EUS-Guided Ethanol Ablation of Insulinomas: Case Series and Literature Review

Surgical resection is a standard treatment for insulinomas; however, it is associated with a high risk of complications and limited to specific suitable candidates. In recent years, endoscopic ultrasound (EUS)-guided ethanol ablation of insulinomas has emerged as a new therapeutic option, especially for elderly patients and candidates unfit for surgery. We aimed to evaluate the feasibility and safety of this technique for insulinomas.Four patients diagnosed with insulinomas based on EUS–fine-needle aspiration and immunohistochemistry results underwent EUS-guided 95% ethanol ablation. A comprehensive literature review was performed to understand the current status of the feasibility, safety, and effects of EUS-guided ethanol ablation of insulinomas.EUS-guided ethanol ablation of insulinomas was successfully completed in all the 4 patients. There were no perioperative or postoperative complications. The patients were discharged at 3 days after the procedure. No recurrence of hypoglycemia or tumors was noted during follow-up (range, 3–6 months). Literature review showed 8 patients with insulinomas who underwent EUS-guided ethanol ablation. All the procedures were successful, with no need for further surgical treatment. Among these reviewed cases, 6 patients had no post-procedural complications, while other 2 patients showed a mild increase in the serum levels of lipase and/or pancreatic enzymes within 48 h post-procedure; furthermore, 1 of these 2 patients presented at a later date with medically controllable hematoma and ulceration. During follow-up, 6 patients remained asymptomatic and normoglycemic, while the 2 patients who presented post-procedural complications developed occasional mild confusion.EUS-guided ethanol ablation of insulinomas is an effective and safe modality, with an acceptable level of post-procedural complications. However, the long-term effects of this new therapeutic option need to be validated in a large randomized controlled trial with longer follow-up.     

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.     

Endoscopy-guided ablation of pancreatic lesions:Technical possibilities and clinical outlook

Endoscopic ultrasound(EUS) and endoscopic retrograde cholangiopancreatography(ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer(LAPC), pancreatic neuroendocrine tumours(PNETs), and pancreatic cystic lesions(PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as wel as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting.Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches,and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.     

The safety and efficacy of endoscopic ultrasound-guided ablation therapy for solid pancreatic tumors: a systematic review

Abstract

Background and aims

Recently, endoscopic ultrasound (EUS)-guided ablation therapy, as a minimally invasive technique, has shown its potential to substitute surgery in treating solid pancreatic tumors, such as small potential malignant pancreatic tumors, small insulinomas and locally advanced pancreatic ductal adenocarcinoma (LAPDAC). Therefore, we conducted this systematic review to assess the safety and efficacy of EUS-guided ablation therapy for solid 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.     

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.     

Appraisal of needle-based confocal laser endomicroscopy in the diagnosis of pancreatic cysts

Nearly 2.5% of cross-sectional imaging studies will report a finding of a cystic pancreatic lesion. Eventhough most of these are incidental findings, it remains very concerning for both patients and treating clinicians. Differentiating and predicting malignant transformation in pancreatic cystic lesions is clinically challenging. Current evaluation of suspicious cystic lesions includes a combination of radiologic imaging, endoscopic ultrasound(EUS) and cyst fluid analyses. Despite these attempts, precise diagnostic stratification among nonmucinous, mucinous, and malignant cystic lesions is often not possible until surgical resection. EUS-guided needle based confocal laser endomicroscopy(n CLE) for evaluation of pancreatic cysts is emerging as a powerful technique with remarkable potential. Though limited imaging data from 3 large clinical trials(INSPECT, DETECT and CONTACT) are currently the reference standard for n CLE imaging, nonetheless these have not been validated in large studies. The aim of this review article is to review the evolving role of EUS-guided n CLE in management of pancreatic cystic lesions in terms of its significance, adverse events, limitations, and implications.     

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.     

Preoperative diagnosis of extrapancreatic neural invasion in pancreatic cancer.

