Skip to main content
SpringerLink
Log in

Confocal Laser Endomicroscopy

  • Chapter
  • First Online:
Diagnostic and Therapeutic Procedures in Gastroenterology

Part of the book series: Clinical Gastroenterology ((CG))

  • 1842 Accesses

Abstract

Confocal laser endomicroscopes (CLEs) provide the highest magnification in clinical endoscopy and have been commercially available since 2005 [1]. A CLE is an instrument providing ×1,000 black and white imaging that is comparable to standard microscopic examination. The principle technique is a summary of display images that are reconstructed from a pinhole that filters only a focused light and reflected plane. In addition, the pinhole reduces light scatter below and above the plane (Fig. 10.1). Therefore, only a single point in one plane, called “confocal,” can be seen at once [2]. During the examination, the confocal system can display a stream of images with 1–12 frames/second. In other words, it resembles real-time endoscopic histology images [3–7].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kiesslich R, Burg J, Vieth M, Gnaendiger J, Enders M, Delaney P. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology. 2004;127:706–13.

    Article  PubMed  Google Scholar 

  2. Meining A. Confocal endomicroscopy. Gastrointest Endosc Clin N Am. 2009;19(4):629–35.

    Article  PubMed  Google Scholar 

  3. Polglase AL, McLaren WJ, Skinner SA, Kiesslich R, Neurath MF, Delaney PM. A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest Endosc. 2005;62(5):686–95.

    Article  PubMed  Google Scholar 

  4. Kakeji Y, Yamaguchi S, Yoshida D, Tanoue K, Ueda M, Masunari A, et al. Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study. Endoscopy. 2006;38(9):886–90.

    Article  CAS  PubMed  Google Scholar 

  5. Kitabatake S, Niwa Y, Miyahara R, Ohashi A, Matsuura T, Iguchi Y, et al. Confocal endomicroscopy for the diagnosis of gastric cancer in vivo. Endoscopy. 2006;38(11):1110–4.

    Article  CAS  PubMed  Google Scholar 

  6. Hoffman A, Goetz M, Vieth M, Galle PR, Neurath MF, Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy. 2006;38(12):1275–83.

    Article  CAS  PubMed  Google Scholar 

  7. Nguyen NQ, Leong RW. Current application of confocal endomicroscopy in gastrointestinal disorders. J Gastroenterol Hepatol. 2008;23(10):1483–91.

    Article  PubMed  Google Scholar 

  8. Committee AT. Confocal laser endomicroscopy. Gastrointest Endosc. 2014;80(6):928–38.

    Article  Google Scholar 

  9. Giovannini M. Needle-based confocal laser endomicroscopy. Endosc Ultrasound. 2015;4(4):284–8.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Shahid MW, Crook JE, Meining A, Perchant A, Buchner A, Gomez V, et al. Exploring the optimal fluorescein dose in probe-based confocal laser endomicroscopy for colonic imaging. J Interv Gastroenterol. 2011;1(4):166–71.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Becker V, von Delius S, Bajbouj M, Karagianni A, Schmid RM, Meining A. Intravenous application of fluorescein for confocal laser scanning microscopy: evaluation of contrast dynamics and image quality with increasing injection-to-imaging time. Gastrointest Endosc. 2008;68(2):319–23.

    Article  PubMed  Google Scholar 

  12. Dunbar KB, Okolo P 3rd, Montgomery E, Canto MI. Confocal laser endomicroscopy in Barrett’s esophagus and endoscopically inapparent Barrett’s neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc. 2009;70(4):645–54.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, Roesch T, et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther. 2010;31(5):548–52.

    Article  CAS  PubMed  Google Scholar 

  14. Obstoy B, Salaun M, Veresezan L, Sesboue R, Bohn P, Boland FX, et al. Safety and performance analysis of acriflavine and methylene blue for in vivo imaging of precancerous lesions using fibered confocal fluorescence microscopy (FCFM): an experimental study. BMC Pulm Med. 2015;15:30.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bisschops R, Bergman J. Probe-based confocal laser endomicroscopy: scientific toy or clinical tool? Endoscopy. 2010;42(6):487–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wang KK, Sampliner RE. Practice Parameters Committee of the American College of G. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103(3):788–97.

    Article  PubMed  Google Scholar 

  17. American Society for Gastrointestinal Endoscopy Standards of Practice C, Anderson MA, Appalaneni V, Ben-Menachem T, Decker GA, Early DS, et al. The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc. 2013;77(2):167–74.

    Article  Google Scholar 

  18. Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatol Off J Int Assoc Pancreatol. 2012;12(3):183–97.

    Article  Google Scholar 

  19. Sharma P, Brill J, Canto M, DeMarco D, Fennerty B, Gupta N, et al. White paper AGA: advanced imaging in Barrett’s esophagus. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2015;13(13):2209–18.

