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.     

Interventional endoscopic ultrasound for pancreatic neuroendocrine neoplasms

The proximity of the endoscopic ultrasound (EUS) transducer to the pancreas and the possibility to place needles or other accessories into a target located adjacent to the wall of the GI tract have encouraged researchers to develop various EUS-guided local treatments directed towards pancreatic neuroendocrine neoplasms (PanNENs). The use of pre-operative EUS-guided tattooing or fiducial marker placement to facilitate intraoperative tumor localization has proven effective in reducing operative time of laparoscopic surgeries. To reduce the mortality and morbidity rates of surgical resection, which is presently the mainstay treatment of PanNENs. EUS-guided loco-regional treatments, such as injection of alcohol and radiofrequency ablation have been proposed and results are hitherto promising. The present paper summarizes currently available data in the field of EUS-guided interventions to pancreatic neuroendocrine tumors, as well as possible future applications.     

Endoscopic ultrasound-guided treatments: Are we getting evidence based - a systematic review

The continued need to develop less invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound (EUS)-guided treatments. These include EUS-guided drainage of pancreatic fluid collections, EUS-guided necrosectomy, EUS-guided cholangiography and biliary drainage, EUS-guided pancreatography and pancreatic duct drainage, EUS-guided gallbladder drainage, EUS-guided drainage of abdominal and pelvic fluid collections, EUS-guided celiac plexus block and celiac plexus neurolysis, EUS-guided pancreatic cyst ablation, EUS-guided vascular interventions, EUS-guided delivery of antitumoral agents and EUS-guided fiducial placement and brachytherapy. However these procedures are technically challenging and require expertise in both EUS and interventional endoscopy, such as endoscopic retrograde cholangiopancreatography and gastrointestinal stenting. We undertook a systematic review to record the entire body of literature accumulated over the past 2 decades on EUS-guided interventions with the objective of performing a critical appraisal of published articles, based on the classification of studies according to levels of evidence, in order to assess the scientific progress made in this field.     

EUS-guided fine-needle aspiration of the pancreas: evaluation of pancreatitis as a complication

BACKGROUND: EUS-guided fine-needle aspiration is rapidly becoming the procedure of choice for the diagnostic evaluation of pancreatic masses. Acute pancreatitis has been reported after EUS-guided fine-needle aspiration of the pancreas. This study evaluated the effect of EUS-guided fine-needle aspiration on the pancreas by serial measurement of amylase and lipase levels and determining the frequency of acute pancreatitis after EUS-guided fine-needle aspiration of pancreatic masses. METHODS: In 100 consecutive patients referred for EUS-guided fine-needle aspiration of a pancreatic mass, amylase and lipase levels were determined immediately before and within 2 hours after the procedure. Additionally, patients were questioned as to the occurrence of symptoms of acute pancreatitis within 48 hours after EUS-guided fine-needle aspiration. RESULTS: For 2 of 100 patients (2%) there was clinical and biochemical evidence of acute pancreatitis after EUS-guided fine-needle aspiration. Both patients had a history of recent pancreatitis. In addition, there was a significant increase in postprocedure lipase levels (p = 0.40) compared with amylase levels in this patient subset. CONCLUSION: The frequency of acute pancreatitis after EUS-guided fine-needle aspiration of the pancreas was 2% in this study. A history of recent pancreatitis appears to be a potential risk factor. Amylase and lipase levels can be elevated after EUS-guided fine-needle aspiration and in most cases have no clinical significance.     

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.     