BACKGROUND & AIMS: Pancreatic cancer recurs in most patients after resection with curative intent. Recurrence is particularly common in patients with extrapancreatic neural invasion (EPNI), the presence of which correlates with poor prognosis. Macroscopic EPNI may be detected with conventional noninvasive imaging and endoscopic ultrasound (EUS) imaging, but microscopic EPNI has required postoperative pathologic examination of surgical specimens. We report the preoperative diagnosis of cancer infiltration into celiac ganglia. We hypothesized that microscopic pancreatic cancer metastasis to neural ganglia can be detected by EUS-guided biopsy examination. METHODS: We performed a retrospective review of patients with pancreatic cancer undergoing EUS in whom celiac ganglia were sampled to exclude malignant infiltration. RESULTS: Six patients with pancreatic cancer underwent EUS-guided fine-needle aspiration or trucut biopsy examination of presumed celiac ganglia. Metastatic cancer was found in ganglia of 2 patients. Specimen review identified adenocarcinoma and neural tissue in the absence of lymphocytes. At laparoscopy, 1 of the 2 patients with positive celiac biopsy specimens also had several unexpected peritoneal metastatic deposits. The other patient was considered to have locally advanced unresectable disease. Both patients are receiving supportive care. CONCLUSIONS: EPNI may be shown preoperatively in patients with pancreatic cancer using EUS-guided sampling of celiac ganglia. A preoperative diagnosis of EPNI has the potential to improve staging accuracy and patient outcomes.     

Interventional EUS for the treatment of pancreatic cancer

Since the curved linear array echoendoscope (linear EUS) was developed in the 1990s, EUS has evolved from EUS imaging, to EUS-guided FNA, and now to EUS-guided fine needle injection (FNI), giving EUS even wider application. This advancement has brought “interventional EUS” into the pancreato-biliary field. Interventional EUS for pancreatic cancer includes delivery of contrast agents, drainage/anastomosis, celiac neurolysis (including ganglion neorolysis), radiofrequency ablation, photodynamic therapy, brachytherapy, and delivery of a growing number of anti-tumor agents. This review will focus on interventional EUS in the treatment of pancreatic cancer.     

EUS-guided alcohol ablation of an insulinoma

BACKGROUND: Surgical resection is currently considered to be the criterion standard for treatment of insulinomas. Alternative treatments, despite medication with diazoxide, are lacking. EUS-guided ethanol ablation of endocrine tumors has not been reported before. INTERVENTION: A 78-year-old woman was referred with typical symptoms of an insulinoma. Diagnosis was confirmed by laboratory findings, EUS, and EUS-guided FNA. Because of severe complications during several hypoglycemic episodes, a poor general condition, and strict refusal of surgical resection, the decision was made to ablate the insulinoma by EUS-guided alcohol injection. A total of 8 mL 95% ethanol was injected into the tumor. RESULTS: The patient was discharged and exhibited no further hypoglycemic episodes, and her general condition improved rapidly. Based on clinical, morphologic, and biochemical criteria, we achieved a durable complete remission of the tumor. CONCLUSIONS: EUS-guided ablation may become a minimally invasive alternative for patients with insulinomas in whom surgery is not feasible.     

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.     

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.     

内镜超声引导下无水乙醇消融术治疗胰腺囊性肿瘤的初步研究(含视频)

目的 评价内镜超声引导下无水乙醇消融术（EUS-EA）治疗胰腺囊性肿瘤的可行性、安全性及有效性。方法 回顾性分析2013年7月至2017年4月在上海长海医院接受EUS-EA的10例胰腺囊性肿瘤患者的基本信息、EUS特征、术后并发症、随访情况等资料。根据术后随访的影像学资料评估EUS-EA疗效。结果 10例患者瘤体最长径平均为（2.95±1.56）cm,囊液分析结果显示6例浆液性囊腺瘤,3例黏液性囊腺瘤,1例未定型囊腺瘤。10例患者共行12次EUS-EA,手术均成功,未出现有临床意义的感染、胰腺炎、出血、胰瘘等严重并发症。术后中位随访时间4.0个月（3.0~12.0个月）,3例完全缓解,6例部分缓解,1例稳定,无进展病例。结论 EUS-EA治疗胰腺囊性肿瘤手术成功率高、并发症少、总体疗效较好。     

Uncommon complications of therapeutic endoscopic ultrasonography: What,why, and how to prevent

