Download PDF
Endosc Int Open 2016; 04(01): E1-E16
DOI: 10.1055/s-0034-1393079
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Solutions for submucosal injection in endoscopic resection: a systematic review and meta-analysis

Alexandre Oliveira Ferreira   *
1   Department of Gastroenterology, Hospital Beatriz Ângelo, Lisboa, Portugal
,
Joana Moleiro   *
2   Department of Gastroenterology, Instituto Português do Oncologia de Lisboa, Lisboa, Portugal
,
Joana Torres
1   Department of Gastroenterology, Hospital Beatriz Ângelo, Lisboa, Portugal
,
Mario Dinis-Ribeiro
3   Department of Gastroenterology, Instituto Português do Oncologia do Porto, Porto, Portugal
4   CIDES/CINTESIS, Faculty of Medicine – University of Porto, Porto, Portugal
› Author Affiliations
Further Information

Publication History

submitted: 06 December 2014

accepted after revision: 11 August 2015

Publication Date:
06 October 2015 (online)

Also available at
   Permissions and Reprints

Background and aims: Submucosal injection is standard practice in endoscopic mucosal resection of gastrointestinal lesions. Several solutions are used. Our aim was to systematically review their efficacy and safety.

Patients and methods: We performed a systematic review and meta-analysis using a random effects model of randomized controlled trials (RCTs) from MEDLINE. Studies in animal models were qualitatively assessed for efficacy and safety.

Results: In total, 54 studies were qualitatively assessed. Eleven RCTs were analyzed, two of which were on endoscopic submucosal dissection (ESD). The quantitative synthesis included nine RCTs on endoscopic mucosal resection (EMR), comprising 792 subjects and 793 lesions. Mean lesion size was 20.9 mm (range 8.5 – 46 mm). A total of 209 lesions were randomized to sodium hyaluronate (SH) vs normal saline (NS), 72 to 50 % dextrose (D50) vs NS, 82 to D50 vs SH, 43 to succinylated gelatin, 25 to hydroxyethyl starch and 36 to fibrinogen. In total, 385 were randomized to NS as controls. NS and SH are the best studied solutions and seem to be equally effective in achieving complete resection (OR 1.09; 95 %CI 0.82, 1.45). No solution was proven to be superior in complete resection rate, post-polypectomy bleeding or coagulation syndrome/perforation incidence. Many solutions have been tested in animal studies and most seem more effective for mucosal elevation than NS.

Conclusions: There are several solutions in clinical use and many more under research, but most are poorly studied. SH seems to be clinically equivalent to NS. There are no significant differences in post-polypectomy complications. Larger RCTs are needed to determine any small differences that may exist between solutions.

* These authors contributed equally to the study.


 

