title: Hyaluronic acid is a useful tool for intraoperative sentinel node detection in gastric cancer surgery.
abstract: BACKGROUND
  We assessed whether a mixture of hyaluronic acid (HA) and dye can facilitate dye-guided sentinel node (SN) mapping in gastric surgery. Although dye-guided, SN-navigated surgery is clinically applied for the treatment of early gastric cancer, there are still some practical problems. Because dyes are carried out from the SN within 20 to 30 minutes, it is sometimes difficult to detect SNs accurately, especially when they are located in a deep area in obese patients.
  
  
  METHODS
  Patent blue or ferumoxides, superparamagnetic iron nanocolloids, with or without HA, were injected into the gastrointestinal tract of the pig, and the time course of dye transfer through the lymphatic system of the pig mesentery was assessed.
  
  
  RESULTS
  When a mixture of HA and patent blue at a volume ratio of 1:4 was injected into the submucosal layer, the time to stain the SN did not differ from that with patent blue alone; however, HA markedly prolonged the time the blue dye was retained in the SN. Patent blue alone stained the efferent lymphatics of the SN and spread to other lymph nodes within 20 minutes after submucosal injection. At the same time point, in contrast, blue stain was restricted to a part of the SN, and the efferent lymphatics were not stained for 2 hours when patent blue was mixed with HA. When a mixture of HA and ferumoxides was used as the tracer, the ferumoxides were still observed in the mesenteric SN even at 2 days after injection. Iron staining showed that Fe was trapped primarily in cells in the peripheral sinus of the SN, suggesting that the iron nanoparticles were mostly incorporated by phagocytic macrophages in the SN within a few hours.
  
  
  CONCLUSIONS
  Our data indicate that a mixture with HA prolongs the stay of a dye tracer in the SN and thus enables easy and accurate detection of the SN. HA may be a useful tool to develop a more sophisticated SN mapping technique.
authors.affiliation: Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. kitayama-1su@h.u-tokyo.ac.jp <kitayama-1su@h.u-tokyo.ac.jp>
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Hironori
authors.initials: H
authors.lastname: Ishigami
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Soma
authors.forename: Hideyo
authors.initials: H
authors.lastname: Miyato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000493:pharmacokinetics; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans; D004338:Drug Combinations; D052203:Ferrosoferric Oxide; D006651:Histocytochemistry / Q000379:methods; D006820:Hyaluronic Acid; D007501:Iron / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000503:physiopathology; D008208:Lymphatic System / Q000378:metabolism; D058185:Magnetite Nanoparticles; D010087:Oxides / Q000493:pharmacokinetics; D010587:Phagocytosis; D021701:Sentinel Lymph Node Biopsy; D013194:Staining and Labeling; D013274:Stomach Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D013552:Swine; D013997:Time Factors
chemical_list: D004396:Coloring Agents; D003287:Contrast Media; D003911:Dextrans; D004338:Drug Combinations; D058185:Magnetite Nanoparticles; D010087:Oxides; D006820:Hyaluronic Acid; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide