腺疾病,其中有32例行细针穿刺活检.结果:(1)62例胰腺疾病中胰腺癌26例、慢性胰腺炎20例、胰腺囊肿10例、胰岛细胞瘤2例;(2)B超、CT、EUS/EU...     

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic cysts by combined cytopathology and cystic content analysis

Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUS-guided FNA and the cytological diagnosis for pancreatic cysts.     

Endoscopic ultrasound-guided tissue acquisition of pancreatic masses

Endoscopic ultrasound (EUS) has assumed an increasing role in the management of pancreaticobiliary disease over the past 2 decades but its impact is particularly evident in the management of pancreatic masses. EUS helps improve patients′ outcomes by enhancing tumor detection and staging while providing safe and reliable tissue diagnosis. This review provides an evidence-based approach to the use of EUS for the diagnosis of pancreatic cancer, its staging, and for the determination of resectability compared to other imaging modalities. We will focus on techniques specific to obtaining tissue from solid pancreatic masses and will review best practices in EUS-guided tissue acquisition.     

Interventional endoscopic ultrasound: Therapeutic capability and potential

The linear echoendoscope, introduced in the 1990s, opened the era of interventional endoscopic ultrasound (IEUS). The linear echoendoscope enabled EUS guided Fine Needle Aspiration (EUS-FNA) allowing the path of the needle to be traced during the puncture process. After EUS-FNA, other interventional procedures were introduced in clinical practice. Tissue acquisition was the first EUS-guided interventional procedure and its higher diagnostic quality has undoubtedly been established. After EUS-FNA, Celiac plexus neurolysis (CPN) and block (CPB), pancreatic pseudocyst drainage, abdominal and mediastinal collections/abscesses drainage, and in selected cases, pancreatic and biliary ductal system drainage, were introduced in clinical practice. EUS-guided fine needle injection with local delivery of antitumor agents is considered a promising modality. We have reviewed published data on EUS guided interventional procedures with the object of summarizing the diagnostic capability of endoscopic ultrasound and elaborates in detail its therapeutic capability and potential.     

Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma

BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.     

内镜超声引导细针穿刺对胰腺癌的诊断价值

目的了解内镜超声(EUS)引导细针穿刺(FNA)对胰腺癌的临床价值及安全性。方法选择临床诊断或临床及影像学疑诊胰腺癌患者共21例,男13例,女8例,平均年龄(59.8±15.3)岁。EUS发现病变后,在实时超声引导下用超声穿刺针行FNA,对3例无法手术的胰腺癌患者行FNA同时,以无水乙醇阻滞腹腔神经丛治疗癌痛。结果B超共检出胰腺占位16例(16/21),未检出的5例中3例经CT检出,CT共检出胰腺占位19例;EUS检出全部21例胰腺占位,5例位于胰体尾,16例位于胰头。18例患者EUS-FNA获满意标本,17例诊断为胰腺癌,1例诊断为慢性胰腺炎,胰腺癌诊断敏感性为85.0%、特异性为100.0%、准确度为85.7%。3例行无水乙醇阻滞后疼痛减轻。术后发生轻度胰腺炎1例、发热1例。结论EUS能有效检出胰腺占位,结合FNA可提高诊断的特异性及准确性。     

EUS-Guided Antitumor Therapy for Pancreatic Tumors

Endoscopic ultrasound (EUS) is a very useful modality for the diagnosis and staging of pancreatic masses. With the advent of EUS-guided fine-needle aspiration technology, this modality has made a tremendous leap from imaging modality to histologic diagnosis and therapeutic intervention. EUS offers high-resolution images of and unparalleled access to the pancreas. After locating the tip of the echoendoscope in the duodenum or stomach, several drugs or local treatment modalities can be delivered directly into the pancreas. EUS-guided ethanol lavage with/without paclitaxel injection has been tested for the treatment of cystic tumors of the pancreas, with complete resolution of cystic tumor being observed in up to 70-80% of patients. Ethanol injection is also performed for the management of solid neuroendocrine tumors of the pancreas. Various type of EUS-guided injection have also been investigated for the treatment of pancreatic cancer. An activated allogenic mixed lymphocyte culture (Cytoimplant) was injected in patients with advanced pancreatic cancer. A replication-deficient adenovirus vector carrying the tumor necrosis factor-alpha gene was also delivered intratumorally by EUS. ONYX-015 is an oncolytic attenuated adenovirus that exhibits replication preferentially in malignant cells, causing cell death, and this has also been injected into pancreatic cancers under EUS guidance. EUS-guided local ablation therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy are also under investigation. EUS-guided fine-needle injection for various solid or cystic lesions is a rapidly expanding field. This article reviews the various applications of EUS for the treatment of pancreatic tumors.     

Echo-endoscopy: new therapeutic frontiers

Endoscopic ultrasound (EUS) has been established as a valuable diagnostic modality as it offers high-resolution imaging and fine-needle biopsy, which is essential in detecting and staging malignancies. Since the introduction of EUS-guided fine needle aspiration (EUS-FNA) in 1992, numerous novel EUS-based interventions and techniques have emerged. Currently, established interventional EUS techniques include celiac plexus block and neurolysis, drainage of pancreatic pseudocysts and pelvic fluid collections, and implantation of fiducial markers and radioactive seeds into the malignant tumors. Emerging EUS-guided experimental techniques include antitumor injection, ablation of tumors, and vascular access. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used for failed ERCP procedures or inaccessible ducts. Interventional EUS is a very promising technique with many potential applications. The future holds promise for substantial progress in EUS-guided therapeutic interventions and their applications in clinical gastroenterology.     

内镜超声检查的发展现状

内镜超声近年来获得迅猛发展,应用范围已覆盖全消化道和邻近器官。造影增强内镜超声、弹性成像诊断术以及计算机图形识别等多项无创诊断技术已应用于临床;内镜超声引导下细针抽吸活检、切割针活检和细胞刷检可借助细胞病理学对病变进行准确定性;借助细针注射途径则可对病变进行多种药物的局部注射或植入治疗。随着内镜超声设备和技术的不断进步,其应用前景将愈加广阔。     

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors

Background/objectivesStudies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens.MethodsPatients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed.ResultsThree-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482).ConclusionOur study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.     

Utility of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and management of pancreatic cystic lesions: Differences between the guidelines

Recent advances and frequent use of cross-sectional imaging studies have increased opportunities for incidental diagnoses of pancreatic cystic lesions (PCL). In the management of PCL, distinguishing between mucinous versus non-mucinous and malignant versus benign cysts is important to diagnose pancreatic cancer in its early stage. For this reason, there have been several guidelines to manage PCL. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) play important roles in the guidelines, although there are some differences in their roles. In this review, we aimed to evaluate the current status of EUS and EUS-FNA in the management of PCL and the status of these procedures in the guidelines.