EUS-guided trucut needle biopsies in patients with solid pancreatic masses: a prospective study

BACKGROUND: A trucut needle biopsy device that can be used to obtain specimens from the pancreas and other perigastric organs under EUS guidance has been developed and successfully tested in animals. Moreover, EUS-guided trucut needle biopsy has been used safely in humans and appears to provide more accurate results than EUS-guided FNA. This study prospectively assessed the clinical utility of this new device in patients with solid pancreatic masses. METHODS: Twenty-three consecutive patients with radiologically detected solid pancreatic masses underwent EUS-guided trucut needle biopsy. Pancreatic malignancy detected by EUS-guided trucut needle biopsy was considered a definitive diagnosis. Further diagnostic procedures and clinical course were used to establish or exclude the presence of malignancy in all other patients. RESULTS: Pancreatic tissue was obtained in 17 of the 23 patients (74%), including all patients in whom the transgastric approach was used. No acute or long-term complication was observed. Histopathologic evaluation revealed pancreatic cancer in 12 patients. CT-guided biopsy specimens were obtained in 4 of the 5 patients with a negative EUS-guided trucut needle biopsy result; two were positive for adenocarcinoma. Overall diagnostic accuracy was 61%. Subgroup analysis of the 16 patients in whom EUS-guided trucut needle biopsy was successful and who were available for follow-up revealed a diagnostic accuracy of 87.5%. CONCLUSIONS: This prospective study demonstrates that EUS-guided trucut needle biopsy, when performed transgastrically, is safe and accurate in the evaluation of patients with solid pancreatic masses.     

Palliative endoscopic ultrasound-guided drainage of a malignant pancreatic cyst causing gastric outlet obstruction.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts has been well described but it is not an established therapy for malignant pancreatic cystic neoplasms. We report the first EUS-guided cystogastrostomy for the palliative treatment of a cystic pancreatic adenocarcinoma. CASE REPORT: We describe a 70-year-old male with a nonresectable cystic pancreatic adenocarcinoma causing partial gastric outlet obstruction treated successfully with palliative EUS-guided cystogastrostomy stent placement. The diagnosis was confirmed by EUS-guided fine needle aspiration. Computerized tomography (CT) and EUS staging revealed vascular invasion precluding the patient from surgical resection. Cystogastrostomy was performed entirely under EUS guidance utilizing a 10-Fr double pigtail stent. After cystogastrostomy stent placement, the patient developed dramatic symptomatic improvement of gastric outlet obstructive symptoms, although subsequent imaging did not reveal complete collapse of the cystic structure. CONCLUSION: EUS-guided cystogastrostomy can be considered in the palliative treatment of nonresectable pancreatic cystic neoplasms. Cyst decompression may result in significant symptomatic improvement, although the architecture of malignant cysts may prevent complete resolution.     

EUS-Guided Celiac Plexus Neurolysis for Pain due to Chronic Pancreatitis or Pancreatic Cancer Pain: A Meta-Analysis and Systematic Review

The objective of this study was to evaluate the efficacy of EUS-guided CPN for pain relief in patients with chronic pancreatitis and pancreatic cancer. An initial search identified 1,439 reference articles, of which 130 relevant articles were selected and reviewed. Data was extracted from 8 studies (N = 283) for EUS-guided CPN for pain due to pancreatic cancer and nine studies for chronic pancreatitis (N = 376) which met the inclusion criteria. With EUS-guided CPN, the pooled proportion of patients with pancreatic cancer that showed pain relief was 80.12% (95% CI = 74.47–85.22). In patients with pain due to chronic pancreatitis, EUS-guided CPN provided pain relief in 59.45% (95% CI = 54.51–64.30). In conclusion, EUS-guided CPN offers a safe alternative technique for pain relief in patients with chronic pancreatitis or pancreatic cancer. In patients with pain due to chronic pancreatitis, better techniques or injected materials are needed to improve the response.     

