EUS-guided Fine-needle Injection Research Articles

Abstract B004: EUS guided local administration of large surface area microparticle paclitaxel with neoadjuvant chemotherapy in locally advanced pancreatic cancer: A single center experience

Abstract Background: Locally advanced pancreatic cancer (LAPC) is defined as an unresectable tumor due to extensive vascular involvement without evidence of metastatic spread. Neoadjuvant chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-nab-paclitaxel (gem-nab) are the preferred treatments in LAPC. These treatments downstage LAPC to resectable disease in about 10%–35% of patients resulting in an increase in median survival. However, intravenous paclitaxel's hydrophobic, protein-bound nature, short half-life, and intermittent dosing hamper tumor tissue exposure time, resulting in suboptimal intratumoral bioavailability that may facilitate tumor resistance. Limited downstaging to R0 resection is likely due, in part, to the desmoplastic, fibrotic tumor microenvironment in LAPC and poorly vascularized stroma reducing availability of IV drug to tumor cells. To address this, large surface area microparticle paclitaxel (LSAM-PTX) was developed (NanOlogy LLC) for intratumoral (IT) delivery with a mean particle size (DV50) of about 2.5 µm and 3-fold increase in specific surface area over unprocessed drug. The relatively large particle size facilitates tumor retention, and increased surface area allows continuous drug release in tumor over an extended time, along with negligible systemic exposure. Methods: Data were collected prospectively on 6 of 13 (46%) subjects with LAPC who received EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX in addition to neoadjuvant chemotherapy and subsequently underwent surgery at our institution from 2018 to 2019 (NCT03077685). Each subject underwent two EUS-FNI procedures four weeks apart to deliver IT LSAM-PTX suspension (15 mg/mL) in a volume equivalent to 20% of the tumor volume up to 5 mL of drug. Histopathological and immunophenotypic profiling using multiplex immunofluorescence (mIF) was performed on tumor site tissue from pre-LSAM-PTX biopsies and the resected tumor. Results: The mean duration from EUS-FNI to surgery was 6.91 months (range: 3.68-12.22 months). Histopathology was evaluated from the resected specimens to assess treatment response. Five of six subjects (83%) had R0 resections. Of the five R0 resections, one subject had a pathologic complete response, one had 10% and two had 10-20% viable tumor, and one had a partial response with tumor regression. Focal necrosis was also reported in the lone subject with an R1 resection. Immunophenotypic profiling of tissue showed an increase in adaptive and innate immune cell density, an increase in NK cells in the tumor microenvironment, and a decrease in the myeloid/MDSC populations. Conclusions: EUS-FNI of LSAM-PTX, added to neoadjuvant chemotherapy, was safe and resulted in a significant reduction in tumor volume, along with significant tumor necrosis, and favorable changes in tumor immunophenotypic configuration. These preliminary results suggest that adding LSAM-PTX to neoadjuvant chemotherapy could increase the rate of downstaging of LAPC to resectable disease and improve clinical outcomes. Citation Format: Harishankar Gopakumar, Aqsa Khan, Christina M. Zelt, Ashley Rumple, Mariajose Rojas de Leon, Neil R. Sharma. EUS guided local administration of large surface area microparticle paclitaxel with neoadjuvant chemotherapy in locally advanced pancreatic cancer: A single center experience [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B004.

Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol

AimsA novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs. MethodsSubjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL). ResultsSix BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX). ConclusionIn this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

A Review of Endoscopic Ultrasound-Guided Chemoablative Techniques for Pancreatic Cystic Lesions.

Pancreatic cystic lesions (PCLs) are known precursors to pancreatic cancer, one of the deadliest types of cancer worldwide. Surgical removal or pancreatectomies remain the central approach to managing precancerous high-risk PCLs. Endoscopic ultrasound (EUS)-guided therapeutic management of PCLs is a novel management strategy for patients with prohibitive surgical risks. Various ablation techniques have been explored in previous studies utilizing EUS-guided fine needle injection (FNI) of alcohol and chemotherapeutic agents. This review article focuses on EUS-FNI and chemoablation, encompassing the evolution of chemoablation, pancreatic cyst selection, chemotherapy drug selection, including novel agents, and a discussion of its safety and efficacy.

Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma is associated with worse prognosis.

Carbohydrate sulfotransferase 15 (CHST15) synthesizes matrix proteoglycan that regulates various pathogenic mediators and contributes to tissue remodeling and fibrosis during injury. CHST15 has been reported to promote tumor growth and invasion in various types of cancer. Our previous study reported the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, a double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. The present study aimed to determine the expression and clinicopathological characteristics of CHST15 in pancreatic cancer. Immunohistochemical staining was performed for CHST15 using pancreatic tissues from 64 patients (28 males and 36 females; age, 69.0±9.6 years) with pancreatic cancer who underwent surgery. For the evaluation of fibrosis, two categories were defined (mature and immature), based on the existence of collagen, myxoid stroma and fibroblasts, using hematoxylin and eosin specimens. The positive percentage of CHST15 was quantified, patients were divided into two groups according to high and low CHST15 expression in both the cancer and stroma tissues, and the association between CHST15 expression in cancer cells and the stroma was analyzed. Additionally, the present study analyzed the association between CHST15 expression and clinicopathological information, including overall and disease-free survival. The expression levels of CHST15 were detected in the cytoplasm of pancreatic cancer cells and fibroblasts in the cancer stroma. CHST15 expression in cancer cells was not identified to be associated with overall survival (P=0.52). However, patients with high CHST15 expression in the stroma exhibited worse overall survival compared with patients with low CHST15 expression (P=0.02). CHST15 expression in the stroma exhibited a positive association with that in cancer cells (P=0.01). High CHST15 expression in the stroma group was associated with a higher incidence of immature fibrosis (P=0.02) compared with mature fibrosis. CHST15 expression in cancer cells was associated with Union for International Cancer Control stage (P=0.02) and invasive front. Age and sex were not associated with CHST15 expression. The present study revealed that overexpression of CHST15 in stroma was associated with worse overall survival and immature fibrosis. Overexpression of CHST15 in cancer cells was associated with tumor stage. These results suggested that targeting therapy for CHST15 may be useful for stroma fibroblasts and cancer cells.

Evaluation of the feasibility of intrapancreatic delivery of drug-loaded microparticles via EUS-guided fine needle injection using a swine model.

Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer

Carbohydrate sulfotransferase 15 (CHST15) promotes tumor growth and invasion and is considered to be an emergent therapeutic target for pancreatic cancer. The aim of this study wasto evaluate the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, the double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. Six patients with unresectable pancreatic cancer, treated at Tokyo Metropolitan Geriatric Hospital, were used in this open-labeled, investigator-initiated trial. A total of 16 mL STNM01 (250 nM) was injected into the tumor through EUS-FNI. The study's primary endpoint was safety, with a secondary endpoint of tumor response 4 weeks after the initial injection. Some patients received a series of infusions as extensions. The local expression of CHST15 and overall survival (OS) were also evaluated. There were no adverse events. The mean tumor diameter changed from 30.7 to 29.3mm 4 weeks after injection. Four patients exhibited necrosis of tumor in biopsy specimens. CHST15 was highly expressed at baseline, with 2 patients showing large reductions of CHST15 at week 4. The mean OS of these 2 patients was 15 months, whereas it was 5.7 months for the other 4 patients. EUS-FNI of STNM01 in pancreatic cancer is safe and feasible. The CHST15 reduction could predict tumor progression and OS. Injections of STNM01 during the beginning of treatment may reduce CHST15 and warrants further investigation.

