A feasibility study of chemically assisted endoscopic submucosal mechanical dissection using mesna for superficial esophageal squamous cell carcinomas



Injection of mesna into submucosal layers was recently reported to chemically soften connective tissue and facilitate the gastric endoscopic submucosal dissection (ESD) procedure. This study aimed to evaluate the safety and feasibility of similarly using mesna for esophageal ESD (mesna ESD).


We performed mesna ESD in 20 consecutive patients with superficial esophageal squamous cell carcinomas (SESCCs). To do this, a submucosal fluid cushion was initially formed using sodium hyaluronate, and the esophageal lesion was circumferentially isolated with a short blade needle-knife. Mesna solution was then injected into the submucosal layer, which was dissected mechanically by cleavage using the tip of a cap-fitted endoscope. The number of electrosurgical incisions was recorded by computer software in real time. The data from 20 conventional ESD procedures without mesna (consecutive 10 SESCCs pre and post the 20 consecutive mesna ESD) were used for comparison to evaluate the mesna ESD.


The mesna ESDs achieved en bloc and R0 resection success rates of 100 and 95 %, respectively. There was no perforation or uncontrollable hemorrhage during and after mesna ESD, and the median procedural time of submucosal dissection was significantly less with mesna ESD than with conventional ESD (median; 8 vs. 15 min, P < 0.05). There were also significantly fewer electrosurgical incisions made during the mesna ESD than with conventional ESDs (median; 65 vs. 183 times, P < 0.01).


Mesna ESD for SESCCs is a safe procedure with the potential to facilitate esophageal ESD.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Fig. 1
Fig. 2
Fig. 3



Endoscopic submucosal dissection


Superficial esophageal squamous cell carcinoma


Endoscopic mucosal resection


Squamous cell carcinoma


High-grade intraepithelial neoplasia


Narrow band imaging




Lamina propria mucosae


Muscularis mucosae




  1. 1.

    Oyama T, Tomori A, Hotta K, Morita S, Kominato K, Tanaka M, Miyata Y (2005) Endoscopic submucosal dissection of early esophageal cancer. Clin Gastroenterol Hepatol 3:S67–S70

  2. 2.

    Ono S, Fujishiro M, Niimi K, Goto O, Kodashima S, Yamamichi N, Omata M (2009) Long-term outcomes of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. Gastrointest Endosc 70:860–866. doi:10.1016/j.gie.2009.04.044

  3. 3.

    Fujishiro M, Kodashima S, Goto O, Ono S, Niimi K, Yamamichi N, Oka M, Ichinose M, Omata M (2009) Endoscopic submucosal dissection for esophageal squamous cell neoplasms. Dig Endosc 21:109–115. doi:10.1111/j.1443-1661.2009.00837

  4. 4.

    Higuchi K, Tanabe S, Azuma M, Katada C, Sasaki T, Ishido K, Naruke A, Katada N, Koizumi W (2013) A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901). Gastrointest Endosc 78:704–710. doi:10.1016/j.gie.2013.04.182

  5. 5.

    Isomoto H, Yamaguchi N, Minami H, Nakao K (2013) Management of complications associated with endoscopic submucosal dissection/endoscopic mucosal resection for esophageal cancer. Dig Endosc 25(Suppl 1):29–38. doi:10.1111/j.1443-1661.2012.01388

  6. 6.

    Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F (2009) Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy 41:751–757. doi:10.1055/s-0029-1215053

  7. 7.

    Neuhaus H, Wirths K, Schenk M, Enderle MD, Schumacher B (2009) Randomized controlled study of EMR versus endoscopic submucosal dissection with a water-jet hybrid-knife of esophageal lesions in a porcine model. Gastrointest Endosc 70:112–120. doi:10.1016/j.gie.2008.10.042

  8. 8.

    Farhat S, Chaussade S, Ponchon T, Coumaros D, Charachon A, Barrioz T, Koch S, Houcke P, Cellier C, Heresbach D, Lepilliez V, Napoleon B, Bauret P, Coron E, Le Rhun M, Bichard P, Vaillant E, Calazel A, Bensoussan E, Bellon S, Mangialavori L, Robin F, Prat F, SFED ESD study group (2011) Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development. Endoscopy 43:664–670. doi:10.1055/s-0030-1256413

  9. 9.

    Akahoshi K, Minoda Y, Komori K, Motomura Y, Kubokawa M, Otsuka Y, Hamada S, Fukuda S, Iwao R, Gibo J, Oya M, Nakamura K (2013) Endoscopic submucosal dissection using the “Clutch Cutter” for early esophageal squamous cell carcinoma. Endoscopy 45:1035–1038. doi:10.1055/s-0033-1344863

  10. 10.

    Fujishiro M, Kodashima S, Goto O, Ono S, Muraki Y, Kakushima N, Omata M (2008) Successful en bloc resection of superficial esophageal cancer treated by endoscopic submucosal dissection with a splash needle. Endoscopy 40(Suppl 2):E81–E82. doi:10.1055/s-2007-995538

  11. 11.

    Fujinami H, Hosokawa A, Ogawa K, Nishikawa J, Kajiura S, Ando T, Ueda A, Yoshita H, Sugiyama T (2014) Endoscopic submucosal dissection for superficial esophageal neoplasms using the stag beetle knife. Dis Esophagus 27:50–54. doi:10.1111/dote.12039

  12. 12.

    Kawahara Y, Hori K, Takenaka R, Nasu J, Kawano S, Kita M, Tsuzuki T, Matsubara M, Kobayashi S, Okada H, Yamamoto K (2013) Endoscopic submucosal dissection of esophageal cancer using the Mucosectom2 device: a feasibility study. Endoscopy 45:869–875. doi:10.1055/s-0033-1344229

  13. 13.

    Dobashi A, Sumiyama K, Gostout CJ, Ohya TR, Kobayashi M, Imazu H, Tajiri H (2013) Can mechanical balloon dissection be applied to cleave fibrotic submucosal tissues? A pilot study in a porcine model. Endoscopy 45:661–666. doi:10.1055/s-0033-1344126

  14. 14.

    Sumiyama K, Tajiri H, Gostout CJ, Kawamura M, Imazu H, Ohya TR, Ikeda K, Goda K, Saito S, Kato T (2010) Chemically assisted submucosal injection facilitates endoscopic submucosal dissection of gastric neoplasms. Endoscopy 42:627–632. doi:10.1055/s-0029-1244223

  15. 15.

    Sumiyama K, Gostout CJ, Rajan E, Bakken TA, Knipschield MA (2008) Chemically assisted endoscopic mechanical submucosal dissection by using mesna. Gastrointest Endosc 67:534–538. doi:10.1016/j.gie.2007.10.041

  16. 16.

    Sumiyama K, Toyoizumi H, Ohya TR, Dobashi A, Hino S, Kobayashi M, Goda K, Imazu H, Kawakita Y, Kato T, Tajiri H (2014) 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 79:756–764. doi:10.1016/j.gie.2013.09.027

  17. 17.

    Gostout CJ, Knipschield MA (2012) Submucosal endoscopy with mucosal resection: a hybrid endoscopic submucosal dissection in the porcine rectum and distal colon. Gastrointest Endosc 76:829–834. doi:10.1016/j.gie.2012.05.037

  18. 18.

    Willingham FF, Gee DW, Sylla P, Lauwers GY, Rattner DW, Brugge WR (2009) En bloc esophageal mucosectomy for concentric circumferential mucosal resection (with video). Gastrointest Endosc 69:147–151. doi:10.1016/j.gie.2008.09.010

  19. 19.

    Inoue H, Honda T, Nagai K, Kawano T, Yoshino K, Takeshita K, Endo M (1997) Ultra-high magnification endoscopic observation of carcinoma in situ of the esophagus. Dig Endosc 9:16–18

  20. 20.

