Therapeutic Eus 2008


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A recen t summary of therapeutic EUS

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  • Therapeutic Eus 2008

    1. 1. Interventional EUS William R. Brugge, MD Massachusetts General Hospital Boston, MA USA
    2. 2. Therapeutic EUS Modes of Approach <ul><li>Drainage </li></ul><ul><ul><li>Pseudocysts </li></ul></ul><ul><ul><li>Phlegmons </li></ul></ul><ul><ul><li>Abscesses </li></ul></ul><ul><li>Injection </li></ul><ul><ul><li>Ethanol </li></ul></ul><ul><ul><li>Gene therapy </li></ul></ul><ul><ul><li>Chemotherapeutic agents </li></ul></ul><ul><li>Delivery </li></ul><ul><ul><li>Heat </li></ul></ul><ul><ul><li>Cold </li></ul></ul><ul><ul><li>Brachytherapy </li></ul></ul><ul><ul><li>Devices </li></ul></ul>
    3. 3. End Viewing Echoendoscope
    4. 4. Moving towards Interventional EUS Therapeutic EUS scope
    5. 5. Drainage Therapy <ul><li>EUS guided biliary drainage </li></ul><ul><li>Transgastric access to intrahepatic ducts </li></ul><ul><li>Transduodenal access to extrahepatic bile duct </li></ul><ul><li>FNA guidewire placement </li></ul><ul><li>Stent placement </li></ul>
    6. 6. EUS Guided Biliary Drainage <ul><li>8 pts (in 10 interventions) underwent this new biliary drainage procedure. The routes were transesophageal (n = 1), transgastric (n = 4), and transjejunal (n = 3, including a rendezvous technique with ERCP [n = 1]). </li></ul><ul><li>5 pts (62.5%) received a metal stent, and 3 (37.5%) had a plastic prosthesis (8.5-Fr double-pigtail). The technical success rate was 90% (9/10) and the clinical success rate was 88.9% (8/9). </li></ul>Will U, Thieme A, Fueldner F, Gerlach R, Wanzar I, Meyer F. Treatment of biliary obstruction in selected patients by endoscopic ultrasonography (EUS)-guided transluminal biliary drainage. Endoscopy. 2007 Apr;39(4):292-5. Epub 2007 Mar 15.
    7. 7. Principles of EUS-directed Pseudocyst Drainage <ul><li>Cautery access </li></ul><ul><li>Wire placement </li></ul><ul><li>Contrast injection </li></ul><ul><li>Site dilation </li></ul><ul><li>Stent placement </li></ul>Barthet M, Lamblin G, Gasmi M, Vitton V, Desjeux A, Grimaud JC. Clinical usefulness of a treatment algorithm for pancreatic pseudocysts. Gastrointest Endosc. 2008 Feb;67(2):245-52. Introducer Balloon dilation Pig Tail Stent
    8. 8. Pancreatic Pseudocyst Drainage: EUS vs EGD <ul><li>Thirty patients were randomized to undergo pseudocyst drainage by EUS (n = 15) or EGD (n = 15) over a 6-month period. </li></ul><ul><li>Pts (n = 14) randomized to an EUS underwent successful drainage (100%), the procedure was technically successful in only 5 of 15 patients (33%) randomized to an EGD </li></ul><ul><li>All 10 pts who failed drainage by EGD underwent successful drainage of the pseudocyst on a crossover to EUS. There was no significant difference in the rates of treatment success between EUS and EGD after stenting, either by intention-to-treat (ITT) analysis (100% vs 87%; P = .48) or as-treated analysis (95.8% vs 80%; P = .32). </li></ul><ul><li>Major procedure-related bleeding was encountered in 2 patients in whom drainage by EGD was attempted; one resulted in death and the other necessitated a blood transfusion. Technical success was significantly greater for EUS than EGD </li></ul>Varadarajulu S, Christein JD, Tamhane A, Drelichman ER, Wilcox CM. Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc. 2008 Jul 18. [Epub ahead of print]
    9. 9. Imaging of EUS-guided pseudocyst drainage
    10. 10. Injection Therapy (examples of drug delivery) <ul><li>Ethanol therapy </li></ul><ul><ul><li>Celiac neurolysis </li></ul></ul><ul><li>Ethanol for cyst ablation </li></ul><ul><li>Retroviral therapies </li></ul><ul><ul><li>Adenovirus </li></ul></ul><ul><li>Chemotherapeutic agents </li></ul><ul><li>Hemostatic agents </li></ul>
    11. 11. Celiac Neurolysis <ul><li>Retrogastric orientation </li></ul><ul><li>Localized injection into the celiac space </li></ul><ul><li>Bupivacaine and/or ethanol are commonly used agents </li></ul>needle Direct injection into ganglia Levy MJ, Topazian MD, Wiersema MJ, Clain JE, Rajan E, Wang KK, de la Mora JG, Gleeson FC, Pearson RK, Pelaez MC, Petersen BT, Vege SS, Chari ST. Initial evaluation of the efficacy and safety of endoscopic ultrasound-guided direct Ganglia neurolysis and block. Am J Gastroenterol. 2008 Jan;103(1):98-103. Epub 2007 Oct 26.
    12. 12. EUS-guided ethanol lavage pancreatic cystadenoma Cyst fluid epithelium cyst ↓ cyst fluid ↓ DNA, ↓ CEA Cell necrosis Denuded epithelium 80% ethanol
    13. 13. <ul><li>Technique </li></ul><ul><ul><li>Cyst aspiration </li></ul></ul><ul><ul><li>Evacuation of cyst </li></ul></ul><ul><ul><li>Cyst fluid for sample </li></ul></ul><ul><ul><li>Lavage of 80% ethanol </li></ul></ul><ul><ul><li>3-5 minutes </li></ul></ul><ul><ul><li>Evacuation cyst </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Pancreatitis </li></ul></ul><ul><ul><li>Complex cystic lesion </li></ul></ul><ul><ul><li>Evidence of malignancy </li></ul></ul>Principles of Ethanol Lavage Saline Lavage Ethanol Lavage
    14. 14. Example of Ethanol Lavage
    15. 15. Monitoring of EUS Ethanol Ablation <ul><li>Ethanol injection caused focal necrosis </li></ul><ul><li>Subtle 1cm hypoechoic lesion </li></ul><ul><li>Avascular by Doppler </li></ul><ul><li>i.v. injection of microspheres enhanced the normal pancreatic parenchyma </li></ul><ul><li>Contrast-enhanced EUS with microspheres improves visualization </li></ul>Giday SA, Magno P, Gabrielson KL, Buscaglia JM, Canto MI, Ko CW, Clarke JO, Kalloo AN, Jagannath SB, Shin EJ, Kantsevoy SV. The utility of contrast-enhanced endoscopic ultrasound in monitoring ethanol-induced pancreatic tissue ablation: a pilot study in a porcine model. Endoscopy. 2007 Jun;39(6):525-9.
    16. 16. Ethanol Ablation of Pancreatic Neuroendocrine Tumor (NET) Enhancing 1cm mass Before After ethanol injection Ethanol-ablated NET Jürgensen C, Schuppan D, Neser F, Ernstberger J, Junghans U, Stölzel U. EUS-guided alcohol ablation of an insulinoma. Gastrointest Endosc. 2006 Jun;63(7):1059-62.
    17. 17. EUS-Guided Injection of Chemotherapy <ul><li>OncoGel is a novel depot formulation of paclitaxel designed for intralesional injection with a sustained paclitaxel delivery over approximately 6 weeks </li></ul><ul><li>OncoGel was injected into 18 superficially accessible advanced solid cancerous lesions among 16 adult patients for whom no curative therapy </li></ul><ul><li>OncoGel injections were generally well tolerated. There was one report of grade 3 injection site pain. </li></ul><ul><li>Systemic levels of paclitaxel were detectable only in 3.3% of the samples analyzed (range: 0.53–0.71 ng/ml). </li></ul><ul><li>stable disease was noted among 6/14 patients and progressive disease among 8 patients. </li></ul>Vukelja SJ, Anthony SP, Arseneau JC, Berman BS, Cunningham CC, Nemunaitis JJ, Samlowski WE, Fowers KD. Phase 1 study of escalating-dose OncoGel (ReGel/paclitaxel) depot injection, a controlled-release formulation of paclitaxel, for local management of superficial solid tumor lesions. Anticancer Drugs. 2007 Mar;18(3):283-9.
    18. 18. EUS-Guided OncoGel Injection Matthes K, Mino-Kenudson M, Sahani DV, Holalkere N, Fowers KD, Rathi R, Brugge WR. EUS-guided injection of paclitaxel (OncoGel) provides therapeutic drug concentrations in the porcine pancreas (with video). Gastrointest Endosc. 2007 Mar;65(3):448-53.
    19. 19. EUS-Guided Oncogel Injection Matthes K, Mino-Kenudson M, Sahani DV, Holalkere N, Fowers KD, Rathi R, Brugge WR. EUS-guided injection of paclitaxel (OncoGel) provides therapeutic drug concentrations in the porcine pancreas (with video). Gastrointest Endosc. 2007 Mar;65(3):448-53. <ul><li>Therapeutic concentrations of Taxol </li></ul><ul><li>Diffuse into normal tissue </li></ul><ul><li>2-3cm area of therapeutic levels </li></ul>
    20. 20. Ethanol-Taxol Lavage <ul><li>Taxol inhibits formation of cysts in ADPKD </li></ul><ul><li>14 Patients with pancreatic cystic lesions (3cm) </li></ul><ul><li>EUS guided lavage of 88% ethanol </li></ul><ul><li>EUS guided injection of Taxol 3 mg/ml </li></ul><ul><li>11/14 resolution of cyst </li></ul><ul><li>2/14 partial resolution of cyst </li></ul>Oh HC, Seo DW, Lee TY, Kim JY, Lee SS, Lee SK, Kim MH. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc. 2008 Apr;67(4):636-42. Courtesy of Dr .Seo
    21. 21. EUS-Guided Brachytherapy of the Pancreas <ul><li>Investigation of the feasibility and safety of EUS guided brachytherapy </li></ul><ul><li>Modified 18 gauge needle </li></ul><ul><li>Radioactive seeds implanted into pig pancreas </li></ul><ul><li>Animal monitored for 14 days </li></ul><ul><li>Pancreatic tissue changes: necrosis and fibrosis </li></ul>Sun S, Xu H, Xin J, et al. Endoscopic ultrasound-guided interstitial brachytherapy of unresectable pancreatic cancer: results of a pilot trial. Endoscopy 2006; 38: 399-403.
    22. 22. EUS-Guided Brachytherapy <ul><li>22 pts were successfully implanted : ave 10 seeds and a maximum of 30 seeds per procedure. Partial remission was achieved in three cases (13.6 %). </li></ul><ul><ul><li>EUS19 ga Needle Placement </li></ul></ul>Seeds on Xray 125 Iodine Pain relief Survival curve Jin Z, Du Y, Li Z, Jiang Y, Chen J, Liu Y. Endoscopic ultrasonography guided interstitial implantation of iodine 125 seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study Endoscopy Feb 19 2008
    23. 23. Radio-frequency Ablation RFA generator EUS RF needle catheter FNA needle with RFA catheter <ul><li>Gastrointest Endosc. 1999 Sep;50(3):392-401 </li></ul><ul><ul><li>EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. </li></ul></ul><ul><ul><li>Goldberg SN, Mallery S, Gazelle GS, Brugge WR. </li></ul></ul>
    24. 24. RFA of the Pancreas Gross image of pancreas After RFA : note sharp border CT scan of RFA lesion In pancreas, 2 weeks after RFA. Histology of RFA P: intact panc C : dead tissue
    25. 25. Cryo-Therm Ablation of the Pancreas <ul><li>Flexible bipolar probe--RFA energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) </li></ul><ul><li>Application time range was 120 - 900 seconds in 14 pigs </li></ul><ul><li>Good correlation between RFA time and size of ablation </li></ul><ul><li>2/14 pigs showed histochemical pancreatitis, which was clinically overt in one. </li></ul><ul><li>Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. </li></ul><ul><li>EUS – guided RFA provides pancreatic ablation </li></ul>Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Campagnol M, Ambrosi A, Doglioni C, Testoni PA. Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study. Endoscopy. 2008 Apr;40(4):321-6. ERBE
    26. 26. Cryo-Therm Ablation Courtesy of Dr. Enderle Flexible fiber Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Neugebauer A, Campagnol M, Doglioni C, Testoni PA. 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. 2008 Aug 13. [Epub ahead of print]
    27. 27. PDT of the Pancreas Chan HH, Nishioka NS, Mino M, Lauwers GY, Puricelli WP, Collier KN, Brugge WR. Gastrointest Endosc. 2004 Jan;59(1):95-9. EUS-guided photodynamic therapy of the pancreas: a pilot study.
    28. 28. PDT of the Pancreas Yusuf TE, Matthes K, Brugge WR. EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video). Gastrointest Endosc. 2008 May;67(6):957-61. Epub 2008 Feb 21. <ul><li>Applications for PDT in the pancreas </li></ul><ul><ul><ul><li>Neuroendocrine tumors </li></ul></ul></ul><ul><ul><ul><li>Local ablation of adenocarcinoma </li></ul></ul></ul><ul><ul><ul><li>Intraductal papillary tumors </li></ul></ul></ul><ul><ul><ul><li>Cystic lesions </li></ul></ul></ul>CT Guided PDT
    29. 29. TNFerade ™ Biologic <ul><li>TNFerade is a second-generation (E1-, partial E3-, and E4-deleted) group C adenovector carrying the transgene encoding for TNF  </li></ul><ul><li>A radiation-inducible promoter (Egr-1) is incorporated in the construct to optimize spatial and temporal gene expression following ionizing radiation </li></ul>Chang KJ, Lee JG, Holcombe RF, Kuo J, Muthusamy R, Wu ML. Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol. 2008 Feb;5(2):107-11.
    30. 30.           Survival of Pancreatic Cancer Patients Treated with TNFerade ™ Biologic , by Dose 4x10 9 PU 4x10 10 PU 4x10 11 PU 1x10 12 PU 0.00 0.25 0.50 0.75 1.00 Months since start of treatment 0 3 6 9 12 15 18 21 24 27 30 33 36 Probability Farrell et al. DDW 2006 10.9 18% 8.4 11.2 8.8 6.6 Median 34% 5% 0% 18-month rate 15.2 8.8 8.0 Mean
    31. 31. EUS guided Lymph Node Marker Injection <ul><li>Mediastinal and celiac lymph nodes were identified and injected with 1 mL tantalum suspension </li></ul><ul><li>Excellent opacification </li></ul><ul><li>Stable for 4 weeks </li></ul><ul><li>No signs of infection, inflammation, tissue damage, or necrosis. </li></ul>Gastrointest Endosc. 2007 Aug;66(2):387-92. EUS-guided implantation of radiopaque marker into mediastinal and celiac lymph nodes is safe and effective. Magno P, Giday SA, Gabrielson KL, Shin EJ, Buscaglia JM, Clarke JO, Ko CW, Jagannath SB, Canto MI, Sedrakyan G, Kantsevoy SV.
    32. 32. EUS guided Lymphadenectomy <ul><li>Selected nodes were punctured with a 19-gauge EUS needle. </li></ul><ul><li>Traction applied using needle and thread </li></ul><ul><li>In 2 of 6 examinations, the entire sequence of the procedure, node tagging, gastric-wall incision, lymphadenectomy, and wall closure was performed. No serious complication occurred. </li></ul>Gastrointest Endosc. 2006 Feb;63(2):302-6. Endoscopic transgastric lymphadenectomy by using EUS for selection and guidance. Fritscher-Ravens A, Mosse CA, Ikeda K, Swain P.
    33. 33. EUS guided hemostasis <ul><li>Five consecutive pts with gastric varices were enrolled </li></ul><ul><li>Injection of cyanoacrylate-lipiodol in gastric varices with 22-gauge needles by EUS guidance. </li></ul><ul><li>EUS-guided injection of the perforating veins by using cyanoacrylate-lipiodol was successful in eradicating gastric varices in the 5 patients </li></ul><ul><li>No recurrent bleeding or other complications during the study follow-up. </li></ul><ul><li>EUS-guided injection of cyanoacrylate at the level of the perforating veins in the treatment of gastric varices seems to be a safe, efficient, and accurate approach </li></ul>Romero-Castro R, Pellicer-Bautista FJ, Jimenez-Saenz M, Marcos-Sanchez F, Ortiz-Moyano C, Gomez-Parra M, Herrerias-Gutierrez JM. EUS-guided injection of cyanoacrylate in perforating feeding veins in gastric varices: results in 5 cases. Gastrointest Endosc. 2007 Aug;66(2):402-7.
    34. 34. Conclusions <ul><li>Interventional EUS </li></ul><ul><ul><li>Ductal access </li></ul></ul><ul><ul><li>Pseudocyst drainage </li></ul></ul><ul><ul><li>Tumor ablation </li></ul></ul>