    Google Scholar 

  20. Lee SK. Usefulness and future prospects of confocal laser endomicroscopy for gastric premalignant and malignant lesions. Clin Endosc. 2015;48(6):511–5.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chu CL, Zhen YB, Lv GP, Li CQ, Li Z, Qi QQ, et al. Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012;107(6):864–74.

    Article  PubMed  Google Scholar 

  22. Venkatesh K, Cohen M, Abou-Taleb A, Thomas S, Taylor C, Thomson M. A new method in the diagnosis of reflux esophagitis: confocal laser endomicroscopy. Gastrointest Endosc. 2012;75(4):864–9.

    Article  PubMed  Google Scholar 

  23. Pittayanon R, Aumkaew S, Rerknimitr R, Wisedopas N, Kullavanijaya P. Flexible spectral imaging color enhancement and probe-based confocal laser endomicroscopy in minimal change esophageal reflux disease. Korean J Gastroenterol. 2016;68(1):29–35.

    Article  PubMed  Google Scholar 

  24. Kiesslich R, Gossner L, Goetz M, Dahlmann A, Vieth M, Stolte M, et al. In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2006;4(8):979–87.

    Google Scholar 

  25. Dunbar KB, Canto MI. Confocal laser endomicroscopy in Barrett’s esophagus and endoscopically inapparent Barrett’s neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc. 2010;72(3):668.

    Article  PubMed  Google Scholar 

  26. Pohl H, Rosch T, Vieth M, Koch M, Becker V, Anders M, et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett’s oesophagus. Gut. 2008;57(12):1648–53.

    Article  CAS  PubMed  Google Scholar 

  27. Wallace MB, Sharma P, Lightdale C, Wolfsen H, Coron E, Buchner A, et al. Preliminary accuracy and interobserver agreement for the detection of intraepithelial neoplasia in Barrett’s esophagus with probe-based confocal laser endomicroscopy. Gastrointest Endosc. 2010;72(1):19–24.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gaddam S, Mathur SC, Singh M, Arora J, Wani SB, Gupta N, et al. Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett’s esophagus. Am J Gastroenterol. 2011;106(11):1961–9.

    Article  PubMed  Google Scholar 

  29. Sharma P, Meining AR, Coron E, Lightdale CJ, Wolfsen HC, Bansal A, et al. Real-time increased detection of neoplastic tissue in Barrett’s esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial. Gastrointest Endosc. 2011;74(3):465–72.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wang KK, Carr-Locke DL, Singh SK, Neumann H, Bertani H, Galmiche JP, et al. Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. United European Gastroenterol J. 2015;3(3):230–54.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pech O, Rabenstein T, Manner H, Petrone MC, Pohl J, Vieth M, et al. Confocal laser endomicroscopy for in vivo diagnosis of early squamous cell carcinoma in the esophagus. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2008;6(1):89–94.

    Google Scholar 

  32. Deinert K, Kiesslich R, Vieth M, Neurath MF, Neuhaus H. In-vivo microvascular imaging of early squamous-cell cancer of the esophagus by confocal laser endomicroscopy. Endoscopy. 2007;39(4):366–8.

    Article  CAS  PubMed  Google Scholar 

  33. Liu H, Li YQ, Yu T, Zhao YA, Zhang JP, Zuo XL, et al. Confocal laser endomicroscopy for superficial esophageal squamous cell carcinoma. Endoscopy. 2009;41(2):99–106.

    Article  CAS  PubMed  Google Scholar 

  34. Prueksapanich P, Pittayanon R, Rerknimitr R, Wisedopas N, Kullavanijaya P. Value of probe-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in diagnosing early squamous cell neoplasms in esophageal Lugol’s voiding lesions. Endosc Int Open. 2015;3(4):E281–8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Li WB, Zuo XL, Li CQ, Zuo F, Gu XM, Yu T, et al. Diagnostic value of confocal laser endomicroscopy for gastric superficial cancerous lesions. Gut. 2011;60(3):299–306.

    Article  PubMed  Google Scholar 

  36. Li Z, Zuo XL, Li CQ, Liu ZY, Ji R, Liu J, et al. New classification of gastric pit patterns and vessel architecture using probe-based confocal laser endomicroscopy. J Clin Gastroenterol. 2016;50(1):23–32.

    Article  CAS  PubMed  Google Scholar 

  37. Li Z, Zuo XL, Yu T, Gu XM, Zhou CJ, Li CQ, et al. Confocal laser endomicroscopy for in vivo detection of gastric intestinal metaplasia: a randomized controlled trial. Endoscopy. 2014;46(4):282–90.