EUS-guided FNA in the diagnosis of pancreatic neuroendocrine tumors before surgery

BACKGROUND: The use of EUS for precise preoperative evaluation of pancreatic neuroendocrine tumors is well established; up to 80% of insulinomas can be localized. However, the EUS appearance of pancreatic neuroendocrine tumors can be similar to that of benign peripancreatic lymph nodes. The aim of this study was to evaluate the role of EUS-guided FNA in this setting. METHODS: Thirty patients (18 women, 12 men) with 33 pancreatic/peripancreatic lesions confirmed by surgery underwent EUS-guided FNA between February 1997 and September 2002. Transabdominal US and CT were obtained in all patients before EUS. The diagnosis of pancreatic neuroendocrine tumor was established based on morphologic appearance and immunohistochemical staining of cytologic and surgical specimens. RESULTS: EUS detected 32 of the 33 (96.9%) lesions (mean diameter 20 mm, range 5-97 mm). There was one complication (abdominal pain). For the 30 patients, the following diagnoses were made: functioning pancreatic neuroendocrine tumor (16 patients), non-functioning pancreatic neuroendocrine tumor (7), peripancreatic lymph node (5), inflammatory intrapancreatic nodule (1), and peripancreatic splenosis (1). Sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-guided FNA were 82.6%, 85.7%, 95%, 60%, and 83.3%, respectively. There was one false-positive diagnosis by EUS-guided FNA and 4 false-negative diagnoses. In two of the latter cases, EUS-guided FNA was unsuccessful. CONCLUSIONS: EUS-guided FNA is accurate and safe for the diagnosis of pancreatic neuroendocrine tumor and may have a role in determining management strategy.     

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 FNA of pancreatic metastasis from renal cell carcinoma

BACKGROUND: The prognosis for patients with renal cell carcinoma metastatic to the pancreas is better than that for patients with primary pancreatic adenocarcinoma. In patients with a history of renal cell cancer, it would, therefore, appear necessary to obtain cytologic or histopathologic evidence of the tumor type. EUS-guided FNA is considered the technique of choice for this purpose. This study retrospectively assessed the efficacy of EUS-guided FNA and specific technical considerations when the procedure is performed for this indication. METHODS: Over 2 years, EUS-guided FNA was performed in 11 consecutive patients with a history of renal cell carcinoma and a solid mass within the pancreas. OBSERVATIONS: After EUS-guided FNA yielded a negative result in two patients, the sampling technique was modified, namely short aspiration with low negative vacuum pressure. This resulted in the detection of metastases of renal cell cancer in the remaining 9 patients. There was no procedure-related complication. CONCLUSIONS: EUS-guided FNA is safe and accurate for the diagnosis of pancreatic metastases of renal cell carcinoma. However, effective sampling requires techniques that differ from those used for solid pancreatic masses.     

Endoscopic ultrasound-guided ethanol ablation therapy for tumors

Endoscopic ultrasonography (EUS) has evolved into a useful therapeutic tool for treating a broad range of tumors since being introduced into clinical practice as a diagnostic modality nearly three decades ago. In particular, EUS-guided fine-needle injection has proven a successful minimally invasive approach for treating benign lesions such as pancreatic cysts, relieving pancreatic pain through celiac plexus neurolysis, and controlling local tumor growth of unresectable malignancies by direct delivery of anti-tumor agents. One such ablative agent, ethanol, is capable of safely ablating solid or cystic lesions in hepatic tissues via percutaneous injection. Recent research and clinical interest has focused on the promise of EUS-guided ethanol ablation as a safe and effective method for treating pancreatic tumor patients with small lesions or who are poor operative candidates. Although it is not likely to replace radical resection of localized lesions or systemic treatment of metastatic tumors in all patients, EUS-guided ablation is an ideal method for patients who refuse or are not eligible for surgery. Moreover, this treatment modalitymay play an active role in the development of future pancreatic tumor treatments. This article reviews the most recent clinical applications of EUS-guided ethanol ablation in humans for treating pancreatic cystic tumors, pancreatic neuroendocrine tumors, and metastatic lesions.     

内镜超声引导下经胃穿刺覆膜金属支架引流胰腺假性囊肿的初步临床研究

目的评价临床应用胆道覆膜自膨式金属支架引流胰腺假性囊肿的有效性、可行性和安全性。方法回顾分析2013年9月至2014年5月在长海医院接受内镜超声（EUS）引导下经胃胰腺假性囊肿全覆膜自膨式金属支架引流的11例患者病例和随访资料。引流方法采用EUS引导下经胃壁穿刺至囊腔,置入导丝,用囊肿切开刀进行针道扩张,置入金属覆膜支架引流。术后定期随访,囊肿消失后拔除支架。评价操作成功率、治愈成功率、并发症发生率。结果11例患者均完成囊肿穿刺、全覆膜金属支架置入引流术,手术成功率为100％,2例患者并发感染,1例患者发生支架移位,无出血、穿孔、死亡病例。其中7例已完成支架拔除术,囊肿均完全消失。结论EUS引导下经胃穿刺胆道覆膜金属支架引流胰腺假性囊肿手术成功率、治愈率高,并发症发生率较低。     

EUS-guided rendezvous drainage of obstructed biliary and pancreatic ducts: Report of 6 cases

BACKGROUND: Only a few cases have been reported of EUS-guided drainage of obstructed pancreatic or bile ducts. An initial experience with EUS-guided rendezvous drainage after unsuccessful ERCP is reported. METHODS: EUS-guided transgastric or transduodenal needle puncture and guidewire placement through obstructed pancreatic (n=4) or bile (n=2) ducts was attempted in 6 patients. Efforts were made to advance the guidewire antegrade across the papilla or surgical anastomosis. If guidewire passage was successful, rendezvous ERCP with stent placement was performed immediately afterward. RESULTS: EUS-guided duct access and intraductal guidewire placement was accomplished in 5 of 6 cases, with successful traversal of the obstruction, and rendezvous ERCP, with stent placement in 3 of 6 cases (two biliary, one pancreatic). The procedure was clinically effective in all successful cases (two patients with malignant obstructive jaundice, one with relapsing pancreatitis after pancreaticoduodenectomy). There was one minor complication (transient fever) but no pancreatitis or duct leak after successful or unsuccessful procedures. CONCLUSIONS: EUS is a feasible technique for allowing rendezvous drainage of obstructed biliary or pancreatic ducts through native papillae or anastomoses after initially unsuccessful ERCP.     

Endoscopic ultrasound-guided drainage of peripancreatic fluid collections: What impacts treatment duration?

Background: Peripancreatic fluid collections(PFCs) are complications resulting from acute or chronic pancreatitis and require treatment in certain clinical conditions. The present study aimed to identify the factors influencing the duration of endoscopic ultrasound(EUS)-guided drainage of symptomatic pancreatic pseudocysts(PPCs), walled-off necrosis(WON), and acute necrotic collections(ANCs). Methods: This was a retrospective cohort study of 68 patients with PFCs who underwent EUS-guided drainag...     

The role of endoscopic ultrasonography in the diagnosis and management of pancreatic cancer

EUS with FNA is highly sensitive and specific for diagnosing pancreatic cancer. However, in certain situations, such as in patients with chronic pancreatitis, this high sensitivity and specificity can significantly diminish. The use of new technology, such as EUS elastography, CE-EUS, and gene mutations detection in FNA specimens, can help to differentiate chronic pancreatitis from pancreatic cancer. EUS has evolved from a diagnostic procedure to a therapeutic intervention in pancreatic cancer. EUS-guided fiducial insertion and EUS-guided delivery of antitumor agents, in addition to celiac plexus neurolysis, are the main therapeutic applications of EUS in pancreatic cancer.     

The learning curve for EUS-guided FNA of pancreatic cancer

BACKGROUND: EUS-guided FNA is an effective and safe method for tissue diagnosis of pancreatic cancer. However, EUS-guided FNA is technically challenging and requires special training. The number of cases required to become proficient and the technical steps required to achieve proficiency are unknown. METHODS: The first 57 EUS-guided FNAs of pancreatic masses by a trained endosonographer were analyzed retrospectively. For 50 masses, the histopathologic diagnosis ultimately was cancer. The sensitivity for the EUS-guided FNA diagnosis of adenocarcinoma was compared in quintiles of 10 procedures. RESULTS: Sensitivity for the diagnosis of pancreatic cancer from first to last quintile were, respectively, 50%, 40%, 70%, 90%, and 80%. There was a significant increase in sensitivity for the first 30 cases after improvement in specific technical skills: shortening of echoendoscope position, scrupulous maintenance of the US view of the needle tip at all times, swift jabbing punctures, sampling multiple areas of the mass in each pass, and performing more than 10 "jiggles" per needle pass. Sensitivity for the diagnosis of pancreatic cancer was greater than 80% for the last 20 of the 57 cases, a level that was maintained for cases 51 through 80. CONCLUSIONS: The current American Society for Gastrointestinal Endoscopy guideline of 25 supervised EUS-FNA procedures for the diagnosis of pancreatic adenocarcinoma is reasonable.     

Endoscopic ultrasound-guided anastomosis: Is it ready for prime time?

Significant advancements in endoscopic ultrasound (EUS)-guided drainage procedures and EUS-guided anastomosis have recently been described. The described procedures include EUS-guided drainage of pancreatic fluid collections, biliary drainage, pancreatic duct drainage, gallbladder drainage, and gastroenterostomy. These procedures have been made possible with novel devices that can reduce the difficulties of the procedures and potentially reducing the risk of adverse events. The procedures are also becoming standardized, which is essential for dissemination of the techniques. Furthermore, results from randomized studies are becoming available showing definite benefits associated with these procedures. In this paper, we will provide a review on EUS-guided anastomotic procedures.     

Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies

BACKGROUND: The factors that affect the number of needle passes needed to diagnose pancreatic malignancies using endoscopic ultrasound (EUS) -guided fine-needle aspiration are unknown. METHODS: Patient and endosonographic data were prospectively recorded on 121 consecutive patients with pancreatic malignancy. Of these, 110 underwent EUS-guided fine-needle aspiration. A cytopathologist was in attendance for all aspiration procedures. RESULTS: Initial EUS detected a pancreatic mass in 96% of cases; 23% of these were not seen by computed tomography. EUS-guided fine-needle aspiration was performed in 109 of 110 (99%) patients, including 95 masses, 7 lymph nodes, and 7 hepatic metastases. EUS-guided fine-needle aspiration provided a cytologic diagnosis of malignancy in 104 of 110 (95%). Only tumor differentiation and the site of aspiration affected the number of passes. CONCLUSIONS: With the participation of a cytopathologist, EUS-guided fine-needle aspiration can diagnose pancreatic malignancies with a high degree of accuracy. Only the aspiration site (mass versus node/liver metastasis) can be used to direct the number of passes if a cytopathologist is not present. Without a cytopathologist in attendance, 5 to 6 passes should be made for pancreatic masses and 2 to 3 for liver metastases or lymph nodes; however, this approach will be associated with a 10% to 15% reduction in definitive cytologic diagnoses, extra procedure time, increased risk and additional needles.     

内镜超声引导下细针穿刺对胰腺占位病变的诊断价值

目的 通过超声内镜结合细针穿刺活检确定胰腺占位病变的性质，并评价该法对胰腺病变的诊断价值。方法 对经CT、MRI、体表腹部超声及内镜超声发现的23例胰腺局限性占位病变进行内镜超声检查，以明确病变大小、形态、位置，并观察有无淋巴结转移。在内镜超声引导下对病变行细针穿刺活检。结果 23例患者中，21例得到了充足的细胞量，15例得到组织块，12例最终确定为胰腺肿瘤的患者，经组织细胞学检查10例为阳性（其中胰腺癌8例；胰腺囊腺瘤癌1例；无功能神经内分泌肿瘤1例），敏感性为83％，特异性为100％。全部结果经手术（16例）及临床随访（7例）证实。无1例出现不良反应。结论 超声内镜结合细针穿刺是诊断胰腺病变安全、有效的方法。