There is an increasing role for endoscopic ultrasound (EUS)-guided interventions in the treatment of many conditions. Although it has been shown that these types of interventions are effective and safe, they continue to be considered only as alternative treatments in some situations. This is in part due to the occurrence of complications with these techniques, which can occur even when performed by experienced endosonographers. Although common complications have been described for many procedures, it is also crucial to be aware of uncommon complications. This review describes rare complications that have been reported with several EUS-guided interventions. EUS-guided biliary drainage is accepted as an alternative treatment for malignant biliary obstruction. Most of the uncommon complications related to this procedure involve stent malfunction, such as the migration or malposition of stents. Rare complications of EUS-guided pancreatic pseudocyst drainage can result from air embolism and infection. Finally, a range of uncommon complications has been reported for EUS-guided celiac plexus neurolysis, involving neural and vascular injuries that can be fatal. The goal of this review is to identify possible complications and promote an understanding of how they occur in order to increase general awareness of these adverse events with the hope that they can be avoided in the future.     

What are the current and potential future roles for endoscopic ultrasound in the treatment of pancreatic cancer?

Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Due to the aggressive tumor biology and late manifestations of the disease, long-term survival is extremely uncommon and the current 5-year survival rate is 7%. Over the last two decades, endoscopic ultrasound(EUS) has evolved from a diagnostic modality to a minimally invasive therapeutic alternative to radiologic procedures and surgery for pancreatic diseases. EUSguided celiac plexus intervention is a useful adjunct to conventional analgesia for patients with pancreatic cancer. EUS-guided biliary drainage has emerged as a viable option in patients who have failed endoscopic retrograde cholangiopancreatography. Recently, the use of lumen-apposing metal stent to create gastrojejunal anastomosis under EUS and fluoroscopic guidance in patients with malignant gastric outlet obstruction has been reported. On the other hand, anti-tumor therapies delivered by EUS, such as the injection of anti-tumor agents, brachytherapy and ablations are still in the experimental stage without clear survival benefit. In this article, we provide updates on well-established EUS-guided interventions as well as novel techniques relevant to pancreatic cancer.     

直接胰管镜下活检及胰管内射频消融诊治混合型胰腺导管内乳头状黏液瘤1例（含视频）

不能耐受或拒绝外科手术的主胰管型/混合型胰腺导管内乳头状黏液瘤（intraductal papillary mucinous neoplasm，IPMN）目前缺乏有效的治疗方式。报道一例既往未确诊病因的复发性胰腺炎患者，经直接胰管镜观察及活检确诊混合型IPMN，并进行多次胰管内射频消融姑息性治疗，术后随访20个月，未再发胰腺炎，疾病较前无进展。直接胰管镜下活检及胰管内射频消融治疗作为IPMN的姑息性内镜治疗方式存在巨大的潜在价值。     

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.     

Pancreatic insulinoma:current issues and trends

BACKGROUND:Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms.The incidence in general population is 1-4 per 1 000 000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features,and the current WHO classification has been re-evaluated.This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas. DATA SOURCES:A Medline search using terms"insulinoma", "treatment"and"neuroendocrine tumors"was conducted. Additional references were sourced from key articles. RESULTS:Surgery is the treatment of choice for insulinoma and has an extremely high success rate.Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment.Preoperative localization is necessary for planning the surgical approach.Many methods exist for localization of an insulinoma and can be invasive and non-invasive.The combination of biphasic thin section helical CT and endoscopic ultrasonography(EUS)has an almost 100% sensitivity in localizing insulinomas.Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors.EUS-guided fine needle tattoing is an alternative method of localization in case of lack of laparoscopic ultrasound. CONCLUSION:Laparoscopic resection for benign insulinomas is the procedure of choice,whereas pancreatectomy is reserved for large,potentially malignant tumors.     

Ampullary neuroendocrine tumor diagnosed by endoscopic papillectomy in previously confirmed ampullary adenoma

Ampullary adenoma is a common indication for endoscopic papillectomy. Ampullary neuroendocrine tumor(NET) is a rare disease for which complete surgical resection is the treatment of choice. However, because of the morbidity and mortality associated with surgical resection, endoscopic papillectomy is increasingly used in selected cases of low grade, with no metastasis and no invasion of the pancreatic or bile duct. Also, confirmed and complete endoscopic resection of ampullary NET accompanied by adenoma has not been reported to date. We report herein a rare case of an ampullary NET accompanied with adenoma, which was successfully and completely resected via endoscopic papillectomy. Prior to papillectomy, this case was diagnosed as an ampullary adenoma.