    Article  PubMed  Google Scholar 

  38. Liu T, Zheng H, Gong W, Chen C, Jiang B. The accuracy of confocal laser endomicroscopy, narrow band imaging, and chromoendoscopy for the detection of atrophic gastritis. J Clin Gastroenterol. 2015;49(5):379–86.

    Article  PubMed  Google Scholar 

  39. Guo YT, Li YQ, Yu T, Zhang TG, Zhang JN, Liu H, et al. Diagnosis of gastric intestinal metaplasia with confocal laser endomicroscopy in vivo: a prospective study. Endoscopy. 2008;40(7):547–53.

    Article  PubMed  Google Scholar 

  40. Pittayanon R, Rerknimitr R, Wisedopas N, Ridtitid W, Kongkam P, Treeprasertsuk S, et al. Flexible spectral imaging color enhancement plus probe-based confocal laser endomicroscopy for gastric intestinal metaplasia detection. J Gastroenterol Hepatol. 2013;28(6):1004–9.

    Article  PubMed  Google Scholar 

  41. Lim LG, Yeoh KG, Srivastava S, Chan YH, Teh M, Ho KY. Comparison of probe-based confocal endomicroscopy with virtual chromoendoscopy and white-light endoscopy for diagnosis of gastric intestinal metaplasia. Surg Endosc. 2013;27(12):4649–55.

    Article  PubMed  Google Scholar 

  42. Correa P, Piazuelo MB, Wilson KT. Pathology of gastric intestinal metaplasia: clinical implications. Am J Gastroenterol. 2010;105(3):493–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rokkas T, Filipe MI, Sladen GE. Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 1991;32(10):1110–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Pittayanon R, Rerknimitr R, Wisedopas N, Khemnark S, Thanapirom K, Thienchanachaiya P, et al. The learning curve of gastric intestinal metaplasia interpretation on the images obtained by probe-based confocal laser endomicroscopy. Diagn Ther Endoscopy. 2012;2012:278045.

    Google Scholar 

  45. Leong RW, Nguyen NQ, Meredith CG, Al-Sohaily S, Kukic D, Delaney PM, et al. In vivo confocal endomicroscopy in the diagnosis and evaluation of celiac disease. Gastroenterology. 2008;135(6):1870–6.

    Article  PubMed  Google Scholar 

  46. Gunther U, Daum S, Heller F, Schumann M, Loddenkemper C, Grunbaum M, et al. Diagnostic value of confocal endomicroscopy in celiac disease. Endoscopy. 2010;42(3):197–202.

    Article  CAS  PubMed  Google Scholar 

  47. Pohl H, Tanczos BT, Rudolph B, Meining A, Khalifa AC, Rosch T, et al. Probe-based confocal laser microscopy identifies criteria predictive of active celiac sprue. Dig Dis Sci. 2012;57(2):451–7.

    Article  PubMed  Google Scholar 

  48. Shahid MW, Buchner A, Gomez V, Krishna M, Woodward TA, Raimondo M, et al. Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging in detection of dysplasia in duodenal polyps. J Clin Gastroenterol. 2012;46(5):382–9.

    Article  PubMed  Google Scholar 

  49. Pittayanon R, Rerknimitr R, Imraporn B, Wisedopas N, Kullavanijaya P. Diagnostic values of dual focus narrow band imaging and probe-based confocal laser endomicroscopy in FAP-related duodenal adenoma. Endoscopy Int Open. 2015;3(5):E450–5.

    Article  Google Scholar 

  50. Kiesslich R, Goetz M, Lammersdorf K, Schneider C, Burg J, Stolte M, et al. Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis. Gastroenterology. 2007;132(3):874–82.

    Article  PubMed  Google Scholar 

  51. Neumann H, Vieth M, Atreya R, Grauer M, Siebler J, Bernatik T, et al. Assessment of Crohn’s disease activity by confocal laser endomicroscopy. Inflamm Bowel Dis. 2012;18(12):2261–9.

    Article  PubMed  Google Scholar 

  52. Li CQ, Xie XJ, Yu T, Gu XM, Zuo XL, Zhou CJ, et al. Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy. Am J Gastroenterol. 2010;105(6):1391–6.

    Article  PubMed  Google Scholar 

  53. Liu JJ, Wong K, Thiesen AL, Mah SJ, Dieleman LA, Claggett B, et al. Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest Endosc. 2011;73(6):1174–80.

    Article  PubMed  Google Scholar 

  54. Turcotte JF, Wong K, Mah SJ, Dieleman LA, Kao D, Kroeker K, et al. Increased epithelial gaps in the small intestine are predictive of hospitalization and surgery in patients with inflammatory bowel disease. Clin Transl Gastroenterol. 2012;3:e19.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Atreya R, Neumann H, Neufert C, Waldner MJ, Billmeier U, Zopf Y, et al. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease. Nat Med. 2014;20(3):313–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rasmussen DN, Karstensen JG, Riis LB, Brynskov J, Vilmann P. Confocal laser endomicroscopy in inflammatory bowel disease – a systematic review. J Crohns Colitis. 2015;9(12):1152–9.

