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Published in:

01-01-2014

Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy

Authors: Jun Yan, Shuangmu Zhuo, Gang Chen, Jeffrey W. Milsom, Hui Zhang, Jianping Lu, Weifeng Zhu, Shusen Xie, Jianxin Chen, Mingang Ying

Published in: Surgical Endoscopy | Issue 1/2014

Abstract

Background

Multiphoton microscopy (MPM), based on advances in the field of nonlinear optics and femtosecond lasers, has been shown to provide detailed real-time information on tissue architecture and cell morphology in live tissue. The purpose of this study was to evaluate the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancers.

Methods

Thirty fresh, unfixed, and unstained full-thickness surgical margins of low rectal cancers underwent MPM examination and then went through intraoperative frozen procedures and routine pathological procedures. MPM images were compared with the gold standard hematoxylin–eosin (H–E) stained images.

Results

MPM images were acquired by two channels: broadband autofluorescence from cells and second harmonic generation (SHG) from tissue collagen. Peak multiphoton signal intensity was detected in mucosa excited at 800 nm. There were significant differences between negative surgical margins and positive surgical margins under MPM examination. In negative surgical margins, MPM revealed regular tissue architecture and cell morphology, including a typical foveolar pattern with central, round crypt openings, and glands lined by epithelial and goblet cells. SHG signals could be detected around the glands. In positive surgical margins, MPM demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphisms. Cancer cells were characterized by an irregular size and shape, enlarged nuclei, and an increased nuclear–cytoplasmic ratio. SHG signals were significantly decreased in positive surgical margins compared with negative surgical margins. MPM images were comparable to H–E stained images.

Conclusions

We demonstrated the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancer. With the miniaturization and integration of colonoscopy or probes, MPM has the potential to provide real-time noninvasive optical diagnosis for surgical margins in low rectal cancer in the near future.

Jeyarajah S, Sutton CD, Miller AS, Hemingway D, Leicester Colorectal Specialist Group (2007) Factors that influence the adequacy of total mesorectal excision for rectal cancer. Colorectal Dis 9:808–815PubMedCrossRef

Cecil TD, Sexton R, Moran BJ, Heald RJ (2004) Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer. Dis Colon Rectum 47:1145–1150PubMedCrossRef

Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK (1998) Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg 133:894–899PubMedCrossRef

MacFarlane JK, Ryall RD, Heald RJ (1993) Mesorectal excision for rectal cancer. Lancet 341:457–460PubMedCrossRef

Vernava AM III, Moran M, Rothenberger DA, Wong WD (1992) A prospective evaluation of distal margins in carcinoma of the rectum. Surg Gynecol Obstet 175:333–336PubMed

Wibe A, Rendedal PR, Svensson E, Norstein J, Eide TJ, Myrvold HE, Søreide O (2002) Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer. Br J Surg 89:327–334PubMedCrossRef

Quirke P, Dixon MF (1998) The prediction of local recurrence in rectal adenocarcinoma by histopathological examination. Int J Colorectal Dis 3:127–131CrossRef

Adam IJ, Mohamdee MO, Martin IG, Scott N, Finan PJ, Johnston D, Dixon MF, Quirke P (1994) Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 344:707–711PubMedCrossRef

Luna-Perez P, Bustos-Cholico E, Alvarado I, Maffuz A, Rodríguez-Ramírez S, Gutiérrez de la Barrera M, Labastida S (2005) Prognostic significance of circumferential margin involvement in rectal adenocarcinoma treated with preoperative chemoradiotherapy and low anterior resection. J Surg Oncol 90:20–25PubMedCrossRef

10.

Nagtegaal ID, Quirke P (2008) What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 26:303–312PubMedCrossRef

11.

Zipfel WR, Williams RM, Webb WW (2003) Nonlinear magic: multiphoton microscopy in the biosciences. Nat Biotechnol 21:1369–1377PubMedCrossRef

12.

Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat Methods 2:932–940PubMedCrossRef

13.

Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW (2003) Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci USA 100:7075–7080PubMedCrossRef

14.

Mukherjee S, Wysock JS, Ng CK, Akhtar M, Perner S, Lee M, Rubin MA, Maxfield FR, Webb WW, Scherr DS (2009) Human bladder cancer diagnosis using multiphoton microscopy. Proc Soc Photo Opt Instrum Eng 7161. doi: 10.1117/12.808314

15.

Zhuo S, Chen J, Luo T, Zou D (2006) Multimode nonlinear optical imaging of the dermis in ex vivo human skin based on the combination of multichannel mode and Lambda mode. Opt Exp 14:7810–7820CrossRef

16.

