Effective new membrane for preventing postthoracotomy pleural adhesion by surface water induction technology

RESEARCH ARTICLE Effective new membrane for preventing postthoracotomy pleural adhesion by surface water induction technology Akiko Uemura1☯*, Mary Nakata1, Seijirow Goya1, Toshiharu Fukayama2, Ryou Tanaka1☯* 1 Tokyo University of Agriculture and Technology Animal Medical Center, Fuchu-shi, Tokyo, Japan, 2 National Cerebral and Cardiovascular Center, Suita, Osaka, Japan a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 ☯ These authors contributed equally to this work. * (AU); (RT) Abstract Background OPEN ACCESS Citation: Uemura A, Nakata M, Goya S, Fukayama T, Tanaka R (2017) Effective new membrane for preventing postthoracotomy pleural adhesion by surface water induction technology. PLoS ONE 12 (6): e0179815. https://doi.org/10.1371/journal. pone.0179815 Editor: Fan Yang, Peking University People’s Hospital, CHINA Received: August 16, 2016 Accepted: June 5, 2017 Published: June 27, 2017 Copyright: © 2017 Uemura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This research was funded by the Japan Science and Technology Agency (National Research and Development Agency); however, the sponsor played no role in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Therefore, the authors have declared that no competing interests exist. After thoracic surgery, adhesions between the pleura can cause substantial complications. This study investigated the effectiveness of a novel membrane utilizing surface water induction technology to prevent adhesions. Methods Eight beagles were divided into an experimental group (five males) and a control group (three females). The experimental group underwent thoracotomy on both the left and right sides of the chest. Both sides received the membrane, and the membrane on one side was glued to the pleura using tissue adhesive. The control group underwent thoracotomy only on the left side. Two weeks postoperatively, all dogs were sacrificed and adhesions were evaluated macroscopically and microscopically. Results Severe adhesion was seen between the parietal and visceral pleura in all control dogs, whereas the experimental group showed minor adhesion in only one dog on one side. Conclusions Our novel anti-adhesive membrane appeared highly effective in preventing postthoracotomy pleural adhesions. Introduction Postoperative adhesions occur at a high rate following surgical operations. In thoracic surgery, these adhesions prevent normal re-expansion of the lungs and thus interfere with respiratory function [1], as well as protracting the time until subsequent surgery can be performed, PLOS ONE | https://doi.org/10.1371/journal.pone.0179815 June 27, 2017 1 / 12 New membrane effective for preventing postthoracotomy pleural adhesion in dogs Competing interests: This study was carried out as a collaborative development project contracted by the Japan Science and Technology Agency as recommissioned research for a membrane utilizing surface water induction technology to prevent pleural adhesions. This does not alter our adherence to PLOS ONE policies on sharing data and materials. increasing the risk of hemorrhage, restricting the field of view, and damaging pulmonary blood vessels [2–4]. In Japan, a total of 67,325 cardiovascular operations were performed in 2013, along with 75,306 general thoracic surgeries [5], compared with 903,813 abdominal operations (based on the 2013 Diagnosis Procedure Combination data distributed by the Ministry of Health, Labour and Welfare). Preventing postoperative adhesions has long been the subject of research [6–9], and a membrane for preventing abdominal postoperative adhesions has already been developed and commercialized under the brand name Seprafilm1 (Kaken Pharmaceutical, Tokyo, Japan) [10, 11]. Japanese sales of Seprafilm1 in FY2014 exceeded about 95 million US dollars (Kaken Pharmaceutical). Various studies are addressing the great need for materials to prevent postoperative pleural adhesions, but no product has yet been brought to market. This study investigated the effectiveness of a novel adhesion-preventing membrane that utilizes surface water induction technology to prevent adhesions following thoracic surgery. In a previous study utilizing this principle, Noishiki and Shintani reported that this membrane is more effective than Seprafilm1 in preventing postthoracotomy pleural adhesions in dogs [12]. However, according to that study [12], although the membrane was highly effective in preventing adhesions in the immediate vicinity, severe adhesions formed at other locations. The present study employed hyaluronic acid, which has a long history as a highly hydrated and safe pharmaceutical, instead of the glycerin used by Noishiki and Shintani [12]. Our novel adhesion-preventing membrane is stored under refrigeration in the form of a dried sheet. After immersion in physiological saline, the membrane can be simply placed at the desired location after thoracotomy, and does not require any special reagents or equipment for either storage or use. Recent studies have used aldehyde dextran and ε-poly (L-lysine) powder (D-L powder) [13], cross-linked poly(gamma-glutamic acid) powder (XL powder) [14], and Prevadh1 polyethylene glycol-containing film [15] as materials for preventing postoperative pleural adhesions. D-L powder successfully reduced the length of adhesions compared with a control group, but did not prevent them altogether. Similarly, although XL powder reduced adhesion scores between the lungs and pleura, adhesions still occurred. Prevadh1 polyethylene glycolcontaining film has been found to be highly effective in preventing adhesions, but these results were obtained from the small pleural cavities of rats, and no data are available regarding efficacy in larger animals. Seprafilm1 has been found to exert significant anti-adhesion effects in pediatric cardiac surgery [16] and during thoracotomy in rats [17], but has been shown to be less effective than surface water induction technology in preventing postoperative pleural adhesions [12]. None of the anti-adhesive materials developed to date have successfully prevented the formation of postoperative pleural adhesions or have been brought into actual clinical use. This study reports the implantation of our novel anti-adhesion membrane during thoracotomy in dogs. After two weeks, adhesions were evaluated by macroscopic and histopathological examinations. We also verified the ease of membrane handling during surgery. Materials and methods Experimental operations were carried out in accordance with the Regulations on Animal Experiments of Toky (...truncated)