Safety of Argon Plasma Coagulation for Hemostasis During Endoscopic Mucosal Resection Mitsuhiro Fujishiro, MD,* Naohisa Yahagi, MD,* Masanori Nakamura, MD,* Naomi Kakushima, MD,* Shinya Kodashima, MD,* Satoshi Ono, MD,* Katsuya Kobayashi, MD,* Takuhei Hashimoto, MD,* Nobutake Yamamichi, MD,* Ayako Tateishi, MD,* Yasuhito Shimizu, MD,w Masashi Oka, MD,w Masao Ichinose, MD,w and Masao Omata, MD* Abstract: Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR. Key Words: argon plasma coagulation, endoscopic mucosal resection, tissue damage, hemostasis (Surg Laparosc Endosc Percutan Tech 2006;16:137–140) E ndoscopic mucosal resection (EMR) is actively per- formed especially in Japan for the treatment of esophageal, gastric, and colorectal tumors. One of the major EMR complications is bleeding 1 and argon plasma coagulation (APC) has been applied, as well as hemoclips, injection therapy or other thermocoagulation techniques, to prevent or cope with bleeding. 2–7 Although APC is considered to be an innovative, effective and safe endoscopic tool for devitalization of tissue and hemo- stasis in the gastrointestinal tract, the data showing the safety of APC were obtained from the coagulation over the mucosal surface. 8 No study was performed showing the safety over the exposed submucosal layer, which situation was clinically experienced in hemostasis during/ after EMR. MATERIALS AND METHODS As an ex vivo study, porcine stomachs were used within 2 hours after resection. Before application of APC, mucosal defects imitating those during or immediately after EMR were made on the stomachs as followings: (1) Five milliliters of normal saline containing 0.0005% epinephrine and 0.005% indigo carmine was injected into the submucosal layer at separate sites of the stomachs, using a disposable syringe and a 23-gauge needle. (2) The elevated mucosal layer made by injection was resected roundly using scissors to make mucosal defects contain- ing the injected fluid with approximately 3 to 5 cm in the maximal diameter. EMR was usually performed by using a polypectomy snare and a high-frequency current, but scissors were used in this study because the size of resected area could be easily controlled and thermocoa- gulation for resection might influence tissue damage, which complicated the data analysis. The unit used was the standard APC equipment consisting of a high- frequency generator (Erbotom ICC 200), an automati- cally regulated argon source (APC 300), and a flexible APC applicator, 2.3 mm in diameter. All of them were products of ERBE Elektromedizin, Tu¨bingen, Germany. The power setting was 40 or 60 W and argon gas flow was 1 or 2 L/min, which was usually used for hemostasis in the clinical practice. Although the pulse duration needed for hemostasis was less than 5 seconds from our clinical experiences, pulse duration of 2, 4, 8, 20 seconds was tested to check the safety of APC. As separations of 2 mm or shorter between a probe and a tissue were necessary to produce a coagulation arc, 8 a jet of ionized argon plasma was radiated on the tissue from a separation distance of 2 mm at a 90-degree angle. As the controls, mucosal defects without submucosal injection, which were made by pealing the mucosa away from the remaining muscle layer by using a knife, were also examined in the same settings. After the coagulation was performed, the speci- mens were cut on the points of coagulation and fixed with formalin and embedded in paraffin. A histologic section was made from each block and stained with hematoxylin Copyright r 2006 by Lippincott Williams & Wilkins Received for publication May 13, 2005; accepted February 11, 2006. From the *Department of Gastroenterology, Graduate school of Medicine, University of Tokyo, Tokyo, Japan; and wSecond Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. Reprints: Mitsuhiro Fujishiro, MD, Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan (e-mail: mtfujish-kkr@umin.ac.jp). ORIGINAL ARTICLE Surg Laparosc Endosc Percutan Tech  Volume 16, Number 3, June 2006 137