    Goda K, Tajiri H, Ikegami M, Yoshida Y, Yoshimura N, Kato M, Sumiyama K, Imazu H, Matsuda K, Kaise M, Kato T, Omar S (2009) Magnifying endoscopy with narrow band imaging for predicting the invasion depth of superficial esophageal squamous cell carcinoma. Dis Esophagus 22:453–460. doi:10.1111/j.1442-2050.2009.00942

  21. 21.

    Benassi L, Lopopolo G, Pazzoni F, Ricci L, Kaihura C, Piazza F, Vadora E, Zini C (2000) Chemically assisted dissection of tissues: an interesting support in abdominal myomectomy. J Am Coll Surg 191:65–69 S1072-7515(00)00296-9

  22. 22.

    Reinhart WH, Baerlocher GM, Cerny T, Owen GR, Meiselman HJ, Beer JH (1999) Ifosfamide-induced stomatocytosis and mesna-induced echinocytosis: influence on biorheological properties of blood. Eur J Haematol 62:223–230

  23. 23.

    Ajmal N, Riordan CL, Cardwell N, Nanney LB, Shack RB (2003) Chemically assisted capsulectomy in the rabbit model: a new approach. Plast Reconstr Surg 112:1449–1454. doi:10.1097/01.PRS.0000081069.87802.98 discussion 1462-3

  24. 24.

    The Japan Esophageal Society (2008) Japanese Classification of Esophageal Cancer, 10th edn. Kanehara & Co Ltd Tokyo, Japan

  25. 25.

    Ono H, Kondo H, Gotoda T, Shirao K, Yamaguchi H, Saito D, Hosokawa K, Shimoda T, Yoshida S (2001) Endoscopic mucosal resection for treatment of early gastric cancer. Gut 48:225–229

  26. 26.

    Sato H, Inoue H, Ikeda H, Grace R, Santi E, Yoshida A, Onimaru M, Kudo S (2013) Clinical experience of esophageal perforation occurring with endoscopic submucosal dissection. Dis Esophagus. doi:10.1111/dote.12125

  27. 27.

    Bombeck CT, Dillard DH, Nyhus LM (1966) Muscular anatomy of the gastroesophageal junction and role of phrenoesophageal ligament; autopsy study of sphincter mechanism. Ann Surg 164:643–654

  28. 28.

    Goda K, Fujishiro M, Hirasawa K, Kakushima N, Morita Y, Oda I, Takeuchi M, Yamamoto Y, Uedo N (2012) How to teach and learn endoscopic submucosal dissection for upper gastrointestinal neoplasm in Japan. Dig Endosc 24(Suppl 1):136–142. doi:10.1111/j.1443-1661.2012.01274

Download references


A part of this paper was presented as a video poster at United European Gastroenterology Week, 12-16th October 2013, Berlin, Germany.


Drs. Akira Dobashi, Kenichi Goda, Kazuki Sumiyama, Masakuni Kobayashi, Tomohiko R Ohya, Masayuki Kato, Hirobumi Toyoizumi, Tomohiro Kato, Masato Matsushima, and Hisao Tajiri have no conflicts of interest or financial ties to disclose.

Author information

Correspondence to Akira Dobashi.

Electronic supplementary material

Below is the link to the electronic supplementary material.

The procedural steps of mesna ESD with mechanical submucosal dissection. (WMV 47662 kb)

The procedural steps of mesna ESD with mechanical submucosal dissection. (WMV 47662 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dobashi, A., Goda, K., Sumiyama, K. et al. A feasibility study of chemically assisted endoscopic submucosal mechanical dissection using mesna for superficial esophageal squamous cell carcinomas. Surg Endosc 29, 3373–3381 (2015) doi:10.1007/s00464-014-4031-7

Download citation


  • Endoscopic resection
  • Endoscopic submucosal dissection
  • Mechanical submucosal dissection
  • Mesna
  • Superficial esophageal squamous cell carcinoma