  • References

  • 1 Ferlay J, Shin HR, Bray F et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917
    CrossrefPubMedSearch in Google Scholar
  • 2 Zauber AG, Winawer SJ, O'Brien MJ et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. NEJM 2012; 366: 687-696
    CrossrefPubMedSearch in Google Scholar
  • 3 Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. NEJM 1993; 329: 1977-1981
    CrossrefPubMedSearch in Google Scholar
  • 4 Hartgrink HH, Jansen EP, van Grieken NC et al. Gastric cancer. Lancet 2009; 374: 477-490
    CrossrefPubMedSearch in Google Scholar
  • 5 Ajani JA, Bentrem DJ, Besh S et al. Gastric cancer, version 2. 2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 2013; 11: 531-546
    CrossrefPubMedSearch in Google Scholar
  • 6 Isomoto H, Shikuwa S, Yamaguchi N et al. Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study. Gut 2009; 58: 331-336
    CrossrefPubMedSearch in Google Scholar
  • 7 Choi KS, Jung HY, Choi KD et al. EMR versus gastrectomy for intramucosal gastric cancer: comparison of long-term outcomes. Gastrointest Endosc 2011; 73: 942-948
    CrossrefPubMedSearch in Google Scholar
  • 8 Rosenberg N. Submucosal saline wheal as safety factor in fulguration or rectal and sigmoidal polypi. AMA Arch Surg 1955; 70: 120-122
    CrossrefPubMedSearch in Google Scholar
  • 9 Deyhle P, Jenny S, Fumagalli I. [Endoscopic polypectomy in the proximal colon. A diagnostic, therapeutic (and preventive?) intervention]. Dtsch Med Wochenschr 1973; 98: 219-220
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Akiyama M, Ota M, Nakajima H et al. Endoscopic mucosal resection of gastric neoplasms using a ligating device. Gastrointest Endosc 1997; 45: 182-186
    CrossrefPubMedSearch in Google Scholar
  • 11 Inoue H, Takeshita K, Hori H et al. Endoscopic mucosal resection with a cap-fitted panendoscope for esophagus, stomach, and colon mucosal lesions. Gastrointest Endosc 1993; 39: 58-62
    CrossrefPubMedSearch in Google Scholar
  • 12 Kantsevoy SV, Adler DG, Conway JD et al. Endoscopic mucosal resection and endoscopic submucosal dissection. Gastrointest Endosc 2008; 68: 11-18
    CrossrefPubMedSearch in Google Scholar
  • 13 Moss A, Bourke MJ, Williams SJ et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011; 140: 1909-1918
    CrossrefPubMedSearch in Google Scholar
  • 14 Park YM, Cho E, Kang HY et al. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: a systematic review and metaanalysis. Surg Endosc 2011; 25: 2666-2677
    CrossrefPubMedSearch in Google Scholar
  • 15 Lian J, Chen S, Zhang Y et al. A meta-analysis of endoscopic submucosal dissection and EMR for early gastric cancer. Gastrointest Endosc 2012; 76: 763-770
    CrossrefPubMedSearch in Google Scholar
  • 16 Cao Y, Liao C, Tan A et al. Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy 2009; 41: 751-757
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Sumiyama K, Toyoizumi H, Ohya TR et al. A double-blind, block-randomized, placebo-controlled trial to identify the chemical assistance effect of mesna submucosal injection for gastric endoscopic submucosal dissection. Gastrointest Endosc 2014; 79: 756-764
    CrossrefPubMedSearch in Google Scholar
  • 18 Kim YD, Lee J, Cho JY et al. Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms. World J Gastroenterol 2013; 19: 3069-3076
    CrossrefPubMedSearch in Google Scholar
  • 19 Hurlstone DP, Fu KI, Brown SR et al. EMR using dextrose solution versus sodium hyaluronate for colorectal Paris type I and 0-II lesions: a randomized endoscopist-blinded study. Endoscopy 2008; 40: 110-114
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Yoshida N, Naito Y, Inada Y et al. Endoscopic mucosal resection with 0.13% hyaluronic acid solution for colorectal polyps less than 20 mm: a randomized controlled trial. J Gastroenterol Hepatol 2012; 27: 1377-1383
    CrossrefPubMedSearch in Google Scholar
  • 21 Kishihara T, Chino A, Uragami N et al. Usefulness of sodium hyaluronate solution in colorectal endoscopic mucosal resection. Dig Endosc 2012; 24: 348-352
    CrossrefPubMedSearch in Google Scholar
  • 22 Yamamoto H, Yahagi N, Oyama T et al. Usefulness and safety of 0.4% sodium hyaluronate solution as a submucosal fluid "cushion" in endoscopic resection for gastric neoplasms: a prospective multicenter trial. Gastrointest Endosc 2008; 67: 830-839
    CrossrefPubMedSearch in Google Scholar
  • 23 Katsinelos P, Kountouras J, Paroutoglou G et al. A comparative study of 50% dextrose and normal saline solution on their ability to create submucosal fluid cushions for endoscopic resection of sessile rectosigmoid polyps. Gastrointest Endosc 2008; 68: 692-698
    CrossrefPubMedSearch in Google Scholar
  • 24 Varadarajulu S, Tamhane A, Slaughter RL. Evaluation of dextrose 50% as a medium for injection-assisted polypectomy. Endoscopy 2006; 38: 907-912
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Lee SH, Park JH, do Park H et al. Clinical efficacy of EMR with submucosal injection of a fibrinogen mixture: a prospective randomized trial. Gastrointest Endosc 2006; 64: 691-696
    CrossrefPubMedSearch in Google Scholar
  • 26 Fasoulas K, Lazaraki G, Chatzimavroudis G et al. Endoscopic mucosal resection of giant laterally spreading tumors with submucosal injection of hydroxyethyl starch: comparative study with normal saline solution. Surg Laparosc Endosc Percutan Tech 2012; 22: 272-278
    CrossrefPubMedSearch in Google Scholar
  • 27 Moss A, Bourke MJ, Metz AJ. A randomized, double-blind trial of succinylated gelatin submucosal injection for endoscopic resection of large sessile polyps of the colon. Am J Gastroenterol 2010; 105: 2375-2382
    CrossrefPubMedSearch in Google Scholar
  • 28 Lee SH, Chung IK, Kim SJ et al. Comparison of postpolypectomy bleeding between epinephrine and saline submucosal injection for large colon polyps by conventional polypectomy: a prospective randomized, multicenter study. World J Gastroenterol 2007; 13: 2973-2977
    CrossrefPubMedSearch in Google Scholar
  • 29 Wen W, Shi C, Shi Y et al. A pilot animal and clinical study of autologous blood solution compared with normal saline for use as an endoscopic submucosal cushion. Exp Ther Med 2012; 4: 419-424
    PubMedSearch in Google Scholar
  • 30 Dobrowolski S, Dobosz M, Babicki A et al. Prophylactic submucosal saline-adrenaline injection in colonoscopic polypectomy: prospective randomized study. Surg Endosc 2004; 18: 990-993
    CrossrefPubMedSearch in Google Scholar
  • 31 Polymeros D, Kotsalidis G, Triantafyllou K et al. Comparative performance of novel solutions for submucosal injection in porcine stomachs: An ex vivo study. Dig Liver Dis 2010; 42: 226-229
    CrossrefPubMedSearch in Google Scholar
  • 32 Hyun JJ, Chun HR, Chun HJ et al. Comparison of the characteristics of submucosal injection solutions used in endoscopic mucosal resection. Scand J Gastroenterol 2006; 41: 488-492
    CrossrefPubMedSearch in Google Scholar
  • 33 Fujishiro M, Yahagi N, Kashimura K et al. Tissue damage of different submucosal injection solutions for EMR. Gastrointest Endosc 2005; 62: 933-942
    CrossrefPubMedSearch in Google Scholar
  • 34 Conio M, Rajan E, Sorbi D et al. Comparative performance in the porcine esophagus of different solutions used for submucosal injection. Gastrointest Endosc 2002; 56: 513-516
    CrossrefPubMedSearch in Google Scholar
  • 35 Fujishiro M, Yahagi N, Nakamura M et al. Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar. Gastrointest Endosc 2006; 63: 243-249
    CrossrefPubMedSearch in Google Scholar
  • 36 Sohn DK, Chang HJ, Choi HS et al. Does hyaluronic acid stimulate tumor growth after endoscopic mucosal resection?. J Gastroenterol Hepatol 2008; 23: 1204-1207
    CrossrefPubMedSearch in Google Scholar
  • 37 Matsui Y, Inomata M, Izumi K et al. Hyaluronic acid stimulates tumor-cell proliferation at wound sites. Gastrointest Endosc 2004; 60: 539-543
    CrossrefPubMedSearch in Google Scholar
  • 38 Eun SH, Cho JY, Jung IS et al. Effectiveness of sodium alginate as a submucosal injection material for endoscopic mucosal resection in animal. Gut Liver 2007; 1: 27-32
    CrossrefPubMedSearch in Google Scholar
  • 39 Akagi T, Yasuda K, Tajima M et al. Sodium alginate as an ideal submucosal injection material for endoscopic submucosal resection: preliminary experimental and clinical study. Gastrointest Endosc 2011; 74: 1026-1032
    Search in Google Scholar
  • 40 Kusano T, Etoh T, Akagi T et al. Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer. Dig Endosc 2014; 26: 638-645
