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Margin diagnosis for endoscopic submucosal dissection of early gastric cancer using multiphoton microscopy

  • Xiaoling Zheng
  • Ning Zuo
  • Hongxin Lin
  • Liqin Zheng
  • Ming Ni
  • Guizhu WuEmail author
  • Jianxin Chen
  • Shuangmu ZhuoEmail author
Article

Abstract

Background and Aims

Endoscopic submucosal dissection (ESD) has become the primary option for the treatment of early gastric cancer (EGC). Thus, it is necessary to diagnose whether residual cancer cells exist in the ESD specimen margins, which can affect tumor recurrence and survival rates in the future. Multiphoton microscopy (MPM) can be suitably used for nondestructive imaging of biological tissue on a cellular level to enable real-time guidance during endoscopic therapy. Considering this, the objective of this study is to explore the practicality of MPM for the diagnosis of ESD specimen margins in the case of EGC.

Methods

First, a total of 20 surgical samples was imaged using the proposed MPM technique to obtain two-photo excited fluorescence signal from the intrinsic fluorescent substances within cells and second-harmonic generation signal from collagen; these signals were used to determine MPM pathological features for margin diagnosis. Then, a double-blind study of 50 samples was conducted to evaluate the diagnosis results based on the obtained MPM pathological features.

Results

Multiphoton microscopy can accurately identify the cytological and morphological differences between tissue in the negative and positive margin. The sensitivity, specificity, accuracy, negative predictive, and positive predictive values of MPM in the diagnosis of ESD specimen margins were 97.62, 75.00, 94.00, 95.35, and 85.71%, respectively.

Conclusion

These results indicate that MPM can be used as an effective, real-time, and label-free novel method to determine intraoperative resection margins.

Keywords

Multiphoton microscopy Early gastric cancer Resection margin ESD 

Notes

Acknowledgements

This project was supported by the National Natural Science Foundation of China (81771881), the National Key Basic Research Program of China (2015CB352006), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R10), the Natural Science Foundation of Fujian Province (2018J07004, 2016J01433, 2018J01170, and 2018J01784), the Special Funds of the Central Government Guiding Local Science and Technology Development (2017L3009), the Science and Technology Planning Project of Guangdong Province (2016A020220014), and the Fujian Provincial Youth Top-notch Talent Support Program.

Disclosures

Xiaoling Zheng, Ning Zou, Hongxin Lin, Liqin Zheng, Ming Ni, Guizhu Wu, Jianxin Chen, and Shuangmu Zhuo, have no conflicts of interest or financial ties to disclose.

References

  1. 1.
    Ajani JA, Bentrem DJ, Besh S et al (2013) Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw 11(5):531–546CrossRefGoogle Scholar
  2. 2.
    Muto M, Miyamoto S, Hosokawa A et al (2005) Endoscopic mucosal resection in the stomach using the insulated-tip needle-knife. Endoscopy 37(2):178–182CrossRefPubMedGoogle Scholar
  3. 3.
    Jin SJ, Jeen YT, Kim ES et al (2009) Therapeutic outcomes in 1000 cases of endoscopic resection for gastric neoplastic lesions: single center study. Gastrointest Endosc 69(5):AB322Google Scholar
  4. 4.
    Yan J, Chen JX, Chen G et al (2011) A pilot study of using multiphoton microscopy to diagnose gastric cancer. Surg Endosc 25(5):1425–1430CrossRefPubMedGoogle Scholar
  5. 5.
    Lin HX, Lin LY, Wang GX et al (2018) Label-free classification of hepatocellular-carcinoma grading using second harmonic generation microscopy. Biomed Opt Express 9(8):3783–3793CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhuo SM, Yan J, Chen G et al (2011) Label-free monitoring of colonic cancer progression using multiphoton microscopy. Biomed Opt Express 2(3):615–619CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yan J, Zhuo SM, Gang C et al (2014) Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy. Surg Endosc 28(1):36–41CrossRefPubMedGoogle Scholar
  8. 8.
    Skala MC, Squirrell JM, Vrotsos KM et al (2005) Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues. Cancer Res 65(4):1180–1186CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Balu M, Zachary CB, Harris RM et al (2015) In vivo multiphoton microscopy of basal cell carcinoma. Jama Dermatol 151(10):1068–1074CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Tang S, Jung W, McCormick DT et al (2009) Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning. J Biomed Opt 14(3):034005CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Guillaume D, Pierre L, Tigran M et al (2015) Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal. Sci Rep 5:18303Google Scholar
  12. 12.
    Rivera D (2013) Multiphoton endoscopy. Opt Lett 28(11):902–904Google Scholar
  13. 13.
    Zhuo SM, Yan J, Kang YZ et al (2014) In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy. Appl Phys Lett 105:023701CrossRefGoogle Scholar
  14. 14.
    Oda I, Gotoda T, Hamanaka H et al (2005) Endoscopic submucosal dissection for early gastric cancer: technical feasibility, operation time and complications from a large consecutive series. Dig Endosc 17(1):54–58CrossRefGoogle Scholar
  15. 15.
    Skala MC, Riching KM, Gendron-Fitzpatrick A et al (2007) In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia. Proc Natl Acad Sci USA 104(49):19494CrossRefPubMedGoogle Scholar
  16. 16.
    Lacomb R, Nadiarnykh O, Townsend SS et al (2008) Phase matching considerations in second harmonic generation from tissues: effects on emission directionality, conversion efficiency and observed morphology. Opt Commun 281(7):1823–1832CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zipfel WR, Williams RM, Christie R et al (2003) Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci USA 100(12):7075–7080CrossRefPubMedGoogle Scholar
  18. 18.
    Ferlay J, Shin H, Bray F et al (2012) GLOBOCAN 2008 Cancer incidence and mortality worldwide: IARC CancerBase No. 10. Int J Cancer J Int Du Cancer 136(5):E359–E386CrossRefGoogle Scholar
  19. 19.
    Allemani C, Weir HK, Carreira H et al (2015) Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2. Lancet 385(9972):977–1010CrossRefPubMedGoogle Scholar
  20. 20.
    Kakushima N, Fujishiro M et al (2008) Endoscopic submucosal dissection for gastrointestinal neoplasms. World J Gastroenterol 14(19):2962–2967CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Javaid G, Shah OJ, Dar MA et al (2015) Role of endoscopic ultrasonography in preoperative staging of gastric carcinoma. ANZ J Surg 74(3):108–111CrossRefGoogle Scholar
  22. 22.
    East JE, Tan EK, Bergman JJ et al (2008) Meta-analysis: narrow band imaging for lesion characterization in the colon, oesophagus, duodenal ampulla and lung. Aliment Pharmacol Ther 28(7):854–867CrossRefPubMedGoogle Scholar
  23. 23.
    Nakayoshi T, Tajiri H, Matsuda K et al (2004) Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video). Endoscopy 36(12):1080–1084CrossRefPubMedGoogle Scholar
  24. 24.
    Banno K, Niwa Y, Miyahara R et al (2010) Confocal endomicroscopy for phenotypic diagnosis of gastric cancer. J Gastroenterol Hepatol 25(4):712–718CrossRefPubMedGoogle Scholar
  25. 25.
    Peter S, Council L, Ji YB et al (2014) Poor agreement between endoscopists and gastrointestinal pathologists for the interpretation of probe-based confocal laser endomicroscopy findings. World J Gastroenterol 20(47):17993–18000CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ji R, Zuo XL, Li CQ et al (2011) Confocal endomicroscopy for in vivo prediction of completeness after endoscopic mucosal resection. Surg Endosc 25(6):1933–1938CrossRefPubMedGoogle Scholar
  27. 27.
    Buchner AM, Shahid MW, Heckman MG et al (2010) Comparison of Probe-based confocal laser endomicroscopy with virtual chromoendoscopy for classification of colon polyps. Gastroenterology 138(3):834–842CrossRefPubMedGoogle Scholar
  28. 28.
    Fu L, Jain A, Xie H et al (2006) Nonlinear optical endoscopy based on a double-clad photonic crystal fiber and a MEMS mirror. Opt Express 14(3):1027–1032CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endoscopy, Fujian Provincal Hospital, Fujian Medical University & College of Photonic and Electronic EngineeringFujian Normal UniversityFuzhouChina
  2. 2.Fujian Provincial Key Laboratory for Photonics Technology & Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of EducationFujian Normal UniversityFuzhouChina
  3. 3.School of Biological Sciences & EngineeringYachay Tech UniversitySan Miguel de UrcuquíEcuador
  4. 4.Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghaiChina

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