Since the development of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the early 1990s, its application has been extended to various diseases. For pancreatic cancer, EUS-FNA can obtain specimens from the tumor itself with fewer complications than other methods. Interventional EUS enables various therapeutic options: local ablation, brachytherapy, placement of fiducial markers for radiotherapy, and direct injection of antitumor agents into cancer. This paper will focus on EUS-guided oncologic therapy for pancreatic cancer. 1. Introduction Since endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was first utilized in clinical practice in the early 1990s, it has become a widely acceptable diagnostic procedure in gastrointestinal and pancreaticobiliary lesions [1]. Recently, its applications have been extended to therapeutic purposes for various diseases, including pancreatic cancer [2–4]. Pancreatic ductal adenocarcinoma is one of the most difficult tumors to treat, and patients with this disease have a poor prognosis. Only 15 to 20% of patients have resectable disease at diagnosis; approximately 40% have metastatic disease, and another 30 to 40% have locally advanced unresectable tumors. Despite the tremendous efforts of researchers and clinicians, the 5-year survival of patients with unresectable pancreatic cancer is still <5% [5]. To improve this dismal prognosis, endoscopic therapy (local therapy alone or in combination with systemic therapy) is considered as one option for such advanced cancers. The conventional approach is percutaneous image-guided delivery, for example, computed tomography (CT) guided, but this technique is cumbersome. EUS may be a suitable procedure for approaching the cancer itself via the gastrointestinal tract under real-time color Doppler, thus avoiding blood vessels or other organs. In this paper, we consider a variety of EUS-guided oncologic therapies for pancreatic cancer. 2. EUS-Guided Ablation Even though pancreatic cancer is considered to be a systemic disease, local ablation therapy has the potential to reduce tumor volume, thereby improving patients’ symptoms and prognosis. 2.1. Photodynamic Therapy Photodynamic therapy (PDT) provides localized tissue ablation through the use of an appropriate photosensitizer and light exposure. Photosensitizers (e.g., meso-tetra(hydroxyphenyl)chlorin, porfimer sodium, and verteporfin), which have unique characteristics and accumulate more in tumors than in normal tissue, are usually injected intravenously before the procedure. Light is generated with small
References
[1]
P. Vilmann, G. K. Jacobsen, F. W. Henriksen, and S. Hancke, “Endoscopic ultrasonography with guided fine needle aspiration biopsy in pancreatic disease,” Gastrointestinal Endoscopy, vol. 38, no. 2, pp. 172–173, 1992.
[2]
K. J. Chang and A. Irisawa, “EUS 2008 Working Group document: evaluation of EUS-guided injection therapy for tumors,” Gastrointestinal Endoscopy, vol. 69, no. 2, supplement, pp. S54–S58, 2009.
[3]
D. W. Seo, “EUS-guided antitumor therapy for pancreatic tumors,” Gut and Liver, vol. 4, supplement 1, pp. S76–S81, 2010.
[4]
K. Hara, K. Yamao, N. Mizuno et al., “Interventional endoscopic ultrasonography for pancreatic cancer,” World Journal of Clinical Oncology, vol. 2, no. 2, pp. 108–114, 2011.
[5]
S. F. Sener, A. Fremgen, H. R. Menck, and D. P. Winchester, “Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database,” Journal of the American College of Surgeons, vol. 189, no. 1, pp. 1–7, 1999.
[6]
J. Regula, A. J. MacRobert, A. Gorchein et al., “Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX—a pilot study,” Gut, vol. 36, no. 1, pp. 67–75, 1995.
[7]
B. F. Overholt, M. Panjehpour, E. Tefftellar, and M. Rose, “Photodynamic therapy for treatment of early adenocarcinoma in Barrett's esophagus,” Gastrointestinal Endoscopy, vol. 39, no. 1, pp. 73–76, 1993.
[8]
S. G. Bown, A. Z. Rogowska, D. E. Whitelaw et al., “Photodynamic therapy for cancer of the pancreas,” Gut, vol. 50, no. 4, pp. 549–557, 2002.
[9]
H. H. Chan, N. S. Nishioka, M. Mino et al., “EUS-guided photodynamic therapy of the pancreas: a pilot study,” Gastrointestinal Endoscopy, vol. 59, no. 1, pp. 95–99, 2004.
[10]
T. E. Yusuf, K. Matthes, and W. R. Brugge, “EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video),” Gastrointestinal Endoscopy, vol. 67, no. 6, pp. 957–961, 2008.
[11]
S. N. Goldberg, S. Mallery, G. S. Gazelle, and W. R. Brugge, “EUS-guided radiofrequency ablation in the pancreas: results in a porcine model,” Gastrointestinal Endoscopy, vol. 50, no. 3, pp. 392–401, 1999.
[12]
S. Carrara, P. G. Arcidiacono, L. Albarello et al., “Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study,” Endoscopy, vol. 40, no. 4, pp. 321–326, 2008.
[13]
S. Carrara, P. G. Arcidiacono, L. Albarello et al., “Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study,” Endoscopy, vol. 40, no. 9, pp. 759–763, 2008.
[14]
F. Di Matteo, M. Martino, R. Rea, et al., “EUS-guided Nd:YAG laser ablation of normal pancreatic tissue: a pilot study in a pig model,” Gastrointestinal Endoscopy, vol. 72, no. 2, pp. 358–363, 2010.
[15]
J. Kim, D. J. Chung, S. E. Jung, S. H. Cho, S.-T. Hahn, and J. M. Lee, “Therapeutic effect of high-intensity focused ultrasound combined with transarterial chemoembolisation for hepatocellular carcinoma <5？cm: comparison with transarterial chemoembolisation monotherapy—preliminary observations,” British Journal of Radiology, vol. 85, no. 1018, pp. e940–e946, 2012.
[16]
T. Leslie, R. Ritchie, R. Illing et al., “High-intensity focused ultrasound treatment of liver tumours: post-treatment MRI correlates well with intra-operative estimates of treatment volume,” British Journal of Radiology, vol. 85, no. 1018, pp. 1363–1370, 2012.
[17]
J. Hwang, N. Farr, K. Morrison et al., “Development of ana EUS-guided high-intensity focused ultrasound endoscope,” Gastrointestinal Endoscopy, vol. 73, no. 4S, p. AB155, 2011.
[18]
W. Zhongmin, L. Yu, L. Fenju, C. Kemin, and H. Gang, “Clinical efficacy of CT-guided iodine-125 seed implantation therapy in patients with advanced pancreatic cancer,” European Radiology, vol. 20, no. 7, pp. 1786–1791, 2010.
[19]
K. Kishi, T. Sonomura, S. Shirai et al., “Brachytherapy reirradiation with hyaluronate gel injection of paraaortic lymphnode metastasis of pancreatic cancer: paravertebral approach—a technical report with a case,” Journal of Radiation Research, vol. 52, no. 6, pp. 840–844, 2011.
[20]
S. Sun, L. Qingjie, G. Qiyong, W. Mengchun, Q. Bo, and X. Hong, “EUS-guided interstitial brachytherapy of the pancreas: a feasibility study,” Gastrointestinal Endoscopy, vol. 62, no. 5, pp. 775–779, 2005.
[21]
Z. Jin, Y. Du, Z. Li, Y. Jiang, J. Chen, and Y. Liu, “Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study,” Endoscopy, vol. 40, no. 4, pp. 314–320, 2008.
[22]
D. R. Xie, H. L. Liang, Y. Wang, S. S. Guo, and Q. Yang, “Meta-analysis on inoperable pancreatic cancer: a comparison between gemcitabine-based combination therapy and gemcitabine alone,” World Journal of Gastroenterology, vol. 12, no. 43, pp. 6973–6981, 2006.
[23]
A. C. Pishvaian, B. Collins, G. Gagnon, S. Ahlawat, and N. G. Haddad, “EUS-guided fiducial placement for CyberKnife radiotherapy of mediastinal and abdominal malignancies,” Gastrointestinal Endoscopy, vol. 64, no. 3, pp. 412–417, 2006.
[24]
S. Varadarajulu, J. M. Trevino, S. Shen, and R. Jacob, “The use of endoscopic ultrasound-guided gold markers in image-guided radiation therapy of pancreatic cancers: a case series,” Endoscopy, vol. 42, no. 5, pp. 423–425, 2010.
[25]
K. J. Chang, P. T. Nguyen, J. A. Thompson et al., “Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound—guided fine-needle injection in patients with advanced pancreatic carcinoma,” Cancer, vol. 88, no. 6, pp. 1325–1335, 2000.
[26]
Y. Akiyama, K. Maruyama, N. Nara et al., “Antitumor effects induced by dendritic cell-based immunotherapy against established pancreatic cancer in hamsters,” Cancer Letters, vol. 184, no. 1, pp. 37–47, 2002.
[27]
A. Irisawa, T. Takagi, M. Kanazawa et al., “Endoscopic ultrasound-guided fine-needle injection of immature dendritic cells into advanced pancreatic cancer refractory to gemcitabine: a pilot study,” Pancreas, vol. 35, no. 2, pp. 189–190, 2007.
[28]
Y. Hirooka, A. Itoh, H. Kawashima et al., “A combination therapy of gemcitabine with immunotherapy for patients with inoperable locally advanced pancreatic cancer,” Pancreas, vol. 38, no. 3, pp. e69–e74, 2009.
[29]
J. S. Yu, G. Liu, H. Ying, W. H. Yong, K. L. Black, and C. J. Wheeler, “Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma,” Cancer Research, vol. 64, no. 14, pp. 4973–4979, 2004.
[30]
S. Mulvihill, R. Warren, A. Venook et al., “Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial,” Gene Therapy, vol. 8, no. 4, pp. 308–315, 2001.
[31]
J. R. Hecht, R. Bedford, J. L. Abbruzzese et al., “A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma,” Clinical Cancer Research, vol. 9, no. 2, pp. 555–561, 2003.
[32]
A. Sharma, S. Mani, N. Hanna et al., “An open-label, phase I, dose-escalation study of tumor necrosis factor-α (TNFerade biologic) gene transfer with radiation therapy for locally advanced, recurrent, or metastatic solid tumors,” Human Gene Therapy, vol. 12, no. 9, pp. 1109–1131, 2001.
[33]
N. Senzer, S. Mani, A. Rosemurgy et al., “TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors,” Journal of Clinical Oncology, vol. 22, no. 4, pp. 592–601, 2004.
[34]
J. R. Hecht, J. J. Farrell, N. Senzer et al., “EUS or percutaneously guided intratumoral TNFerade biologic with 5-fluorouracil and radiotherapy for first-line treatment of locally advanced pancreatic cancer: a phase I/II study,” Gastrointestinal Endoscopy, vol. 75, no. 2, pp. 332–338, 2012.