    Article  PubMed  Google Scholar 

  57. Rex DK, Kahi C, O'Brien M, Levin TR, Pohl H, Rastogi A, et al. The American society for gastrointestinal endoscopy PIVI (Preservation and incorporation of valuable endoscopic innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps. Gastrointest Endosc. 2011;73(3):419–22.

    Article  PubMed  Google Scholar 

  58. Sharma P, Gupta N, Kuipers EJ, Repici A, Wallace M. Advanced imaging in colonoscopy and its impact on quality. Gastrointest Endosc. 2014;79(1):28–36.

    Article  PubMed  Google Scholar 

  59. Shahid MW, Buchner AM, Heckman MG, Krishna M, Raimondo M, Woodward T, et al. Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging for small colorectal polyps: a feasibility study. Am J Gastroenterol. 2012;107(2):231–9.

    Article  PubMed  Google Scholar 

  60. Buchner AM, Shahid MW, Heckman MG, Krishna M, Ghabril M, Hasan M, et al. Comparison of probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology. 2010;138(3):834–42.

    Article  PubMed  Google Scholar 

  61. Buchner AM, Gomez V, Heckman MG, Shahid MW, Achem S, Gill KR, et al. The learning curve of in vivo probe-based confocal laser endomicroscopy for prediction of colorectal neoplasia. Gastrointest Endosc. 2011;73(3):556–60.

    Article  PubMed  Google Scholar 

  62. Wanders LK, East JE, Uitentuis SE, Leeflang MM, Dekker E. Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis. Lancet Oncol. 2013;14(13):1337–47.

    Article  PubMed  Google Scholar 

  63. Meining A, Frimberger E, Becker V, Von Delius S, Von Weyhern CH, Schmid RM, et al. Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2008;6(9):1057–60.

    Google Scholar 

  64. Meining A, Chen YK, Pleskow D, Stevens P, Shah RJ, Chuttani R, et al. Direct visualization of indeterminate pancreaticobiliary strictures with probe-based confocal laser endomicroscopy: a multicenter experience. Gastrointest Endosc. 2011;74(5):961–8.

    Article  PubMed  Google Scholar 

  65. Caillol F, Filoche B, Gaidhane M, Kahaleh M. Refined probe-based confocal laser endomicroscopy classification for biliary strictures: the Paris classification. Dig Dis Sci. 2013;58(6):1784–9.

    Article  PubMed  Google Scholar 

  66. Slivka A, Gan I, Jamidar P, Costamagna G, Cesaro P, Giovannini M, et al. Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study. Gastrointest Endosc. 2015;81(2):282–90.

    Article  PubMed  Google Scholar 

  67. Konda VJ, Meining A, Jamil LH, Giovannini M, Hwang JH, Wallace MB, et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy. 2013;45(12):1006–13.

    Article  PubMed  Google Scholar 

  68. Napoleon B, Lemaistre AI, Pujol B, Caillol F, Lucidarme D, Bourdariat R, et al. A novel approach to the diagnosis of pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy. 2015;47(1):26–32.

    PubMed  Google Scholar 

  69. Giovannini M, Caillol F, Poizat F, Bories E, Pesenti C, Monges G, et al. Feasibility of intratumoral confocal microscopy under endoscopic ultrasound guidance. Endosc Ultrasound. 2012;1(2):80–3.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kongkam P, Pittayanon R, Sampatanukul P, Angsuwatcharakon P, Aniwan S, Prueksapanich P, et al. Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of solid pancreatic lesions (ENES): a pilot study. Endosc Int Open. 2016;4(1):E17–23.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, the Thai Red Cross, Bangkok, 10300, Thailand

    Rapat Pittayanon & Rungsun Rerknimitr

Authors
  1. Rapat Pittayanon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rungsun Rerknimitr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rapat Pittayanon .

Editor information

Editors and Affiliations

  1. Advanced Endoscopy, Digestive Health Center, Section of Gastroenterology & Hepatology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

    Subbaramiah Sridhar

  2. Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, Connecticut, USA

    George Y. Wu

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pittayanon, R., Rerknimitr, R. (2018). Confocal Laser Endomicroscopy. In: Sridhar, S., Wu, G. (eds) Diagnostic and Therapeutic Procedures in Gastroenterology. Clinical Gastroenterology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-62993-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-62993-3_10

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-62991-9

  • Online ISBN: 978-3-319-62993-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation