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Transcript of Review Article Endoscopic Ultrasound-Guided Review Article Endoscopic Ultrasound-Guided Therapies in

  • Review Article Endoscopic Ultrasound-Guided Therapies in Pancreatic Neoplasms

    Dennis Yang and Christopher J. DiMaio

    Division of Gastroenterology, Mount Sinai Medical Center, New York, NY 10029, USA

    Correspondence should be addressed to Christopher J. DiMaio; christopher.dimaio@mssm.edu

    Received 29 August 2014; Revised 22 December 2014; Accepted 25 December 2014

    Academic Editor: Tadayuki Oshima

    Copyright Β© 2015 D. Yang and C. J. DiMaio. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Endoscopic ultrasound (EUS) has evolved from being primarily a diagnostic modality into an interventional endoscopic tool for the management of both benign and malignant gastrointestinal illnesses. EUS-guided therapy has garnered particular interest as a minimally invasive approach for the treatment of pancreatic cancer, a disease often complicated by its aggressive course and poor survival. The potential advantage of an EUS-guided approach revolves around real-time imaging for targeted therapy of a difficult to reach organ. In this review, we focus on EUS-guided therapies for pancreatic neoplasms.

    1. Introduction

    Since its introduction over 30 years ago, endoscopic ultra- sound (EUS) has evolved from being primarily a diagnostic tool into a therapeutic modality for various gastrointestinal diseases. This transition towards β€œinterventional EUS” has been facilitated by the advancement of curvilinear-array endoscopes and peripheral devices [1, 2]. EUS-guided fine- needle aspiration (EUS-FNA) is a well-established minimally invasive procedure that has been increasingly used for the investigation and staging of pancreatic neoplasms due to its favorable performance and safety profile when compared with other extracorporeal tissue acquisition techniques [3]. Intuitively, the ability to accurately and safely introduce a needle into a deeply located retroperitoneal organ (i.e., pancreas) serves as a vehicle for localized treatment. This is the basis for EUS-guided fine-needle injection (EUS-FNI) for pancreatic neoplasms: a safe, minimally invasive approach, with real-time imaging to selectively access deeply located targets and provide localized therapy. EUS-guided therapy may provide an important adjunctive treatment in patients with locally advanced, unresectable disease, or for those who are poor surgical candidates. Furthermore, the ability of EUS to accurately localize pancreatic lesions for tumor-marking may help guide systemic therapies and minimally-invasive parenchymal-sparing pancreatic surgery in select cases. In

    this review, we focus on advances of EUS-guided therapeutic approaches for pancreatic neoplasms.

    2. Pancreatic Adenocarcinoma

    Pancreatic ductal adenocarcinoma has a poor prognosis and represents the fourth leading cause of cancer-associated death in the United States. The disease is often advanced and unresectable (80%) at the time of diagnosis [4], limiting treatment options to systemic chemotherapy and/or radiation with considerable associated toxicities. EUS-FNI is a safe approach for the targeted delivery of therapeutic agents, which potentially facilitates direct intratumor therapy and possibly augments the effects of other established local and systemic therapies. Table 1 summarizes human studies on EUS-guided therapies for pancreatic adenocarcinoma.

    2.1. EUS-Guided Immunological Therapy

    2.1.1. Allogenic Mixed Lymphocyte Culture (Cytoimplant). In 2000, Chang and colleagues investigated the feasibility and safety of immunotherapy by EUS-FNI in patients with advanced pancreatic adenocarcinoma [5]. In this phase I clin- ical trial, an allogeneic mixed lymphocyte culture (cytoim- plant) was injected into the pancreatic tumor (𝑛 = 8) under EUS-guidance in a dose-escalating manner. The authors

    Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 731049, 12 pages http://dx.doi.org/10.1155/2015/731049

  • 2 BioMed Research International

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  • BioMed Research International 3

    theorized that the injected cytoimplant would potentially stimulate local immune effector cells and release of cytokines resulting in an immune-mediated tumor regression. There were two partial responses (>50% tumor reduction on imag- ing), one minor response (50%was seen in 2/21 (10%), stable disease in 8, and progressive disease in 11 patients. Median survival timewas 7.5months.Therewere two patients with duodenal perforations and two with sepsis prior to

    adopting a transgastric EUS-FNI approach and prophylactic antibiotics as part of the protocol.

    2.2.2. Selective Delivery of Tumor Necrosis Factor-𝛼 (TNF-𝛼). Tumor necrosis factor-𝛼 has been recognized for its onco- lytic potential through its effects on tumor vasculature and cytotoxicity [11]. TNFerade is an adenoviral vector containing a radiation-inducible Egr-1 promoter gene region upstream of the human TNF-𝛼 gene that, in theory, may selectively induce the antitumor activity of TNF-𝛼 in a specific target while minimizing its systemic toxicity. In 2012, Hecht et al. evaluated the effects of TNFerade combined with chemora- diotherapy on locally advanced pancreatic cancer in a phase I/II study [12]. TNFeradewas administered via EUS-guidance (𝑛 = 27) or percutaneously (𝑛 = 23) once a week for 5 weeks together with radiation and 5-fluorouracil daily. Maximum tolerated dose was set at 4 Γ— 1011 particle units/2mL after 3/9 patients developed dose-limiting toxicity in the 1 Γ— 1012 cohort. Complete response was seen in 1 (2%) patient and partial response in 3 (6%) patients, whereas 12 (24%) and 19 (38%) patients had stable and progressive disease, respect