    CrossrefPubMedSearch in Google Scholar
  • 41 Katsinelos P, Paroutoglou G, Beltsis A et al. Endoscopic mucosal resection of lateral spreading tumors of the colon using a novel solution. Surg Laparosc Endosc Percutan Tech 2006; 16: 73-77
    CrossrefPubMedSearch in Google Scholar
  • 42 Uraoka T, Fujii T, Saito Y et al. Effectiveness of glycerol as a submucosal injection for EMR. Gastrointest Endosc 2005; 61: 736-740
    CrossrefPubMedSearch in Google Scholar
  • 43 Yamasaki M, Kume K, Yoshikawa I et al. A novel method of endoscopic submucosal dissection with blunt abrasion by submucosal injection of sodium carboxymethylcellulose: an animal preliminary study. Gastrointest Endosc 2006; 64: 958-965
    CrossrefPubMedSearch in Google Scholar
  • 44 Kumano I, Ishihara M, Nakamura S et al. Endoscopic submucosal dissection for pig esophagus by using photocrosslinkable chitosan hydrogel as submucosal fluid cushion. Gastrointest Endosc 2012; 75: 841-848
    Search in Google Scholar
  • 45 Hayashi T, Matsuyama T, Hanada K et al. Usefulness of photocrosslinkable chitosan for endoscopic cancer treatment in alimentary tract. J Biomed Mater Res B Appl Biomater 2004; 71: 367-372
    PubMedSearch in Google Scholar
  • 46 Moss A, Bourke MJ, Kwan V et al. Succinylated gelatin substantially increases en bloc resection size in colonic EMR: a randomized, blinded trial in a porcine model. Gastrointest Endosc 2010; 71: 589-595
    CrossrefPubMedSearch in Google Scholar
  • 47 Sumiyama K, Tajiri H, Gostout CJ et al. Chemically assisted submucosal injection facilitates endoscopic submucosal dissection of gastric neoplasms. Endoscopy 2010; 42: 627-632
    Thieme ConnectPubMedSearch in Google Scholar
  • 48 von Renteln D, Dulai PS, Pohl H et al. Endoscopic submucosal dissection with a flexible Maryland dissector: randomized comparison of mesna and saline solution for submucosal injection (with videos). Gastrointest Endosc 2011; 74: 906-911
    CrossrefPubMedSearch in Google Scholar
  • 49 Giday SA, Magno P, Buscaglia JM et al. Is blood the ideal submucosal cushioning agent? A comparative study in a porcine model. Endoscopy 2006; 38: 1230-1234
    Thieme ConnectPubMedSearch in Google Scholar
  • 50 Sato T. A novel method of endoscopic mucosal resection assisted by submucosal injection of autologous blood (blood patch EMR). Dis Colon Rectum 2006; 49: 1636-1641
    CrossrefPubMedSearch in Google Scholar
  • 51 Al-Taie OH, Bauer Y, Dietrich CG et al. Efficacy of submucosal injection of different solutions inclusive blood components on mucosa elevation for endoscopic resection. Clin Exp Gastroenterol 2012; 5: 43-48
    PubMedSearch in Google Scholar
  • 52 Lee SH, Cho WY, Kim HJ et al. A new method of EMR: submucosal injection of a fibrinogen mixture. Gastrointest Endosc 2004; 59: 220-224
    CrossrefPubMedSearch in Google Scholar
  • 53 Fernandez-Esparrach G, Shaikh SN, Cohen A et al. Efficacy of a reverse-phase polymer as a submucosal injection solution for EMR: a comparative study (with video). Gastrointest Endosc 2009; 69: 1135-1139
    CrossrefPubMedSearch in Google Scholar
  • 54 Tran RT, Palmer M, Tang SJ et al. Injectable drug-eluting elastomeric polymer: a novel submucosal injection material. Gastrointest Endosc 2012; 75: 1092-1097
    CrossrefPubMedSearch in Google Scholar
  • 55 Uraoka T, Kawahara Y, Ohara N et al. Carbon dioxide submucosal injection cushion: an innovative technique in endoscopic submucosal dissection. Dig Endosc 2011; 23: 5-9
    CrossrefPubMedSearch in Google Scholar
  • 56 Chandrasekhara V, Sigmon Jr JC, Surti VC et al. A novel gel provides durable submucosal cushion for endoscopic mucosal resection and endoscopic submucosal dissection. Surg Endosc 2013; 27: 3039-3042
    CrossrefPubMedSearch in Google Scholar
  • 57 Yoshida N, Naito Y, Kugai M et al. Efficacy of hyaluronic acid in endoscopic mucosal resection of colorectal tumors. J Gastroenterol Hepatol 2011; 26: 286-291
    Search in Google Scholar
  • 58 Ishizuka T, Ishihara M, Aiko S et al. Experimental evaluation of photocrosslinkable chitosan hydrogel as injection solution for endoscopic resection. Endoscopy 2009; 41: 25-28
    Thieme ConnectPubMedSearch in Google Scholar