Camilleri-Brennan J, Steele RJ (2002) Objective assessment of morbidity and quality of life after surgery for low rectal cancer. Colorectal Dis 4:61–66PubMedCrossRef

17.

Zolciak A, Bujko K, Kepka L, Oledzki J, Rutkowski A, Nowacki MP (2006) Abdominoperineal resection or anterior resection for rectal cancer: patient preferences before and after treatment. Colorectal Dis 8:575–580PubMedCrossRef

18.

Pollett WG, Nicholls RJ (1983) The relationship between the extent of distal clearance and survival and local recurrence rates after curative anterior resection for carcinoma of the rectum. Ann Surg 198:159–163PubMedCrossRef

19.

Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely V, Zerbib F (2005) Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule. Ann Surg 241:465–469PubMedCrossRef

20.

Tewari AK, Shevchuk MM, Sterling J, Grover S, Herman M, Yadav R, Mudalair K, Srivastava A, Rubin MA, Zipfel WR, Maxfield FR, Xu C, Webb WW, Mukherjee S (2011) Multiphoton microscopy for structure identification in human prostate and periprostatic tissue: implications in prostate cancer surgery. BJU Int 108(9):1421–1429PubMedCentralPubMedCrossRef

21.

Rogart JN, Nagata J, Loeser CS, Roorda RD, Aslanian H, Robert ME, Zipfel WR, Nathanson MH (2008) Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo. Clin Gastroenterol Hepatol 6:95–101PubMedCentralPubMedCrossRef

22.

Zhuo S, Chen J, Xie S, Hong Z, Jiang X (2009) Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals. J Biomed Opt 14(2):020503PubMedCrossRef

23.

Yan J, Chen G, Chen J, Liu N, Zhuo S, Yu H, Ying M (2011) A pilot study of using multiphoton microscopy to diagnose gastric cancer. Surg Endosc 25(5):1425–1430PubMedCrossRef

24.

Ying M, Zhuo S, Chen G, Zhuo C, Lu J, Zhu W, Xie S, Chen J, Yan J (2012) Real-time noninvasive optical diagnosis for colorectal cancer using multiphoton microscopy. Scanning 34(3):181–185PubMedCrossRef

25.

Wu X, Chen G, Lu J, Zhu W, Qiu J, Chen J, Xie S, Zhuo S, Yan J (2013) Label-free detection of breast masses using multiphoton microscopy. PLoS One 8(6):e65933PubMedCentralPubMedCrossRef

26.

Zhuo S, Zheng L, Chen J, Xie S, Zhu X, Jiang X (2010) Depth-cumulated epithelial redox ratio and stromal collagen quantity as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues. Appl Phys Lett 97:173701CrossRef

27.

Makino T, Jain M, Montrose DC, Aggarwal A, Sterling J, Bosworth BP, Milsom JW, Robinson BD, Shevchuk MM, Kawaguchi K, Zhang N, Brown CM, Rivera DR, Williams WO, Xu C, Dannenberg AJ, Mukherjee S (2012) Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia. Cancer Prev Res (Phila) 5(11):1280–1290CrossRef

28.

Bird D, Gu M (2003) Two-photon fluorescence endoscopy with a micro-optic scanning head. Opt Lett 28(17):1552–1554PubMedCrossRef

29.

Jung JC, Schnitzer MJ (2003) Multiphoton endoscopy. Opt Lett 28:902–904PubMedCrossRef

30.

Liu G, Xie T, Tomov IV, Su J, Yu L, Zhang J, Tromberg BJ, Chen Z (2009) Rotational multiphoton endoscopy with a 1 micron fiber laser system. Opt Lett 34:2249–2251PubMedCentralPubMedCrossRef

31.

Tang S, Jung W, McCormick D, Xie T, Su J, Ahn YC, Tromberg BJ, Chen Z (2009) Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning. J Biomed Opt 14:034005PubMedCentralPubMedCrossRef

32.

Ouzounov DG, Moll KD, Foster MA, Zipfel WR, Webb WW, Gaeta AL (2002) Delivery of nanojoule femtosecond pulses through large-core microstructured fibers. Opt Lett 27:1513–1515PubMedCrossRef

33.

König K (2008) Clinical multiphoton tomography. J Biophotonics 1:13–23PubMedCrossRef

Title: Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy
Authors: Jun Yan
Shuangmu Zhuo
Gang Chen
Jeffrey W. Milsom
Hui Zhang
Jianping Lu
Weifeng Zhu
Shusen Xie
Jianxin Chen
Mingang Ying
Publication date: 01-01-2014
Publisher: Springer US
Published in: Surgical Endoscopy / Issue 1/2014
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI: https://doi.org/10.1007/s00464-013-3153-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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