EUS-Guided Fine Needle Injection Is Superior to Direct Endoscopic Injection of 2-octyl Cyanoacrylate for the Treatment of Gastric Variceal Bleeding

EUS-Guided Fine Needle Injection Is Superior to Direct Endoscopic Injection of 2-octyl Cyanoacrylate for the Treatment of Gastric Variceal Bleeding

Endoscopic Ultrasound-Guided Direct Intervention for Solid Pancreatic Tumors.

Development and use of linear-array echoendoscope and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) have made endoscopic ultrasound (EUS) more of an interventional procedure than a purely diagnostic procedure. This is a literature review of previously published clinical studies on EUS-guided direct intervention for solid pancreatic tumors, including EUS-guided fine needle injection (EUS-FNI) of antitumor agents, EUS-guided fiducial marker placement, EUS-guided brachytherapy and EUS-guided tumor ablation.

Endoscopic ultrasonography‐guided tumor ablation

Real-time guidance of needle advancement has transformed endoscopic ultrasound (EUS) from a diagnostic to an interventional procedure. EUS-guided fine-needle puncture has application in various interventional procedures (drainage of pseudocyst, biliary intervention, and injection of drugs). Celiac plexus or ganglion neurolysis for pain control is the major current EUS-guided fine-needle injection procedure. Feasibility and safety to accurately position needle devices and/or inject under real-time EUS imaging with precise delivery of interventional agent have expanded the use of EUS to ablate tumors. These include radiofrequency ablation, or delivery of fiducial markers, potential antitumor agents, or radioactive seeds, in the cancer mass. Minimally invasive EUS-guided antitumor therapy is primarily used for pancreatic cancer because of better anatomic access (vs other imaging modality) and the dismal prognosis (despite improvements in surgery and chemoradiation). Also, the response to parenteral chemotherapy in pancreatic cancer is poor because of suboptimal drug delivery resulting from hypovascularity and abundant desmoplasia. Other targets for EUS-guided tumor ablation are pancreatic neuroendocrine tumor and pancreatic cyst lesion, which are less aggressive and curable by resection. However, patients non-eligible for surgery may benefit from local EUS-guided ablation.

EUS-Guided Radiofrequency Ablation for the Management of Pancreatic Tumors

Endoscopic ultrasound (EUS) became an indispensable tool not only for the diagnosis but also for the management of pancreatic tumors. With the modification of EUS-guided fine needle aspiration (EUS-FNA) technology, EUS-guided fine needle injection (EUS-FNI), EUS-guided ablation and other interventions can be applied for various solid or cystic lesions in the pancreas. Local ablative modalities such as radiofrequency ablation (RFA) or photodynamic therapy (PDT) are also applied to pancreas in animal studies. RFA is primarily delivered to liver percutaneously or intraoperatively. EUS-guided RFA in a pig model proved that this modality can also be delivered to the pancreas trans-gastrically and cause well-demarcated coagulation zone. This modality, however, should be improved and refined to reduce the possible complications such as pancreatitis, gastric burn or perforation. Our group conducted EUS-guide RFA human trial for unresectable pancreatic cancer and showed technical feasibility and safety of EUS-RFA for pancreatic cancer. Further studies are required to see the long-term efficacy and survival benefit of this adjunctive modality for pancreatic cancer. EUS-RFA can be applied for the management of small pancreatic or peripancreatic tumors such as neuroendocrine tumor, adrenal tumor and small lymph node metastasis. Initial studies using EUS-RFA for the treatment of pancreatic neuroendocrine tumor showed very promising result without any serious complication. EUS-RFA seems to be very useful especially for the management of insulinoma. Since the patient presents with recurrent hypoglycemic attack, insulinoma is generally small in size at the time of diagnosis. It can be easily ablated under EUS-RFA and the functionality can be controlled very effectively. EUS-RFA is also applied for the management of cystic tumor of the pancreas. However, only animal study are reported using GB and cystic duct of pig and more studies are required before direct human application. In conclusion, EUS-guided approach offers minimally invasive access for delivery of local ablation modalities including EUS-RFA. This area is a continuously evolving field and many studies are currently undergoing. Although many of these approaches are still investigational but will play a key role in the treatment of benign and malignant pancreatic disease in the future.

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 well 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.

EUS-guided fine-needle injection of gemcitabine for locally advanced and metastatic pancreatic cancer

Among the greatest hurdles to pancreatic cancer (PC) therapy is the limited tissue penetration of systemic chemotherapy because of tumor desmoplasia. The primary study aim was to determine the toxicity profile of EUS-guided fine-needle injection (EUS-FNI) with gemcitabine. Secondary endpoints included the ability to disease downstage leading to an R0 resection and overall survival (OS) at 6 months, 12 months, and 5 years after therapy. In a prospective study from a tertiary referral center, gemcitabine (38 mg/mL) EUS-FNI was performed in patients with PC before conventional therapy. Initial and delayed adverse events (AEs) were assessed within 72 hours and 4 to 14 days after EUS-FNI, respectively. Patients were followed for≥5 years or until death. Thirty-six patients with stage II (n= 3), stage III (n= 20), or stage IV (n= 13) disease underwent gemcitabine EUS-FNI with 2.5 mL (.7-7.0 mg) total volume of injectate per patient. There were no initial or delayed AEs reported. Thirty-five patients (97.2%) were deceased at the time of analysis with a median 10.3 months of follow-up (range, 3.1-63.9). OS at 6 months and 12 months was 78% and 44%, respectively. The median OS was 10.4 months (range, 2.7-68). Among patients with stage III unresectable disease, 4 (20%) were downstaged and underwent an R0 resection. Our study suggests the feasibility, safety, and potential efficacy of gemcitabine EUS-FNI for PC. Additional data are needed to verify these observations and to determine the potential role relative to conventional multimodality therapy.

Immediate control of acute intracystic arterial hemorrhage after EUS-FNA by EUS-guided fine-needle injection

Immediate control of acute intracystic arterial hemorrhage after EUS-FNA by EUS-guided fine-needle injection

Mo1485 Comparison of Direct Endoscopic Injection (DEI) and EUS-Guided Fine Needle Injection (EUS-FNI) of 2-Octyl-Cyanoacrylate for Treatment of Gastric Varices

Mo1485 Comparison of Direct Endoscopic Injection (DEI) and EUS-Guided Fine Needle Injection (EUS-FNI) of 2-Octyl-Cyanoacrylate for Treatment of Gastric Varices

Mo1486 The Diagnostic Utility of Endoscopic Ultrasonography in Assessing the Depth of Tumor Invasion in Early Gastric Cancer

Mo1486 The Diagnostic Utility of Endoscopic Ultrasonography in Assessing the Depth of Tumor Invasion in Early Gastric Cancer

Local Chemotherapy for Pancreatic Cancer: Potential of Injectable Drug-Loaded Microparticles

Introduction: A key limitation of systemic delivery of chemotherapy in pancreatic adenocarcinoma (PDAC) is poor drug penetrance to the tumor due to the surrounding desmoplastic reaction. Systemic side effects also interfere with treatment continuity. These can be circumvented with a local delivery method via endoscopic ultrasound (EUS) fine needle injection. Poly(lactic-co-glycolic acid) (PLGA) is an FDA-approved polymer that can be utilized to create spherical microparticles (MPs) containing encapsulated chemotherapy that is slowly eluted with particle degradation. Methods: Local delivery of gemcitabine encapsulated within MPs (GMPs) to the the pancreas was previously explored by our lab in a 3-phase experiment. In phase I, blank MPs were injected into mouse pancreata to assess for adverse effects from the polymer and none were noted. In phase II, GMPs were injected into pancreatic tumors grown in nude mice. Injected tumors showed evidence of apoptosis compared to control pancreatic tumors. In Phase III, EUS-guided fine needle injection of GMPs into the porcine pancreas was performed. Survival was assessed for 14 days. GMPs were not localized in pancreatic tissue, calling into question if GMPs entered pancreatic tissue upon injection. This study evaluates if MPs containing fluorescently labelled protein can be localized in porcine pancreatic tissue after direct needle injection. We also present a methodology of simultaneous fluorescent labeling of PLGA and encapsulation of gemcitabine. Pancreata were harvested from pigs within 1 hour of euthanasia and placed in PBS for transport. MPs were injected into the pancreas aiming to approximate EUS conditions. Results: The tissue was H&E stained for light microscope visualization and MPs were visualized in the parenchyma and within interlobular septae. MPs were not visualized in control sections of porcine pancreatic tissue. Albumin-fluorescein isothiocyanate (BSA-FITC) was encapsulated in MPs and the injection experiments were repeated to confirm localization. Conclusion: This provided preliminary evidence that MPs enter the pancreatic tissue after injection and can be visualized. Thereafter, BSA-FITC was covalently bonded to the PLGA polymer allowing concurrent fluorescence and gemcitabine encapsulation. Visualization of the MPs in the porcine pancreas is rationale for repeating EUS fine needle injection into the pig pancreas, with the goal of developing a versatile and practical methodology for localized chemotherapy delivery to human pancreatic tumors.

Utility of endoscopic ultrasound in patients with portal hypertension.

Endoscopic ultrasound (EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate (Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors and analysis of free abdominal fluid. Using specialized EUS-guided needle biopsy, a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease. EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics, and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt.

Endoscopic Ultrasound-Guided Treatment beyond Drainage: Hemostasis, Anastomosis, and Others.

Since the introduction of endoscopic ultrasound (EUS) in the 1990s, it has evolved from a primarily diagnostic modality into an instrument that can be used in various therapeutic interventions. EUS-guided fine-needle injection was initially described for celiac plexus neurolysis. By using the fundamentals of this method, drainage techniques emerged for the biliary and pancreatic ducts, fluid collections, and abscesses. More recently, EUS has been used for ablative techniques and injection therapies for patients with for gastrointestinal malignancies. As the search for minimally invasive techniques continued, EUS-guided hemostasis methods have also been described. The technical advances in EUS-guided therapies may appear to be limitless; however, in many instances, these procedures have been described only in small case series. More data are required to determine the efficacy and safety of these techniques, and new accessories will be needed to facilitate their implementation into practice.

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 modality may 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.

Tumors and new endoscopic ultrasound-guided therapies

With the advent of linear echoendoscopes, endoscopic ultrasound (EUS) has become more operative and a new field of oncological application has been opened up. From tumor staging to tissue acquisition under EUS-guided fine-needle aspiration, new operative procedures have been developed on the principle of the EUS-guided puncture. A hybrid probe combining radiofrequency with cryotechnology is now available, to be passed through the operative channel of the echoendoscope into the tumor to create an area of ablation. EUS-guided fine-needle injection is emerging as a method to deliver anti-tumoral agents inside the tumor. Ethanol lavage, with or without paclitaxel, has been proposed for the treatment of cystic tumors in non-resectable cases and complete resolution has been recorded in up to 70%-80%. Many other chemical or biological agents have been investigated for the treatment of pancreatic adenocarcinoma: activated allogenic lymphocyte culture (Cytoimplant), a replication-deficient adenovirus vector carrying the tumor necrosis factor-α gene, or an oncolytic attenuated adenovirus (ONYX-015). The potential advantage of treatment under EUS control is the real-time imaging guidance into a deep target like the pancreas which is extremely difficult to reach by a percutaneous approach. To date there are no randomized controlled trials to confirm the real clinical benefits of these treatments compared to standard therapy so it seems wise to reserve them only for experimental protocols approved by ethics committees.